AIDS: NAPLEX Review Initial treatment: NNRTI + 2 NRTIs or PI + 2 NRTIs NRTIs: o MOA: interfere with HIV viral RNA-dependent DNA polymerase, resulting in chain termination & inhibition of viral replication o Class toxicities: Lactic acidosis, sever hepatomegaly with steatosis Most require renal dosing (except abacavir) o Do not use lamivudine & emtricitabine together (chemically similar) o Do not use zidovudine with stavudine together (both require thymidine for activation) o Do not use didanosine with stavudine during pregnancy (increased risk of lactic acidosis & liver damage) o The “D” drugs cause pancreatitis & peripheral neuropathy & lactic acidosis ddI (didanosine), d4T (stavudine), ddC (zalcitabine) o Low pill burden o All are prodrugs requiring 2-3 phosphorylations for activation o Zidovudine (Retrovir): AZT, ZDV SE: bone marrow suppression, GI intolerance Dosage forms available: IV, 200 mg (10 mg/mL); syrup 50 mg/5 mL in 240 mL; capsule, 100 mg & tablet 300 mg o Lamivudine (Epivir): 3TC Minimal toxicity o Abacavir (Ziagen): ABC SE: hypersensitivity reaction that can be fatal with rechallenge o Didanosine (Videx, Videx EC): ddI Take ½ hour before or 2 hours after meals (empty stomach) SE: pancreatitis, peripheral neuropathy o Stavudine (Zerit): D4T SE: pancreatitis, peripheral neuropathy o Zalcitabine (Hivid): ddC SE: pancreatitis, peripheral neuropathy o Tenofovir (Viread): TDF SE: renal insufficiency o Emtricitabine (Emtriva): FTC Minimal toxicity o Combination products: Zidovudine 300 mg + lamivudine 150 mg (Combivir) Zidovudine 300 mg + lamivudine 150 mg + abacavir 300 mg (Trizivir) Tenofovir 300 mg + emtricitabine 200 mg (Truvada) Lamivudine 300 mg + abacavir 600 mg (Epzicom) NNRTIs: o MOA: bind to reverse transcriptase at a different site than the NRTIs, resulting in inhibition of HIV replication o Class toxicities: rash & hepatoxicity o All should be dosed for hepatic impairment o Most are affected by food (except efavirenz) o Efavirenz is CI in pregnancy Page 1 o o o PIs: o o o o o o o o o o o o o o o o Efavirenz (Sustiva): EFV Take on an empty stomach SE: CNS side effect; false + cannabinoid test Nevirapine (Viramune): NVP Autoinducer SE: rash, symptomatic hepatitis, including fatal hepatic necrosis Delavirdine (Rescriptor): DLV SE: rash, increased LFTs MOA: inhibit protease, which then prevents the cleavage of HIV polyproteins & subsequently induces the formation of immature noninfectious viral particles All should be dosed for hepatic impairment Most should be taken with food (except amprenavir & indinavir) Amprenavir & fosamprenavir are chemically similar- avoid combination Atazanavir & indinavir require normal acid levels in stomach for absorption Ritonavir is the most potent Lopinavir/ritonavir, ritonavir, & saquinavir gel caps require refrigeration Class toxicities: lipodystrophy, hyperglycemia, hyperlipidemia, hypertriglyceridemia, bleeding in hemophiliace, osteonecrosis & avascular neocrosis of the hips, osteopenia & osteoporosis All are CYP3A4 inhibitors Lopinavir + ritonavir (Kaletra): SE: GI intolerance Refrigerate caps stable until date on label; stable for 2 months at room temperature Atazanavir (Reyataz): ATV SE: increased indirect hyperbilirubinemia, prolonged PR interval Fosamprenavir (Lexiva): f-APV SE: rash Sulfonamide Oral solution contains propylene glycol Amprenavir (Agenerase): APV SE: rash Sulfonamide Avoid high fat meal Saquinavir: SQV-hard gel cap (HGC)- (Invirase): • SE: GI intolerance • Room temperature SQV- soft gel cap (SGC)- (Fortovase): • SE: GI intolerance • Refrigerated caps stable until date on label; stable for 3 months at room temperature HGC & SGC are not bioequivalent & should not be interchanged Nelfinavir (Viracept): NFV SE: diarrhea Needs 500 kCal of food for absorption; take after eating Ritonavir (Norvir) RTV SE: GI intolerance Refrigerated caps stable for 1 month at room temp Page 2 Indinavir (Crixivan): IDV SE: nephrolithiases- drink at least 48 oz. daily to prevent Take on an empty stomach Fusion inhibitors: o MOA: binds to gp41 on HIV surface, which inhibits HIV binding to CD4 cell o Enfuvirtide (Fuzeon) T20 Salvage regimens Reconstituted form should be stored in the refrigerator- stable for 24 hours Post-exposure Prophylaxis (PEP): o Start therapy within 1-2 hours of exposure o Length of therapy is 4 weeks o Treatment options: AZT 200 mg po Q8h or 300 mg po Q12h AND 3TC(lamivudine) 150 mg po Q12h AZT 200 mg po Q8h or 300 mg po Q12 + 3TC 150 mg po Q12h + Indinavir 800 mg Q8h • OR Nelfinvir 750 mg po Q8h or 1250 mg Q12h PCP treatment: o A protozoan, but may be more closely related to fungi o Treat when CD4+ cells fall below 200 o DOC: trimethoprim-sulfamethoxazole (Bactrim DS) DS po QD o Alternatives: TMP + dapsone Atovaquone (Mepron) Pentamidine (NebuPent; Pentam-300) • Comes as injection & powder for nebulization Clindamycin + primaquine Trimetrexate (NeuTrexin) + folinic acid o Treatment for PCP also covers prophylaxis for: toxoplasmosis CMV: Cytomegalovirus o Ganciclovir (Cytovene, Vitrasert): Use: treatment of CMV retinitis in immunocompromised individuals, including patients with AIDS CI: ANC <500/mm3 or PLT <25,000/mm3 Dosage forms: • Capsule (Cytovene) • Implant, intravitreal (Vitrasert)- 4.5 mg released gradually over 5-8 months • Injection, powder for reconstitution o Alzheimer’s Disease: Donepezil (Aricept): o Cholinesterase inhibitor o MOA: reversibly & noncompetitively inhibits centrally active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine o Available dosage forms: tablets, ODT o Max dose: 10 mg QD Galantamine (Razadyne, Razadyne ER, Reminyl-old name): o Acetylcholinesterase inhibitor o Max dose: IR tablet or solution: 24 mg/day (in 2 divided doses) ER capsule: 24 mg/day Memantine (Namenda): o Low affinity, non-competitive, voltage dependent NMDA receptor antagonist o Neuroprotective o Less cognitive decline & improves cognition in impaired patients Page 3 o After depolarization, Namenda leaves the site & allows sodium & calcium entry into the cell o Behaves like magnesium o Approved for moderate to severe Alzheimer’s Disease Rivastigmine (Exelon): o Acetylcholinesterase inhibitor (central) o MOA: increases acetylcholine in the CNS through reversible inhibition of its hydrolysis by cholinesterase o SE: GI upset o Dosage forms: capsules & solution Anemia: Folic acid deficiency would also be called: macrocytic anemia, pernicious anemia Macrocytic (large cell): o Megaloblastic: Vitamin B12 deficiency • Lack of intrinsic factor results in pernicious anemia Folic acid deficiency Hct, Hgb, RBC, MCH Normochromic, normocytic: o Aplastic anemia o Anemia of chronic disease Hypochromic (low hemoglobin content), microcytic (small cell): o Iron deficiency TIBC, MCV, MCH, MCHC, Hgb o Genetic anomalies: Sickle cell anemia, thalassemia Treatment: o Darbepoetin Alpha (Aranesp): Recombinant human erythropoietin Caution in patients with HTN or with a hx of seizures • Can cause hypo- or hypertension Available as an injection o Epoetin Alpha (Epogen): Colony stimulating factor Onset of action: several days Peak effect: 2-3 weeks SQ 1-3X per week SE: HTN Antidotes: Acetaminophen overdose: o Antidote: Acetylcysteine (Mucomyst, Acetadote): MOA: thought to reverse APAP toxicity by providing substrate for conjugation with the toxic metabolites Dose: oral- 140 mg/Kg followed by 17 doses of 70 mg/Kg Q4h; repeat dose if emesis occurs within 1 hour of administration Albuterol overdose: o Antidote: propranolol or beta blocker Anticholinergic overdose: o Antidote: Physostigmine (Antilirium): Do not use if solution is cloudy or dark brown Arsenic overdose: o Antidote: Succimer (Chemet) or dimercaprol (British anti-lewisite, BAL in oil) Benzodiazepine overdose: o Antidote: flumazenil (Romazicon) -blocker overdose: Page 4 o Antidote: glucagon (GlucaGen) CCB overdose: o Antidote: calcium chloride 10% or glucagon (GlucaGen) Carbamates overdose: o Antidote: atropine Coumadin overdose: o Antidote: Vitamin K1 or phytonadione (Mephyton, AquaMEPHYTON); fresh frozen plasma Digoxin overdose: o Antidote: digoxin immune antibody fragment (Digibind, DigiFab) Iron overdose: o Antidote: deferoxamine (Desferal) Isoniazid overdose: o Antidote: pyridoxine (Vitamin B6) Lead overdose: o Antidotes: Succimer (Chemet) Dimercaprol; also called British anti-lewisite (only for lead encephalopathy) Calcium disodium EDTA (calcium disodium versenate) Leucovorin: o Antidote for folic acid antagonists (methotrexate, trimethoprim, pyrimethamine) o Water soluble vitamin Magnesium overdose: o Death due to muscle relaxation (includes heart failure) o Antidote: calcium Methanol or Ethylene glycol overdose: o Antidote: Ethanol 10% o Antidote: Fomepizole (Antizol) AKA: 4-methylpyrazole or 4-MP MOA: competitively inhibits alcohol dehydrogenase, an enzyme which catalyzes the metabolism of ethanol, ethylene glycol, & methanol to their toxic metabolites ?Decreases metabolism of methanol Methemoglobinemia overdose: o Antidote: methylene blue Opioid overdose: o Antidote: Naloxone (Narcan) MOA: opioid antagonist that competes at all three CNS opioid receptors (mu, kappa, & delta) o Antidote: Nalmefene (Revex) Organophosphates overdose: o Antidote: atropine or pralidoxime (Protopam) Salicylate overdose: o Antidote: sodium bicarbonate TCAs overdose: o Antidote: sodium bicarbonate Type Ia antiarrhythmics overdose: o Antidote: sodium bicarbonate Asthma: Drugs available for nebulization: o Budesonide 0.25 & 0.5 mg (Respules®) o Cromolyn (Intal®) Mast cell stabilizer Use: adjunct in the prophylaxis of allergic disorders, including asthma; prevention of exerciseinduced bronchospasm • Nasal: for prevention & treatment of seasonal & perennial allergic rhinitis o Albuterol Page 5 o Ipratropium o Ipratropium & Albuterol Drugs available as MDI: o Beclomethasone HFA 40 mcg/puff & 80 mcg/puff (QVAR®) o Flunisolide 250 mcg/puff (Aerobid®) o Fluticasone 44, 110, 220 mcg/puff (Flovent®) o Cromolyn (Intal®) o Nedocromil (Tilade®) o Albuterol (Proventil®, Ventolin®) o Pirbuterol (Maxair Autohaler®) o Ipratropium (Atrovent®) o Ipratropium & Albuterol (Combivent®) Drugs available as turbuhaler: o Budesonide 200 mcg/inhalation (Pulmicort®) Drugs available for dry powder inhalation (DPI): o Fluticasone (Flovent Rotadisk®) o Fluticasone-salmeterol (Advair Diskus®) o Formoterol (Foradil Aerolizer®) o Salmeterol (Servent Diskus®) Stable for 6 weeks after removing foil 1 inhalation BID Drugs available as MDI/spacer: o Triamcinolone 100 mcg/puff (Azmacort®) Class of drugs to use to prevent a child allergic to pollen from having an asthma attack- could use antihistamines, cromolyn or inhaled corticosteroids A patient would monitor their asthma from home with a peak flow meter which measures the FEV1 o Goal: 80% of personal best Montelukast (Singulair): o MOA: selective leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor o Dosing; 6-23 months: 4 mg oral granules 2-5 years: 4 mg chewable tablet or oral granules 6-14 years: 5 mg chewable tablet >15 years: 10 mg tablet Take in evening o Granules must be used within 15 minutes of opening Zafirlukast (Accolate): o MOA: selectively & competitive leukotriene-receptor antagonist of leukotriene D4 & E4 o Use: prophylaxis & chronic treatment of asthma in adults & children >5 years old o Dose: 20 mg BID o Administer 1 hour before or 2 hours after meals o Monitor: LFTs o Extensively hepatically metabolized via CYP2C9 Theophylline: o 0.80 AT = T o SE: 15-25 mcg/ML: GI upset, N/V/D, nervousness, headache, insomnia, agitation, dizziness, muscle cramp, tremor 25-35 mcg/mL: tachycardia, occasional PVC > 35 mcg/mL: ventricular tachycardia, frequent PVC, seizure o Theophylline + erythromycin increased levels of theophylline A patient who has had too much albuterol could be given a cardioselective beta blocker Bioterrism: Ebola: virus; no cure Page 6 Anthrax: bacteria (aerobic, gram + bacillus); ciprofloxacin or doxycycline for 60 days BPH: Cancer: Tamulosin (Flomax) & Alfuzosin (Uroxatrac): o Greater affinity to -1 in prostate o Less SE o Work quickly for instant relief Finasteride (Proscar/Propecia) & Dutasteride (Avodart): o Great for a large prostate o Take longer to work Doxazosin (Cardura) & terazosin (Hytrin) also used for BPH Saw palmetto Chemo drugs that should be refrigerated: cyclophosphamide (after reconstitution) Antimetabolites: o Pyrimidine analogs: interfere with the synthesis of pyrimidine bases & thus DNA synthesis Can cause mucositis Capecitabine (Xeloda) Fluorouracil; 5-FU (Adrucil) Cytarabine (Cytosar) Gemcitabine (Gemzar) o Folic acid analog: interferes with synthesis of pyrimidine bases & thus DNA synthesis Methotrexate • After reconstitution with preservative: may refrigerate o Purine analogs: interfere with synthesis of purine bases & thus DNA synthesis Mercaptopurine (Purinethol) • DI with allopurinol Thioguanine (Tabloid) Fludarabine (Fludara) Cladribine (Leustatin) Pentostatin (Nipent) Plant alkaloids: o Vinca alkaloids: bind to tubulin to prevent formation of microtubules during mitosis Fatal if administered intrathecally Vincristine (Oncovin): • Neurotoxic Vinblastine (Velban) Vinorelbine (Navelbine) o Podophyllotoxins: bind to tubulin, inhibiting topoisomerase II to cause DNA strand breaks Etoposide; VP-16 (VePesid) Teniposide (Vumon) o Taxanes: bind to tubulin, promotes synthesis of nonfunctional microtubules Paclitaxel (Taxol) • Use a in-line filter; non-PVC Docetaxel (Taxotere) o Camptothecins: inhibits topoisomerase I, stabilizing single-strand breaks in DNA Irinotecan (Camptosar)- *Diarrhea* Topotecan (Hycamtin) Alkylating Agents: cross-link between DNA bases or between DNA strands to inhibit DNA replication o Nitrogen Mustard Derivative: Mechlorethamine (Mustargen) Melphalan (Alkeran) Chlorambucil (Leukeran) Ifosfamide (Ifex) Page 7 o Other: Carmustine (BiCNU) Lomustine (CeeNU) Stretozocin (Zanosar) Thiotepa (Thiopex) Busulfan (Myleran) Dacarbazine (DTIC) Antitumor antibiotics: o Anthracycline: Cardiotoxic: 450-550 mg/m2 cumulative lifetime dose Doxorubicin (Adriamycin): • MOA: appears to directly bind to DNA & inhibit DNA repair (via topoisomerase II inhibition) resulting in the blockade of DNA & RNA synthesis & fragmentation of DNA • Turns urine & all other body fluids red • SE: myelosupression, cardiotoxicity, extravasation • Decrease dose in renal impairment Daunorubicin (Cerubidine) Idarubicin (Idamycin) Mitoxantrone (Novaantrone) o Other: Mitomycin C (Mutamycin) Bleomycin (Blenoxane) Heavy Metals: o Cisplatin (Platinol) o Carboplatin (Paraplatin) o Oxaliplatin (Eloxatin) Antiandrogens: inhibit uptake & binding of testosterone & dihydrotestosterone in prostatic tissue o Flutamide (Eulexin) o Bicalutamide (Casodex) o Nilutamide (Nilandron) Progestins: suppress release of LH & increase estrogen metabolism (decrease available estrogen for estrogendependent tumors) o Megestrol (Megase): also used to stimulate appetite o Medroxyprogesterone (Provera) Estrogens: estramustine is combination of estrogen plus nitrogen mustard; estrogen facilitates uptake, nitrogen mustard released to alkylate cancer cells o Estramustine (Emcyt) Antiestrogens: bind to estrogen receptor in breast tissue, preventing binding by estrogen & thereby reducing estrogen-stimulated tumor growth o Tamoxifen (Nolvadex) o Toremifine (Fareston) Gonadotropin-releasing hormone analogs: turn off negative-feedback release of FSH & LH, reducing testosterone & estrogen production in testes & ovaries o Leuprolide (Lupron (breast/prostate); Eligard (prostate); Viadur (prostate)) o Goserelin (Zoladex) Aromatase inhibitors: blocks enzyme responsible for conversion of circulating androgens to estrogens o Anastrazole (Arimidex): For breast cancer Can increase LDL Cannot use with Tamoxifen AE: vasodilation, headache, pain, depression, hot flashes, HTN, osteoporosis o Letrozole (Femara) Other miscellaneous agents for cancer: o Asparaginase (Elspar) o Hydroxyurea (Hydrea) Page 8 Tyrosine kinase inhibitors: Imatinib mesylate (Gleevec) Erlotinib (Tarceva) Gefitinib (Iressa) o 26S Proteasome inhibitor: Bortezomib (Velcade) o Biological Response Modifiers Immune therapies: • Aldesleukin (Proleukin) • Interferon-alpha 2b (Intron A) • Levamisole (Ergamisol) o Monoclonal antibodies: Rituximab (Rituxan) Trastuzumab (Herceptin): works at HER-1 receptor Gemtuzumab (Mylotarg) Alemtuzumab (Campath) Bevacizumab (Avastin) Cetuximab (Erbitux) Denileukin diftitox (Ontak) Ibritumomab tiuxetan (Zevalin) Tositumomab (Bexxar) Mesna is given with cyclophosphamide & ifosfamide to prevent hemorrhagic cycstitis Colony Stimulating Factors: o Filgastrim (Neupogen): MOA: granulocyte colony stimulating factor (G-CSF); stimulation of granulocyte production in patients with malignancies Increases production of neutrophils Does not cause agraulocytosis—used to treat it SE: bone pain Store in refrigerator Injection o Pegfilgrastim (Neulasta): MOA: stimulates the production, maturation, & activation of neutrophils; activates neutrophils to increase both their migration & cytotoxicity Prolonged duration of effect relative to filgastrim & reduced renal clearance Store in refrigerator SE: bone pain Injection Octreotide (Sandostatin): o Somatostatin analog o Use: antidarrheal agent for diarrhea secondary to cancer o MOA: mimics natural somatostatin by inhibiting serotonin release, & the secretion of gastrin, VIP, insulin, glucagons, secretin, motilin & pancreatic polypeptide o Dosage forms available: injection only High emetic potential: o Cisplatin, cyclophosphamide, cytarabine, dacarbazine, ifosfamide, melphalan, mitomycin, mechlorethamine Prevention of Acute Chemotherapy-Induced N/V: o 5-HT3 receptor antagonist: Dolasetron (Anzemet) Granisetron (Kytril) Ondansetron (Zofran) Palonosetron (Aloxi) o Phenothiazines: Prochlorperazine (Compazine) o Page 9 o o o o o o Chlorpromazine (Thorazine) Promethazine (Phenergan) Butyrophenones: Droperidol (Inapsine) Haloperidol (Haldol) Corticosteroids: Dexamethasone (Decadron) Cannabinoids: Dronabinol (Marinol) Benzodiazepines: Lorazepam (Ativan) Benzamides: Metoclopramide (Reglan) Neurokinin-1 Antagonist: Aprepitant (Emend): • Substance P/neurokinin 1 receptor antagonist • Uses: prevention of acute & delayed N/V associated with highly-emetogenic chemotherapy in combination with a corticosteroid (i.e. dexamethasone) & 5-HT3 (ondansetron) receptor antagonist • Avoid with grapefruit juice (CYP3A4) • MOA: prevents acute & delayed vomiting by selectively inhibiting the substance P/neurokinin 1 (NK1) receptor • Dose: oral: 125 mg on day 1, followed by 80 mg on days 2 & 3 o 1st dose should be given 1 hour prior to chemotherapy Cardiology: ACEI: o Benazepril (Lotensin) o Captopril (Capoten): Used to decrease the progression of CHF SE: rash, hyperkalemia, angioedema, cough Strengths: • Tablets: 12.5, 25, 50, & 100 mg Dosed BID-TID o Enalapril (Vasotec): Enalaprilat (Vasotec): only ACEI available as IV • 1.25 mg/dose given over 5 minutes Q6 hours 40 mg/day max dose o Fosinopril (Monopril) o Lisinopril (Prinvil, Zestril) o Moexipril (Univasc) o Perindopril (Aceon) o Quinapril (Accupril) o Ramipril (Altace) o Trandolapril (Mavik) o Proven to decrease mortality in CHF o Ineffective as monotherapy in African Americans o MOA: inhibit the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) o SE: increased SCr, cough, angioedema, sexual dysfunction, hyperkalemia, rash o CI: bilateral renal artery stenosis; pregnancy Alpha agonists: o MOA: causes decreased sympathetic outflow to the cardiovascular system by agonistic activity on central -2 receptors o Clonidine (Catapres) More withdrawal Unlabeled use: heroin or nicotine withdrawal Page 10 Guanabenz (Wytensin) Guanfacine (Tenex) Less withdrawal o Methyldopa (Aldomet) o SE: sedation, dry mouth, bradycardia, withdrawal HTN, orthostatic hypotension, depression, impotence, sleep disturbances Alpha blockers: o MOA: blocks peripheral -1 postsynaptic receptors, which causes vasodilation of both arteries & veins (indirect vasodilators) o Causes less reflex tachycardia than direct vasodilators (hydralazine/minoxidil) o Dosazosin (Cardura) o Prazosin (Minipress) o Terazosin (Hytrin) o Counseling: take 1st dose at bedtime, may cause dizziness o SE: weight gain, peripheral edema, dry mouth, urinary urgency, constipation, priapism, postural hypotension No effects on glucose or cholesterol Anti-arrhythmic Drugs: o Arrhythmias: A. Fib or flutter: DOC- digitalis glycoside; alternative- verapamil or propranolol Supraventricular tachycardia: DOC- verapamil or adenosine; alternative- diltiazam or procainamide Ventricular premature complexes: DOC- beta blocker; alternative- beta blocker Ventricular tachycardia: DOC- beta blocker; alternative- amiodarone Ventricular fibrillation: DOC- amiodarone; alternative- beta blocker Digoxin-induced tachyarrhythmia: DOC- lidocaine; alternative- phenytoin Torsades de pointes: DOC- magnesium; alternative- beta blocker Class IA: inhibit fast Na channels • Quinidine o SE: Cinchonism • Procainamide (Pronestyl) o SE: lupus-like syndrome • Disopyramide (Norpace) Class IB: inhibit fast Na channels • Lidocaine (Xylocaine): • Phenytoin (Dilantin) o SE: nystagmus • Tocainide (Tonocard) • Mexiletine (Mexitil) Class IC: inhibit fast Na channels • Moricizine (Ethmozine) • Flecainide (Tambocor) • Propafenone (Rhythmol) Class II: beta-adrenergic agents • Propranolol (Inderal) • Esmolol (Brevibloc) • Acebutolol (Sectral) Class III: primarily block K channels • Bretylium (Bretylol) • Amiodarone (Cordarone®): o SE: IV: phlebitis General: corneal microdeposits, photophobia, LFTs, photosensitivity, blue-gray skin discoloration, pulmonary fibrosis (reduced at low doseso o Page 11 300 mg/d; increases as dose increases), hyper- or hypothyroidism, polyneuropathy o Watch for iodine allergy o Avoid grapefruit juice o Prior to use: check thyroid levels, eye exam • Ibutilide (Corvert) • Sotalol (Betapace) • Dofetilide (Tikosyn) o SE: torsades de pointes Class IV: calcium channel antagonists • Verapamil (Isoptin, Calan) Anticoagulation: o Direct thrombin inhibitors: Argatroban: • A synthetic molecule that reversibly binds to thrombin • Eliminated by the liver • Use if renal impairment Lepirudin (Refludan): • Recombinant DNA-derived polypeptide nearly identical to hirudin • Produces an anticoagulant effect by binding directly to thrombin & does not require AT to produce it effect • Does not bind to other proteins as heparin does • Eliminated by the kidneys • Use if liver impairment o Enoxaparin (Lovenox): Low molecular weight heparin MOA: inhibits factor Xa greater than IIa Dosing: • DVT prophylaxis: 40 mg QD or 30 mg BID • DVT treatment: 1 mg/Kg/dose Q12 hours or 1.5 mg/Kg/dose QD Monitor: anti-Xa, platelets o Heparin: MOA: potentiates the action of antithrombin III & prevents the conversion of fibrinogen to fibrin Dosing: • DVT prophylaxis: 5000 units SQ Q8-12 hours • IV infusion: 10-30 units/Kg/hr • Line flushing: 10 units/mL for infants (<10 Kg); 100 units/mL for older infants, children & adults Monitor: PTT (1.5-2X the upper limit of control; 50-70 sec), platelets o Warfarin (Coumadin, Jantoven) MOA: inhibits reduction of vitamin K to its active form; leads to depletion of vitamin Kdependent clotting factors II, Vii, IX, X & protein C & S Requires 4-5 days before full anticoagulation effect is achieved Recommended starting dose: 5 mg po QD Strengths/Dosage forms: • Injection: 5 mg • Tablets: 1, 2, 2.5, 3, 4, 5, 6, 7.5, 10 mg Most indications want an INR in the 2.0-3.0 range • Mechanical valves require a higher level of anticoagulation (INR 2.5-3.5) Minor bleeding or elevated INR: hold warfarin dose or decrease dose until INR returns to appropriate range Purple Toe Syndrome may occur due to cholesterol microembolization o Acetaminophen is usually a good antipyretic & analgesic choice for patients taking oral anticoagulants Page 12 Risk factors for DVTs: >40 years old; prolonged immobility; major surgery involving the abdomen, pelvis, & lower extremities; trauma, especially fractures of the hips, pelvis, & lower extremities; malignancy; pregnancy; previous venous thromboembolism; CHF or cardiomyopathy; stroke. Acute MI; indwelling central venous catheter; hypercoagulability; estrogen therapy; varicose veins; obesity; IBD; nephrotic syndrome; myeloproliferative disease; smoking Antiplatelet Drugs: o Thienopyridines: MOA: block adenosine diphosphate (ADP)-mediated activation of platelets by selectively & irreversibly blocking ADP activation of the glycoprotein IIb/IIIa complex Clopidogrel (Plavix): • Use: reduce atherosclerotic events (MI, stroke, vascular deaths) • MOA: blocks the ADP receptors, which prevents fibrinogen binding at that site & thereby reducing the possibility of platelet adhesion & aggregation • AE: chest pain, headache, dizziness, abdominal pain, vomiting, diarrhea, arthralgia, back pain, upper respiratory infections Ticlopidine (Ticlid): • Maintenance dose: 250 mg BID • DC if the ANC drops to <1200 or platelet count drops to <80,000 • AE: rash, nausea, dyspepsia, diarrhea, neutropenia, thrombotic thrombocytopenic purpura • Dosage form: 250 mg tablet CI: active bleed, severe liver disease, ticlopidine: neutropenia, thrombocytopenia o Glycoprotein IIb/IIIa inhibitors: Abciximab (Reopro) • No renal dosing adjustment required Eptifibatide (Integrillin) Tirofiban (Aggrastat) • Storage: room temperature, protect from light ARBs: o Candesartan (Atacand) o Eprosartan (Tevetan) o Irbesartan (Avapro) o Losartan (Cozaar) o Olmesartan (Benicar) o Telmisartan (Micardis) o Valsartan (Diovan) Beta Blockers: o Nonselective: Nadolol (Corgard) Penbutolol (Levatol) • Has ISA Pindolol (Visken) • Has ISA Propranolol (Inderal): • Nonselective beta blocker • Can increase cholesterol • Strengths available: o ER capsule (InnoPran XL): 80, 120 mg o SR capsule (Inderal LA): 60, 80, 120, 160 mg o Injection (Inderal): 1 mg/mL o Solution: 4 mg/mL; 8 mg/mL o Tablet (Inderal): 10, 20, 40, 60, 80 mg Timolol (Blockadren) o Cardioselective: o Page 13 o o Mixed: Acebutolol (Sectral) • Has intrinsic sympathomimetic activity (ISA) Betaxolol (Kerlone) Bisoprolol (Zebeta) Metoprolol (Lopressor, Toprol XL) • Strength/dosage forms: o Lopressor: Injection: 1 mg/mL Tablet: 25, 50, or 100 mg ER tablets: 50 & 100 mg o Toprol XL: Tablets: 25, 50, 100, 200 mg Labetalol (Trandate): • Beta blocker (heart rate drop) with alpha-blocking (vasodilation & BP drop) activity Carvedilol (Coreg): • MOA: blocks -1, -2, & -1 receptors • Has had proven effects on patient survival in large clinical trials for HF • Take with food • Antioxidant effects • Preferred in HF patients who BP is poorly controlled due to its greater hypertensive effect • Increases stroke volume MOA: competitively blocks response to beta-adrenergic stimulation: Blocked secretion of renin; decrease cardiac contractility, thereby decreasing CO; decreased central sympathetic output; decreased HR, thereby decreasing CO CCBs: o MOA: inhibit the influx of Ca ions through slow channels in vascular smooth muscle & cause relaxation of both coronary & peripheral arteries SA & AV nodal depression & decrease in myocardial contractility (nondihydropyridines) o Nondihydropyridines: o SE: conduction defects, worsening of systolic dysfunction, gingival hyperplasia Diltiazem (Cardizem, LA & CD, Dilacor XR, Tiaziac) • SE: nausea, headache • Cardizem: 30, 60, 90, 120 mg tablets • Cardizem LA: 120, 180, 240, 300, 360, 420 mg • Cardizem CD: 120, 180, 240, 300, 360 mg capsules Verapamil: • IR: (Calan, Isoptin) • LA: (Calan SR, Isoptin SR) • Coer: (Covera HS, Verlan PM) • SE: constipation o Dihydropyridines: SE: edema of the ankle, flushing, headache, gingival hyperplasia Amlodipine (Norvasc) Felodipine (Plendil) Isradipine (DynaCirc & CR) Nicardipine (Cardene SR) Nifedipine (Procardia XL, Adalat CC) Nisoldipine (Sular) Combination products: o Amlodipine & benazepril (Lotrel) o Losartan & HCTZ (Hyzaar) Direct vasodilators: o SE: headaches, fluid retention, tachycardia, peripheral neuropathy, postural hypotension Page 14 Hydralazine (Apresoline) Minoxidil (Loniten) Hirsutism Diuretics: o Monitor: urine output, edema, weight o Loops: MOA: reduction of total fluid volume through the inhibition of Na & Cl reabsorption in the ascending loop of Henle, which causes increased excretion of water, Na, Cl, Mg, & Ca Are more effective that thiazides in patients with renal failure (SCr >2 mg/dL or GFR < 30 mL/min) AE: ototoxicity at high doses; photosensitity; may increase blood glucose in diabetics; orthostatic hypotension; hypokalemia; gout DI: aminoglycosides (increase risk of ototoxicity), NSAIDs (blunt diuretic response), Class Ia or III antiarrhythmics (may cause torsades de pointes with diuretic induced hypokalemic); probenecid (blocks loop effects by interfering with excretion into the urine) Bumetanide (Bumex) Furosemide (Lasix) • Available dosage forms: injection, solution, tablet Torsemide (Demadex) o Thiazides: MOA: direct arteriole dilation; reduction of total fluid volume through the inhibition of Na reabsorption in the distal tubules, which causes increased excretion of Na, water, K, & hydrogen; increase the effectiveness of other antihypertensive agents by preventing re-expansion of plasma volume Significant decrease in efficacy in renal failure (SCr > 2 mg/dL or GFR < 30 mL/min) DI: steroids (cause salt retention & antagonize thiazide action), NSAIDs (blunt thiazide response), Class Ia or III antiarrhythmics (may cause torsades de pointes with diuretic induced hypokalemic); probenecid & lithium(blocks thiazide effects by interfering with excretion into the urine), lithium (thiazides decrease lithium renal clearance & increase risk of lithium toxicity) AE: increased cholesterol & glucose (short term); decreased: K, Na, Mg; increased: uric acid & Ca; photosensitivity; pancreatitis; impotence; sulfonamide-type reactions Bendroflumethiazide (Naturetin) Benzthiazide (Aquatag, Exna) Chlorothiazide (Diuril) Chlorthalidone (Hygroton, Hylidone) Hydrochlorothiazide (HydroDIURIL, Microzide) Hydroglumethiazide (Saluron, Diucardin) Meethyclothiazide Polythiazide (Renese) Trichlormethiazide (Metahydrin, Naqua) o Thiazide-like: Less or no hypercholesterolemia compared to other thiazides; decreased microalbuminuria in DM Metolazone (Mykrox, Zaroxolyn) Indapamide (Lozol) o Potassium-sparing: MOA: interferes with K/Na exchange in the distal tubule; decreases Ca excretion, increases Mg loss AE: hyperkalemia Amiloride (Midamor) Triamterene (Dyrenium) • Avoid with history of kidney stones or hepatic disease o Aldosterone Blocker: Eplerenone (Inspra): • Selective • CI: DM type II; K > 5.5; ClCr < 30 mL/min o o Page 15 • PO- tablet 25 & 50 mg • K sparing Spironolactone (Aldactone) Epinephrine (Adrenalin): o MOA: stimulates -, -1, & -2 adrenergic receptors resulting in relaxation of smooth muscle of the bronchial tree, cardiac stimulation, & dilation of skeletal muscle vasculature o Sensitive to light & air- protection is recommended Oxidation turns drug pink, then a brown color Solutions should not be used if they are discolored or contain a precipitate Admixture is stable at room temperature for 24 hours Heart failure: o Drugs that can worsen or precipitate: Antiarrhythmics: disopyramide, flecainide, propafenone Beta blockers CCB: verapamil & diltiazem Oral antifugals: itraconazole & terbinafine Cardiotoxic drugs: doxorubicin, daunorubicin, cyclophosphamide, alcohol Na & water retention: NSAIDs, glucocorticoids, rosiglitazone, pioglitazone o Metoprolol, bisoprolol, & carvedilol have all shown to be effective in HF o Digoxin (Lanoxin): Does not improve mortality, but does produce symptomatic benefits MOA: inhibits Na-K-ATPase pump, which results in an increase in intracellular Ca, which causes a + inotropic effect • Reduces sympathetic outflow from the CNS AE: arrhythmias, bradycardia, heart block, anorexia, abdominal pain, N/V, visual disturbances, confusion, fatigue • Toxicity is more commonly associated with serum concentrations > 2 ng/mL, but may occur at lower levels if patients have hypokalemia, hypomagnesemia, & in the elderly Serum levels: 0.5-1.0 ng/mL 60-80% is eliminated renally- dosage requirement for renal insufficiency o ACEI & beta blockers improve mortality o Aldosterone antagonist reduce the risk of death & hospitalization o Diuretics- symptomatic relief Inotropes: o Dobutamine (Dobutrex): MOA: stimulates -1 receptors causing increased contractility & heart rate, with little effect on -2 or alpha receptors • -1 > -2 > • Increases CO & vasodilates Use: inotropic support for patients with shock & hypotension Dosage: start at 3 mcg/Kg/min & titrate to 20 mcg/Kg/min o Dopamine (Intropin): MOA: depends on the given dose • 1-5 mcg/Kg/min: renal dose; increases urine output o Stimulates dopamine receptors • 5-15 mcg/Kg/min: increases contractility, HR o Stimulates -1 & -2 receptors • >15 mcg/Kg/min: increases BP o Stimulates -1 receptors Extravasation: give phentolamine o Milrinone (Primacor): MOA: inhibits phosphodiesterase III, increases cAMP, resulting in positive inotropic & vasodilating effects Use: short-term IV therapy of CHF; calcium antagonist intoxification Dosage: 50 mcg/kg LD over 10 min; followed by 0.375 mg/Kg/min Page 16 Preferred over amrinone because of decreased risk of thrombocytopenia MONA-B for MI: o Morphine, oxygen, NTG, Aspirin, beta blockers Norepinephrine (Levophed): o MOA: stimulates -1 adrenergic receptors & -adrenergic receptors causing increased contractility & HR as well as vasoconstriction thereby increasing systemic BP & coronary blood flow Alpha effects > beta effects o Readily oxidized, protect from light o Do not use if brown coloration o Admixture stable at room temperature for 24 hours Postganglionic adrenergic neuron blockers: o Guanadrel (Hylorel) o Guanethidine (Ismelin) o Reserpine (Serpasil) Can cause depression Torsades de pointes: o Common drugs that can cause it: quinidine, dofetilide (Tikosyn), sotalol (Betapace), thioridazine, ziprasidone (Geodon) Thrombolytics: o Use: ST-elevation > 1 mm in 2 or more contiguous leads or left bundle branch block Presentation within 12 hours or less of symptoms onset In patients >75 years old may be useful & appropriate Can be used in STEMI when time to therapy is 12-24 hours if chest pain is ongoing Should NOT be used if the time to therapy is >24 hours, & the pain is resolved CI in a patient with NSTEMI o Drugs: Streptokinase (SK, Streptase) Tissue plasminogen activator (tPA, Alteplase) Tenecteplase (TNK, TNKase) o Vasodilators: o Nitroprusside (Nitropress): Vasodilator Use: hypertensive crises; CHF Watch for cyanide toxicity (especially with hepatic dysfunction) Watch for thiocyanate toxicity (especially with renal dysfunction or prolonged infusions) Highly sensitive to light • Normally a brownish color • A blue color indicates almost complete degradation & breakdown to cyanide o Nesirtide (Natrecor): B-type natriuretic peptide that increases diuresis & is an arterial & venous dilator o Nitroglycerin (NitroBid, Nitrostat): Venous dilator but also an arterial dilator at higher doses Compatibility: Drugs that must be mixed with sterile water: o Amphotericin B: no electrolytes, mix in D5W, & reconstitute with sterile water Conversions: 1 lb = 454 gm 1 in = 2.54 cm 1 grain = 64.8 mg 1 avoirdupois pound = 454 gm 1 fluid ounce = 29.57 mL Page 17 1 gallon = 128 fluid ounces o Also 3785 mL, 4 quarts, 8 pints 1 pint = 473 mL (round to 480 mL) COPD: 1st line therapy: beta-2 agonist or ipatropium Counseling Points: Calcitonin (Miacalcin): o For injection: Keep vials in refrigerator Stable for 2 weeks at room temperature Give injection in upper arm, thigh or buttock o Nasal spray: Store unopened bottle in refrigerator Once pump has been activated, store at room temperature • Good for 30 days Must prime prior to first use or if it has been greater than 5 days o Adequate vitamin D & calcium intake is essential for osteoporosis o May cause increased warmth & flushing (should last only about 1 hour after administration) Take in evening to minimize discomfort Sulfa eye drops: burns Nicotine gum: chew until peppery taste appears, then park Cystic Fibrosis: Autosomal recessive disease of exocrine gland function resulting in abnormal mucus production Genetic mutation on the long arm of chromosome 7 o The protein encoded by this gene, the cystic fibrosis transmembrane regulator (CFTR), is a channel involved in the transport of water & electrolytes o Most common genetic mutation involves a 3-base-pair deletion at position F508 Antibiotics for Cystic Fibrosis: o Cover for Staphylococcus aureus, H. flu, & pseudomonas Double coverage of antibiotics when pseudomonas (most common) is suspected • Antipseudomonal PCN: piperacillin (Pipracil), mezlocillin (Mezlin), piperacillintazobactam (Zosyn), ticarcillin-clavulanate (Timentin), ticarcillin (Ticar), aztreonam (Azactam), meropenem (Merrem), or imipenem (Primaxin) • Or a cephalosporin: ceftazidime (Fortaz, Tazidime, Tazicef) • AND an aminoglycoside: tobramycin Vancomycin for MRSA Burkholderia & Stenotrophomonas species are commonly resistant • Trimethoprim-sulfamethoxazole (Bactrim), chloramphenicol (Chloromycetin), ceftazidime, doxycycline, piperacillin o Fluoroquinolones are the ONLY oral antibiotics with good coverage against pseudomonas Pulmozyme (dornase alfa): o Recombinant human deoxyribonuclease o Use: for management of CF patient to reduce the frequency of respiratory infections that require parenteral antibiotics, & to improve pulmonary function o MOA: reduces mucous viscosity resulting in airflow improvement o Used with a nebulizer (jet nebulizer) o Must be stored in the refrigerator & should be protected from light Should not be exposed to room temp for a total of 24 hours Should not be mixed with or diluted with other drugs in the nebulizer Devices: Swan Ganz catheter: Page 18 o Inserted into right side of heart into the pulmonary circulation o Measures pulmonary capillary wedge pressure o Takes accurate measurement of BP You must measure the scrotum to fit a swimmer’s athletic support Crutches: o Armpits should be 2 inches away from crutches Diabetes: Insulin: o Rapid-acting: Lispro (Humalog) Aspart (NovoLog) Glulisine (Apidra) Onset: <15 min Peak: 30-90 min Duration: 3-5 hours o Short-acting: Regular- human (Humulin R, Novolin, Velosulin BR) Regular- purified (Regular Ilentin II-pork) Onset: 30-60 min Peak: 2-3 hours Duration: 3-6 hours o Intermediate-acting: NPH- isophane insulin suspension (NPH Iletin II- pork) Human (Humulin N, Novolin N) Lente- insulin zinc suspension (Lente Iletin II- pork) Human (Humulin L, Novolin L) Onset: 2-4 hours Peak: 6-12 hours Duration: 10-18 hours o Long-acting: Ultralente- extended insulin zinc suspension; human (Humulin U, Ultralente) • Onset: 6-10 hours • Peak: 10-16 hours • Duration: 18-20 hours Insulin glargine (Lantus) • Onset: 5 hours • Peak: none • Duration; 20-24 hours • Cannot mix with any other insulin o Premixed products: 50/50: 50% regular with 50% NPH • Rapid acting for pre-meal & intermediate acting to control later hyperglycemia 70/30: 30% regular with 70% NPH 70/30 analogue: 30% aspart with 70% neutral protamine aspart insulin analogue 75/25: 25% lispro with 75% neutral protamine lispro insulin analogue o MOA: decreases blood glucose & assists with glucose control by: Increasing glucose uptake & utilization by peripheral tissues (primarily in muscle) Increasing glycogenesis (glucose glycogen; primarily in liver) Decreasing glycogenolysis (glycogen glucose) Decreasing gluconeogenesis (amino acids glucose) Decreasing lipolysis & ketogenesis (fats ketone bodies) Converting amino acids to increase protein Converting triglycerides & fatty acids to increase adipose tissue o Appearance: Page 19 Clear (solution): aspart, lispro, glulisine, glargine, regular Cloudy (suspension): NPH, lente, ultralente, all premixed insulin products o Sites of injection: abdomen > arm > hip > thigh > buttock In order of greater & more rapid absorption to lesser & slower absorption o There’s 1000 units in a 10 mL bottle Insulin secretagogues: o MOA: stimulates pancreatic cells to secrete insulin o 1st generation sulfonylureas: can cause a disulfiram-like rxn Acetohexamide (Dymelor) Chlorpropamide (Diabinese) Tolazamide (Tolinase) Tolbutamide (Orinase) o 2nd generation sulfonylureas Glimepiride (Amaryl) • Max dose: 8 mg/day Glipizide (Glucotrol, Glucotrol XL)- use in renal impairment Glyburide (Diabeta, Micronase)- safe in pregnancy Glyburide micronized (Glynase) o Regular meal times are necessary- must not skip o SE: hypoglycemia & weight gain Alpha-glucosidase Inhibitors: o Acarbose (Precose) o Miglitol (Glyset) Least likely to cause hypoglycemia even when fasting o Should be taken with the first bite of a meal o MOA: delays carbohydrate metabolism & absorption (due to competitive & reversible inhibition of intestinal alpha-glucoside hydrolase & pancreatic alpha-amylase) o SE: GI intolerance o To treat a hypoglycemic attack: treat with oral glucose Sucrose or fructose would not work Biguanide: o Metformin (Glucophage, Fortamet, Riomet): MOA: insulin resistance • 1° in liver; 2° in periphery Dosage: start with 500 mg po BID or 875 mg po QD • Max: ~2500 mg QD (850 mg TID) When to hold: in patients undergoing diagnostic radiology procedures that use an iodinated contrast media; hold for 48 hours after the radiology drug is administered • i.e. angiogram SE: GI, megaloblastic anemia, & lactic acidosis (Scr men <1,5, women <1.4- don’t use) Thiazoladinediones (glitazones or TZDs): o Pioglitazone (Actos) o Rosiglitazone (Avandia): need AST prior to starting Wait 3 months before deciding on therapeutic failure o MOA: insulin resistance 1° in periphery; 2° in liver o SE: edema, anemia, weight gain, exacerbation of CHF, URIs, resumption of ovulation Meglitinides (nonsulfonylurea secretagogues): o Repaglinide (Prandin) Max daily dose: 16 mg/day o Nateglinide (Starlix) o MOA: stimulates pancreatic cells to secrete insulin o SE: hypoglycemia, weight gain, GI Combination drugs: o Glyburide + Metformin (Glucovance) Page 20 o Glipizide + Metformin (Metaglip) o Rosiglitazone + Metformin (Avandamet) Example of question: Diabeta is most like Prandin Glyset will not cause hypoglycemia o Only sulfonylureas & insulin will lower blood sugar in non-diabetics Glucagon (GlucaGen): o Use: management of hypoglycemia Unlabeled use: beta blocker & CCB overdose o MOA: stimulates adenylate cyclase to produce increased cAMP, which promotes hepatic glycogenolysis & gluconeogenesis, causing a rise in blood glucose levels o 1 unit = 1 mg Diabetic nephropathy: o Microalbuminuria (30-300 mg albumin/24 hours) used to diagnosis o Annual screening for DM type II measures microalbumin-creatinine ratio (normal <30) Diabetic neuropathy: o Treat with TCA’s o Neurontin, carbazepine o ACEI treat the decreased renal function, NOT the neuropathy itself DKA: o A potentially fatal complication that occurs in up to 5% of patients with Type I annually o Seen less frequently in Type II o Precipitating factors: interruption of insulin therapy, sepsis, trauma, MI, pregnancy o Clinical features: N/V, vaguely localized abdominal pain; dehydration, respiratory distress, shock & coma can occur o Lab evulation: anion gap metabolic acidosis & positive serum ketones; plasma glucose is usually elevated Hyponatremia, hyperkalemia, azotemia, & hyperosmolality o Treatment: Supportive measures Fluids Insulin therapy Dextrose (5%)- once plasma glucose decreases to 250 mg/dL & the insulin infusion rate decreased to 0.05 U/Kg/hr Potassium Bicarbonate therapy Phosphate & magnesium Drug-Drug Interactions: Sertraline (Zoloft) & diltiazem (Cardizem; Cartia XT; Dilacor XR; Diltia XT; Taztia XT; Tiazac) Epilepsy: Pharmacotherapy: o Carbamazepine (Tegretol): Na channel blocker An autoinducer Tegretol XL: ghost tablets in stool SE: rash (rarely causing DC), folate deficiency, hepatotoxicity, aplastic anemia Teratogenic Cannot be given for status epilepticus o Felbamate (Felbatol): Rarely used MOA: blocks glycine on N-Methyl-D-Aspartate receptor (NMDA) SE: hepatotoxicity, aplastic anemia 50% renal elimination o Gabapentin (Neurontin): Page 21 o o o o o o o o o MOA: unknown; structurally related to GABA but does not interact with GABA receptors Also used for peripheral neuropathies 100% renal elimination- no DI that effect drug metabolism Al or Mg containing antacids may decrease absorption Lamotrigine (Lamictal): MOA: decrease glutamate & aspartate release, delays repetitive firing of neurons, blocks Na channels SE: life-threatening skin rash • Titrate slowly to avoid Levetiracetam (Keppra): MOA: may prevent hypersynchronization of epileptiform burst firing & propagation of seizure activity Adjust in renal dysfunction Oxycarbazepine (Trileptal): MOA: Na channel blocker PKS: active metabolite- 10-monohydroxycarbazepine (MHD) SE: hyponaturemia; blood dysrasias Phenobarbital (Barbital, Luminal, Solfoton): MOA: increases GABA-mediated Cl- influx SE: drowsiness, dizziness, hyperactivity, folate deficiency, hepatic failure, SJS Teratogenic Decreases effectiveness of BC pills Phenytoin (Dilantin): MOA: Na channel blocker Can only prepare in NS @ 50 mg/mL Highly protein bound SE: peripheral neuropathy, hydantoin faces, acne, hirsutism, gingival hyperplasia, osteomalacia, vitamin K- deficient hemorrhagic disease, folate deficiency, hepatic failure, SJS Teratogenic DC tube feedings 2 hours before & after a dose of phenytoin Available dosage forms: suspension, chewable tablet, prompt-release capsule, ER capsule, injection Need albumin level to calculate phenytoin level Primidone (Mysoline): MOA: increase GABA-mediated Cl- influx Metabolized to Phenobarbital & phenylethylmalonamide (PEMA) Primidone, Phenobarbital, & PEMA all have anti-epileptic activity Tiagabine (Gabitril): MOA: blocks GABA reuptake in presynaptic neuron Topiramate (Topamax): MOA: blocks Na channels, enhances GABA activity, antagonizes AMPA/kainite activity • Also a weak carbonic anhydrase inhibitor Elimination: primarily renal SE: drowsiness, dizziness, kidney stones, oligohidrosis (may not sweat) Sprinkle capsules can be opened & sprinkled onto a small amount of cool, soft food (i.e. applesauce or yogurt) Drink plenty of fluids Valproic acid: MOA: blocks T-type Ca currents, blocks Na channels, increases GABA production SE: weight gain, alopecia, thrombocytopenia, increased LFTs, heptotoxicity (fatal), hemorrhagic pancreatitis (fatal), folic acid deficiency Available dosage forms: • Sodium valproate (Depacon): injection • Divalproex sodium: o Depakene: syrup & gel capsule Page 22 o Depakote Sprinkles: capsules o Depakote: delayed-release tablets o Depakote ER: ER tablet o Zonisamide (Zonegran): MOA: Na channel blocker, blocks T-type Ca channels (currents) • Weak carbonic anhydrase inhibitor SE: kidney stones, weight loss, oligiohidrosis Sulfa drug Nonpharmacologic therapy: o Ketogenic diet: devised in the 1920’s High in fat & low in carbohydrates & protein Leads to acidosis & ketosis Most calories are provided in the form of cream & butter No sugar allowed Fluids are also controlled Status epilepticus: seizure lasting longer than 5 minutes or 2 discrete seizures between which there is incomplete recovery of consciousness o Treatment: ABC’s: airway, breathing, circulation 1st line: benzodiazepines • Lorazepam (Ativan): rapid onset • Diazepam (Valium) IV phenytoin (Dilantin) • provided patient was not on phenytoin at home • Can only mix with NS • 15-20 mg/Kg • Contains propylene glycol- cardiotoxic therefore do not infuse faster than 50 mg/min • Fosphenytoin (Cerebyx): o Prodrug of phenytoin o Improves water solubility of phenytoin o Can be admixed with any IV solution o Dosed in PE (phenytoin equivalents): 1 mg of phenytoin = 1.5 mg of fosphenytoin o Can be give at a rate of 150 mg/min IV Phenobarbital (20 mg/Kg)or begin a continuous infusion of midazolam Begin a medically-induced coma • Must be on a vent Equations: BMI: body mass index o Men = 66 + (13.7 X W) + (5 X H) – (6.8 X A) o Women = 665 + (9.6 X W) + (1.8 X H) – (4.7 X A) o Where W= adjusted body weight in Kg; H= height in centimeters; A= age in years o 1 in = 2.54 cm CrCl = (140- age) (IBW) X 0.85 (if woman) (72) (SCr) IBWman= 50 + 2.3 (inches over 5’) IBWwoman= 45.5 + 2.3 (inches over 5’) ABW = IBW + 0.4 (Actual – ideal) Henderson Hasselbach: o pH= pka + log [base]/[acid] o log values: log 100 = 2 log 10 = 1 log 1 = 0 Page 23 log 0.1 = -1 log 0.001 = -2 T1/2 = 0.693 VD/Cl Fanconi’s Syndrome: A congenital anemia due to low production of RBC’s Can also be induced by anything that causes failure of the proximal renal tubules Patients develop polyuria (cannot concentrate the urine), osteomalacia, & reduced growth size At one time it was associated with the use of out-dated tetracycline but this is no longer a problem since the product has been reformulated o The filler was the actual culprit GERD: H2RA: o o o o PPIs: o o Cimetidine (Tagamet) Famotidine (Pepcid) Nizatidine (Axid) Ranitidine (Zantac) MOA: suppresses gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump Rabeprazole (AcipHex): Strength/dosage form: delayed-release EC 20 mg tablet o Esomeprazole (Nexium): Strength/dosage form: • Capsule: delayed release 20 & 40 mg • Injection, powder for reconstitution: 20 & 40 mg o Lansoprazole (Prevacid): Strength/dosage form: • Capsule: delayed release 15 & 30 mg • Granules, for oral suspension: 15 & 30 mg/packet • Injection, powder for reconstitution: 30 mg • ODT: 15 & 30 mg o Omeprazole (Prilosec): Do not put in OJ- not stable in an acidic environment Cannot sprinkle onto food Strength/dosage form: • Capsule: delayed release 10 & 20 mg • Oral suspension (Zegerid): 20 & 40 mg • Tablet: delayed release 20 mg (OTC) o Pantoprazole (Protonix): Strength/dosage form: • Injection, powder for reconstitution: 40 mg • Tablet: delayed release 20 & 40 mg o Take 15-30 minutes before breakfast to maximize efficacy GERD can exacerbate asthma Glaucoma: Increased intraocular pressure, which causes pathologic changes in the optic nerve & typical visual field defects Open-angle glaucoma: o Primary glaucoma o The angle of the anterior chamber remains open in an eye, but filtration of aqueous humor is gradually diminished because of the tissues of the angle o 80-90% of cases Angle-closure (narrow angle) glaucoma: o Primary glaucoma Page 24 Shallow anterior chamber & narrow angle; filtration of aqueous humor is compromised as a result of the iris blocking the angle Therapy: o -adrenergic antagonists: MOA: decrease in aqueous humor formation with slight increase in outflow (beta selective) Often DOC for open-angle glaucoma AE: cardiac effects, worsening pulmonary effects, depression, dizziness Nonselective: • Timolol (Timoptic) • Carteolol (Ocupress) • Levobunolol (Betagen) • Metipranolol (OptiPranolol) Selective: • Betaxolol (Betoptic) • Levobexaxolol (Betaxon) o Carbonic anhydrase inhibitors: MOA: decrease in aqueous humor formation AE: lethargy, decreased appetite, GI upset, urinary frequency Do not use with sulfa allergy Acetazolamide (Diamox) • Tablets, capsules Dorzolamide (Trusopt) Brinzolamide (Azopt) Methazolamide (Neptazane) • Tablets o Prostaglandin analogs: MOA: increased uveoscleral outflow without effect on aqueous humor formation Also used as 1st line agents or in combination with beta blockers AE: iris pigmentation, eyelid darkening, macular edema Latanoprost (Xalatan) • Administer 1 drop at bedtime • Refrigerate • Can change blue eyes to brown Bimatoprost (Lumigan) • Can cause darkening of eyelids & eye lashes Travoprost (Travatan) • Frequent ocular hyperemia Unoprostone (Rescula) o -2 adrenergic agonists: MOA: decrease in aqueous humor formation AE: tachycardia, dry mouth, eyelid elevation, CNS effects in the old & young Brimonidine (Alphagan) • Wait at least 15 minutes after using before placing soft contacts o Other -adrenergic agonists: MOA: increase in aqueous humor outflow AE: tachycardia, increased BP, allergic responses Dipivefrin (Propine) • Prodrug of epinephrine Pilocarpine (Pilocar) • Once weekly dose form called Ocuserts o Combination: Timolol & dorzolamide (Cosopt) o Gout: Page 25 Treatment of acute attack: o Colchicine: MOA: inhibits phagocytosis of urate crystals by leukocytes; anti-inflammatory agent without analgesic activity • Decrease leukocyte mobility thereby decreasing inflammation Dosed until resolution of symptoms, severe GI symptoms occur, or max of 8 mg Available PO (0.6 mg) & IV (0.5 mg/mL) o Indomethacin o Corticosteroids Effective when given intra-articularly, IV, or PO Used when there is failure to colchine and NSAIDS Prophylaxis: o Colchicine (low dose: 0.6-1.2 mg/d) o Colchicine + probenecid (ColBenemid) o Probenecid (Benemid): MOA: uricosuric agent that promotes the excretion of UA by blocking its reuptake at the proximal convoluted tubule • Inhibits renal absorption of UA from the urine into the blood Should drink at least 2 L of water/day to decrease the risk of UA stone formation Avoid use with aspirin o Sulfinpyrazone (Anturane): MOA: uricosuric agent that promotes the excretion of UA by blocking its reuptake at the proximal convoluted tubule Drink at least 2 L of water/day Do not use with CrCl < 50 mL/min o Allopurinol (Zyloprim): MOA: allopurinol & its metabolite oxypurinol, inhibit xanthine oxides formation, which is the rate-limiting step in UA synthesis; this facilitates the clearance of the more water soluble precursors of UA, oxypurines • Inhibits xanthine oxides which reduces UA formation from the metabolism of purine bases of DNA & RNA Take with food Watch for rash- SJS can occur DI: azathioprine & 6-mercaptopurine Hemorrhoids: Therapy: o Soap suds enema QD o Sitz bath QD o Fiber therapy o Sitting on a doughnut o Cleaning anal area with soap & water after each defecation o Dibucaine (Nupercainal): OTC local anesthetic for fast temporary relief of pain & itching due to hemorrhoids o Pramoxine (Anusol ointment, ProctoFoam NS, Tucks): OTC local anesthetic for fast temporary relief of pain & itching due to hemorrhoids Hepatic Encephalopathy: Syndrome of disordered consciousness & altered neuromuscular activity seen in patients with acute or chronic hepatocellular failure or portosystemic shunting Precipitating factors: azotemia; use of tranquilizer, opioid, or sedative-hypnotic medication; GI hemorrhage; hypokalemia & alkalosis; constipation; infection; high-protein diet Monitor: ammonia levels Treatment: o Fleet’s enema Page 26 o o o o Herbs: Protein restriction; special diet (vegetable protein or branched-chain amino acid enriched) Nonabsorbable disaccharides: lactulose (Cephulac, Constulose, Enulose, Generlac, Kristalose), lactitol, & lactose Lactulose syrup 30 mL of 50% solution QID; diminish to BID when 3 or more bowel movements a day occur daily Neomycin Metronidazole Chamomile: o Uses: dyspepsia, oral mucositis, dermatitis, ADHD o Might have anti-inflammatory effects; might bind to GABA receptors o DI: benzodiazepines, tamoxifen, CNS depressants, warfarin, estrogens, CYP1A2 & CYP3A4 substrates o CROSS-ALLERGENICITY: German chamomile may cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family; members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs Chasteberry: o Uses: PMS, BPH, menstrual irregularities, female infertility, insect repellant o DI: antipsychotics, contraceptives, dopamine agonists, estrogens, metoclopramide Cholesterol: garlic Depression: o St. John’s Wort, SAM-e (& OA), DHEA, Kava-kava (anxiety, stress) Dong quai: o Used for PMS & menopausal symptoms o Interaction with warfarin- made up of several coumarin constitutes Increase INR Feverfew: o Use: migraines, arthritis, allergies o DI: anticoagulants, antiplatelets, CYP (1A2, 2C9, 2C19, 3A4) Glucosamine: o Use: OA, TMJ, glaucoma o Glucosamine is an amino sugar, which is a constituent of cartilage proteoglycans. It is derived from marine exoskeletons or produced synthetically o DI: APAP, antidiabetic agents, warfarin Kava Kava: o Uses: insomnia, anxiety, stress, benzodiazepine withdrawal o May adversely affect the liver- increase LFTs o DI: xanax, CNS depressants CYP (1A2, 2C19, 2C9, 2D6, 2E1, 3A4), hepatotoxic drugs, levodopa Milk thistle: o Used for liver disorders; dyspepsia o Interactions with CYP2C9 (warfarin, elavil, diazepam), CYP3A4 substrates, estrogens o Avoid with hormone sensitive cancers Hot flashes & menopausal symptoms: black cohosh Passion Flower: o Used for anxiety, GAD, opioid withdrawal o Interactions with CNS depressants Podophyllin: o Uses: applied locally for wart removal; o Can increase LFTs SAM-e: o Uses: depression & OA o S-adenosylmethionine (SAMe) is a naturally occurring molecule that is distributed throughout virtually all body tissues and fluids; concentrations are highest in childhood & decrease with age o Plays an essential role in >100 biochemical rxn involving enzymatic transmethylation Page 27 It contributes to the synthesis, activation &/or metabolism of hormones, neurotransmitters, nucleic acids, proteins, phospholipids, & some drugs o DI: antidepressants, dextromethorphan, levodopa, meperidine St. John’s Wort: o Uses: depression, anxiety o Two constituents that play a significant role are hypericin & hyperforin o MOA: believed to act as a serotonergic 5-HT3 and 5-HT4 receptor antagonist, & down-regulate betaadrenergic, & serotonergic 5-HT1 & 5-HT2 receptors when used chronically in animals o DI: triptans, xanax, elavil, antidepressants, barbiturates, plavix, OCs, cyclosporine, dextromethorphan, CYP (1A2, 2C9, 3A4), warfarin Valerian: o Used for anxiety, stress, insomnia o A sedative; similar effects to Ambien o Avoid with: etoh, benzadiazepines, CNS depressants, CYP3A4 substrates Some herbs that affect platelet aggregation: angelica, clove, danshen, dong quai, garlic, ginger, ginkgo, feverfew, Panax ginseng, horse chestnut, red clover, turmeric o Hyperkalemia: Sodium polystyrene disulfonate (Kayexalate): cation exchange resin- promotes the exchange of Na for K in GIT o Can be administered as a retention enema IV insulin o Causes K to shift into the cells & temporarily lowers the plasma K Calcium gluconate o Decreases membrane excitability o Administer 1st with hyperkalemia & EKG changes Other: IV NaHCO3 (shifts K into cells); -2 adrenergic agonists (promote the cellular uptake of K); Loop & thiazide diuretics (enhance K excretion if renal function is adequate); dialysis If the patient also has EKG changes the usual treatment (in order) is: o IV calcium first o Then IV bolus of 10-20 units of regular insulin with 25 gm of glucose (prevents hypoglycemia) o 150 mEq of sodium bicarbonate is one liter of D5W forces K into cells o Beta-2 agonists (i.e. Albuterol) nebulized or SQ o Combination of loop & thiazide (i.e. Lasix + Diuril) if the renal function is adequate o Kayexalate (slow to work) o Hemodialysis is best overall, if the time is available & K is severe o Peritoneal dialysis is less effective Hyperlipidemia: Bile Acid Sequestrants: o Effects on cholesterol: TC: TG: or <--> LDL: HDL: o Cholestyramine Resin (Questran, Prevalite): MOA: forms a nonabsorable complex with bile acids in the intestine, releasing chloride ions in the process; inhibits enterohepatic reuptake of intestinal bile salts & thereby increases the fecal loss of bile salt-bound low density lipoprotein cholesterol o Colesevelam (WelChol) Strength/dosage forms: 625 mg tablet o Colestipol (Colestid) o Not absorbed; safest for pregnant women Fibrates: o Effects on cholesterol: TC: Page 28 o o o o TG: LDL: or <--> HDL: MOA: increase catabolism (breakdown) of triglycerides Can cause pancreatitis & liver problems Fenofibrate (Tricor) Changed from 160 mg (with meals) to 145 mg • Made it nanocrystals for better bioavailability Gemfibrozil (Lopid) Take 30 minutes before breakfast & dinner Clofibrate (Atromid-S) o Statins: o Effects on cholesterol: TC: TG: LDL: HDL: o MOA: HMG-CoA reductase inhibitors o Atorvastatin (Lipitor) o Fluvastatin (Lescol, Lescol XL) Shortest t1/2 o Lovastatin (Mevacor, Altoprev- with niacin) Strengths/Dosage forms: • Tablet: 10, 20, 40 mg • Mevacor: 20, 40 mg ER tablets • Altoprev: 10, 20, 40, 60 mg tablets No grapefruit o Pravastatin (Pravachol) Not metabolized in the liver- therefore statin with the least amount of DIs o Rosuvastatin (Crestor) o Simvastatin (Zocor) No grapefruit o All except for Lipitor & Crestor should be administered in the evening o Pregnancy category: X o Monitor: LFTs, CK Cholesterol Absorption Inhibitor: o Effects on cholesterol: TC: TG: LDL: HDL: or <--> o Ezetimibe (Zetia): Monitor for muscle pain & increased liver enzymes Niacin (Niacor, Niaspan, Slo-Niacin: OTC): o Synonyms: Nicotinic acid; vitamin B3 o Effects on cholesterol: TC: TG: LDL: HDL: o MOA: inhibits the synthesis of VLDL o Target dose: 1.5-6 g/day in 3 divided doses with or after meals o SE: flushing (pretreat by taking aspirin 30 minutes prior), dizziness, lightheadedness o Caution in DM & gout Combination products: Page 29 Niacin & lovastatin (Advicor) Ezetimibe & simvastatin (Vytorin) Aspirin & pravastatin (Pravigard PAC)- aspirin tablets & pravastatin tablets are separate tablets within the PAC Exercise will help to raise HDL o o o Hyperthyroidism: Thyrotoxicosis Graves disease- most common cause Thyroid storm is a life threatening, sudden exacerbation of all the symptoms of thyrotoxicosis characterized by fever, tachycardia, delirium, & coma Can be caused by drugs such as amiodarone & iodine S/Sx: heat intolerance, weight loss, weakness, palpitation, anxiety, tremor, tachycardia, eyelid sag, warm or moist skin Diagnosis: T4 or T3, TSH Three modes of treatment: o Surgery o Radioactive iodine (RAI) o Antithyroid (thionamide) drugs: Propylthiouracil (PTU): • MOA: inhibit the synthesis of thyroid hormones by preventing the incorporation of iodine into iodotyrosines & by inhibiting the coupling of monoiodotyrosine & diiodotyrosine to form T4 & T3; also inhibits the peripheral conversion of T4 to T3 • Dosage form: tablets Methimazole (Tapazole): • MOA: inhibit the synthesis of thyroid hormones by preventing the incorporation of iodine into iodotyrosines & by inhibiting the coupling of monoiodotyrosine & diiodotyrosine to form T4 & T3 SE: fever, headache, paresthesias, rash, arthralgia, urticaria, jaundice, hepatitis, agranulocytosis, leucopenia, bleeding o Iodide drugs: Strong iodine solution (Lugol’s Solution): • Dosage form: solution- 5% iodine & 10% K iodide; delivers 6.3 mg iodine per drop Saturated solution of potassium iodide (SSKI) • Dosage form: solution- 1 g/mL; delivers 38 mg iodine per drop of saturated solution MOA: blocks hormone release, inhibits thyroid hormone synthesis Hypokalemia: Diarrhea is associated with liquid KCl Hyponatremia: Drugs can cause by 1 of 3 mechanisms: o Stimulation of vasopressin release (i.e. nicotine, carbamazepine, Lithium, TCA’s, antipsychotic agents, antineoplastic drugs, narcotics) o Potentiation of antidiuretic action of vasopressin (i.e. chlorpropamide, methylxanthines, NSAIDs) o Vasopressin analogs (i.e. oxytocin, DDAVP) Hypothyroidism: Deficient thyroid hormone production Hashimoto’s disease is the cause of 90% of primary hypothyroidism o Autoimmune resulting from cell- & antibody-mediated thyroid injury S/Sx: cold intolerance, fatigue, somnolence, constipation, menorrhagia, myalgias, hoarseness, thyroid gland enlargement or atrophy, bradycardia, edema, dry skin, weight gain o Body slows down Page 30 Thyroxine (T4) is the major hormone secreted by the thyroid, which is converted to the more potent triiodothyronine (T3) in tissues o Thyroxine secretion is stimulated by thyroid stimulating hormone (TSH) o Diagnosis: TSH, T4 Drug therapy: o Levothyroxine sodium, T4 (Synthroid, Levothroid, Levoxyl, Unithroid, Thyro-Tabs): Usually DOC Typical dose is 100-125 mcg po QD; reduce dose to 50 mcg for elderly & 25 mcg in patients with CAD to reduce risk of precipitating angina Dose changes are made within a 6-8 week interval o Desiccated thyroid USP (Armour Thyroid, Nature-Throid, Westhroid) o Liothyronine, T3 (Cytomel, Triostat) o Liotrix, T4 & T3 in a 4:1 ratio (Thyrolar) o Take 30 minutes before breakfast o Don’t take antacids, calcium, or iron supplements within 4 hours of levothyroxine o SE: tachycardia, arrhythmia, angina, MI, tremor, headache, nervousness, insomnia, diarrhea, vomiting, weight loss, excessive sweating, hair loss Body speeds up ID: Aminoglycosides: o MOA: bactericidal; interferes with bacterial protein synthesis by binding to 30S & 50S ribosomal subunits resulting in a defective bacterial cell membrane o For serious aerobic gram + infections o Poorly absorbed for GIT o Renally eliminated by glomerular filtration o Watch for oto- & nephrotoxicity o Target serum concentrations: Amikacin peak: 15-30 mcg/mL Amikacin trough: <5 mcg/mL Gentamicin & tobramycin peak: 4-10 mcg/mL Gentamicin & tobramycin trough: <2 mcg/mL o Amikacin (Amikin) Least susceptible to resistance Rule of nines (see gentamicin) o Gentamicin (Garamycin): Rule of eights to determine dosing interval • SCr X 8 • i.e. 2 X 8 = 16- - dose Q16 hours o Netilmicin (Netromycin) o Tobramycin: Should be given after dialysis and be a routine loading dose Amphotericin B: o Amphotericin B-conventional (Amphocin; Fungizone) Premedicate 30-60 minutes prior with NSAID or APAP with or without diphenhydramine • Or hydrocortisone Reconstitute ONLY with sterile water without preservatives, not bacteriostatic water Can add D5W o Amphotericin B- lipid complex (Abelcet) May also need to premedicate o Amphotericin B-liposomal (AmBisome) May also need to premedicate o Amphotericin B Cholesteryl Sulfate Complex (Amphotec) May also need to premedicate ANC: absolute neutrophil count Page 31 Neutrophils = bands + segs i.e. 5 + 65 = 70 This means that 70% of the WBCs are neutrophils If WBC= 14000 cells per cubic millimeter X 0.70 = 9800 neutrophil cells Neutrophils are elevated with bacterial infections Lymphocytes are elevated with viral infections Not much elevation with fungal infections o Granulocytes= bands + segs + basophils + eosinophils Anti-influenza drugs: o Amantadine (Symmetrel) Blocks influenza A; no activity against influenza B Effective when initiated within 48 hours of initial symptoms & continued for 7-10 days SE: GI disturbances & CNS dysfunction, including dizziness, nervousness, confusion, slurred speech, blurred vision, & sleep disturbances May lower seizure threshold- avoid with seizure history o Rimantadine (Flumadine) Blocks influenza A; no activity against influenza B Effective when initiated within 48 hours of initial symptoms & continued for 7-10 days SE: GI disturbances & CNS dysfunction, including dizziness, nervousness, confusion, slurred speech, blurred vision, & sleep disturbances • Fewer SE than with amantadine o Zanamivir (Relenza) Blocks influenza A & B neuraminidases Powder for inhalation (rotadisk with Diskhaler) 1-2 day improvement in symptoms in patients who are symptomatic for no longer than 48 hours SE: headache, GI disturbances, dizziness, upper respiratory symptoms o Oseltamivir (Tamiflu) Block influenza A & B neuraminidases 1-2 day improvement in symptoms in patients who are symptomatic for no longer than 48 hours SE: N/V/D Oral capsules & suspension Anti-viral agents: o Acyclovir (Zovirax): Counseling: avoid sexual intercourse when lesions are present; this is not a cure for herpes; can take with food; maintain adequate hydration (2-3 L/day); may cause lightheadedness or dizziness o Valacyclovir (Valtrex): Uses: treatment of herpes zoster (shingles), herpes labialis (cold sores) & genital herpes MOA: rapidly & nearly completely converted to acyclovir by intestinal & hepatic metabolism; inhibits DNA synthesis & viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase & being incorporated into viral DNA Reduce dose with renal dysfunction Aspergillus: o Fungus o Amphotericin B (Amphotec, Abelcet, AmBisome), itraconazole (Sporanox), voriconazole (VFEND), caspofungin (Cancidas) NOT ketoconazole Chlamydia: o STD o S/SX: Males: urethritis, epdidymitis, proctitis, reiter syndrome, testicular pain Females: cervictis, urethral syndrome, endometritis, PID, urethral or cervical discharge, pelvic pain o Treatment: doxycycline, azithromycin, erythromycin (pregnant) Tetracyclines & quinolones CI in children & pregnant women Clostridium difficile: o Page 32 Gram +, anaerobic rod Treatment: DOC: metronidazole Vancomycin Enterococcus faecalis: penicillin, ampicillin, vancomycin, linezolid, aminoglycosides, quinupristin & dalfopristin (Synercid)- for vanco resistant enterococcus (VRE) o Chloramphenicol, streptomycin, bactrim o Gram + o Clindamycin or cefazolin (cephalosporins ) will not treat Escherichia coli: o DOC: cefazolin (Ancef), cephalixin (Keflex, Biocef), cefotaxime (Claforan), gentamicin (Gentak) Fluoroquinolones: o MOA: bactericidal; inhibit bacterial DNA topoisomemrase & disrupt bacterial DNA replication o Can cause QT prolongation o AE: crystalluria, tendon rupture o Avoid PO in children under 18 years old- may cause cartilage growth suppression o 2nd generation: Ciprofloxacin (Cipro): • MOA: inhibits DNA-gyrase in suspectible organisms; inhibits relaxation of supercoiled DNA & promotes breakage of double-stranded DNA • Cipro ear drops: o Ciprofloxacin & dexamethasone (Ciprodex): Antibiotic/corticosteroid Treatment of acute otitis media in peds with tympanostomy tubes or acute otitis externa in children & adults o Ciprofloxacin & hydrocortisone (Cipro HC): Antibiotic/corticosteroid Treatment of acute otitis externa (swimmer’s ear) Gonorrhea: o Neisseria gonorrhoeae o Gram – o Cefixime, ceftriaxone, ciprofloxacin, ofloxacin Inhibit cell wall synthesis: o Vancomycin, PCNs, cephalosporins Legionella pneumophilia: o DOC: azithromycin, clarithromycin, erythromycin o Alternative: Rifampin, ciprofloxacin, levofloxacin Lincosamides: o Treat gram + & anaerobic infections o Lincomycin (Lincocin) o Clindamycin (Cleocin) Macrolides: o Bacteriostatic o Clarithromycin (Biaxin): Should not be stored in the refrigerator o Erythromycin: Oral products: • Erythromycin base (E-Mycin, Ery-Tab, PCE (polymer coated ery), Eryc) o Sensitive to acid o Coating on most products o Administer on an empty stomach • Erythromycin stearate (Erythrocin stearate, Wyamycin S) o Properties similar to ery base but better absorbed • Erythromycin estolate (Ilosone) o Most hepatotoxic o o Page 33 o Better absorbed than ery base Erythromycin ethylsuccinate (Eryped, EES) o Best absorbed form from GIT o Available in liquid formulation o 400 mg of EES = 250 mg erythromycin base Parenteral products: • Erythromycin lactobionate • Erythromycin gluceptate Topical products: • Erythromycin (Staticin, Emgel)- for acne (colorless) • Erythromycin (Ilotycin)- ophthalmic use MOA: bacteriostatic macrolide antibiotic; may be bactericidal in high concentrations or when used against highly susceptible organisms. It penetrates the bacterial cell membrane & reversibly binds to the 50 S subunit of bacterial ribosomes Reacts with theophylline by altering hepatic metabolism • Also increases levels of carbamazepine, cyclosporine, triazolam, lovastatin, simvastatin, valproate o Azithromycin (Zithromax): More gram – activity than erythromycin or clarithromycin Suspension & capsules: take on an empty stomach Tablet: with or without food Not for children < 6 months old Meningitis: o Inflammation of the meninges that is identified by an abnormal number of WBC in the CSF o Causative organisms: many gram + & - species Bacterial agents are associated with a large increase in WBCs, increased CSF protein, & decreased CSF glucose Fungal & viral agents exhibit smaller increases in CSF WBCs, smaller increases in CSF protein, & limited decreases in CSF glucose Mycoplasma pneumoniae: o Erythromycin, tetracycline, doxycycline, fluoroquinolones, azithromycin, clarithromycin Other: o Daptomycin (Cubicin): Used for resistant gram + infections MOA: binds to bacterial membrane causing rapid depolarization of membrane potential which leads to inhibition of protein, DNA & RNA synthesis, resulting in bacterial cell death Dosing: 4-6 mg/Kg QD o Linezolid (Zyvox): Available dosage forms: IV, powder for oral suspension, tablet For resistant gram + skin infections, vancomycin-resistant E. faecium Monitor for myelosuppression, thrombocytopenia, & HTN (especially if used with tyraminecontaining foods) Do not combine with SSRIs because of potential for serotonin syndrome Bacteriostatic/bactericidal agent Adjustment with renal dysfunction o Metronidazole (Flagyl): Use: treatment of bacterial vaginosis & trichomonias MOA: after diffusing into the organism, interacts with DNA to cause a loss of helical DNA structure & strand breakage resulting in inhibition of protein synthesis & cell death in susceptible organisms Avoid with etoh o Nystatin: Brand names: Bio-Statin; Mycostatin; Nystat; Nystop; Pedi-Dri Antifungal agent for the treatment of susceptible cutaneous, mucocutaneous, & oral cavity fungal infections caused by the Candida species • Page 34 MOA: binds to sterols in fungal cell membrane, changing the cell wall permeability allowing for leakage of cellular contents Systemic relief in 24-72 hours from candidiasis Oral: poorly absorbed Available dosage forms: cream, lozenge (DSC), ointment, powder for compounding, suspension, tablet, vaginal tablet Mycolog cream contains a corticosteroid (triamcinolone) as well as an antifungal (nystatin) • Could be used for a patient with an ileostomy pouch • Would also treat the inflammation that can occur from what are basically “tape burns” o Vancomycin (Vanocin, Vancole): MOA: inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization through binding tightly to D-alanyl-D-alanine portion of cell wall precursor Alternative to other antimicrobials, including penicillins & cephalosporins for serious gram + infections (resistant strains of strep, MRSA) Watch for ototoxicity Red man’s syndrome: rapid drop in BP accompanied by maculopapular rash in neck or chest area often associated with rapid IV infusion • Should be infused slowly >60 mins Draw peak 1 hour after infusion has completed; draw trough just before next dose Therapeutic peak: 25-40 mcg/mL (>80 toxic) Therapeutic trough: 5-12 mcg/mL Otitis media: o 1st line drugs: ampicillin, amoxicillin, bacampicillin o 2nd generation cephalosporin (cefaclor- Ceclor, cefuroxime- Ceftin, cefprozil-Cefzil, loracarbef-Lorabid) o Zithromax, Biaxin, Bactrim o Most common causative organisms: Streptococcus pneumoniae (pneumococcus), H. flu, moraxella catarrhalis, pseudomonas, klebsiella P. acne: o Clindamycin, erythromycin, & tetracycline are effective o Erythromycin & benzoyl peroxide (Benzamycin): Apply BID This product contains benzoyl peroxide which may bleach or stain clothing Available as a topical gel or Benzamycin Pak (supplied with diluent containing alcohol Penicillins: o Resistance to PCN is caused by beta lactamase enzyme production & alteration of PCN-binding proteins Pseudomembranous enterocolitis (PE): Clostridium difficile overgrowth o Caused by clindamycin & lincomycin o Treat PE with fluid & electrolyte replenishment, oral metronidazole (IV if patient cannot take po), &/or vancomycin (oral only) Pseudomonas: o Aerobic, gram – bacillus o Treatment: Antipseudomonal PCN (mezlocillin, piperacillin, carbenicillin, ticarcillin) Ceftazidime (Fortaz, Tazidime, Tazicef), Cefepime (Maxipime) + aminoglycoside Quinolone + imipenem Sulfonamide derivates: o SJS o The only sodium sulfa salt suitable for ophthalmic use is sulfacetamide sodium (Sodium Sulamyd, Bleph10) o Metabolized via acetylation o Eliminated renally- good for UTIs o Can result in crystalluria- drink sufficient amounts of water to prevent (2-3 L/day) o Sulfamethoxazole & trimethoprim (Bactrim, Septra): MOA: Page 35 • • Sulfamethoxazole interferes with bacterial folic acid synthesis & growth via inhibition of dihydrogolic acid formation form paraaminobenzoic acid (PABA) Trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway Staphylococcus aureus: o DOC: dicloxacillin, nafcillin, oxacillin, o PCN allergy: erythromycin, clindamycin, TCN, linezolid, synercid, vancomycin Systemic fungal infection: o Would NOT use nystatin o Fluconazole (Diflucan) TB: o Initial therapy involves RIPE: As therapy continues, therapy may go to RIP & then RI May continue for 6-18 months Rifampin (Rifadin, Rimactane): • Potent enzyme inducer • Orange discoloration of all bodily fluids- stains contacts Isoniazid (Nydrazid): • May cause vitamin B6 deficiency- give B6 (pyridoxine) with use Pyrazinamide: Ethambutol (Myambutol) o Monitor TB drugs with: LFTs AST Or other transferases Tetracyclines: o Broad spectrum o Doxycycline (Atridox, Doryx, Periostat, Vibra-Tabs, Vibramycin): MOA: bacteriostatic effects by blocking the synthesis of bacterial proteins Long-acting (BID) TCN Eliminated via non-renal routes- good choice for renal impairment DI with trivalent cations- Al (compatible with divalent cations) Thrush: o Normally found in the mouth o It is a fungal infection of the mouth consisting of white spots UTI- pyelonephritis: o E. coli o Bactrim, fluoroquinolones. Ampicillin + gentamicin o UTI & sulfa allergy- treat with a FQ Do not give FQ to children Inflammatory Bowel Disease: Ulcerative colitis: an idiopathic chronic inflammatory disease of the colon & rectum Crohn’s disease: can affect any part of the tubular GIT & is characterized by transmural inflammation of the gut wall Treat with: o Sulfasalazine (Azulfidine, Sulfazine) o Mesalamine (Asacol, Canasa, Pentasa, Rowasa) o Olsalazine (Dipentum) o Glucocorticords o Immunosuppressive agents (6-mercaptopurine, azathioprine, methotrexate, cyclosporine) o Antibiotics (metronidazole) o Infliximab (Remicade) Sulfasalazine (Azulfidine®): o Used in the treatment of inflammatory bowel disease (ulcerative colitis) & RA Page 36 o o Watch for sulfa allergy, salicylate allergy, & urinary discoloration Sulfasalazine sulfapyridine + mesalamine (5-aminosalicyclic acid; 5-ASA) 5-ASA is more active If patient cannot tolerate sulfasalazine because of a sulfa hypersensitivity, mesalamine (Asacol, Pentasa, Rowasa) may be used Immunosuppressive Therapy: Calcineurin inhibitors: o Cyclosporine (Sandimmune, Neoral) o Tacrolimus (Prograf) mTOR inhibitors: o Sirolimus (Rapamune) Antiproliferative agents: o Azathioprine (Imuran) o Mycophenolate mofetil (CellCept) o Mycophenolate sodium (Myfortic) o Leflunomide (Arava) Monoclonal antibodies: o Muromonab-CD3 (Orthoclone OKT 3) o Basliximab (Simulect) o Daclizumab (Zenepax) Polyclonal antibodies: o Anti-thymocyte globulin (Atgam): equine o Anti-thymocyte globulin (Thymoglobulin): rabbit Insomnia, Anxiety, or both: Benzodiazepines: o Most undergo oxidation to active metabolites in liver o Lorazepam (Ativan), oxazepam (Serax), & temazepam (Restoril) undergo glucuronidation to inactive metabolites Useful in elderly & those with liver disease o Can experience seizures & delirium with sudden discontinuation o Hypnotic agents: Estazolam (ProSom) Flurazepam (Dalmane) Quazepam (Doral) Temazepam (Restoril) Triazolam (Halcion) Trazodone (Desyrel): o Antidepressant that is useful for severe anxiety or insomnia o Highly sedating, causing postural hypotension & is associated with priapism o Doses: Sedation: 25-50 mg Depression: 150 mg divided into 3 daily doses; max 600 mg/day Zolpidem (Ambien): o An imidazopyridine hypnotic agent o MOA: has much or all of its actions explained by its effects on benzodiazepine receptors, especially the omega-1 receptor binds the benzodiazepine (BZ) receptor subunit of the GABA-A receptor complex o No withdrawal symptoms, rebound insomnia or tolerance o Rapid onset good for initiating & maintaining sleep o SE: headache, daytime somnolence, GI upset o Avoided in patients with obstructive sleep apnea Zaleplon (Sonata) o Nonbenzodiazepine hypnotic Page 37 o MOA: interacts with benzodiazepine GABA receptor complex o T1/2 is ~1 hour & has no active metabolites o SE: drowsiness, dizziness, & impaired coordination o Caution in those with compromised respiratory function Eszopiclone (Lunesta): o MOA: may interact with GABA-receptor complexes OTC sleep aids: o Doxylamine (Unisom) o Diphenhydramine (Nytol, Sominex) o Diphenhydramine + APAP (Tylenol PM, Unisom Pain Relief) o Diphenhydramine + ASA (Bayer PM) Lupus: Autoimmune inflammatory condition Systemic Lupus Erythematosus (SLE) Drugs that can contribute: procainamide**, phenytoin, chlorpromazine, hydralazine*, quinidine, methyldopa, & isoniazid Therapy: o Arthritis: NSAIDs or glucocorticoids o Dermatologic complications: hydroxychloroquine (Plaquenil) o Thrombocytopenia: glucocorticoid therapy o Refractory cases: cyclophosphamide Metabolic acidosis: Give sodium acetate- acetate ion converts to bicarbonate Bicitra: o Sodium citrate & citric acid o Other brand names: Cytra-2 & Oracit o AKA: Modified Shohl’s solution o Use: treatment of metabolic acidosis; alkalinizing agent in conditions where long-term maintenance of an alkaline urine is desirable Also solution antacid pre-op if patient has eaten just before emergency surgery or delivery of child o Dosing: oral- 10-30 mL with water after meals (to avoid laxative effect) & at bedtime o SE: N/V/D, hyperkalemia, tetany Migraines: Triptans: o Selective serotonin receptor agonists that activate 5-HT1B/5-HT1D & to a lesser extent 5-HT1A/5-HT1F o Agents: Almotriptan (Axert): tablets; CYP450 & MAO metabolism Sumatriptan (Imitrex): tablets, nasal spray, injection; MAO metabolism • Can re-dose oral tablets & nasal spray if no response after 2 hours • Can re-dose injection if no response after 1 hour Eletriptam (Relpax): tablets; CYP 3A4 metabolism Frovatriptan (Frova): tablet; renal 50% Rizatriptan (Maxalt): tablet/wafer; MAO metabolism Zolmitriptan (Zomig): tablet/wafer; CYP450 & MAO metabolism Naratriptan (Amerge): tablets; renal 70% & CYP450 o SQ sumatriptan has the fastest onset followed by sumatriptan nasal spray o Rizatriptan may have a slightly faster onset of action than the others o Migraine recurrence rates may be lower with long half-life triptans such as naratriptan & frovatriptan o SE: tingling & paresthesias; sensations of warmth in the head, neck, chest, & limbs; dizziness; flushing; neck pain or stiffness o Do not give sumatriptan to patients who have risk factors for CAD Page 38 o CI: in patients with hx of ischemic heart disease, MI, uncontrolled HTN, or other heart disease; pregnancy Ergot derivatives: o CI: pregnancy, peripheral vascular disease, CAD, sepsis, hepatic or renal impairment o Dihydroergotamine (DHE 45, Migranal): Migraines: with or without aura MOA: ergot alkaloid alpha-adrenergic blocker directly stimulates vascular smooth muscle to vasoconstrict peripheral & cerebral vessels; also has effects on serotonin receptors • 5-HT1D receptor agonist Max: 6 mg/week Patient takes too much: N/V/D, dizziness, paresthesia, peripheral ischemia, peripheral vasoconstriction Available dosage forms: injection & intranasal spray Miscellaneous Drugs: Acetylcysteine (Mucomyst, Acetadote): o MOA: exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity; thought to reverse APAP toxicity by providing substrate for conjugation with the toxic metabolites Adalimumab (Humira): o Tumor necrosis factor (TNF) blocking agent o MOA: binds to human tumor necrosis factor alpha (TNF-alpha) receptor sites Elevated TNF levels in the synovial fluid are involved in pathologic pain o Use: treatment of active RA in patients with inadequate response to one or more DMARDs; psoriasis o Dose: 40 mg SQ EOW o Before starting therapy: TB test, measure rheumatoid factor, PT Adefovir (Hepsera): o Antiretroviral agent; reverse transcriptase inhibitor (nucleoside) o MOA: acyclic nucleotide reverse transcriptase inhibitor (adenosine analog) which interferes with HBV viral RNA dependent DNA polymerase resulting in inhibition of viral replication o Use: treatment of chronic hepatitis B Atropine (AtroPen; Atropine-Care; Isopto; Sal-Tropine): o AtroPen formulation is available for use primarily by the department of defense o MOA: blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands & the CNS; increases CO, dries secretions, antaonizes histamine & serotonin Bismuth subsalicylate, metronidazole, tetracycline (Helidac): o If patient has + urea breath test indicating H. pylori present Chlorhexidine (Periogard): o Antibacterial agent for oral rinse o Bactericidal o Uses: disinfectant; gingivitis; periodonitis; inhibits plaque formation Cromolyn (NasalCrom): o Dose: use 1 spray in each nostril 3-4 times per day Cyclosporin (Gengraf, Neoral, Restasis, Sandimmune): o Neoral & Sandimmune are NOT therapeutically equivalent o Immunosuppressant agent o MOA: inhibition of production & release of interleukin II & inhibits interleukin II-induced activation or resting T-lymphocytes Desmopressin (DDAVP, Stimate): o Vasopressin analog o Uses: diabetes insipidus; control bleeding in hemophilia A & van Willebrand disease; primary noctural enuresis o Strengths/dosage forms: Injection (IV): 4 mcg/mL Solution, intranasal: 100 mcg/mL Tablets Page 39 Dicyclomine (Bentyl); o MOA: anticholinergic agent o Uses: treatment of functional disturbances of GI motility such as irritable bowel syndrome o NOT used for GERD Etancercept (Enbrel): o Disease modifying agent o MOA: binds to TNF & blocks its interaction with cell surface receptors TNF blocker o Use: moderate-severe RA; chronic plaque psoriases o Dose: 25 mg injection SQ twice weekly or 50 mg injection SQ once weekly o Initial storage of drug: in refrigerator (not frozen) o Stability of vials after reconstitution: 14 days in refrigerator o Allow prefilled syringes 15-30 minutes at room temperature prior to injection o Some foaming is normal Guaifensin: o MOA: expectorant which acts by irritating the gastric mucosa & stimulating respiratory tract secretions, thereby increasing respiratory fluid volumes & decreasing mucus viscosity Hyaluronate (Hyalgan, Biolon, Healon, Hylaform, Orthovisc, Provisc, Restylane, Supartz, Synvisc, Vitax): o MOA: sodium hyaluronate is a polysaccharide which is distributed widely in the extracellular matrix of connective tissue in man. It forms a viscoelastic solution in water (at physiological pH & ionic strength) which makes it suitable for aqueous & vitreous humor in ophthalmic surgery & functions as a tissue &/or joint lubricant o Use: intra-articular injection (Synvisc)- treatment of pain in OA in knee in patients who have failed nonpharmacologic treatment & simple analgesics • No weight bearing exercise for 48 hours Intradermal- correction of moderate to severe facial wrinkles Ophthalmic- surgical aid in cataract extraction, intraocular implantation, corneal transplant, glaucoma filtration, & retinal attachment surgery Topical- management of skin ulcers & wounds Hydroxyzine (Atarax, Vistaril): o MOA: competes with histamine for H1 receptor sites on effector cells in the GIT, blood vessels, & respiratory tract; possesses skeletal muscle relaxing, bronchodilator, antihistamine, antiemetic, & analgesic properties o Use: treatment of anxiety; preoperative sedative; antipruritic o Not to be confused with Hydralazine Interferon beta 1b (Betseron): o Use: treatment of MS o Can cause hepatotoxicity- monitor LFTs Isotretinoin (Accutane, Amnesteem, Clarais, Sotret): o Retinoic acid derivative o MOA: reduces sebaceous gland size & reduces sebum production; regulates cell proliferation & differentiation o Use: treatment of sever recalcitrant nodular acne unresponsive to conventional therapy o RiskMAP, S.M.A.R.T., S.P.R.I.T., I.M.P.A.R.T. programs Cannot be dispensed unless the rx is affixed with a yellow, self-adhesive qualification sticker filled out by the prescriber Telephone, fax, or computer-generated rxs are no longer valid Rx cannot be written for more than a 1-month supply, must be dispensed with a patient education guide Females must have their rxs filled within 7 days of the qualification date- considered expired if > 7days o Pregnancy risk factor: X Females must have 2 methods of contraception; 1 month prior to starting therapy & 1 month after discontinuation of therapy Page 40 Therapy is begun after 2 negative pregnancy tests SE: increased triglycerides, elevated blood glucose, photosensivitivity Avoid additional vitamin A supplements Dose: 0.5-2 mg/Kg/day in 2 divided doses Take with food; limit exercise while on therapy; capsules can be swallowed, or chewed & swallowed; capsule may be opened with a large needle & contents placed on applesauce or ice cream o Excerbation of acne may occur during the 1st weeks of therapy o Accutane, Amnesteem, & Sotret contains soybean oil (Claravis does not) Lansoprazole (30 mg), amoxicillin (1 g), clarithromycin (500 mg) (Prevpac): o For H. pylori o Taken together BID for 10-14 days Leflunomide (Arava): o Disease modifying agent o MOA: inhibits pyrimidine synthesis, resulting in antiproliferative & anti-inflammatory effects o Use: treatment of active RA; indicated to reduce signs & symptoms, & to retard structural damage & improve physical function Luride: source of fluoride to prevent dental caries o Supplied as sodium fluoride in chewable tablets that provide 0.25 mg, 0.5 mg, & 1 mg of fluoride ion per tab o Prolonged ingestion with excessive doses may result in dental fluorosis (staining or hypoplasia of the enamel of the teeth) & osseous changes Malathion (Ovide): o Class: organophosphate; pediculicide o Uses: pediculosis capitis; lice o MOA: acts via cholinesterase inhibition. It exerts both lousicidal & ovicidal actions in vitro. o Safety not established in children under 6 years old o Lotion Mannitol (Osmitrol, Resectisol): o Osmotic diuretic o MOA: increases osmotic pressure of glomerular filtrate, which inhibits tubular reabsorption of water & electrolytes & increases urinary output Mebendazole (Vermox): o Anthelmintic agent o MOA: selectively & irreversibly blocks glucose uptake & other nutrients in susceptible adult intestinedwelling helminthes o Dosing: Pinworms: 100 mg po ASD; may need to repeat after 2 weeks; treatment should include family members in close contact with patient Whipworms, roundworms, hookworms: 1 tablet BID, morning & evening on 3 consecutive days; if patient is not cured within 3-4 weeks, a 2nd course of treatment may be administered Capillariasis: 200 mg BID for 20 days o Strengths/dosage forms: Tablet, chewable: 100 mg Methotrexate (Rheumatrex; Trexall): o MOA: inhibits dihydrofolate reductase causing interference with DNA synthesis, repair, & cellular replication o Juvenile RA: oral, IM: 10 mg/m2 once weekly o Does cause alopecia o Causes myelosuppression & thrombocytopenia NOT thrrombocytosis (increased PLT) Misoprostol (Cytotec): o MOA: synthetic prostaglandin E1 analog that replaces the protective prostaglandins consumed with prostaglandin-inhibiting therapies (i.e. NSAIDs); has been shown to induce uterine contractions o Dosing: Prevention of NSAID-induced ulcers: 200 mcg po QID with food (to decrease diarrhea) o o o o Page 41 Labor induction or cervical ripening: intravaginal- 25 mcg (1/4 of a 100 mcg tablet) • Do not use in patients with previous cesarean delivery or prior major uterine surgery Fat absorption in CF (unlabeled use): 100 mcg QID (ages 8-16) Nimodipine (Nimotop): o MOA: calcium channel blocker o Use: spasm following subarachnoid hemorrhage from ruptured intracranial aneurysms o Has a greater effect on cerebral arteries- may be due to the drug’s increased lipophilicity o Dosing: 60 mg po Q4h x 21 days; start 96 hours after subarachnoid hemorrhage o If the capsules cannot be swallowed, the liquid may be removed by making a hole in each end of the capsule with an 18-guage needle & extracting the contents via syringe Oxybutynin (Ditropan): o Urinary antispasmodic agent o MOA: Non-selective muscarinic receptor antagonist with a higher affinity for M1 & M3 receptors Increases bladder capacity, decreases uninhibited contractions, & delays desire to void o Dosage forms available: syrup, tablet (IR, XR), patch (Oxytrol) Palivilizumab (Synagis): o Use: monoclonal antibody used for prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in infants & children < 2 years o MOA: exhibits neutralizing & fusion-inhibitory activity against RSV Ribavirin (Copegus, Rebetol, Ribasphere, Virazole) also used to treat RSV Pancuronium: o Nondepolarizing neuromuscular blocking agent o MOA: blocks neural transmission at the myoneural junction by binding with cholinergic receptor sites o Onset: 2-4 minutes o Duration after single dose: 40-60 minutes o Use: adjunct to general anesthesia to facilitate endotracheal intubation & to relax skeletal muscles during surgery; does not relieve pain or produce sedation o DOC for neuromuscular blockade EXCEPT in patients with renal failure, hepatic failure, or cardiovascular instability o AE: increased pulse rate, elevated BP & CO, edema, flushing, rash, bronchospasm, hypersensitivity rxn Peginterferon Alfa-2a (Pegasys): o Use: hepatitis C o Refrigerate; protect from light Permethrin(Acticin, Elimite, Nix Creme Rinse, Pronto, Rid, A200 Lice Control) o OTC available with same ingredient: Nix PhosLo: o Calcium acetate o Use: Oral: control of hyperphosphatemia in end-stage renal failure; does not promote aluminum absorption IV: calcium supplementation in parenteral nutrition therapy o MOA: combines with dietary phosphate to form insoluble calcium phosphate which is excreted in the feces Physostigmine (Antilirium): o Propofol (Diprivan): o General anesthetic; no analgesic properties o Avoid abrupt discontinuation- titrate slowly o Propofol emulsion contains soybean oil, egg phosphatide & glycerol o “Propofol infusion syndrome”: symptoms include sever, sporadic metabolic acidosis &/or lactic acidosis which may be associated with tachycardia, myocardial dysfunction, &/or rhabdomyolysis o Short duration of action: 3-10 minutes o If on concurrent parenteral nutrition, may need to adjust the amount of lipid infused o Provides 1.1 kCal/mL Riopan: Page 42 o Magaldrate (antacid) & simethicone (antiflatulent) combination o Substitutes can be found in the Non-Prescription Handbook & Facts & Comparisons Vecuronium: o Nondepolarizing neuromuscular blocker agent o MOA: blocks acetylcholine from binding to receptors on motor endplate by inhibiting depolarization o Onset: 2-4 minutes o DOA: 30-45 minutes o Use: adjunct to general anesthesia to facilitate endotracheal intubation & to relax skeletal muscles during surgery; does not relieve pain or produce sedation o AE: bradycardia, edema, flushing, hypersensitivity rxn, hypotension, tachycardia, rash Miscellaneous Facts: Danger of decreasing DKA too fast: cerebral edema Genetic polymorphism exists as acetylation Albumin is important for measuring calcium levels o Corrected calcium = serum calcium + 0.8(4 – patient’s albumin) Caffeine treats respiratory distress in neonates Emergency bee sting kit: o Epinephrine & APAP o EpiPen auto-Injector 0.3 mg SQ dose of 1:1000 epinephrine in a 2 mL disposable prefilled injector Liposyn III (fat emulsion) is stored at room temperature MedWatch: a list of reported side effect o Completely voluntarily reported Stain dermatologists use for fungus identification: KOH Kayexlate + sorbitol use: to prevent constipation o Store at room temperature Hypercalcemia: almost always caused by increased entry of Ca into the extracellular fluid & decreased renal Ca clearance o More that 90% of cases are due to primary hyperparathyroidism or malignancy Hypocalcemia in renal impairment: o Phosphorus & calcium levels are altered due to: Phosphorus retention, resulting in a rise in serum phosphorus levels & a reciprocal fall in calcium levels, with resultant stimulation of parathyroid hormone (PTH) secretion Decreased generation of 1,25-dihyroxyvitamin D3, further contributing to low serum calcium levels & decreasing suppression of PTH o Addition of a phosphate binder prevent GI phosphate absorption: Calcium carbonate 500-1000 mg po with meals Sevelamer (Renagel): lacks aluminum & calcium Cheilitis: inflammation of the lips Herpes simplex I (cold sore): avoid the sunlight Goodpasture’s syndrome: glomerulonephritis associate with pulmonary hermorrhage & circulating antibodies against basement membrane antigens Myasthenia Gravis: An autoimmune disorder that involve antibody-mediated disruption of postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction & is often associated with thymus tumors Treatment: o Anticholinesterase drugs: Pyridostigmine Neostigmine o Thymectomy o Immunosuppressive drugs High-dose prednisone Azathioprine Page 43 Cyclosporine Cyclophosphamide Orange Book: AKA: Approved Drug Products with Therapeutic Equivalence Evaluations Codes: o A: Drug products that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products, i.e., drug products for which: there are no known or suspected bioequivalence problems. These are designated AA, AN, AO, AP, or AT, depending on the dosage form; or actual or potential bioequivalence problems have been resolved with adequate in vivo and/or in vitro evidence supporting bioequivalence. These are designated AB AA Products in conventional dosage forms not presenting bioequivalence problems AB, AB1, AB2, AB3... Products meeting necessary bioequivalence requirements AN Solutions and powders for aerosolization AO Injectable oil solutions AP Injectable aqueous solutions &, in certain instances, intravenous non-aqueous solutions AT Topical products o B: Drug products that FDA at this time, considers NOT to be therapeutically equivalent to other pharmaceutically equivalent products, i.e., drug products for which actual or potential bioequivalence problems have not been resolved by adequate evidence of bioequivalence. Often the problem is with specific dosage forms rather than with the active ingredients. These are designated BC, BD, BE, BN, BP, BR, BS, BT, BX, or B*. B* Drug products requiring further FDA investigation & review to determine therapeutic equivalence BC Extended-release dosage forms (capsules, injectables & tablets) BD Active ingredients & dosage forms with documented bioequivalence problems BE Delayed-release oral dosage forms BN Products in aerosol-nebulizer drug delivery systems BP Active ingredients & dosage forms with potential bioequivalence problems BR Suppositories or enemas that deliver drugs for systemic absorption BS Products having drug standard deficiencies BT Topical products with bioequivalence issues BX Drug products for which the data are insufficient to determine therapeutic equivalence Osteopenia/Ostoporosis: T scores are used for diagnosis: o Osteopenia: T score -1 to -2.5 SD below the young adult mean o Osteoporosis: T score -2.5 SD below the young adult mean Bisphosphonates: o Could worsen esophagitis o Take with a full glass of water fir thing in the AM & at least 30 minutes before the 1st food or beverage of the day o Maximize therapy by taking calcium + vitamin D o Alendronate (Fosmax): Prevention dose: 5 mg QD or 35 mg Q week Treatment dose: 10 mg QD or 70 mg Q week Dosage forms: solution & tablet o Ibandronate (Boniva): Prevention dose: 2.5 mg QD; 150 mg Q month may be considered Treatment dose: 2.5 mg QD or 150 mg Q month o Risedronate (Actonel): Prevention dose: 5 mg QD or 35 mg Q week may be considered Treatment dose: 5 mg QD or 35 mg Q week Page 44 Selective Estrogen Receptor Modulator: o Raloxifene (Evista): MOA: estrogen receptor agonist at the skeleton decreases resorption of bone & overall bone turnover 60 mg QD for treatment & prevention of osteoporosis SE: increased risk of thromboembolism, hot flashes, nausea, dyspepsia, weight gain Teriparatide (Forteo): o Parathyroid hormone (PTH) analog for osteoporosis o MOA: stimulates osteoblast function, increases GI calcium absorption, increases renal tubular reabsorption of calcium o Dosage: injection o Storage: refrigerate; discard pen 28 days after 1st injection OTC: Aluminum hydroxide (ALternaGel, Amphojel): o Use: for treatment of hyperacidity & hyperphosphatemia o MOA: neutralizes hydrochloride in stomach to form Al(Cl)3 salt + H2O o Dose: Hyperphosphatemia: 300-600 mg TID with meals (within 20 minutes of meal) Hyperacidity: 600-1200 mg between meals & at bedtime o Aluminum may accumulate in renal impairment o Dose should be followed with water Antidiarrheal agents: o Bismuth subsalicylate (Kaopectate) Has both antisecretory & antimicrobial actions while possibly providing anti-inflammatory action as well Atopic dermatisis: o Hydrocortisone Capsacin (Zostrix, Capzasin): o MOA: induces the release of substance P, the principle chemomediator of pain impulses from the periphery to the CNS; after repeated application, the neuron is depleted of substance P o Apply to the affected area at least 3-4 times/day If applied less than this, decreased efficacy o Strength: 0.025%, 0.075% Diaper rash: o Breast-fed infants have less diaper rash than do bottle-fed infants o Skin protectants to treat: Allantoin, calamine, cod liver oil (in combination), dimethicone, kaolin, lanolin (in combination), mineral oil, petrolatum, talc, topical cornstarch, white petrolatum, zinc oxide, zinc oxide ointment Loratidine (Claritin, Alavert): o Nonsedating antihistamine o Patients with liver or renal impairment should start with a lower dose (10 mg QOD) o Do not use in children <2 o Dosing: 2-5 years old: 5 mg QD >6: 10 mg QD o Take on an empty stomach o Available as: syrup, tablet, rapidly disintegrating tablets Nicotine Replacement therapy: o Products: patch, gum, lozenge, inhaler Ostomy care: o Three basic types of ostomies: Ileostomy Colostomy (most common) Urinary diversion Page 45 Effect of food on stoma output: Foods that thicken: • Applesauce, bananas, bread, buttermilk, cheese, pasta, potatoes, pretzels, rice yogurt Foods that loosen: • Alcohol, chocolate, beans, fried or greasy foods, spicy foods, leafy veg Foods that cause stool odor: • Asparagus, beans, cheese, eggs, fish, garlic Foods that cause urine odor: • Asparagus, seafood, spices Foods that combat urine odor: • Buttermilk, cranberry juice, yogurt o Local complications: Local irritation: can occur because the output from the intestines or kidneys can irritate the skin around the stoma • Patient can use: karaya powder, pectin base powder, ostomy creams, or barriers to protect the skin Alakaline dermatitis: occurs in patients with urinary diversions because of the alkaline nature of the output • Major cause of blood in the pouch because it renders the stoma extremely friable • Treatment is acidification of the urine (cranberry juice 2-3 quarts daily) Excoriation: caused by erosion of the epidermis by digestive enzymes • The eroded or denuded epidermis may bleed, & is painful when touched when applying the appliance • Treatment: karaya or pectin-based powder may be applied to the peristomal skin prior to application of the pouch, more frequent changing of the pouch Infection: candida species • 2% miconzaole powder or nystatin powder o Fitting an ostomy: Pouch opening may be cut to fit or presized • If they are cut to fit, the stoma pattern is traced onto the skin barrier-wafer surface of the pouch & then cut out before being applied The diameter of the round stoma is measured at the base, where the mucosa meets the skin, which is considered the widest measurement Oval stomas should be measured at both their widest & narrowest diameters A stoma may swell if the appliance fits too tightly or slips, or if the patient falls or experiences a hard blow to the stoma Other consideration include: body contour, stoma location, skin creases & scars, & type of ostomy To prevent leakage, the pouch should be emptied when it is 1/3 – 1/2 full The flange & skin barrier may be left in place for 3-7 days, depending on the condition of the skin & skin barrier Water will not enter the stoma so it is not necessary to cover it while swimming, bathing, or showering Oxymetazoline (Afrin): o Adrenergic agonist; vasoconstrictor o Rebound congestion may occur with extended use (>3 days) o Caution in the presence of HTN, DM, hyperthyroidism, CAD, asthma o Increased toxicity with MAOI o Do not use if it changes color or becomes cloudy o MOA: stimulates alpha-adrenergic receptors in the arterioles of the nasal mucosa to produce vasoconstriction o Approved for >6 years old Poison ivy: o Topical anesthetics: benzocaine & pramoxine o Hydrocortisone o Page 46 Astringents: Aluminum acetate (Burrow’s solution, Domeboro Powder), zince oxide, zinc acetate, sodium bicarbonate, calamine, witch hazel (hamamelis waters) o Colloidal oatmeal baths to help to provide skin hydration, to aide in cleansing or removing skin debris, & to allay the drying & tightening symptoms o Antihistamines Robitussin: o Guaifenesin: an expectorant used to help loosen phlegm & thin bronchial secretions to make coughs more productive Warts: o Plantar warts: Clear Away Wart Remover: Salicyclic acid 40% Wart off Dr. Scholls Clear Away o Pain: Pure Mu Agonists: strong opioids for severe pain o Fentyl: Sublimaze: injection Duragesic: transdermal patch (change Q 3 days) • 5 patches per box Actiq: lozenge o Hydromorphone (Dilaudid): Can cause seizures Dosage forms: tablet, liquid, suppository, injection (a slight yellowish discoloration has not been associated with loss of potency o Levoophanol (Levo-Dromoran) Dosage forms: tablet & injection o Meperidine (Demerol, Meperitab): MOA: binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of & response of pain Hepatic metabolite, normeperidine, can buildup & cause seizures • Do not use in patients with seizure disorders Avoid use with MAOIs • Isocarboxazid (Marplan) • Selegiline (Eldepryl, Deprenyl)- Parkinson’s • Phenelzine (Nardil) • Tranylcypromine (Parnate) o Methadone (Dolophine, Methdose): Dosage forms: tablet, liquid, injection o Morphine (Astramorph/PF, Avinza, DepoDur, Duramorph, Infumorph, Kadian, MS Contin (ER or SR), MSIR (IR), Oramorph SR, RMS, Roxanol): MOA: binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of & response of pain Can cause: hypotension, bradycardia, respiratory depression Vasodilatory properties Dosage forms: • Capsules (ER, SR) • Infusion • Injection (ER liposomal suspension for lumbar epidural injection) • Injection, solution • Solution • Suppository • Tablet (CR, ER, SR) o Oxycodone (OxyIR, Roxicodone, Percocet, OxyContin (CR)): Page 47 Oxymorphone (Numorphan-suppository) Dosage forms: injection & suppository Pure mu agonists: mild to moderate pain o Codeine (Tylenol #3) o Hydrocodone: With APAP: • Vicoden 5/500; Vicoden ES 7.5/750; Lorcet or Vicodin HP 10/650; Lortab 2.5/500, 5/500, 7.5/500, 10/500; Norco 5/325, 7.5/325, 10/325 With IBU: • Vicoprofen 7.5/200 o Propoxyphene: Propoxyphene/APAP: • Darvocet-N-50 (50/325); Darvocet-N-100 (100/650) • Darvon 32, 65 mg Agonists-antagonists: o Buprenorphine (Buprenex) o Butorphanol (Stadol) Available as: injection & nasal spray o Dezocine (Dalgan) o Nalbuphine (Nubain) Injection only o Pentazocine: 50 mg tablet: Talwin 50 mg/naloxone 0.5 mg tablet: Talwin NX 12.5/ASA 325 tablet: Talwin Compound Miscellaneous: o Tramadol (Ultram) 400 mg max o Ultracet (Tramadol/APAP 37.5/325) NSAIDS: o Indomethacin (Indocin): Dosage: • Inflammatory/RA: 25-50 mg/day 2-3 times/day; max 200 mg/day Dosage forms: IR & SR capsule, injection & suspension o Ketorolac (Toradol): Do NOT use for more than 5 days Acular: ophthalmic dosage form o Nabumetone (Relafen): For OA & RA Dosing: 1000 mg/day; an additional 500-1000 mg may be needed in some patients; may be administered QD or BID; NMT 2000 mg/day Take with food or milk to decrease GI upset o Diclofenac (Voltaren) o Etodolac (Lodine) o Tolmetin (Tolectin) o Sulindac (Clinoril) o Fenoprofen (Nalfon) o Flurbiprofen (Ansaid) o Ibuprofen (Motrin) o Ketoprofen (Orudis, Oruvail-SR) o Naproxen (Naprosyn) o Oxaprozin (Daypro) o Meclofenamate (Meclomen) o Piroxicam (Feldene) o Celecoxib (Celebrex) o Page 48 o Interferes with ACEIs, ARBs, & diuretics Conversions: o Usual ratio is Morphine 8 to dilaudid 1 o Methadone 10 mg = hydromorphone 7.5 mg (po) & 1.5 mg (IM) Parkinson’s: A chronic progressive neurologic disorder with symptoms that present as a variable combination of rigidity, tremor, bradykinesia, & changes in posture & ambulation Primary Parkinson’s- no identified cause Secondary Parkinson’s- may be the result of drug use (i.e. reserpine, metoclopramide, antipsychotics), infections, trauma, or toxins Progressive degeneration of the substantia nigra in the brain with a decrease in dopaminergic cells Drug therapy: o Want medications that will increase dopamine or dopamine activity by directly stimulating dopamine receptors or by blocking acetylcholine activity, which results in increased dopamine effects o Carbidopa-levodopa (Sinemet): MOA; levodopa increases DA; carbidopa prevents metabolism of levodopa allowing more to enter the blood brain barrier Take on an empty stomach & eat shortly after to prevent N/V o Direct stimulation of DA receptors: Bromocriptine (Parlodel) Pergolide (Permax) Pramipexole (Mirapex) Ropinirole (Requip) o Selegiline (Eldepryl, Carbex, Atapryl, Selpak): MOA: inhibits MAOB; increases DA & 5-HT o Inhibits COMT; increases DA: Entacapone (Comtan) Tolcapone (Tasmar) o Amantadine (Symmetrel): MOA: may increase presynaptic release of DA, blocks reuptake o Blocks acetylcholine, may balance DA: Benztropine (Cogentin) Trihexyphenidyl (Artane) o Vitamin E- antioxidant; mixed results Pediatrics: EES ointment given in neonate to prevent gonorrhea infection in the eyes Vitamin K is given to babies until they can produce their own Colfosceril (Exosurf): respiratory surfactant o Administered intrathecheally Neural tube defects are a result of a decrease in folic acid (while pregnant) Acetaminophen: o <12 years: 10-15 mg/Kg/dose Q 4-6 hours prn (NMT 5 doses: 2.6 g in 24 hours) Ibuprofen: o 6 months – 12 years Temperature <102.5°F: 5 mg/Kg/dose Temperature >102.5°F: 10 mg/Kg/dose Q 6-8 hours; max daily dose: 40 mg/Kg/day Theophylline can be used as a respiratory stimulant in babies Pharmaceutics: Bioavailability: refers to the rate & extent of absorption o Absolute bioavailability: the fraction (or %) of a dose administered non-IV (or extravascularly) that is systemically available (compared to an IV dose) Page 49 If given orally, absolute bioavailability (F) is: • F = (DIV/DPO) X (AUCPO/AUCIV) o Relative bioavailability: the fraction of a dose administered as a test formulation that is systemically available as compared to a reference formulation: F = (AUCtest formulation/AUCreference) X ( Dreference/Dtest formulation) Compounding: o Glycerin, talc, starch, witch hazel = suspension Talc is not soluble Starch is not very soluble o To make a oleaginuous base use: white petrolatum Filters: o 0.22 micron filter does NOT remove pyrogens Methylcellulose: a suspending agent (semisynthetic hydrocolloids) Selected dosage forms: o Butorphanol (Stadol) Injection, intranasal spray o Calcitonin (Miacaclin) Injection, intranasal spray Stored in refrigerator o Desmopressin (DDAVP, Stimate) Injection, intranasal spray, tablets o All three above come in a nasal inhaler o Budesonide: Capsules (Entocort), nasal suspension, powder for oral inhalation, suspension for oral inhalation o Fluticasone: Aerosol for oral inhalation, cream (Cutivate), ointment, powder for oral inhalation, suspension intranasal spray Rizatriptan (Maxalt), loratadine (Claritin), ondansetron (Zofran) are all available as an orally disintegrating tablet (ODT) Mg sterate: lubricant in tablet o Excess will cause alteration in tablet dissolution due to decreased rate of tablet break down (would slow down) Incompatibility: o Pick pair of drugs with one acid & one base Storage: o Liposyn-II Fat emulsion May be stored at room temperature Do not store partly used bottle for later use Do not use if emulsion appears to be oiling out o Room temperature antibiotic suspensions: Clarithromycin (Biaxin); sulfamethoxazole-trimethoprim (Bactrim); azithromycin (Zithromax); cefdinir (Omnicef) Furosemide has a pka of 3.7 at physiologic pH will it be 25% ionized, 75% ionized, all ionized, all ionized or can’t determine? o Furosemide (one word generic name) is an acid; acids are all non-ionized at acidic pH but are ionized at basic pH; physiologic pH is 7.4 which is quite alkaline compared to 3.7; means furosemide ionized to non-ionized ratio would be > 1:1000, so totally ionized o Naproxen pka = 4.2 what would happen at plasma pH? Same as above because naproxen is also an acid Typical pharmaceutical ingredients: o Antifungal preservative: used in liquid & semisolid formulations to prevent growth of fungi Ex: benzoic acid, butylparaben, ethylparaben, sodium benzoate, sodium propionate o Antimicrobial preservative: used in liquid & semisold formulations to prevent growth of microorganisms Ex: benzalkonium chloride, benzyl alcohol, cetylpyridinium chloride, phenyl ethyl alcohol Page 50 o o o o o o o o o o o Antioxidant: used to prevent oxidation Ex: ascorbic acid, ascorbyl palmitate, sodium ascorbate, sodium bisulfate, sodium metabisulfite Emulsifying agent: used to promote & maintain dispersion of finely divided droplets of a liquid in a vehicle in which it is immiscible Ex: acacia, cetyl alcohol, glyceryl monostearate, sorbitan monostearate Surfactant: used to reduce surface or interfacial tension Ex: polysorbate 80, sodium lauryl sulfate, sorbitan monopalmitate Plasticizer: used to enhance coat spread over tablets, beads, & granules Ex: glycerin, diethyl palmitate Suspending agent: used to reduce sedimentation rate of drug particles dispersed throughout a vehicle in which they are not soluble Ex: Carbopol, hydroxymethylcellulose, hydroxypropyl cellulose, methylcellulose, tragacanth Binder: used to cause adhesion of powder particles in tablet granulations Ex: acacia, alginic acid, ethylcellulose, starch, povidone Diluent: used as fillers to create desired bulk, flow properties, & compression characteristics in tablet & capsule preparations Ex: kaolin, lactose, mannitol, cellulose, sorbitol, starch Disintegrant: used to promote disruption of solid mass into small particles Ex: microcrystalline cellulose, carboxymethylcellulose calcium, sodium alginate, sodium starch, glycolate, alginic acid Glidant: used to improve flow properties of powder mixture Ex: colloidal silica, cornstarch, talc Lubricant: used to reduce friction during tablet compression & facilitate ejection of tablets from the die cavity Ex: calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate Humectant: used for prevention of dryness of ointment & creams Ex: glycerin, propylene glycol, sorbitol Pharmacokinetics: Tests used to test for drug absorption in GI: o Dissolution o Disintegration: must occur before dissolution can occur o Hardness: hardness of a tablet influences its ability to break apart in the stomach o All can be tested in vitro Pregnancy: Tocolytics (stops labor): o Magnesium is a tocolytic Labor inducers: o Prostaglandins and oxytocin both cause labor to start or proceed o Oxytocin (Pitocin) is parenteral only (usually IV) o PGE-2 does come in a gel that is applied to ripen the cervix prior to induction of labor & in suppositories (still technically topical) to induce labor Fetal alcohol syndrome: facial deformities (low nasal bridge, flat midface), postnatal growth retardation, or mental retardation Treatment of patent ductus arteriosus: o *Indocin injection* o Ibuprofen o Oxygen o Diuretics o Purpose of the ductus arteriosus in utero: to shunt blood from the pulmonary artery to the aorta Hydroxyurea (Droxia, Hydrea): use to increase fetal hemoglobin in sickle cell patients Priaprism: Page 51 Causative agents: chlorpromazine, prazosin, trazodone, other phenothiazines, antihypertensives, anticoagulants, corticosteroids, & any drug used to produce an erection o PDE-5 inhibitors: Sildenafil (Viagra) Vardenafil (Levitra) Tadalafil (Cialis) • Can last up to 36 hours Psoriasis: Chronic, epidermal proliferative disease characterized by erythematous, dry scaling patches, recurring remissions & exacerbations Treatment: o Mild to moderate disease: Emollients BID: soft yellow paraffin or aqueous cream; petrolatum or Aquaphor cream (greasier & more effective) Topical, low potency corticosteroids on delicate skin (face, genitals): alclometasone dipropionate, triamcinolone acetonide 0.025%, hydrocortisone 2.5% Topical, medium potency cortisteroids: fluticasone propionate, triamcinolone acetonide 0.1%, hydrocortisone valerate, mometasone furoate Topical, strong potency: betamethasone dipropionate, halcinonide, fluocinonide, desoximetasone Topical, super potency: augmented betamethasone dipropionate, diflorasone diacetate, clobetasol propionate, halobetasol propionate • Limit use to 2 weeks • Avoid occlusive dressings Intralesional corticosteroid: 2-5 mg/mL triamcinolone acetonide Coal tar (Estar, PsoriGel) as an alterative to topical steroids Keratolytic agents to decrease scales: salicyclic acid 6% gel UV lamps & sunlight are effective- best option for pregnancy or young children • Anthralin ointment 1% or higher prior to light o Severe disease: Triamcinolone, intralesional mix Vitamin D analogs (calcipotriene ointment 0.05%- not on face) Acitretin (Soriatane) Tazarotene (Tazorac) Methotrexate, hydroxyurea, azathioprine, or cyclosporine o Triamcinolone (Aristocort A; Aristocort Forte; Aristospan; Azmacort; Kenalog; Nasacort AQ; Nasacort HFA; Tri-Nasal; Triderm) Psychriatric Disorders: ADHD: o Methylphenidate (Concerta, Methadate, Methylin, Ritalin) MOA: reuptake blockade of catecholamine (NE & DA) in presynaptic nerve endings Dosage form of Concerta: 18, 27, 36, 54 mg ER tablets o Atomoxetine (Strattera): BBW for suicide ideation in children MOA: NE reuptake inhibitor Dosed once daily (advantage over Concerta) Antidepressants: o SSRIs: Citalopram (Celexa) Escitalopram (Lexapro) Fluvoxamine (Luvox) Sertraline (Zoloft) Fluoxetine (Prozac): • Does not require tapering because of its long half life Page 52 o o o o • Take in AM Paroxetine (Paxil): • Take in AM to reduce chances of insomnia • Paxil CR incorporates a degradable polymeric matrix (Geomatrix) to control dissolution rate over a period of 4-5 hours o An EC delays the start of drug release until tablets have left the stomach May take 4 weeks to see effects Miscellaneous: Bupropion (Wellbutrin, Zyban): • MOA: dopamine reuptake inhibitor • CI with history of seizure disorder Venlafaxine (Effexor): • MOA: inhibits the reuptake of 5-HT & NE (& DA at higher doses) • Referred to as a serotonin-norepinephrine reuptake inhibitor (SNRI) • XR formulation is available to decrease GI upset • Not recommended in patients with uncontrolled HTN, recent MI, or CV disorders Duloxetine (Cymbalta): • MOA: potent inhibitor of 5-HT & NE (no DA activity) • Indicated for both major depression & diabetic peripheral neuropathic pain • CI: uncontrolled narrow-angle glaucoma Trazodone (Desyrel): • MOA: inhibits 5-HT reuptake & blocks 5-HT2A receptors Nefazodone (Serzone): • MOA: inhibits 5-HT & NE uptake & blocks 5-HT2A receptors Mirtazapine (Remeron): • MOA: antagonizes presynaptic -2 autoreceptors & heteroreceptors that prevent the release of 5-HT & NE (resulting in increased 5-HT & NE in the synapses); antagonizes 5-HT2A & 5-HT3 receptors, resulting in less GI upset & less anxiety Combinations: Olanzapine & fluoxetine (Symbax): • Atypical antipsychotic agent/SSRI • Use: treatment of depressive episodes associated with bipolar disorder MAOIs: Isocarboxazid (Marplan) Phenelzine (Nardil) Tranylcypromine (Parnate) Medications to avoid on MAOIs: • Phenylpropanolamine: tyramine-like reaction • Pseudoephedrine: tyramine-like reaction • Meperidine (Demerol): life-threatening serotonin syndrome-like reaction • Methyldopa (Aldomet): hypertensive crisis • Morphine (Roxanol, MS Contin): CNS depression • Reserpine (Ser-Ap-Es): increased catecholamines • Serotonergic agents (i.e. fluoxetine): serotonin syndrome TCAs: MOA: increase the synaptic concentration of 5-HT &/or NE in the CNS by inhibiting the presynaptic neuronal membrane’s reuptake of 5-HT or NE Amitriptyline (Elavil) • Off label use: neuropathic pain Nortriptyline (Pamelor, Aventyl) Imipramine (Tofranil) Doxepin (Sinequan) Clomipramine (Anafranil) Desipramine (Norpramin) Page 53 Antipsychotics: o Atypical: Arpiprazole (Abilify): • AE: insomnia, +/- weight gain • Once daily dosing benefit • Partial dopamine agonist Clozapine (Clozaril, FazaClo-ODT: • For refractory schizophrenia only • AE: sedation, weight gain, hypersalivation, seizure risk • Weekly CBC with diff required o WBC <3500 or ANC <1500 MUST discontinue Olanzapine (Zyprexa, Zydis-ODT): • MOA: a thienobenzodiazepine antipsychotic that is believed to work by antagonizing dopamine & serotonin activities o It is a selective monoaminergic antagonist with high affinity binding to 5-HT2A & 5-HT2C, dopamine D1-4, muscarinic M1-5, histamine H1 & -1 receptor sites o Binds weakly to GABA-A, BZD, & beta-adrenergic receptors • AE: sedation, orthostasis Quetiapine (Seroquel): • Low EPS risk Risperidone (Resperdal): • Use: schizophrenia, bipolar • Dosage forms: injection, solution, tablet, ODT Ziprasidone (Geodon) • AE: +/- sedation, +/- weight gain, QT prolongation o Typical: Chlorpromazine (Thorazine) Fluphenzaine (Prolixin) Haloperidol (Haldol) Thioridazine (Mellaril) • QT prolongation Anxiolytic agents: o Benzodiazepines: MOA: potentiate the actions of GABA by increasing the influx of Cl ions into neurons Alprazolam (Xanax, Niravam-ODT) Chlordiazepoxide (Librium) • Available as injection Clonazepam (Klonopin) • Available as an orally disintegrating wafer Clorazepate (Tranxene) Diazepam (Valium) • Available as injection Estazolam (Prosam) Flurazepam (Dalmane) Halazepam (Paxipam) Lorazepam (Ativan) • Available as an injection Oxazepam (Serax) Prazepam (Centrax) Quazepam (Doral) Temazepam (Restoril) Trazolam (Halcion) Lorazepam, oxazepam, & temazepam (LOT) are conjugated & preferred in patients with hepatic dysfunction & elderly patients Page 54 Chlordiazepoxide, diazepam, & lorazepam available for IV use Never abruptly discontinue Avoid in pregnancy- cause cleft palate o Buspirone (BuSpar): MOA: unknown. It exhibits high affinity for serotonin (5-HT1A) receptors, moderate affinity for brain D2-dopamine receptors & no significant affinity for benzodiazepine receptors. It has no effect on GABA binding. Non-FDA labeled indication: depression Non-sedating No grapefruit Take consistently either with or without food EPS treatment: o Dystonia: state of abnormal tonicity, sometimes described simplistically as a severe “muscle spasm” Benzotropine mesylate 2 mg Diphenhydramine 50 mg IV or IM Diazepam 5-10 mg by slow IV push Lorazepam 1-2 mg IM o Akathisia: inability to sit still & being functionally mortor restless Diazepam 5 mg TID Propanolol 10 mg QD Nadolol 80 mg QD • Beta 2 selective are less effective o Pseudoparkinsonism: an AP-induced extrapyramidal side effect, resembles idiopathic Parkinson’s Disease Patient may have slurred speech & a drooping face Trihexyphenidyl 2-5 mg TID Diphenhydramine 25-50 mg TID Biperiden (Akineton) 2 mg TID Amantadine o Tardive dyskinesia: syndrome characterized by abnormal involuntary movements occurring late in onset in relation to initiation or AP therapy No FDA approved agents -tocopherol (vitamin E) 1200-1600 IU has been tried Lithium (Eskalith CR, Lithobid, Eskalith): o Use: bipolar disorder o CI: renal disease, severe CVD, pregnancy o SE: hyponatremia o Monitor thyroid function o “Lithium does everything that sodium will do” o Reaches steady state in 4-5 days Obtain level 2-8 hours post-dose Toxicity: • Mild (serum levels 1.5-2): o GI upset (N/V/D), muscle weakness, fatigue, fine hand tremor, difficulty with concentration & memory • Moderate (2-2.5): o Ataxia, lethargy, nystagmus, worsening confusion, severe GI upset, coarse tremors, increased deep tendon reflexes • Severe (>3): o Severely impaired consciousness, coma, seizures, respiratory complications, death o Dosage forms: capsules, syrup, tablet (IR, CR, slow release) Tourette’s Syndrome: o Simple tics & 1st line of therapy is short acting benzodiazepines o Next is clonidine which does not cause tardive dyskinesia in these patients Page 55 Intermediate acting benzodiazepines (Ativan) are also useful For severe cases, the choice is an antipsychotic such as haloperidol (Haldol) or pimozide (Orap) but these can cause tardive dyskinesia, dysphoria, & pseudoparkinson’s Anon-sedating anxiolytic for the elderly: buspirone (Buspar) o Has a high affinity for 5-HT & dopamine receptors o Does not affect benzodiazepine GABA receptors o o Questions: Mother has gestational diabetes, what is likely to occur when the baby is born. Mother also has epilepsy & is taking tegretol. o I. high birth weight o II. Baby may have congenital abnormalities o III. Baby is likely to have diabetes o Answer: I & II o Tegretol is a class D drug What strength will Albuterol 0.5% end up based on an order to mix it with 2.5 mL normal saline? o 0.083% Isosorbide dinitrate is dosed BID, what regimen is best 7 am & 12 noon, 7 am & 7 pm, 9 am & 9 pm, 8 am & 5 pm? o 8 am & 5 pm to allow nitrate free period (same as removing NTG patches at bedtime) What substitute can you use for desitin ointment (Balmex, Boudreaux’s Butt Paste)? o Zinc oxide Precose counseling information: o I. Take 30 minutes before meal o II. Causes gas o III. Should not take if meal skipped o Answer: II & III What treatment would increase antibiotic compliance? Patient receiving zithromax 1 tsp QD x 5days o Augment, ceftriaxone, cefuroxime axetil, doxycycline o Answer: the usual method to improve compliance for any type of drug is to reduce the number of doses that must be taken each day & to give a drug with the fewest uncomfortable or dangerous SE (I would chose ceftriaxone- IM single dose treatment) Which of the following could you give a patient on NTG? o I. Cialis o II. Muse (alprostadil) o III. Caverject (alprostadil) o Answer: II & III- alprostadil is prostaglandin used for erectile dysfunction & patent ductus arteriosus Available as: intracavernosal Kit, intracavernosal powder for solution, intracavernosal solution, intraurethral Suppository, & intraurethral solution Patient requesting antihistamine eye drop & having a dark spot in vision- refer to MD Which of the following is available in a liquid formulation? o I. NTG o II. Hydroxyzine o III. Digoxin o Answer: II & III Which is the shortest acting insulin? o Humulin N, Humulin U, Humalog, or regular o Answer: Humalog Who should not get a flu shot? o An infant in day care; 32 yo type II diabetic; 65 yo retired lady; 35 yo nurse working in hospital Answer: 32 yo type II diabetic Which of the following cannot be self monitored? o Glucose level; K level; cholesterol levels; hormone used in pregnancy test o Answer: K levels Cytoxan is most similar to mechlorethamine, procarbazine, or 5-FU? Page 56 o Answer: mechlorethamine A patient with Traveler’s diarrhea too PeptoBismol 4 tsp Q ½ hour. After 3 days he began experiencing ringing in the ears. What does he have? Bismuth toxicity or salicylate toxicity? o Answer: salicylate toxicity o Bismuth toxicity would cause neurotoxicity Which of the following are OTC hemorrhoid treatments: o I. TUCKs pads o II. Nupercainal ointment o III. Rowasa o Answer: I & II Which of the following is an ER Morphine? o A. MSIR B. MS Contin C. Diluadid D. Oxycontin o Answer: B Which of the following agents should be administered to a person exposed to Anthrax? o A. Flagyl B. Cipro C. Zovirax D. Valtrex o Answer: B Erythromycin exhibits its anti-infective properties by- blocking protein synthesis via binding & inhibition of the 50-S subunit of bacterial ribosomes Patient has pseudomembranous colitis & allergy to metronidazole. Which of the patient’s medications could have caused the pseudomembrane colitis? o A. Ibuprofen B. Tylenol C. Flagyl D. Cleocin E. Zantac o Answer: D o This person could be treated with? A. Flagyl B. VancomycinC. Doxycycline D. Lincomycin E. Ampicillin Answer: B o The DOC for the treatment of pseudomembraneous colitis is: A. Metronidazole B. Erythromycin C. Clindamycin D. Ampicillin E. Lincomycin Answer: A Which of the following NSAIDs has an ophthalmic preparation: o A. Ibuprofen B. Naproxen C. Diclofenac D. Ketoprofen o Answer: C- Voltaren Cedax acts by- inhibiting the use of pencillin binding proteins in bacterial cell wall synthesis Acetylcysteine in the treatment of CF is best given: o A. IV B. By inhalation C. IM D. Orally o Answer: B A patient is given a rx for fentanyl 100 mcg/hr patch for 1 month. How many boxes should you dispense? o A. 1 B. 2 C. 3 D. 4 E. 5 o Answer: 2; 1 patch= 3 days, so you need 10 patches; comes in boxes of 5 patches so you need 2 Which of the following is not an erythropoetin formulation? o A. Epogen B. Procrit C. Aranesp D. Neupogen o Answer: Neupogen Which of the following fluoroquinolones has an otic preparation? o Answer: ofloxacin (Floxin- also has an ophthalmic); o Eye drops only: levofloxacin, gatifloxacin, moxifloxacin The use of this agent is CI in children? o A. Erythromycin B. Bactrim C. Ciprofloxacin D. Cephalexin o Answer: C What is the recommended daily dosage of calcium for an adult? o A. 300-500 mg B. 600-800 mg C. 800-1000 mg D. 100-1500 mg o Answer: D Due to difficulty in coordinating their inhalations, older patients should use: o A. Nebulizer B. Peak flow meter C. Spacers D. Spirometer o Answer: C Monitoring of asthma at home can be done with: Page 57 o A. Nebulizer B. Peak flow meter C. Spacers o Answer: B A patient using a One-Touch machine will also need: o A. Ketostix B. Cuff C. Lancing device o Answer: C D. Spirometer D. Sphygmomanometer Raynaud’s Phenomenon: Reversible vasospasm of the digital arteries that can result in ischemia of the digits Avoid exposure to cold CCB’s (i.e. nifedipine) are the preferred initial agents Alternative vasodilators, such as prazosin (Minipress), may be helpful Aggregated by beta blockers Sepsis: Hypotension Drotrecogin alpha (Xigris): o Recombinant human activated protein C o Has antithrombic, anti-inflammatory, & profibrinolytic properties o Dosed 24 mcg/kg body weight/hr o CI: increased risk of hemorrhage o MOA: inhibits factors Va & VIIIa, limiting thrombotic effects Silicosis: A form of pneumoconiosis resulting from occupational exposure to & inhalation of silica dust over a period of years Characterized by a slowly progressive fibrosis of the lungs, which may result in impairment of lung function Predisposes person to pulmonary tuberculosis Statistics: Mean: the average of a set of values Median: the middle value in a set of measurement Mode: the value that appears most frequently Statistically significant: the likelihood (probability) of obtaining a given result by chance o p < 0.05 Standard deviation: statistical index of the degree of deviation from central tendency, namely, of the variability within a distribution T Test: used to compare two groups Tests: Blood glucose kits: o Testing without pricking finger: Clinitest Tabs & TesTap- used to test urine sugar then correlate to blood sugar Cholesterol Kits o Advanced cholesterol test kit Need to avoid for at least 4 hours prior to testing: iron, prozac, vitamin c, APAP Heme guaiac exam: o Vitamin C (antioxidant) can interfere with test o Visual limitations can limit test o Hemorrhoids (blood would cause a false +) o Example test: EZ detector Patient with a high PTT & receiving heparin: o Could hold it then restart it at a lower dose Patient on lovenox & warfarin: o Appropriate to monitor: APTT (no) Page 58 PT (yes for warfarin) INR (yes for warfarin) Ovulation tests: o Test a rise in leutinizing hormone (LH) as an indicator for ovulation o Examples include: First Response, Ovutime, Q-Test Pregnancy tests: o Measure a rise in the level of chorionic gonadotropin (HCG, CG) that begins the 2nd week of pregnancy & peeks at about 8 weeks Detect contraception 2 weeks after last missed period Take first thing in the AM Taking BP: o Patients should refrain from smoking or caffeine ingestion for 30 min o Measurement should begin after being seating at least 5-min o Proper size cuff should be used The bladder should encircle at least 80% of the arm & the width of the cuff should be at least 2/3 the length of the upper arm o Position cuff 1 inch above antecubital crease o Ask patient about previous readings o Inflate cuff rapidly to approximately 30 mm Hg above previous readings o Deflate slowly & listen for Korotkoff sounds o Wait 1-2 minutes before repeating o Fluctuation of BP by 10 mm Hg from morning to night is normal Urine glucose test kits: o Clinitest tabs Test method: copper sulfate Urine & water mix in test tube, add reduction method tablet, wait for reaction end, see resulting color on chart o Chemstrip-uG Test method: glucose oxidase Dip stick into urine and wait for color to develop, then read on chart o Clinistix, Diastix, TesTape Test method: glucose oxidase Dip stick in urine read color change on chart; dextrose only o The copper sulfate method is better quantitatively but is subject to more interferences (false +) o The glucose oxidase method is less subject to interferences but is less accurate Vaccines: Active immunity: protection produced by an individual’s own immune system o Vaccination: process of producing active immunity via use of vaccines Passive immunity: protection produced by an animal or human & transferred to another o Ex: immunity infants receive from mother o One source of passive immunity is antitoxins, which contain antibodies against a known toxin Live vaccines: o Influenza (live-attenuated), measles, mumps, rubella, typhoid oral, *varicella*, vaccinia (small pox), yellow fever Avoid with AIDS Inactivated vaccines: anthrax, diphtheria, H. flu type b, hepatitis A & B, influenza, Japanese encephalitis, meningococcal, pertassis (acellular), pneumococcal (polysaccharide & conjugate), rabies, tetanus, typhoid (injectable) Vaccine ok for pregnancy: flu (2nd or 3rd trimester) & tetanus o AVOID MMR for the rubella part & varicella o AVOID live viruses o Do not give till 2nd trimester o Hepatitis B, inactivated polio, & pneumococcal are all recommended if indicated o Vaccine needed in asthma patients: influenza Page 59 Vaccines that come PO & IV: o Polio IPOL: inactivated, trivalent injectable vaccine OPV: oral- discontinued in US because of elimination of wild-type disease Prevnar: vaccine against a collection of bacteria that cause pneumonia o Used in children up to 5 years old & usually delayed until child is 2 Patients with spleenectomy: o Pneumococcal vaccine is most essential o Can also give: Hep A & B, MMR, varicella, flu Vaccines grown in eggs: influenza (CI), measles (“should receive it”), mumps (not a CI) Vaccines that can be given around 2 months of age: hepB, DTaP (diphtheria, tetanus, pertussis), Hib (haemophilus influenza type b), IPV (polio), PCV (pneumococcal) Diphtheria & tetanus: give Q 10 years Vitamins/Minerals/Elements: Elemental calcium: o Calcium carbonate: 40% Tums contains 500 mg of calcium carbonate, therefore 200 mg of element calcium is provided o Calcium phosphate tribasic: 39% o Calcium citrate: 24% Elemental Iron: o Ferrous fumarate (Femiron, Fumerin, Feostat): 33% o Ferrous sulfate (Feosol, Fer-in-Sol): 20% o Ferrous gluconate (Fergon): 12% Weight Loss: Noradrenergic Agents: o Methamphetamine o Amphetamine o Dextroamphetamine (Dexedrine) o Benzphetamine (Didrex) o Amphetamine/dextroamphetamine mixture (Adderall) o Phendimetrazine (Prelu-2, Bontril, Plegine, X-Trazine) o Phentermine (Fastin, Oby-trim, Adipex-P, Ionamin) o Diethylpropion (Tenuate) o Mazindol (Mazanor, Sanorex) Serotonergic Agents: o Fluoxetine (Prozac) & Sertraline (Zoloft)- unlabeled uses Noradrenergic/Serotonergic Agents: o Sibutramine (Meridia) CYP3A4 Strength: 5, 10 & 15 mg capsules Gastrointestinal Lipase Inhibitor: o Orlistat (Xenical) Oily spotting; fecal incontinence Absorption of fat soluble vitamins may be decreased Strength: 120 mg capsule Wilson’s Disease: An autosomal recessive disorder that results in progressive copper overload The average age at presentation of liver dysfunction is 10-15 years Neuropsychiatric disorders can manifest later Treatment: o Copper-chelating agents: Penicillamine (Cuprimine, Depen) Page 60 • MOA: chelates with lead, copper, mercury, & other heavy metals to form stable, soluble complexes that are excreted in urine Trientine (Syprine): • MOA: an oral chelating agent structurally dissimilar from penicillamine & other available chelating agents Zinc salts Women’s Health: Birth Control: o Sunday start for BC pills means: start the pack on the Sunday after the period starts o Estrogen:’ Prevent development of a dominant follicle by suppression of FSH; does not block ovulation • SE: breast tenderness, heavy bleeding, headache o Progestin: Blocks ovulation; contributes to production of thick & impermeable cervical mucus; contributes to involution & atrophy of endometrium • SE: depression, headache, irritability o Progesterone: decreases the risk of endometrial cancer o Progestin-only (minipill): Appropriate for use in breastfeeding women Efficacy is less than that of combined oral contraceptives Free of cardiovascular risks associated with estrogen-containing products Ortho Micronor, Errin, Nor-QD, Nora-BE, Camila, Ovrette o Biphasic oral contraceptives: Ortho-Novum 10/11, Necon 10/11 o Yasmin: Ethinyl estradiol & drospirenone • Drospirenone is a spironolactone analogue with antimineralocorticoid & antiandrogenic activity PMS: o Symptoms: depressed mood, mood swings, irritability, difficulty concentrating, fatigue, edema, breast tenderness, headaches, sleep disturbances Postmenopausal hormone replacement therapy: o Women with an intact uterus must be treated with estrogen + progestin o Women with out a uterus- estrogen only o Ingredients in PremPro or Premphase: conjugated estrogen & medroxyprogesterone Levonorgestrel (Plan B, Mirena-intrauterine system): o For emergency contraception: 1 tablet (0.75 mg) asap within 72 hours of unprotected sexual intercourse; a 2nd tablet (0.75 mg) should be taken 12 hours after the 1st dose; can be used at any time during the menstrual cycle Zollinger-Ellison Syndrome: A triad of: o Markedly elevate gastric acid secretion o Peptic ulcer disease o A gastrinoma or non-beta islet cell tumor of the pancreas or duodenal wall which produces gastrin DOC: o PPIs: Omeprazole 60-120 mg/day Lansoprazole 60-180 mg/day Rabeprazole 60-100 mg/day Pantoprazole 40-240 mg/day o H2 blockers: Cimetidine 300 mg Q6h; up to 1.25-5 gm/day Ranitidine 150 mg Q12h; up to 6 gm/day Famotidine 20 mg at bedtime; up to 800 mg QD Page 61
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