Peripheral Nervous System Pharmacology 2

Question 1

Nicotine (Nicorette)

Answer 1

agonist at Nm and Nn receptors, complex action on the peripheral nervous system, stimulates catecholamine release

used to help quit smoking, metabolites from liver are excreted by the kidney

caution with patients with hypertension, pheochromocytoma, insulin-dependent diabetes, vasospastic diseases or thyroid disease resulting in thyrotoxicosis, can increase BP

Question 2

Varenicline

Answer 2

partial agonist at a4B2 nicotinic receptors (central receptors in brain) with moderate 5-HT3 receptor affinity

smoking cessation aid(reward for smoking nicotine is diminished and cravings are diminished) , that is secreted 92% unchanged in urine

side effects include insomnia, vivid dreams and black box warning for changes in behavior or mood leading to hostility, agitation or suicidal thoughts or behaviors

Question 3

Name the 3 classes of ACh inhibitors.

Answer 3

Simple alcohols (edrophonium)
carbamic acid esters (neostigmine, physostigmine)
organophophates (diisopropylfluorophophate)

Question 4

What does the catalytic triad describe in relationship to the active site of cholinesterase?

Answer 4

its a chain of glutamate, histamine and serine linked together that interact with the ester in ACh in order for it to be hydrolyzed from choline

Question 5

Describe the covalent bonding that occurs as cholinesterase acts on ACh.

Answer 5

serine residue of the esteric part of the catalytic portion of the enzyme loose a H bond with near by histadine residue and bond covalently to acetyl group

acetyl group is removed by incoming water and H bond between serine and histadine is restored

Question 6

Physostigmine (Antilirium)

Answer 6

competitive inactivator of acetylcholinesterase causing and increase in ACh (carbamoyl ester class)

used to counteract the toxic anticholinergic effects of other drugs , as an ophthalmic AChE inhibitor and as a second line treatment for glaucoma

side effects are systemic consequences of excess acetylcholine (irregular pulse, bradycarida, hyper salivation, urinary urgency, bronchospasm, dyspnea, increased secretions, mitosis, lacrimation, blurred vision)

precautions with: asthma, GI obstruction, ileum, UT obstuction, peptic ulcer, heart disease, hyperthyroidism

Question 7

Neostigmine (Prostigmin)

Answer 7

competitive occupies active site of acetylcholinesterase, increases ACh concentration (carbamoyl ester class)

effects are specific to the periphery, no central effects

used as a tx, of myasthenia gravis, or postop neuromuscular blockade (not is 10 tabs QD because duration of action is 2-4 hours)

all normal precautions and adverse effects as excess ACh in the system

Question 8

Edrophonium (Tensilon, Enlon)

Answer 8

competitive occupies active site of AChE (alcohol class)

rapid acting, short duration inhibitor use din diagnosis myasthenia gravis, or reversing effects of non depolarizing neuromuscular blockers after surgery or ileum

expected adverse reactions and precautions

Question 9

When are organophosphate cholinesterase inhibitors used? What is their mechanism of action?

Answer 9

“irreversible” cholinesterase inhibitors covalently bind to AChE without treatment, as the enzyme ages, it becomes impossible to remove the organophophate (when second R group attaches to additional amino acid, then the binding is irreversible)

used in glaucoma, insecticides (malathion), and nerve gases (sarin)– (diisopropylfluorophosphate is a known as a nerve gas and as organophosphate insecticide)

Question 10

Echothiophate (Phospholine)

Answer 10

phophorylates AChE, increasing ACh

second line treatment for chronic open-angle glaucoma, long acting (~100hrs)

Question 11

Pralidoxime

Answer 11

reactivates AChE by displacing the phosphoric group form AChE that has been inhibited by organophophates

anecdote for organophosphate poisoning, given within 24 hrs. of exposure (farming accidents and in war)

precaution if patient is suffering renal insufficiency or is being treated with AChE inhibitor (MG)

Question 12

Atropine (Sal-Tropine)

Answer 12

competitive muscarinic receptor antagonist

used to treat bradycardia, reduce post op secretions and as a mydriatic agent

decreases secretions, dilates pupil, paralyzes ciliary muscle, increases HR, decreases bladder tone and GI muscle, causes bronchodilation

adverse reactions include confusion, amnesia, hallucinations, delirium, insomnia, CV conduction abnormalities, PVC, SVT, QT prolongation

risk of acute MI, elevate core body temp

Question 13

Oxybutynin

Answer 13

competitive muscarinic receptor antagonist

use particularly as a bladder muscle relaxant, treating neurogenic bladder to treat urge incontinence (effect 4-10x greater than atropine)

CYP3A4 metabolism

most adverse reactions associated with oxybutynin stem from the anticholinergic and antispasmolytic activity of the drug

caution with GI obstruction, toxic megacolon, urinary retention, uncontrolled narrow angle glaucoma

Question 14

Ipratropium (Atrovent)

Answer 14

muscarinic receptor antagonist, blocks ACh effect on bronchial smooth muscle

used as a tx. for acute asthmatic episode (often formulated with B2 antatongist) , first line therapy in COPD once symptoms are persistent

doesn’t cross the blood brain barrier well, adverse reactions associated with inhaled application, glaucoma, urinary retention and bladder obstruction