Cholinergic Drugs

Question 1

Nicotinic receptor

Answer 1

inotropic, 5 protein subunits surrounded by central pore

excitatory, quick response, short lasting effect

Question 2

Nicotinic agonist effects

Answer 2

Assorted SympNS and ParaNS autonomic ganglia

• release of epi by adrenal medulla (SNS) –> CV effects
• Tetanus (sk. musc)
• Direct stim of nicotinic receptors in aortic and carotid bodies

DRUGS: nicotine, anti-AChE’s

Question 3

Nicotinic antagonist effects

Answer 3

• Predom system overridden by less dominant system (mostly SNS effects)
• inhibition of epi release by adrenal medulla
• muscle weakness/paralysis

DRUGS: hexamethonium (only affects autonomic ganglia)

Question 4

Muscarinic receptor

Answer 4

Metabotropic, 7TM G protein linked receptor

Excitatory OR inhibitory, slow response, long last effect

Question 5

Muscarinic agonist effects

Answer 5

parasympathomimetics!!!

• sweating (remember, they are SNS driven but have muscarinic receptors!!!!)
• vasodilation

DRUGS: bethanechol, muscarine, pilocarpine, antiAChE’s (drugs that cross BBB can have CNS effects)

Question 6

Muscarinic antagonist effects

Answer 6

decreased PNS, parasympatholytics

• sweat inhibition
• normal blood vessels (no dilation)

Question 7

Botulinum toxin Indications

Answer 7

blepharospasm, strabismus, focal dystonia, hyperhidrosis, and more

Question 8

Botulinum mechanism

Answer 8

decreased cholinergic activity by preventing exocytosis in synapse

Question 9

Botulinum dose/timing

Answer 9

injection lasting for 2-6 months

Question 10

Botulinum adverse effects

Answer 10

Death (womp womp)

Question 11

Botulinum, notes

Answer 11

HC blocks cholinesterase receptor in synapse, LC blocks exocytosis of ACh vesicles

Question 12

Edrophonium (type and indications)

Answer 12

• Anticholinesterase
• muscle weakness, alzheimers

Forms electrostatic or hydrogen bonds to cholinesterase, short acting. TRULY REVERSIBLE CARBAMATE

Question 13

Physostigmine & Neostigmine (type and indications)

Answer 13

• Anticholinesterase
• Muscle weakness from myasthenia gravis.

Increases ACh activity, ester group mimics ACh and competitively binds active site of cholinesterase; longer acting

Question 14

Physostigmine adverse effects

Answer 14

^SNS output, CNS side effects, biphasic effects

Question 15

PNS innervation - preganglionic

Answer 15

ACh, nicotinic receptor

Question 16

PNS innervation - postganglionic

Answer 16

ACh, muscarinic receptor

Question 17

SNS innervation - preganglionic

Answer 17

ACh, nicotinic

Question 18

SNS innervation - postganglionic

Answer 18

Norepinephrine, Adrenergic Receptor (alpha, beta)

Question 19

Adrenal medulla innervation + sweat gland (PNS exceptions)

Answer 19

Adr. med: ACh - nicotinic R –> release epinephrine to blood

Sweat: ACh, muscarinic (sns mediated)

Question 20

Anticholinesterases

Answer 20

Prevent breakdown of ACh to increase its activity; can be truly reversible, reversible carbamates, or irreversible/organophosphorus anti-AChE

Question 21

Nicotinic sites of action

Answer 21

1) on the postganglionic neuron @ autonomic preganglionic junction
2) skeletal muscle/NMJ
3) adrenal medulla (ACh/NicoR stimulation causes release of Epi –> blood circulation –> distant targets)

Question 22

Muscarinic sites of action

Answer 22

• on effector cell at ALL PS postganglionic junctions
• sweat gland (symp)
• blood vessels (have muscR which can be acted on by musc agonist)

Question 23

Biphasic effect of long-acting antiAChE’s

Answer 23

enhanced transmission w/ prolonged NT binding/depolarization –> complete transmission block (voltage-dependent-Na channel inactivates and post synaptic cell is incapable of AP generation) aka cholinergic crisis

Question 24

Myasthenia gravis

Answer 24

Muscle weakness caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors at neuromuscular junctions.

Treat w/ carbamates (neostigmine) to increase ACh activity, have to be careful with bephasic effect

Question 25

Alzheimer's disease

Answer 25

death of cholinergic neurons in basal forebrain which regulate cognitive activities Treat w/ truly reversible AChE's to improve mental status

Question 26

Organophosphorus anti-ache's

Answer 26

used as insectisides/chemical warfare - bind irreversibly to active center of AChE; lipid soluble --> CNS effects - excess salivation, drop in bp, suffocation, confusion/seizures ANTIDOTES: atropine and pralidoxine

Question 27

Organophosphorus antidotes

Answer 27

atropine (muscarinic agonist) and pralidoxine (pulls organophosphorus but can't cross BBB); only works 1-2 hours after anti-AChE binding

Question 28

Pralidoxine

Answer 28

used for organophosphate poisoning | pulls organosphosphorus anti-AChE off AChE, must administer w/in two hours, doesn't enter CNS

Question 29

Atropine

Answer 29

Muscarinic inhibitor; used for organophosphate poisoning; out-competes ACh for spots on organophosphate

Question 30

Nicotinic blockers/inhibitors/antagonists

Answer 30

Succinylcholine, pancuronium, vecuronium, rocuronium

Question 31

Succinylcholine

Answer 31

-nicotinic antagonist; short DOA - used as muscle relaxant, used during surgery to use less general anesthesia; - depolarizing blocker (uses biphasic effect) - onset 1--2 mins, lasts 5-8 mins (used for brief procedures like tracheal intubation) AE: fasciculations;

Question 32

Pancuronium

Answer 32

- nicotinic competitive agonist - muscle relaxant used in surgery to use less anesthesia - 406 min onset, lasts 120-180 mins AE: vagal inhibition (decreases input to heart) - long duration

Question 33

Vecuronium

Answer 33

- nicotinic competitive antagonist - muscle relaxant (during surgery) - onset 2-4 mins, lasts 60-90 mins - no vagal side effects

Question 34

rocuronium

Answer 34

- comp nicotinic antagonist - onset 1-2 mins, lasts 30-60 - no vagal side effects