Cholinergic Drugs

CHAPTER 4 Cholinergic Drugs

I. Cholinoreceptor Agonists

A. Muscarinic receptor agonists (Box 4-1)

• Physiologic muscarinic effects (Table 4-1)

1. Pharmacokinetics and classes

a. Choline esters

• Quaternary ammonium compounds

(1) Do not readily cross the blood-brain barrier

TABLE 4-1 Effects of Muscarinic Receptor Agonists

Organ/Organ System	Effects
Cardiovascular	Hypotension from direct vasodilation Bradycardia at high doses Slowed conduction and prolonged refractory period of atrioventricular node
Gastrointestinal	Increased tone and increased contractile activity of gut Increased acid secretion Nausea, vomiting, cramps, and diarrhea
Genitourinary	Involuntary urination from increased bladder motility and relaxation of sphincter Penile erection
Eye	Miosis: contraction of sphincter muscle, resulting in reduced intraocular pressure Contraction of ciliary muscle; accommodated for near vision
Respiratory system	Bronchoconstriction
Glands	Increased secretory activity, resulting in increased salivation, lacrimation, and sweating

Choline esters do not cross BBB.

(2) Inactivation

(a) Acetylcholinesterase (AChE)

(b) Pseudocholinesterase

(3) Carbachol should not be used systemically because it also has unpredictable nicotinic activity

b. Plant alkaloids

(1) Muscarine is used experimentally to investigate muscarinic receptors.

(2) Pilocarpine

(a) A tertiary amine

(b) Can enter the central nervous system (CNS)

Pilocarpine and nicotine cross BBB.

(c) Used to treat glaucoma and increase secretions

Pilocarpine used to treat glaucoma and increase secretions.

c. Synthetic drugs

(1) Cevimeline, a tertiary amine

(2) Binds to muscarinic receptors

(3) Causes an increase in secretion of exocrine glands (including salivary glands)

2. Mechanism of action

• Directly stimulate muscarinic receptors

a. Bethanechol (selectively acts on smooth muscle of the gastrointestinal tract and the urinary bladder)

(1) Urinary retention in the absence of obstruction

(2) Postoperative ileus

(3) Gastric atony and retention after bilateral vagotomy

Bethanechol used to get GI and GU going.

(1) Glaucoma (ophthalmic preparation)

(2) Xerostomia (dry mouth)

• Given orally to stimulate salivary gland secretion

c. Cevimeline used to treat dry mouth in Sjögren’s syndrome

Pilocarpine and cevimeline used to increase secretions.

4. Adverse effects

a. Due to overstimulation of parasympathetic effector organs

b. Treatment of overdose

(1) Atropine to counteract muscarinic effects

(2) Epinephrine to overcome severe cardiovascular reactions or bronchoconstriction

Overdoses of muscarinic agonists can be treated with atropine and/or epinephrine.

B. Cholinesterase inhibitors (Box 4-2; Fig. 4-1; see also Fig. 3-2A)

1. Pharmacokinetics

a. Edrophonium is rapid and short-acting (i.e., effects last only about 10 minutes after injection).

b. Physostigmine crosses the BBB.

c. Drugs used in Alzheimer’s disease cross the BBB.

2. Mechanism of action

a. Bind to and inhibit AChE, increasing the concentration of acetylcholine (ACh) in the synaptic cleft

b. Stimulate responses at the muscarinic receptors as well as nicotinic receptors

c. Stimulate responses at nicotinic receptors at the neuromuscular junction (NMJ), in the ganglia at higher doses and, those that cross the BBB, in the brain

4-1 Interaction of acetylcholine (ACh), physostigmine, or isoflurophate (DFP) with the serine (Ser) hydroxyl at amino acid position 200 of the catalytic site of acetylcholine esterase (AChE).

AChE inhibitors used as drugs, insecticides and warfare agents.

3. Subsets of AChE inhibitors

a. Reversible inhibitors

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Tags: Rapid Review Pharmacology

Apr 8, 2017 | Posted by admin in PHARMACY | Comments Off

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