Cholinergic Agonists

Question 1

Choline Esters

Answer 1

ACh
Methacholine
Bethanechol
Carbachol

Direct-acting; Mimic ACh

Question 2

AcetylCholine

Answer 2

• Short duration/Rapid affect
• Does snot penetrate BBB
• Dec HR/CO
• Rarely used clinically; Opthalmic surgery for Myosis

Question 3

Methacholine

Answer 3

• NOT hydralized by AChE
• Inhalation
• Bronchial challenge test -> Bronchial airway hypersensitivity
• eye drops as a miotic
• Contra: Stroke, MI, Severe asthma, COPD

Question 4

Bethanechol

Answer 4

• NOT hydrolyzed by AChE
• Strong M2/3 agonist
• NO Nicotinic action
• Stimulate neurogenic bladder, GI smooth. Muscle

Question 5

Carbachol

Answer 5

• Also NOT hydrolyzed
• BOTH M and N receptors
• Cardiovascular + GI systems
• Release of EP
• Topically treat Open-angle Glaucoma

Question 6

Alkaloids

Answer 6

• Naturally occurring Cholinomimetics
• Muscarinic
• Pilocarpine
• Nicotine

Question 7

Muscarine

Answer 7

• NOT hydrolyzed
• Does NOT cross BBB
• Diagnosis: history of mushroom ingestion; Cholinergic symptoms esp sweating
• Antidote -> Atropine (competitive muscarine antagonist)
• Administer O2 prior

Question 8

Pilocarpine

Answer 8

• Stable to hydrolysis
• Primarily Muscarinic
• Penetrates BBB; Rapid contraction ofciliary muscle
• Strong stimulations of secretions
• Clinical: Open + Closed angle Glaucoma; Xerostomia; Sjogren’s; Atropine Mydriasis; Iris-lens adhesion

Question 9

Nicotine

Answer 9

• N receptors at autonomic ganglia, NMJ, and Adrenal medulla
• Low Dose-> Stimulant; High Dose - Reward pathway
• INC HR/BP, GI Motility, Vasocontriction
• Overdose: Profuse PSN, respiratory depression, tremors, and convulsions

Question 10

Cevimeline

Answer 10

• Synthetic; oral
• M1/3 agonist
• Exocrine glands -> Xerostomia

*Siponmod: selective S1P receptor modulator for oral use for MS; Risk f SEVER Bradycardia and AV Block

Question 11

Varenicline

Answer 11

• Direct partial agonist of Nicotinic receptor
• Smoking cessation
• Significant decreased craving/withdrawal symptoms

Question 12

Major contraindications for ALL Direct cholinergic

Answer 12

• COPD
• Peptic Ulcer
• Arrhythmias + CVD
• Angle-closure glaucoma
• Hyperthyroidism
• Urinary Obstruction
• Orthostatic hypotension
• Sever Miosis

Question 13

Reversible/Carbamates

Answer 13

• inhibit AChE preventing degradation of ACh
• Physostigmine
• Neostigmine
• Pyridostigmine
• Tacrine, Donbepezil, Rivastigmine, Galantamine

Question 14

Physostigmine

Answer 14

• Tertiary amine
• Works on both; Marked Muscarinic
• Enter CNS; prominent Autonomic effectors
• Clinical: USed for Atony, Severe atropine poisoning (especially CNS), acute glaucoma
• CNS adverse effects
• Contra: Pulmonary disease, Diabetes
• Overdoes -> Cholinergic crisis

Question 15

Neostigmine

Answer 15

• Poorly absorbed; NO CNS
• Prominent SKM
• Clinical: Myasthenia Gravis; Reversal of nondepolarizing NM blockage; Ogilvie’s Syndrome
• Snake bite

Adverse: NOT for atropine toxicity

Administration: Along w/ anti muscarinic glycopyrrolate or atropine

Question 16

Pyridostigmine

Answer 16

• Neostigmine analog
• CHRONIC Management of MG; first line therapy
• Pretreatment for Soman nerve gas in military

Question 17

Organophosphates/ Irreversibles

Answer 17

• Echothiophate
• Parathion
• Malathion
• Nerve Gas

Question 18

Echothiophate

Answer 18

• Generalized cholinergic stimulation in both N/M
• Chronic Aspen angle glaucoma
• Adverse: Seizures, Psychosis, GII upset, Salivation, blurry vision, bradycardia
• NM Blockage

Question 19

Parathion

Answer 19

• Insecticide
• Rapidly absorbed
• NOT rapidly detoxified
• PNS effects + Paralysis + Coma

Question 20

Malathion

Answer 20

• organophosphate; rapidly absorbed + long duration similar to Parathion

Question 21

Nerve Agents

Answer 21

• Organophosphates
• High Potency, severe symptoms
• Treatment: Oxime 2PAM - Atropine - Benzodiazepine

Question 22

2-PAM

Answer 22

• Reactivates AChE

- Can’t penetrate CNS; In conjunctions with atropine for Nerve gas Toxicity

Question 23

Acute antiAChE Toxicity Clinical Findings

Answer 23

SLUDGE

Salivation
Lacrimation
Urinary freq
Diarrhea
GI Upset
Emesis

Question 24

Contra for AntiAChE Agents

Answer 24

• Succinyl Choline
• CV Disease
• Glaucoma
• Renal impairment
• Respiratoruy Disease