Cholinergic blocking drugs interrupt parasympathetic nerve impulses in the central and autonomic nervous systems. These drugs are also referred to as anticholinergic drugs because they prevent acetylcholine from stimulating cholinergic receptors.
Not all receptors are receptive
Cholinergic blocking drugs don’t block all cholinergic receptors, just the muscarinic receptor sites. Muscarinic receptors are cholinergic receptors that are stimulated by the alkaloid muscarine and blocked by atropine.
First come the belladonna alkaloids
The major cholinergic blocking drugs are the belladonna alkaloids:
- atropine (the prototype cholinergic blocking drug)
- belladonna
- homatropine
- hyoscyamine sulfate
- methscopolamine
- scopolamine.
Next come their synthetic sisters
Synthetic derivatives of these drugs (the quaternary ammonium drugs) include:
- glycopyrrolate
- propantheline.
And finally the tertiary and quaternary amines
The tertiary amines include:
Quaternary amines include one drug, trospium.
Atropine may also be used as an antidote for nerve agents (See the appendix, Vaccines and antidotes for biological and chemical weapons.)
Let’s talk about it later
Because benztropine and trihexyphenidyl are almost exclusively treatments for Parkinson’s disease, they’re discussed fully in chapter 3, Neurologic and neuromuscular drugs.
Pharmacokinetics
Here’s how cholinergic blockers move through the body.
Absorption
The belladonna alkaloids are absorbed from the:
- eyes
- GI tract
- mucous membranes
- skin.
The quaternary ammonium drugs and tertiary and quaternary amines are absorbed primarily through the GI tract, although not as readily as the belladonna alkaloids.
If you want it fast, go I.V.
When administered I.V., cholinergic blockers such as atropine begin to work immediately.
Distribution
The belladonna alkaloids are distributed more widely throughout the body than the quaternary ammonium derivatives or dicyclomine. The alkaloids readily cross the blood-brain barrier; the other cholinergic blockers don’t.
Metabolism and excretion
The belladonna alkaloids are only slightly to moderately protein-bound. This means that a moderate to high amount of the drug is active and available to produce a therapeutic response. The belladonna alkaloids are metabolized in the liver and excreted by the kidneys as unchanged drug and metabolites.
The quaternary ammonium drugs are a bit more complicated. Hydrolysis is a chemical process whereby a compound cleaved into two or more simpler compounds occurs in the GI tract and the liver; the drugs are excreted in feces and urine.
Dicyclomine’s metabolism is unknown, but it’s excreted equally in feces and urine.
Pharmacodynamics
Cholinergic blockers can have paradoxical effects on the body, depending on the dosage and the condition being treated.
Dual duty
Cholinergic blockers can produce a stimulating or depressing effect, depending on the target organ. In the brain, they do both’low drug levels stimulate, and high drug levels depress.
Conditional considerations
The effects of a drug on your patient are also determined by the patient’s disorder. Parkinson’s disease, for example, is characterized by low dopamine levels that intensify the stimulating effects of acetylcholine. Cholinergic blockers depress this effect. In other disorders, however, they stimulate the central nervous system.
Pharmacotherapeutics
Cholinergic blockers are often used to treat GI disorders and complications.
- All cholinergic blockers are used to treat spastic or hyperactive conditions of the GI and urinary tracts because they relax muscles and decrease GI secretions. These drugs may be used to relax the bladder and to treat urinary incontinence. The quaternary ammonium and amine compounds such as propantheline are the drugs of choice for these conditions because they cause fewer adverse reactions than belladonna alkaloids.
- Belladonna alkaloids are used with morphine to treat biliary colic (pain caused by stones in the bile duct).
- Cholinergic blocking drugs are given by injection before such diagnostic procedures as endoscopy and sigmoidoscopy to relax the GI smooth muscle.
Before surgery
Cholinergic blockers such as atropine are given before surgery to:
- reduce oral, gastric, and respiratory secretions
- prevent a drop in heart rate caused by vagal nerve stimulation during anesthesia.
Brainy belladonna
Belladonna alkaloids also have important therapeutic effects on the heart. Atropine is the drug of choice to treat:
- arrhythmias resulting from the use of anesthetics, choline esters, or succinylcholine.
An eye on the problem
Cholinergic blockers also are used as cycloplegics. That means that they:
- paralyze the ciliary muscles of the eye (used for fine focusing)
- alter the shape of the eye lens.
Moreover, cholinergic blockers act as mydriatics to dilate the pupils, making it easier to measure refractive errors during an eye examination or to perform eye surgery.
Punishing pesticides
The belladonna alkaloids, particularly atropine and hyoscyamine, are effective antidotes to cholinergic and anticholinesterase drugs. Atropine is the drug of choice to treat poisoning from organophosphate pesticides. Atropine and hyoscyamine also counteract the effects of the neuromuscular blocking drugs by competing for the same receptor sites.
Drug interactions
Because cholinergic blockers slow the passage of food and drugs through the stomach, drugs remain in prolonged contact with the mucous membranes of the GI tract. This increases the amount of the drug that’s absorbed and, therefore, increases the risk of adverse effects.
Increased effect…
Drugs that increase the effects of cholinergic blockers include:
- disopyramide
- antidyskinetics such as amantadine
- antiemetics and antivertigo drugs, such as buclizine, cyclizine, meclizine, and diphenhydramine
- antipsychotics, such as haloperidol, phenothiazines, and thioxanthenes
- cyclobenzaprine
- orphenadrine
- tricyclic and tetracyclic antidepressants.
…or decreased effect
Drugs that decrease the effects of cholinergic blockers include:
- cholinergic agonists such as bethanechol
- anticholinesterase drugs, such as neostigmine and pyridostigmine.
Mixing it up some more
Other drug interactions can occur: