Cholinergic agonist

Question 1

Classifying Ach receptor agonist

Answer 1

• direct acting agonist: bind and activate ACh receptors and facilitate ACh signal transduction
• indirect acting agonist: increase synaptic concentration of ACH by inhibiting cholinesterase

Question 2

Direct acting Ach receptor agonist

Answer 2

• Bethanechol (M): GI & urinary stimulation (3 Bs - bethanechol, bowel, bladder)
• Carbachol (N &M): constricts pupil and relieves IOP in glaucoma
• Methacholine (M): challenge test for asthma (diagnoistic procedure ONLY)
• Pilocarpine (M): glaucoma, xerostomia
• Cevimeline (M): xerostomia

Question 3

ACh effect on eye

Answer 3

• contraction of iris sphincter causes miosis (constriction of pupil)
• contraction of ciliary body which controls accommodation ( decrease IOP)
• combination of those effects drains anterior chamber of eye to help glaucoma.

Question 4

Cardiovascular effect of ACh

Answer 4

• heart depends on homeostatic mechanisms and dose
• heart wants to decrease HR and cardiac output and decrease BP
• clinically don’t use drugs with these effects in heart disease
• cardiac side effects occur when muscarinic drugs are given for other reasons

Question 5

Respiratory effect of ACh

Answer 5

• BRONCHOCONSTRICTION: makes it harder to breath
• stimulates secretion of mucus in tracheobronchial tree: fills airways with mucus - makes harder to breath
• clinically: not used for the effect - avoid with asthma and obstructive lung disease

Question 6

GI effects on ACh

Answer 6

• increase secretion of GI tract: salivary glands and gastric glands
• peristalsis of intestine are increase and sphincters are released

Question 7

GU effects of ACh

Answer 7

• ACh stimulate the bladder muscle (contraction) and relaxes the sphincter
• promotes emptying of bladder
• Clinically: use if nerves to bladder are not working
• high doses of these agonist can produce urinary incontinence

Question 8

Additional effects on glands of ACh

Answer 8

-increase sweat, lacrimal, and nasopharyngeal glands secretion

Question 9

Nicotine organ effects

Answer 9

• prototype for drugs that just stimulate the nicotinic receptor
• nicotinic receptors are present in CNS, ganglion in PNS, SNS, and neuromuscular junction so a lot happens when they get activated

Question 10

CNS effects of Nicotine

Answer 10

• low does increases alertness
• higher doses cause tremor, emesis, increase respiration and coma
• addiction results from receptor stimulation in certain brain areas

Question 11

Ganglion effects of nicotine

Answer 11

• initially looks like stimulating PNS and SNS at the same time and the effect that occurs depends on which on wins out
• cardiac effects: SNS response usually wins so get increased HR and BP
• GI and GU: PNS ususally wins so get n/v/d and urination

Question 12

Skeletal neuromuscular junction effects of nicotine

Answer 12

• initally voluntary muscles contract, but the nicotine keeps stimulating the receptor so the muscle never recovers b/c constantly stimulated - paralysis
• clinically: muscle paralysis during anesthesia for surgery

Question 13

Adverse reactions of ACh receptors

Answer 13

• Muscarinic: SLUDGE M (salivation, lacrimation, urination, defecation, gastric emptying, emesis, miosis)
• Nicotinic: MTWTF (muscle cramps, tachycardia, weakness, twitching, fasciculation)

Question 14

Indirect acting ACh receptor agonist

Answer 14

• cholinesterase inhibitors

- divided into 2 groups: reversible and irreversible

Question 15

Reversible cholinesterase inhibitors

Answer 15

• quaternary compounds
• Donepezil, galantamine, rivastigmine: Alzheimer’s
• Neostigmine: myasthenia gravis, reversal of anesthetics
• Physostigmine: antidote for anticholinergic toxicity
• Pyridostigmine: myasthenia gravis, reversal of anesthetics

Question 16

Irreversible cholinesterase inhibitors

Answer 16

• organophosphates
• harder to do adjustments
• Echothiophate: glaucoma
• Malathion: lice

Question 17

Absorption of indirect cholinesterase inhibitors

Answer 17

• reversible: topical absorption is poor and they don’t get into CNS very well
• irreversible: topical absorption is excellent and get into CNS (highly lipid soluble), good at killing bugs, chemical warfare

Question 18

CNS & indirect cholinesterase inhibitors

Answer 18

• low dose have an alerting effect
• high dose cause seizures, respiratory depression, coma
• clinically: used in low doses to help Alzheimer’s

Question 19

Neuromuscular junction & indirect cholinesterase inhibitors

Answer 19

• increase ACh in synapse
• Clinically: myasthenia gravis and reverse muscle paralysis
• myasthenia gravis: disease where the immune system destroys ACh receptors in CNS - drugs help to increase ACh at receptors that are left
• reverse muscle paralysis: drugs increase the concentration of ACh at the receptor pushing off the paralyzing drug binding to the receptor

Question 20

Toxicity of indirect cholinesterase inhibitors

Answer 20

• generally short acting drugs gone before too many problems occur
• drugs that bind tighter to the enzyme that are around long and cause the problems of excess ACh
• exacerbates SLUDGE M
• blurred vision, n/v/d, urination, tearing/drooling, muscle twitch/tremor, muscle paralysis
  clinically: accidental exposure to pesticides