Lecture 12: Cholinergic Drugs Flashcards
1
Q
Direct effects of ACh on CARDIOVASCULAR SYSTEM
A
DIRECT EFFECS OF ACETYLCHOLINE
- Vasodilation (M3 effect).
- Decrease in cardiac rate (M2 effect).
- Decrease in rate of conduction in the SA and AV nodes (M2 effect).
- Decrease in force of contraction (M2 effect).
- Some of these direct effects can be obscured by baroreceptor reflexes.
- IV injection of a small dose of acetylcholine produces a fall in blood pressure due to vasodilation (M3 effect) usually accompanied by reflex tachycardia.
- Larger doses of acetylcholine cause hypotension (M3 effect) and bradycardia (M2 effect).
2
Q
NICOTINIC EFFECTS OF ACH
A
- If muscarinic effects are blocked by atropine, large doses of acetylcholine produce nicotinic effects:
- Increase in blood pressure and vasoconstriction due to stimulation of sympathetic ganglia and release of epinephrine from the adrenal medulla.
3
Q
ACETYLCHOLINE as a drug
A
- No systemic therapeutic applications due to multiplicity of actions, and rapid hydrolysis by both acetylcholinesterase and plasma butyrylcholinesterase.
- USES: Used to obtain rapid miosis after delivery of the lens in cataract surgery and other anterior procedures where rapid miosis is required.
4
Q
NATURAL ALKALOIDS
A
- Muscarine acts almost exclusively at muscarinic receptor sites.
- Arecoline acts at muscarinic and nicotinic receptors.
- Pilocarpine has mainly a muscarinic action.
- Present clinical use of the natural alkaloids is largely restricted to pilocarpine as a sialagogue and miotic agent.
USES Glaucoma
- Second line agent for open angle glaucoma. (Pilocarpine was the most widely used anti-glaucoma drug before timolol was introduced).
- Management of acute angle-closure glaucoma. Treatment includes several drugs: timolol, pilocarpine, apraclonidine, acetazolamide and an osmotic agent, such as oral glycerol and IV mannitol.
ADVERSE
- Can enter brain and cause CNS disturbances.
- Stimulates sweating and salivation.
5
Q
Bethanecol
A
- Not hydrolyzed by acetylcholinesterase
- Inactivated by other esterases.
- Little or no nicotinic actions.
- **Strong muscarinic activity. **
- Treatment of acute postoperative and postpartum urinary retention.
- Neurogenic atony of the urinary bladder with retention.
Adverse Effects
- Sweating
- Salivation
- Flushing
- Low blood pressure
- Nausea
- Abdominal pain
- Diarrhoea
- Bronchospasm
6
Q
CARBACHOL
A
- Both muscarinic and nicotinic agonist.
- Poor substrate for acetylcholinesterase.
- Biotransformed by other esterases at much slower rate.
Uses
- Miosis during surgery.
- Reduces intraocular pressure after cataract surgery.
7
Q
METHACHOLINE
A
- Predominantly muscarinic agonist.
- Hydrolyzed by acetylcholinesterase at considerably slower rate than acetylcholine.
- Almost totally resistant to hydrolysis by nonspecific cholinesterase or butyrylcholinesterase.
- USES: Dx of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma.
8
Q
NICOTINIC RECEPTOR AGONISTS
A
- GANGLION STIMULANTS
- NICOTINE: Affects the NMJ in concentrations only slightly greater than those that affect ganglia.
- Low doses: ganglionic stimulation by depolarization
- CV system: Mainly sympathomimetic effects. Increase in HR and BP due to catecholamine release from adrenergic nerve terminals and from adrenal medulla.
- GI & urinary tracts: Mainly parasympathomimetic effects: nausea, vomiting, diarrhea, voiding of urine.
- Secretions: Stimulation of salivary and bronchial secretions.
- High doses: ganglionic blockade and neuromuscular blockade.
9
Q
Nicotine: Acute poisoning
A
nausea, salivation, abdominal pain, vomiting, diarrhea, cold sweat, mental confusion and weakness.
BP falls; pulse is weak.
Death may occur from paralysis of respiratory muscles and/or central respiratory failure.
10
Q
INDIRECT-ACTING CHOLINERGIC AGENTS (ANTICHOLINESTERASES)
A
- Simple alcohols bearing a quaternary ammonium
* Edrophonium - Carbamates
* Physostigmine, neostigmine, pyridostigmine. - Organophosphates
- Echothiophate, parathion, malathion
- covalent bond formed is extremely stable and hydrolyzes very slowly.
11
Q
ANTICHOLINESTERASES: ORGAN SYSTEM EFFECTS
A
Cholinesterase inhibitors have less marked effects on blood pressure than direct-acting muscarinic agonists.
Few vascular beds receive cholinergic innervation.
There fore the effects of cholinesterase inhibitors on vascular smooth muscle are minimal.
12
Q
Edrophonium
A
- MOA: binds reversibly to the active site of the enzyme; **enzyme-inhibitor complex doesn’t involve a covalent bond and is short- lived. **
- Used in diagnosis of myasthenia gravis. Edrophonium IV leads to rapid increase in muscle strength.
- Also used to reverse the neuromuscular block produced by non-depolarizing muscular blockers.
13
Q
Physostigmine
A
- MOA: form a covalent bond with the enzyme; Can enter and stimulate CNS.
- USES: Treatment of overdoses of anticholinergic drugs; Many drugs have anti-cholinergics (side) effects
- NOTE: Physostigmine should not be given to a patient with suspected TCA overdose because it can aggravate depression of cardiac conduction.
14
Q
Carbamates
A
- The carbamate-cholinesterase bond spontaneously hydrolyzes within 30 minutes - 6 hours. Clinical recovery occurs in several hours; only rarely in more than 24 hours.
- includes physostigmine, neostigmine, pyridostigmine
15
Q
NEOSTIGMINE
A
- Quaternary ammonium
- Doesn’t enter CNS.
USES
- To stimulate bladder and GI tract.
- Antidote for competitive blockers of the NMJ.
- Symptomatic treatment of myasthenia gravis
33
Q
ANTINICOTINIC AGENTS: GANGLION BLOCKERS
A
- Ganglion blockade may occur by the following mechanisms:
- By prolonged depolarization. Example: Nicotine.
- By antagonism of nicotinic receptors. Examples: Hexamethonium, mecamylamine, trimethaphan; used for hypertension in the past but had too many adverse effects
- Effects of ganglion-blockers can be predicted by a knowledge of which division of the autonomic nervous system exercises dominant control of various organs.
