Divisions of the Nervous System
Parasympathetic
Return body to steady
state Stimulates
maintenance
activities"Rest &
digest“
Myers in Modules, Module 3
Sympathetic
*Stimulates body
responses:
“Fight-or-flight” response
*Energetic action
-Increased heart rate
-Increased respiration rate
-Activates adrenal gland
-Delivers more blood to
skeletal muscles
Autonomic Control Centers
• Hypothalamus
– Water balance
– Temperature
– Hunger
• Pons
– Respiration
– Cardiac
– Vasoconstriction
• Medulla
– Respiration
Autonomic nervous system
Sympathatic
Parasympathatic
*origin (1st Th-3rd L)
•Cranio(3,7,9,10)-sacral (2,3,4)origin
*short preganglionic fiber
•* Long preganglionic fiber
*long post ganglionic fiber
*short post ganglionic fiber
Ach is ganglionic transmitter,Most organ receive Dual supply Except:
*D.P,ventricles, most small BV,
sweat glands ,pilomotor muscle
*Stress response(generalized)
*control CVS,metabolism,skin
*C.P, ciliary muscle
*save energy,excretion (discrete)
*predominant in other organs
*Transmitter is Ach
•Transmitter is NA except
SK.M.BV, sweat gland(Ach)
NB:Receptors(Odd e.g ⍺1,B1,M1,3 is stimulatory & Even(⍺2,B2,M2)is inhibitory.
(M3)
(M3)
(M2)
(Isolated M3↦↥EDRF↦ VD)
(M3)
(M1,M3)
(M3)
(M3)
Relax sphincter/contract
wall/ (M3)
( M3↦↥EDRF↦ VD)
Pharmacology of ANS
tyrosine
tyrosine
MAOA
MAOB
+ Gut mucosa
brain,
liver,
placenta,
(-) All amines
(-)DA
SIs:clorgylin,
moclobomide
SIs:
selegiline
(-)metyrapone
T. hydroxylase
Dopa
(-)α Methyl dopa
Uptake 3, intravesicular
(-)Reserpin (irreveriversible.)
dopamine(DA)
Uptake-1,intraneuronal
NA
(-) cocain ,phenothiazine
,phenoxybenzamine,
Tricyclicantidepressant,
amphetamine
NA
DA
Ca,cAMP
Uptake 2 ,extraneuronal
(-)Guanithidine
(-) cortisone ,
phenoxybenzamine
NA
D
B1/3
α1
COMT
(-)tolcapone
Chapter 21: Adrenergics and
Adrenergic Blockers
• Drugs that Stimulate the sympathetic Nervous
System (adrenergics, adrenergic agonists,
sypathomimetics, or adrenomimetics)
• Mimic the sympathetic neruotransmitters
norepinephrine and epinephrine
• Act on one or more adrenergic receptor sites
located on the cells of smooth muscles - heart,
bronchioles, GI tract, bladder, eye
• 4 main receptors (alpha-1, alpha-2, beta-1, beta-2)
SYMPATHETIC RESPONSES
Sympathomimetics/
Adrenomimetics
• Stimulate adrenergic receptors: 3 categories
1. Direct-acting = directly stimulates receptors
(epinephrine or norepinephrine)
2. Indirect-acting = stimulates release of norep. from
terminal nerve endings (amphetamine)
3. Mixed-acting (indirect & direct) = stimulates
receptor sites & release of norep. from nerve
endings (Ephedrine)
Sympathomimetic Agents/
Adrenergics
• Action - Many of the adrenergic drugs stimulate
more than one of the adrenergic receptor sites
(alpha & Beta)
• Response = Inc. BP, pupil dilation, inc. HR, &
bronchodilation
• Use = Cardiac stimulation, bronchodilator,
decongestant
• Side effects = Hyperness in body
Sympathomimetics/Adrenergics
• Albuterol - Beta-2 agonist (bronchodilation)
Use - bronchospasm, asthma, bronchitis
SE - nervousness, restlessness
CI - severe cardiac disease, HTN
• Epinephrine - stimulates alpha & beta
Use - allergic reaction, cardiac arrest
SE - nervousness, agitation
CI - cardiac dysrhythmias
Adrenergic Agents
• Dopamine - alpha-1 & beta-1 stimulation
Use - Hypotension, shock, inc. cardiac
output, improve perfusion to vital organs
SE - N & V, headache
CI - V. Tach
Adrenergic Blockers
(antagonists/sympatholytics)
• Block alpha & beta receptor sites (nonselective)
• direct or indirect acting on the release of
norepinephrine and epinephrine
• Use - Cardiac arrthymias (HR), HTN ( cardiac
output), angina (O2 demand)
• SE - CHF, bronchospasm, bradycardia, wheezing
Nonselective vs Selective Beta
blockers
• Nonselective have an equal inhibitory effect on B1
& B2 receptors - Drugs have lots of interactions due to lots of
alpha/beta receptor sites throughout body
- use with caution on clients with cardiac
failure or asthma
• Selective B1 helpful in asthma clients
Adrenergic Blocking Agents
• Inderal (Propranolol) - Nonselective
Use - angina, dysrhythmias, HTN, migraines
SE - Many d/t nonselective
CI - asthma, heart block > 1st degree
• Minipress (Prazosin) - A blocker
Use - mild to mod. HTN
SE - orthostatic hypotension
• Tenormin (Atenolol), Lopressor (Metoprolol)
B1 (cardio) selective
Use - mild to mod HTN, angina
Actions of Ad.R agonists
uses
Adv. Effect
α 1 •VC(skin, mm, cerebral,
Aanaphylactic shock ,
with LA, Haemost
/decong.,open angle
glaucoma
Gangrene ( ring anesthesia),
↥BP, cerebral Hg,
(#) Supersenstivity
B1 • ↥Heart
•↥ CNS
*↥ renin release, Lipolysis(B3)
•Cardiac arrest (I.C)
•AV block
Tachyarrh., IHD,anxiety,↥
plasm. FFA& (#) Pulmonary.
embolism. ,digitalise ,halothane
B2 • bronchodilation
*asthma *PVD
*hypoglycemia
* contraction ring,
premature labor
*Tremors(↥Ach rel. ,CNS)
*↧BP ↦ reflex ↥HR
*hypertension
*sedation,
*anaesthesia
Sedation,↧BP&HR,
↥Prolactin, Xerostomia
visceral)
*mydriasis
• ↥ blood glucose
•VD (skeletal M.)
•Relax uterus
α 2 •↧symp.flow,NA&rennin
release. • Sedation •↧
lipolysis,insulin rel.
•↥platlet aggregation
D1*Renal VD
*shock,HF
D2 *control behavior,movement
,vomiting ,Pituitary Hs.
*delay gastric emptying
*parkinsonism,
Infertility (↥Prolactine.)
*prokinetic
,Parkinsonism
?
sympathomimetic
•Indirect*Less potent,delayed onset.
*Repeated administ. ↦
tachyphylaxis.
*Sympathectomy ↦ ↧ potency
Direct
Catecholamine: a)selective
*Dobutamine-B1(minimal↥HR)
b)Nonselect.ive:1-Adrenaline
(B1,2, α1,2), SC& Eye drops( Dipiverin)
*MAOIs ↥potency,toxicity
2-Dopamine (D>B.>α) , 2-5 μg/kg/m
.Noncatecholamine (stable,oral,slow
IVI in shock,HF
hepatic el.,longer duration,pass
BBB.)
SD:↧fatigue,Euphoria, depres.
Noncatechol. selective
• Nonselective
α 1: 1-oral (Midodrine)
MD:insomnia,anxiety, tremors
• CNS stim.
Local (xylometrine
LD (hyperpyrexia,pschycosis,
naphazolin ,Phenylephrine)
1-↥NA release
convulsion
B2 *Uterus: Ritodrine
*Amphetamine(>CNS, <↥BP+
*BV: Nylidrine, isoxsuprine
anorexo .e.g phentermine,mazindol,)
*bronchi: salmeterol ,formetrol
*Ephdrine *tyramine
,bambetrol > salbutamol
,fenoterol ,terbutaline
2)↧uptake I (Cocaine)
Actions of Ad.R blockers uses
Adv. Effect
α 1•VD (skin, mm ,cerebral
Hypertension,
, pulmonary hypert.
BPH
Headache, congestion,
↧BP ↦ reflex ↥HR ?
,dizziness
IHD,anti-arrhythmic
Hypertension, anxiety,
tremors ,HF, H. Ob.C,
gluco. ,thyrotoxicosis
↧ H.R, H.block, ↥TG &
cholesterol , depression
,visceral)
*relax prostatic m. *miosis
B1 • ↧Heart
• ↧ CNS
•↧ renin release,Lipolysis (B3)
•↧IOP
B2 • bronchoconstriction
Asthma, claudication,
cold pale skin, worsen
Vaso-spastic angina,
delay hypoglycemia
Recovery,, hypokalemia
•VC (skeletal ,coronary due
to α 1 predominant)
*prevent G. ↥ if hypoglycemia
α , B* ↧BP, heart
pheochromocytoma
?
sympatholytic
Indirect, (medical sympathectomy)
Direct,R.blocker(rapid onset)
e.g.Ad. Neuronal blockers:
Nonselective
B1.2,α1,2 (labetalol,carvidilol)
*↥parasymp., delay onset (2d )
α1,2,D2(Neuroleptics.
b-↧ release :
α1,2(Phenoxybenzamine,phentolamine,
Guanithidine
a-Depletion: (reserpine )
tolazolin , dihydroergotoxin.)
B1,2*Lipophilic(propranolol,timolol)
*Hydrophilic(nadolol,sotalol)
bretylium
*Longer
*shorter duration
*No
*Antiarrhythmic(III)
*Less
*Parotide pain
Selective
*α1 (prazosin,terazosin,doxazocin,indormine) *α2 e.g.Yohimbine(aphrodiasic)
*B1:Lipophilic(metoprolol, esmolol) &Hydrophilic(Atenolol)
α2Agonist:*Eye drops (↧IOP) e.g Apraclonidine,Brimonidine.
*Oral; α CH3 dopa (longer duration, less sedation, safe in pregnancy,allergic
haemolytic anaemia), Clonidine (rebound ↥BP on rapid withdrawal)
Acetylcholine synthesis
Cholinergic Drugs
• Parasympathomimetics or cholinomimetics
• Stimulate parasympathetic nervous system
in same manner as does acetylcholine
• May stimulate cholinergic receptors directly
or slow acetylcholine metabolism at
synapses (affect the enzyme
acetylcholinesterase)
Cholinergic Drugs
• Useful in treating Alzheimer’s Disease,
Myasthenia gravis and to tx atony of the
smooth muscle of the GI system or urinary
system
Cholinergic Drugs
• Normal neuromuscular function,
acetylcholine binds to nicotinic receptors on
cell membranes of muscle cells to cause
contraction
• Myasthenia gravis autoantibodies
presumably destroy nicotinic receptors;
thus, acetylcholine less able to stimulate
muscle contraction. Results in severe
muscle weakness.
Cholinergic Drugs
• Acetylcholine important neurotransmitter
affecting cognitive functioning, memory storage
and retrieval
• In Alzheimer’s disease (AD), abnormalities of the
cholinergic, serotonergic, noradrenergic, and
glutaminergic neurotransmission systems
• In cholinergic system, patient with AD found to
have loss of neurons that secrete acetylcholine
Cholinergic Drugs—GI effects
• Acetylcholine stimulates cholinergic
receptors in the gut to promote normal
secretory and motor activity
• Cholinergic activity in the gut will increase
peristalsis and facilitates movement of
flatus and feces
• The secretory functions of the salivary and
gastric glands also stimulated
Cholinergic Drugs—GU effects
• Acetylcholine stimulates cholinergic
receptors in the urinary system to promote
urination
• Results in contraction of the detrusor
muscle and relaxation of the urinary
sphincter to facilitate emptying of the
urinary bladder
Acetylcholine
• One of the main neurotransmitters of the
ANS is acetylcholine
• Acetylcholine is released at preganglionic
fibers of both the sympathetic and
parasympathetic nervous system
• Also released from postganglionic
sympathetic neurons that innervate the
sweat glands and from motor neurons that
innervate the skeletal muscles
Acetylcholine
• Sympathetic and parasympathetic divisions
of the ANS are antagonistic to each other
• When acetylcholine acts on body cells that
respond to parasympathetic stimulation, it
interacts with two types of cholinergic
receptors: nicotinic and muscarinic
Acetylcholine
• Nicotinic receptors are located in motor
nerves and skeletal muscle
• Stimulation results in muscle contraction
Acetylcholine
• Muscarinic receptors are located in most
internal organs. This includes the
cardiovascular, respiratory, gastrointestinal,
and genitourinary. Stimulation of the
muscarinic receptors may result in either
excitation or inhibition, depending on the
organ involved.
Mechanisms of Action—Direct Acting
Cholinergics
• Direct acting cholinergics are lipid
insoluble
• Do not readily enter the CNS so effects are
peripheral
• Resistant to metabolism by
acetylcholinesterase
• Effects are longer acting than with
acetylcholine
Direct Acting Cholinergic Drugs
cont.
• Widespread systemic effects when they
combine with muscarinic receptors in
cardiac muscle, smooth muscle, exocrine
glands and the eye
Direct-acting Cholinergic Drugs
Effects
• Decreased heart rate, vasodilation, variable
BP effects
• Increased tone and contractility in GI
smooth muscle, relaxation of sphincters,
increased salivary gland and GI secretions
• Increased tone and contractility of smooth
muscle in urinary bladder and relaxation of
the sphincter
Direct Acting Cholinergic Drugs
cont.
• Increased tone and contractility of bronchial
smooth muscle
• Increased respiratory secretions
• Constriction of pupils (miosis) and
contraction of ciliary muscle
Direct Acting Cholinergics
• Bethanecol (Urecholine)—given orally. Not
given IM or IV.
• Used to treat urinary retention due to
bladder atony and for postoperative
abdominal distention due to paralytic ileus
Indirect-Acting Cholinergic Drugs
• Action is by decreasing the inactivation of
acetylcholine in the synapse by the enzyme
acetylcholinesterase
• Accumulation of acetylcholine then occurs
which enhances the activation of the
nicotinic and muscarinic receptors
Indirect-Acting or Anticholinesterase
Drugs cont.
• Anticholinesterase drugs are either
reversible or irreversible inhibitors of
acetylcholinesterase
• Reversible agents are such drugs
as:edrophodium (Tensilon). Used to
diagnose myasthenia gravis and for reversal
of non-depolarizing neuromuscular blockers
Indirect-acting agents cont.
• Neostigmine (Prostigmine)—prototype
anticholinesterase agent. Used for long-term
tx of myasthenia gravis and as an antidote
for tubocurarine and other non-depolarizing
agents in surgery.
• Poorly absorbed orally so requires larger
doses than when given parenterally.
• Can develop resistance to its action over
time
Indirect Acting Agents
• Pyridostigmine (Mestinon) is the
maintenance drug of choice for patients
with Myasthenia gravis. Slow release.
Indirect Acting—Reversible cont.
• Physostigmine (Antilirium)—only
anticholinesterase capable of crossing the
blood brain barrier. Is more lipid soluble.
Used as an antidote for overdosage of
anticholinergics such as: atropine,
antihistamines, TCA, phenothiazines. May
also be used in tx of glaucoma.
Indirect Acting Agents used to treat
Alzheimer’s disease
• Donepezil (Aricept)—said to delay progression of
the disease by up to 55 weeks. Does not cause
liver toxicity.
• Galantamine (Reminyl)—newest kid on the block
• Rivastigmine (Exelon) long acting. Twice a day
dosing.
• Tacrine (Cognex)—hepatoxic. Elevated liver
enzymes usu. Within 18 wks. > in women.
Specific Conditions
• Distinction between cholinergic crisis and a
myasthenic crisis
• Difficult to ascertain as both are
characterized by respiratory difficulty or
failure
• Need to distinguish as require opposite
treatment measures
Specific Conditions—Cholinergic vs.
Myasthenic Crisis
• Myasthenic crisis requires more anticholinesterase
drug whereas cholinergic crisis requires
discontinuation of the anticholinesterase drugs
• Diagnosis can be made by evaluating patient
patient response to their medication (s/s one hour
after medication often is cholinergic crisis, s/s 3 or
more hours after medication often is myasthenic
crisis
Myasthenia Gravis
• If s/s not clearly indicative of the problem,
may have to intubate patient, inject dose of
IV edrophonium. If dramatic improvement
in breathing, diagnosis is myasthenic crisis.
If edrophonium makes s/s worse, the
diagnosis is cholinergic crisis. Patient must
be intubated and assisted with mechanical
ventilation to perform this test.
Toxicity of Cholinergic Drugs
• Atropine is the specific antidote to
cholinergic agents
• Atropine reverses only the muscarinic
effects of cholinergic drugs; heart, smooth
muscle, and glands.
• Atropine cannot reverse the nicotinic effects
of skeletal muscle weakness or paralysis
due to overdose of indirect cholinergic
drugs.
Toxicity of Irreversible
Anticholinesterase Agents
• These agents are lipid soluble
• Can enter the body by the eye,skin,
respiratory system and GI tract.
• Case in point, organophosphate insecticides
(malathion, parathion) or nerve gases (sarin,
tabun, soman)
• These agents cause excessive cholinergic
stimulation (muscarinic) and neuromuscular
blockade
Toxicity cont.
• Cholinergic crisis occurs because the
irreversible anticholinesterase poison binds
to the enzyme acetylcholinesterase and
inactivates it. Thus, acetylcholine remains
in cholinergic synapses causing excessive
stimulation of muscarinic and nicotinic
receptors.
Toxicity cont.
•
1.
2.
3.
Emergency tx includes:
Decontamination of clothing
Flushing poison from skin and eyes
Activated charcoal and lavage for GI
ingestion
4. Atropine to counteract the muscarinic
effects
Toxicity cont.
• To relieve the neuromuscular blockade by
nicotinic effects, give pralidoxime (Protopam), a
cholinesterase reactivator.
• Pralidoxime causes the anticholinesterase poison
to release the enzyme acetylcholinesterase.
• Give Pralidoxime as soon as possible as if too
much time passes, the poison bond becomes too
strong for the pralidoxime to work.
Anticholinergics
• Also called cholinergic blocking agents or
parasympatholytics
• Again, focus is on the parasympathetic
nervous system
• Parasympathetic system acts as a resting
and reparative function
• Functions include digestion, excretion,
cardiac decelertion, anabolism and near
vision
Parasympathetic Nervous System
• 75% of all parasympathetic nerve fibers are
in the vagus nerves
• These nerves supply the thoracic and
abdominal organs, which innervate the
heart, lungs, esophagus, stomach, small
intestine, proximal half of the colon, liver ,
gallbladder, pancreas and upper portions of
the ureters
Parasympathetic Nervous System
• Also supply the muscles of the eyes,
lacrimal, nasal, submaxillary, and parotid
glands; descending colon and rectum; lower
portions of the ureters, bladder and genitalia
• All are regulated by acetylcholine—exerts
excitatory effects at nerve synapses and
neuromuscular junctions; and inhibitory
effects at peripheral sites e.g. heart
Anticholinergics
• Most anticholinergic drugs interact with the
muscarinic receptors in the brain, secretory
glands, heart, and smooth muscle
• A few can also affect the nicotinic
receptors. Glycopyrrolate (Robinul) is an
example
Mechanism of Action and Effects
• Act by occupying receptor sites at
parasympathetic nerve endings, thereby
leaving fewer receptor sites free to respond
to acetylcholine
• Distribution of receptors is broad so effects
of anticholinergics will be diffuse.
Effects on Body Tissues
1. CNS stimulation followed by depression,
can result in coma and death (atropine,
antiparkinson’s)
2. Decreased cardiovascular response to
vagal stimulation resulting in tachycardia.
Increases vagal tone. Ex. Atropine.
3. Bronchodilation and decreased respiratory
tract secretions.
Effects on Body Tissues
• Antispasmotics of GI tract due to decreased
tone and motility.
• Mydriasis and cyclopegia. Normally do not
increase IOP but caution as can precipitate
acute glaucoma.
• Can cause decreased oral secretions,
decreased sweating, relaxation of urinary
bladder
Indications for Use
• Uses include GI, GU, ophthalmic and
respiratory disorders, bradycardia and in
Parkinson’s disease.
• Used preoperatively
Use In GI Disorders
• Helpful in treating irritable colon or colitis
• Useful in gastritis, pylorospasm and
ulcerative colitis as they slow motility
Use in GU disorders
• Antispasmotic effects seen in overactive
bladder and in urinary incontinence
Ophthalmology
• Mydriatic and cycloplegia for examinations
and surgery
Respiratory
• In bronchospasm whether related to asthma
or COPD
• Atrovent very useful for its bronchodilating
effects
Cardiology
• Atropine is used to increase heart rate in
symptomatic bradycardias and higher
blocks
Parkinson’s Disease
• Useful in those with minimal side effects
• Those who cannot take Levodopa
• Helpful in decreasing salivation, spasticity
and tremors
Preop
• Help prevent vagal stimulation and potential
bradycardia
• Reduce respiratory secretions as well
Contraindications
•
•
•
•
•
•
BPH
Myasthenia gravis
Hyperthyroidism
Glaucoma
Tachydysrhythmias
Not in situations whereby delaying of
gastric emptying is a concern
Individual Anticholinergic Drugs
• Atropine—prototype. Antidote. Belladonna
alkaloid.
• Ipratropium (Atrovent). Useful in rhinorrhea. Also
excellent bronchodilator.
• Scopolamine, similar to atropine. Depresses CNS
and causes amnesia, drowsiness, euphoria,
relaxation and sleep. Also good for motion
sickness. Given parenterally, orally and
transdermally.
Centrally Acting Anticholinergics
• Benztropine (Cogentin)—temporary use in
Parkinson’s disease. Useful for dystonic
reactions caused by antipsychotics.
• Trihexyphenidyl (Trihexy)—also used for
txing EPS by some antipsychotics.
Contraindicated in glaucoma.
Urinary Antispasmotics
• Flavoxate (Urispas)—relieves dysuria, urgency,
frequency, and pain with GU infections
• Oxybutynin (Ditropan) has direct antispasmodic
effects on smooth muscle and anticholinergic
effects. Decreases frequency of voiding.
• Tolterodine (Detrol) is competitive,
antimuscuranic anticholinergic that inhibits
contraction. More selective for this area than
elsewhere in the body.
Toxicity of Anticholinergics
• Anticholinergic overdose syndrome is
characterized by: Hyperthermia, delirium,
dry mouth, tacycardia, ileus, urinary
retention. Seizures, coma and respiratory
arrest may occur.
• Tx—activated charcoal, Antilirium, cooling
agents (ice bags, cooling blankets, tepid
baths).
Ach.
Nn
Choline esters:*M&N e.g. Carbachol (GIT,UB,Eye)
*M:1) Bethanicol (GIT,UB,Eye) ↦Treat Ileus,U. retention,
glucoma . 2) Pilocarpine (Eye,Exceretion ) ↦ glaucoma,hair
lotion, aphrodiasic ,sialogogue
3) Methanicol (CVS) , el. By true Ch.E ↦ Treat PAT
Ch +acetyl-CoA
ChAT
ACh
ACh
(- ) α2,M2,
Ch.E Ch+Acetate
*Atropine (↥CNS&HR, less anti-excretory ,
longer duration) *Initial brady. (CIC in SD) then
tachy
*Hyocine↦ preanaesth.
M1
M2
M3
(-) hyd.(Pirenzeoin,telenzpin)
(-) galamine
Partially selective blockers: -UB: *Hydrophilic (emepronium) & Lipophilic
(oxybutynin , tolterodin , imipramine) ↦ treat U. incontinence
-GIT*Hydro.(propantholine,oxyphenonium,hyocinbutyl bromide) ↦ anticolic
-Eye*Tropicamide (20m/3h,No cyclop.)&,cyclopentolate (30m/6h) &
homatropine(60m/24h) ↦ Fundus examination,treat Irites ,corneal ulcer.
-CNS*Benztropine,trihexphenidyl ↦ antiparkinsonian ,antiemetic , sedation ,
amnesia, delerium
-Bronchi*dilation,↧secreation (ipratropium ↦ treat asthma
- Excretion*Reduction.
Anti-choline estrase
+ E
-
+
E
+ E
-
-
Carbamate
*Rapid dissoc.(5 m du.)
*Tr.:M.graves (worsen
crisis) ,PAT
*Hydrolysis ↦
dissoc.
*Early:Hydrolysis V. slow
*Late:E.phosphorylated(Irr.)
(Reversible)
V.high lipophilic
Tertiaryamine
* ↥CNS
(convulsion)
Quaternary amines
*Sk.m.(D,Ind): (3-6h)pyridostigmin
,*GIT,UB,Sk.m:((½-2h)prostigmine
*War gases.
*Insecticides:
Malathion,parathion
1)Phystogmine ((½-2h) ↦ Tr. Glaucoma
2)Tacrine,velnacrine (4-8h) ↦ Tr
Alzheimer
Ch.E. activator (early) :
Less lipophilic
*oral:1) levamisol (antinematoda)
2)Metrifonate (anti-sch. H.)
1-obuloxime,diacetyl monoxime(pass BBB
*eye drop: echothiophate ,isoflorophate
2-pralidoxime (Not pass)
*Skin:Scabicide(malathione)