Clinical Pharmacology
for Respiratory Diseases
Edited by
Dr. Mudher Z.H. Al-khairalla
Consultant in Respiratory Medicine
M.B.Ch.B. MRCP (UK) CCT Resp & GIM FRCP Lecturer. Department of Medicine
University of Thi-Qar
Designed by: Mubark A. Wilkins
Aims…
 Basic clinical pharmacology for common respiratory diseases
 PDF at the end of the series
 x4 one –hour sessions
Terms…
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Clinical Pharmacology
Pharmacokinetics
Pharmacodynamics
Generic Vs Brand
In Latin!
Montelukast 10mg P.O. nocte 28 days
Common Diseases
 Diseases of the airways
o ASTHMA
o COPD
 Infection
o PNEUMONIA
 CAP
 HAP
o TUBERCULOSIS
o BRONCHIECTASIS
 Interstitial Lung Diseases (ILD)
 Lung Cancer
 Respiratory Failure
o OXYGEN
o Pulmonary Embolism
o Elsewhere!
Common Drugs/Group of Drugs!
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Bronchodilators (SABA/LABA)
Corticosteroids
Antimuscarinic
Leukotriene Receptor Antagonists
Mucolytics
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Methylxanthines
Magnesium sulphate
Penicillins
Cephalosporins
Macrolides
Tetracyclines
Quinolones
Anti-pseudomonal
Anti-Tuberculosis
Pirfenidone
Oxygen
Anti-IgE (Monoclonal antibody)
Methotrexate
Azathioprine
Anti-fungal
Lung Cancer (NSCLC & SCLC)
Palliative Care
Anticoagulation
o Warfarin
Respiratory Condition
 Brief Pathophysiology
 Treatment Goals
 Drug (Generic names)
o Mechanism of Action
o Indications
o Contraindications/Cautions
o Side effects
o Dosage
o Note(s)/Interactions
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Diseases of the Airways
Asthma
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Uncontrolled Vs Severe
COPD
Chronic Obstructive Pulmonary Disease
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SABA
Short Acting Beta Agonist
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Drug Class – Selective Beta2 Agonists
Generic
Salbutamol, Formoterol
Mechanism
bronchodilatation
Indication(s)
Asthma (mild), Reliever, Exercise induced
Caution
Hypokalaemia, tachyarrhythmia, Thyrotoxicosis
Contraindication(s)
Side effects
Tremor, palpitations, headache, tachyarrhythmia, hypokalaemia
Dose
e.g. Salbutamol 100-200mcg 1-2 puffs as required
Note
Usually, Inhaled via MDI or Nebuliser
Interaction(s)
LABA
Long Acting Beta Agonist
Drug Class – Selective Beta2 Agonists
Generic
Formoterol, Salmeterol, Indacaterol
Mechanism
bronchodilatation
Indication(s)
Asthma and COPD (usually in combination with ICS)
Caution
Hypokalaemia, tachyarrhythmia, Thyrotoxicosis
Contraindication(s)
Side effects
Tremor,
palpitations,
hypokalaemia
headache,
Dose
e.g. Formoterol 12mcg b.d. inhaler
Note
Usually, Inhaled via MDI or Nebuliser
tachyarrhythmia,
Interaction(s)
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Drug Class – Selective Beta2 Agonists
Generic
Formoterol, Salmeterol, Indacaterol
Mechanism
bronchodilatation
Indication(s)
Asthma and COPD (usually in combination with ICS)
Caution
Hypokalaemia, tachyarrhythmia, Thyrotoxicosis
Contraindication(s)
Side effects
Tremor, palpitations, headache, tachyarrhythmia, hypokalaemia
Dose
e.g. Formoterol 12mcg b.d. inhaler
Note
Usually, Inhaled via MDI or Nebuliser
Interaction(s)
ICS
Inhaled Corticosteroid
Systemic Steroids, Oral Intravenous
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Drug Class – Corticosteroids
Generic
Beclomethasone, Fluticasone, Budesonide
Mechanism
Reduce airway inflammation (edema) and mucous
Indication(s)
Asthma Prophylaxis, COPD (usually in combination with LABA)
Caution
-
Contraindication(s)
Side effects
Oral thrush
Dose
e.g. Budesonide Turbohaler 200mcg b.d. inhaled
Note
Inhaled corticosteroids are the cornerstone of asthma maintenance.
Systemic side effects are exceedingly rare
Interaction(s)
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LAMA
Long Acting Antimuscarinic Agent
Drug Class – Antimuscarinic
Generic
Tiotropium, Ipratropium, Aclidinium
Mechanism
bronchodilatation
Indication(s)
COPD, Step 4-5 Asthma
Caution
Angle closure glaucoma
Contraindication(s)
Side effects
Dry mouth
Dose
e.g. Tiotropium handihaler 18mcg od
Note Interaction(s)
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ICS/LABA
Dual Combination therapy
SABA & LABA
LRA
Leukotriene Receptor Antagonist
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Drug Class – Leukotriene Receptor Antagonist
Generic
Montelukast
Mechanism
Blocks cysteinyl leukotrienes in the airway
Indication(s)
Asthma prophylaxis
Caution
Churg-Strauss Syndrome
Contraindication(s)
Side effects
Abdominal pain, thirst, somnolence
Dose
e.g. Montelukast 10mg nocte P.O.
Note Interaction(s)
Useful if concomitant Rhintis
Methylxanthines
Drug Class – Methylxanthines
Generic
Aminophylline
Mechanism
Bronchodilatation
Indication(s)
Asthma and COPD
Caution
Hypokalaemia
Contraindication(s)
Side effects
Nausea, vomiting, tachyarrhythmia, convulsions
Dose
e.g. Aminophylline (Phyllocontin) 225mg MR P.O. B.D.
Note
Narrow therapeutic window
Interaction(s)
Should measure plasma levels
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Infections
Community Acquired Pneumonia (CAP)
Hospital Acquired Pneumonia (HAP)
Mycobacterial Tuberculosis (MTB)
Bronchiectasis
CAP
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HAP
48 Hours after hospital admission
MTB
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Bronchiectasis
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Drug Class – Penicillins
Generic
Benzylpenicillin, Amoxicillin, Co-amoxiclav
Mechanism
Bactericidal, interferes with bacterial cell wall synthesis
Indication(s)
Respiratory tract infections, other infections
Caution
Hepatic dysfunction
Contraindication(s)
Hypersensitivity 1-10% (anaphylaxis in 0.05%).
Side effects
Diarrhoea, cholestatic jaundice
Dose
e.g. Co-amoxiclav 625mg t.d.s. P.O.
Note
Co-amoxiclav (Amoxicillin with Calvulanic acid) used for betalactamase-producing strains
Interaction(s)
Drug Class – Cephalosporins
Generic
1st Generation: Cefalexin, 2nd Generation: Cefuroxime, 3rd Generation:
Cefpodoxime, Ceftazidime & Ceftriaxone
Mechanism
bactericidal
Indication(s)
Respiratory tract infections, other infections
Caution
Hepatic dysfunction
Contraindication(s)
Hypersensitivity (in 0.5-6.5% in those allergic to penicillin)
Side effects
Diarrhoea, cholestatic jaundice, N+V
Dose
e.g. Cefuroxime 1.5g t.d.s. i.v.
Note Interaction(s)
Drug Class – Macrolides
Generic
Azithromycin, Clarithromycin, Erythromycin
Mechanism
Inhibits bacterial protein synthesis
Indication(s)
Respiratory Tract infection, particularly atypicals. Other infections
Caution
Can prolong QT interval
Contraindication(s)
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Side effects
NV&D, Abdominal discomfort, Prolongation of QT interval
Dose
e.g. Azithromycin 500mg P.O. o.d.
Note Interaction(s)
Avoid using with Warfarin and Quinolones
Drug Class – Quinolones
Generic
Ciprofloxacin, Moxifloxacin, Levofloxacin
Mechanism
Impairs bacterial replication
Indication(s)
Respiratory Tract Infections
Caution
Epilepsy, G6PD deficiency, avoid in pregnancy (arthropathy)
Contraindication(s)
Side effects
Tendon Rupture, QT prolongation, NV&D, Dizziness
Dose
e.g. Levofloxacin 500mg P.O. o.d.
Note Interaction(s)
Avoid with macrolides
Drug Class – Tetracyclines
Generic
Doxycycline, Tetracycline
Mechanism
Inhibits bacterial protein synthesis
Indication(s)
Respiratory Tract infection especially H.Influenzae in COPD
Exacerbation. Other infections (Acne, Lyme disease)
Caution
Acute Porphyria. Pregnancy.
Contraindication(s)
Side effects
N,V+D
Dose
e.g. Doxycyclince 200mg day one then 100mg daily P.O.
Note Interaction(s)
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Drug Class – Antipseudomonal penicillin
Generic
Piperacillin
Mechanism
Bactericidal, interferes with bacterial cell wall synthesis
Indication(s)
Pseudomonas Aeruginosa infection
Gram +ve, -ve and anaerobic Bacteria
Caution
Hypernatraemia
Contraindication(s)
Hypersensitivity
Side effects
Diarrhoea, hypernatraemia
Dose
e.g. Piperacillin with Tazobactam (Tazocin) 4.5g t.d.s i.v.
Note
With beta-lactamase inhibitor Tazobactam. Not active against MRSA
Interaction(s)
Drug Class – Antituberculous
Generic
Rifampicin
Mechanism
Inhibits bacterial RNA synthesis
Indication(s)
MTB, other infections
Caution
Jaundice, hypersensitivity
Contraindication(s)
Side effects
Discolouration of bodily fluids. Liver toxicity, Flu like, N,V&D
Dose
Weight dependent and in combination with other drugs
Note Interaction(s)
Potent inducer of liver enzymes (contraception, anicoagulation &
steroids)
Generic
Isoniazid
Mechanism
Impairs bacterial cell wall synthesis
Indication(s)
MTB
Caution
Hepatic disorder
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Contraindication(s)
Side effects
Liver toxicity, peripheral neuropathy (add Pyridoxine 10mg daily in
those at risk), N,V&D
Dose
Weight dependent and in combination with other drugs
Note Interaction(s)
Generic
Pyrazinamide
Mechanism
Unknown! May inhibit enzymes responsible for cell synthesis
Indication(s)
MTB
Caution
Acute porphyria
Contraindication(s)
Side effects
Liver toxicity, photosensitivity, N&V
Dose
Weight dependent and in combination with other drugs
Note Interaction(s)
Generic
Ethambutol
Mechanism
Unknown! Bacteriostatic?
Indication(s)
MTB
Caution
Avoid in renal impairment
Contraindication(s)
Side effects
Rarely, retinal toxicity
Dose
Weight dependent and in combination with other drugs
Note Interaction(s)
Notes
 Initial phase 2 months
o Rifampicin, Isoniazid, Pyrazinamide & Ethambutol
 Continuation phase 4 months
o Rifampicin & Isoniazid
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Combination treatment to reduce resistance
Add streptomycin is Isoniazid resistance confirmed/suspected
Pulmonary TB and TB pleuritis (6 months duration of Rx)
Directly Observed Treatment (DOT) is different
Rifater (depending on weight)
Liver function at baseline
Snellen chart at baseline
MDR-TB
XDR-TB
ILD
Interstitial Lung Disease
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Common Drugs/Group of Drugs!
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Bronchodilators (SABA/LABA)
Corticosteroids
Antimuscarinic
Leukotriene Receptor Antagonists
Mucolytics
Methylxanthines
Magnesium sulphate
Penicillins
Cephalosporins
Macrolides
Tetracyclines
Quinolones
Anti-pseudomonal
Anti-Tuberculosis
Pirfenidone
Oxygen
Anti-IgE (Monoclonal antibody)
Methotrexate
Azathioprine
Anti-fungal
Lung Cancer (NSCLC & SCLC)
Palliative Care
Anticoagulation
Lung Carcinoma
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Assessing suspected Lung Cancer
Suspected Lung Cancer Assessment
 Fitness
o FEV1
o ECOG PS
 Disease staging
 Histology
o NSCLC (Non small cell cancer)
o SCLC (small cell cancer)
Outcome
Chemotherapy
 NSCLC
o Pemetrexed/Cisplatin
SE: Hair loss, myelosuppression, GI upset
o Erlotinib/Gefitinib
 SCLC
o Etoposide + Cisplatin/Carboplatin
SE: Hair loss, myelosuppression, GI upset
Best supportive Care (Palliative)
 Pain
o Paracetamol, NSAID, Opiate, Palliative RTH
 Constipation
o Osmotic laxatives e.g. Macrogol, Lactulose
 Nausea
o Metoclopramide, Ondansetron, Domperidone
 Hypercalcaemia, SIADH other paraneoplastic syndromes
 Haemoptysis
o Tranexamic acid, palliative RTH
 SVCO
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o Dexamethasone, stent
 Dyspnoea
o Endoscopic/pleural intervention, Benzodiazepines, Opiates
Respiratory Failure
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Oxygen
 Is a Drug!
 High Flow
 Targeted Oxygen
o Sats 88-92%
o Sats >94%
 LTOT
 Palliative
Drug Class – Oxygen
Generic
Oxygen
Mechanism
Supplements the amount of oxygen in the blood stream and cells
Indication(s)
Hypoxaemia/respiratory failure
Caution
Type 2 Respiratory Failure
Contraindication(s)
Side effects
Lung toxicity (ICU), nasal irritation (cannulae), respiratory
depression
Dose
e.g. Oxygen low flow target Saturation 88-92%
Note Interaction(s)
Pulmonary Embolism (PE)
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Treatment
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Low Molecular Weight Heparin (LMWH)
Heparin
Warfarin
Newer Oral Anticoagulants
o Dabigatran
o Rivaoxaban
o Apixaban
Drug Class – Low molecular weight heparin
Generic
Enoxaparin, Dalteparin
Mechanism
Binds and potentiates anti-thrombin III
Indication(s)
VTE, ACS/MI, Prophylaxis against VTE
Caution
Renal dysfunction, bleeding diatheses, hyperkalaemia
Contraindication(s)
Side effects
Bleeding, HIT (Heparin induced thrombocytopenia)
Dose
e.g. Enoxaparin 150units/kg s/c o.d. (if patient 70kg 10,500units)
Note
Safer than unfractionated heparin. Requires no monitoring
Interaction(s)
Drug Class – Coumarins
Generic
Warfarin
Mechanism
Antagonises the effect of vitamin K
Indication(s)
VTE, AF & Prosthetic cardiac valves
Caution
Liver dysfunction
Contraindication(s)
Hypersensitivity, Bleeding Diatheses, N,V&D
Side effects
Haemorrhage, INR monitoring
Dose
e.g. Warfarin o.d. p.o. as per INR target range (2-3)
Note
Takes 48-72H for the anticoagulation effect
Interaction(s)
Many interactions!
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Questions
1. The following drug is the best at providing maintenance treatment in step 2 asthma (mildpersistent Asthma)
A. Salbutamol
B. Inhaled Beclomethasone
C. Montelukast
D. Warfarin
E. Phyllocontin
2. 64 years-old male is a heavy smoker and presents with progressive dyspnoea (MRC 3).
Spirometry confirms obstructive airflow defect with no reversibility to short acting beta
agonist. Which of the following drugs may help improve his symptoms best?
A. Tiotropium
B. Ipratropium
C. Prednisolone
D. Amoxicillin
E. Doxycycline
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3. 32 years-old female presents with fever, cough and green sputum over 3 days. She had
crackles at the right base of the lung. She was otherwise well. She is allergic to
trimethoprim (rash). Blood Urea was elevated and her systolic blood pressure was 85
mmgh. Respiratory rate was 32 breaths per minute. What is the most likely diagnosis?
A. Mild Community Acquired Pneumonia
B. Severe Hospital Acquired Pneumonia
C. Bronchiectasis
D. Severe Community Acquired Pneumonia
E. Mesothelioma
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4. 32 years-old female presents with fever, cough and green sputum over 3 days. She had
crackles at the right base of the lung. She was otherwise well. She is allergic to
trimethoprim (rash). Blood Urea was elevated and her systolic blood pressure was 85
mmgh. Respiratory rate was 32 breaths per minute. What is the best treatment option?
A. Oral Moxifloxicin
B. i.v. Co-amoxiclav & Clarithromycin
C. Rifampicin and Isoniazid p.o.
D. i.v. Amoxicillin
E. i.v. Ceftriaxone
5. The following side effect can cause petechiae in patients taking Low Molecular Weight
Heparin
A. Hyperkalaemia
B. Headache
C. Sleepiness
D. Dizziness
E. Heparin Induced Thrombocytopenia
6. Which of the following anti-Tuberculosis drugs causes discolouration of bodily fluids
A. Streptomycin
B. Pyrazinamide
C. Isoniazid
D. Rifampicin
E. Ethambutol
7. 44 years-old male presents with haemoptysis, cough
and loss of appetite for one month. Sputum revealed
alcohol-acid fast bacilli.
What is the best regime we should use to start treating
the most likely underlying condition?
A. Rifampicin, Isoniazid, Pyrazinamide & Ethambutol
B. Rifapmicin, Isoniazid & Ethambutol
C. Rifampicin
D. Levofloxacin
E. Rifampicin and Isoniazid
8. A patient was diagnosed with metastatic lung cancer. He developed hypercalcaemia. He
then developed abdominal discomfort.
Which group of drugs may help him?
A. NSAID
B. Paracetamol
C. Anti-spasmodic
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D. Laxatives
E. Benzodiazepines
9. Pemetrexed can cause the following side effect
A. Hair loss
B. Myelosuppression
C. Vomiting
D. None of the above
E. All of the above
10. Which of the following drugs, in carefully selected patients, can help reduce the
progression of Idiopathic Pulmonary Fibrosis
A. Prednisolone
B. Carbocisteine
C. Azithromycin
D. Perfenidone
E. All of the above
11. In asthma and COPD, which of the following drugs has both short acting and long acting
bronchodilator properties?
A. Formoterol
B. Salmeterol
C. Indacaterol
D. Aclidinium
E. Salbutamol
12. The following categories/clinical features are used to determine the appropriate step in
managing COPD patients..
A. Exacerbation Rate
B. Functional Capacity
C. FEV1
D. None of the above
E. All of the above
13. 22 years-old female presents with recurrent bronchial sepsis. Investigations including CT
scan of the chest confirms Bronchiectasis. She has grown Pseudomonas Aeruginosa which
of the following drugs could help treat her infection?
A. Tazobactam and Piperacillin
B. Ceftriaxone
C. Gentamycin
D. Doxycycline
E. Erythromycin
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14. 22 years old heavy smoker presents with acute respiratory distress and was wheezy on
chest auscultation. He received bronchodilator therapy initially but then became tired.
His oxygen saturation on room air on arrival was 86%. What is the most appropriate next
step?
A. Intravenous theophylline
B. Intravenous Hydrocortisone
C. Oxygen high flow non re-breather mask 100%
D. Hudson mask oxygen at 60% concentration
E. 2litres per minute Oxygen via nasal cannulae with target saturation of 88-92%
15. Which of the following drugs can cause insomnia?
A. Montelukast
B. Lorazepam
C. Diazepam
D. Nitrazepam
E. Prednisolone
16. Patients on inhaled corticosteroids who suffer from controlled bronchial asthma and then
develop allergic rhinitis many benefit from …
A. Switching to a combination inhaler containing corticosteroid and long acting beta
agonist
B. Adding Tiotropium
C. Adding Montelukast
D. Discontinuing the inhaled corticosteroid
E. Adding Aspirin
17. Which of the following inhaler devices are hardest for the patients to use and coordinate?
A. Pressurised metered dose inhaler
B. Turbohaler
C. Pressurised metered dose inhaler with a spacer device
D. Accuhaler
E. Handihaler
18. An elderly lady with COPD and Connective Tissue Disease who is on long term oral
corticosteroids. She develops a chest infection. Which of the following drugs should be
avoided most?
A. Amoxicillin
B. Clarithromycin
C. Ciprofloxacin
D. Ceftazidime
E. Doxycycline
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19. A 33-years-old woman is 20 weeks gestation. She has presented with symptoms in
keeping with uncontrolled asthma. Which of the following drugs should be avoided in
pregnancy?
A. Budesonide
B. Fluticasone
C. Prednisolone
D. Tetracycline
E. Azithromycin
20. Amoxicillin 500mg P.O. t.d.s. Is given to the patient..
A. Once daily
B. Twice daily
C. Thrice daily
D. Four times daily
E. Five times daily
Best Wishes
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