Cholinergic blocking drugs

Cholinergic blocking drugs

Cholinergic blocking drugs interrupt parasympathetic nerve im-pulses 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 mus-carine and blocked by atropine.

First come the belladonna alkaloids

The major cholinergic blocking drugs are the belladonna alka-loids:

·                 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:

·                 benztropine

·                 dicyclomine

·                 oxybutynin

·                 trihexyphenidyl

·                 tolterodine.

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 chap-ter 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 be-gin to work immediately.

Distribution

The belladonna alkaloids are distributed more widely throughout the body than the quaternary ammonium derivatives or dicyclo-mine. 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 bel-ladonna 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, de-pending on the dosage and the condition being treated.

Dual duty

Cholinergic blockers can produce a stimulating or depressing ef-fect, 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 character-ized 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 com-plications.

·                 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 ammo-nium 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 col-ic (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

The belladonna alkaloids can affect the brain. For example,scopolamine, given with the pain relievers morphine or meperidine, causes drowsiness and amnesia in a patient having surgery. It’s also used to treat motion sickness.

Belladonna alkaloids also have important therapeutic effects on the heart. Atropine is the drug of choice to treat:

·                 symptomatic sinus bradycardia—when the heart beats too slow-ly, causing low blood pressure or dizziness (see How atropinespeeds the heart rate)

·                 arrhythmias resulting from the use of anesthetics, choline es-ters, 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 ad-verse 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 thio-xanthenes

§    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 pyridostig-mine.

Mixing it up some more

Other drug interactions can occur:

·                  The risk of digoxin toxicity increases when digoxin is taken with a cholinergic blocker. Opiate-like analgesics further slow the movement of food and drugs through the GI tract when taken with a cholinergic blocker.

·                 The absorption of nitroglycerin tablets placed under the tongue is reduced when this drug is taken with a cholinergic blocker. (See Adverse reactions to cholinergic blockers.)