Cholinergic Agonists

Question 1

Which drugs affect ANS , act on which receptors, stimulated by which neurotransmitter?

Answer 1

1-Cholinergic drugs——> muscarinic(M1,M2,M3), Nicotinic(Nm,Nn), Ach
2-Adrenergic drugs—–>alpha (1,2), beta(1,2)….epinephrine & nor epinephrine

Question 2

what is a cholinergic agonist?

Answer 2

That mimics the effects of Ach by binding directly to cholinoceptors( muscarinic or nicotinic)

Question 3

Cholinergic agonists site of actions?

Answer 3

Autonomic’s parasympathetic division.

somatic nervous system.

Question 4

Preganglionic neurotransmitter of ANS is ?

Answer 4

In both Sympathetic and parasympathetic divisions

Ach.( an ester)

Question 5

Muscarinic receptor’s affinity for neurotransmitters?

Answer 5

low to high—-> nicotine,Ach,Muscarine

Question 6

muscarinic receptors and it’s types?

Answer 6

belongs to class of G-protien-coupled receptors(metabotropic receptors)
subtypes= 5 (M1,M2,M3,M4,M5) but 4,5 not clincally imp.

Question 7

Nicotinic receptors function and composition?

Answer 7

functions as ligand-gated ion channel….. composed of 5 subunits.

Question 8

locations of nicotinic receptors?

Answer 8

Neuromuscular junction NMJ in skeletal muscles are Nm( blocked by atracurium)
adrenal medulla, autonomic ganglia are Nn ( ganglionic receptors blocked by mecamylamine)

Question 9

Affinity of nicotinic receptors for neurotransmitters?

Answer 9

Low to high—-> muscarine, Ach, Nicotine

Question 10

Location of Muscarinic receptors?

Answer 10

M1—-> CNS, neurons ganglia, gastric parietal cells ( M1 agonists for treatment of Alzheimer’s disease)
M2—–> Cardiac & smooth muscles
M3—–> Exocrine gland, bladder, smooth muscles, skeletal muscles, vessels, neuromuscarinic end plates.(M3 antagonists for treatment of COPD)

Question 11

Synthesis and Release of Ach from Cholinergic neuron?

Answer 11

Six steps
1-Synthesis ( by choline acetyltransferase)
2-Storage (protects from degradation,contains Ach and cotransmitter)
3-Release ( blocked by botulinum toxin, all release by black widow spider venom)
4-Binding to receptor( to presynaptic memb recpt or postsynaptic memb recp)
5-Degradation of Ach( by acetylcholinestrase)
6- Recycling of choline (inhibited by hemicholinium)

Question 12

name Direct acting cholinergic agonists?

Answer 12

two groups
1- Endogenous choline esters (ABC)
  Ach, bethanechol, carbachol
2-Natural Alkaloids (NP)
 nicotine, pilocarpine
theraputically useful---> Pilocarpine ; Bethanechol

Question 13

theraputic applications of
1-Bethanechol
2-Pilocarpine
3-Carbachol

Answer 13

1- Produce urination(urological treatment), increases intestinal motility(diarrhea) so used in treatment of megacolon mnemonic (UD)
2-drug of choice for emergency treatment of glucoma,treatment of xerostomia & sjogren syndrome(dry mouth, lack of tears)
3-rarely used except as a miotic agent to treat glucoma

Question 14

generalized effects of cholinergic agonists?

Answer 14

SLUD increases (salivation, lacrimation, urination, diarrhea) and Heart rate, BP, cardiac output decreases

Question 15

adverse effects of cholinergic agonists?

Answer 15

1-Diarrhea &abdominal pain/discomfort
2- vomiting
3- miosis
4-urinary urgency
5-Diaphoresis(sweating)
6-Bronchospasm
7- decreased bp
pilocarpine--> blurred vision, night blindness& brow ache

Question 16

name Direct acting agonists which have activity
1- muscarinic
2-nicotinic
3-both

Answer 16

1-bethenechol, pilocarpine (BP)
2-nicotine, varencline (VN as in VAN)
3-ach, carbachol (AC)

Question 17

what is nicotinic toxicity effects?

Answer 17

ganglionic stimualtion and end plate depolarization leading to fasciculation and then paralysis
cns toxicity —> stimulation including convulsions followed by depression.