Cholinergic drugs Flashcards
Cholinomimetics
Mimic action of ACh
a) Direct (receptor agonists)
b) Indirect (AchE inhibitors)
Cholinergic antagonists
Reduce acton of ACh
a) antimuscarinic
b) antinicotinic
Direct acting agonist and which receptors (M/N)
-Acetylcholine-
AChE susceptible
M: Agonist
N: Agonist
Director acting agonists
-Acetylcholine,
-Bethanechol
-Muscarine
-Pilocarpine
-Nicotine
Direct acting agonist and which receptors (M/N)
-Bethanechol-
Not AChE susceptible
M: Agonist
N: No activity
Direct acting agonist and which receptors (M/N)
-Muscarine-
Not AChE susceptible
M: Agonist
N: No activity
Direct acting agonist and which receptors (M/N)
-Pilocarpine-
Not AChE susceptible
M: Agonist
N: No activity
Direct acting agonist and which receptors (M/N)
-Nicotine-
Not AChE susceptible
M: No activity
N: Agonist
Indirect acting agonist (AChE inhibitors)
Physostigmine: intermediate-acting
Echothiophate: long-acting
Antagonists
Atropine: M-
Trimethaphan: NN-
D-tubocurarine (NM-)
Direct receptor agonists: Esters of Choline
Not absorbed/distributed well
a) Acetylcholine
b) Bethanechol
Direct receptor agonists:
Alkaloids
Absorbed and distributed well, even in CNS
a) Muscarine
b) Nicotine
c) Pilocarpine
True of fasle: Most cholinergic receptor agonists used clinically
are receptor sub-type selective
False: They are not receptor sub-type selective
Muscarinic receptor activation activates:
- responses same as PSNS activation
- sweat glands
- endothelial-derived relaxation of blood vessels
Nicotinic receptor activation activates:
- activates PSNS and SNS
- skeletal muscle contraction
(nicotine: initially stimulates then blocks)
What effect would pilocarpine have in the eye?
If pilocaprine gets into the systemic circulation, what effect will it have in the heart
If pilocaprine gets into the systemic circulation, what effect will it have in the blood vessels
If pilocaprine gets into the systemic circulation, what effect will it have in the bronchi
Nicotine activates which nervous response system at ganglia
Both PSNS and SNS (NN)
What does nicotine activation of PSNS and SNS (NN) at ganglia cause
Increase release of ACh and NE in tissues
When both PSNS and SNS systems are activated, response from which is observed
PSNS - it is dominant
SNS response in blood vessels: which receptors cause what
a1: vasoconstriction (organs and skin)
B2: vasodilation (sk. muscle)
Indirect acting choinomimetics: hydrolysis of ACh
ACh –> binds to active site of cholinesterase –> free choline + acetylated enzyme –> +H2O (hydration) –> acetate & choline
How is effect of ACh amplified (hydrolysis of ACh)
Inhibitors bind to AChE - reduce ACh hydrolysis = increase local ACh
Reversible inhibitors and how
-Carbamate esters: (physostigmine)
-Covalent bond between drug and AChE somewhat resistant to hydration (step 2 of hydrolysis) t ½ =
30 min – 6 h
-Poor absorption and distribution (except physostigmine)
Irreversible inhibitors
-Organophosphates: (echothiophate)
-Covalent bond between drug and AChE
phosphate stabilizes bond
t ½ = days to weeks
-Absorbed and distributed well (even in CNS)
Amplification of endogenous ACh causes increased ACh at…
-at PSNS and SNS ganglia
- tissues innervated by autonomic ACh-releasing
neurons
-at skeletal muscle
-in CNS
