Anticholinergic Drugs

“Understand that we’re talking about drugs that are competitive reversible antagonists of atropine and choline at the muscarinic receptor”

If we were to spray some acetylcholine into a pt’s bronchial tree you’d get bronchoconstriction. That can be measured precisely with pulmonary devices. If we do a dose response curve for acetylcholine, there will be a certain point were you start to get significant bronchoconstriction, then no matter how much more you place into the lungs, the receptors are saturated and no more effects will be seen. Now, what if we were to let all of the acetylcholine wash out, and pre-treat the patient with an anticholinergic drug, like atropine? Depending on the dose of atropine, the dose is shifted parallel and to the right. The characteristic of the dose response curve is that it is parallel to the agonist curve, which is good evidence that we’re dealing with a competitive receptor antagonist. This is dose dependent, the more atropine is taken, the more acetylcholine will need to be taken in order to see effects. Theoretically, if the pt is on atropine you could reverse this effect by giving more acetylcholine… if more ACh flows in it will displace the antagonist and you’ll be back to a normal condition. The effects of competitive receptor antagonists is surmountable if you add it up.

“Indications” is a more precise term than “uses” when referring to pharmacology,. We’ve discussed Scopolamine, which is a Belladonna alkaloid (alkaloid means nitrogen containing molecule). Scopolamine’s major use is to combat motion sickness. It is able to penetrate the brain and get to the parts that control vestibular function and is very effective—however because it is also a non-selective muscarinic blocker it will produce other classic anti-cholinergic side effects. Scopolamine used to be used as a form of anesthesia prior to surgery to achieve a dry trachea for anesthesiologists to get a dry field to place an endotracheal tube for inhalation and ventilation during surgery. This is no longer done because it causes a very profound dryness. Scopolamine also had a unique effect on the CNS and as a result the pt had a sort of ‘twilight sleep’ characteristic of the belladonna alkaloid.

Benztopine and Trihexyphenidyl are used for Parkinson’s Disease. Parkinson’s is a deficiency of dopaminergic function in the basal ganglion. These drugs have nothing to do with dopamine or dopamine receptors, yet relative to managing the pt’s symptoms there is a good rationale.

Mydriatics and cycloplegics are used in the optometrist’s office, as a result of these drugs you get profound pupillary dilation. In terms of how we’ll use these drugs, the pupil dilation and ciliary effects are not desirable.

The antispasmotic blocks the spasm of smooth muscle. Almost exclusively used to describe those drugs that diminish the contractility of smooth muscle. Don’t apply that to venous, arterial, or bronchial smooth muscle. The term antispasmotic refers to the muscles of the gut and biliary tract, for example. Or the ureal smooth muscle. These are commonly prescribed agents because of their ability to diminish the spasm associated with overactivity of the cholinergic system—people who have severe gut pain or muscle pain in their abdominal cavity can take a dose to relieve this. But of course there are other effects such as xerostomia and effects on the eye. Listed under antispasmotics is Propantheline, that’s really not the place to put this drug (Dr. Levi did some of the original work on this drug ). Propantheline was used in the 1960s and 70s prior to the intro of the H2 blockers, to combat peptic ulcers. We’ll talk about this drug’s use in dentistry because it has an antisialogogue effect (less salivation).

Urinary incontinance—the urinary bladder is rich in cholinergic pathways. You’ll see commonly in post-menopausal women, who have an emotional physiologic disorder due to their incontinence. The pt will take a drug such as Oxybutynin which will help her urinary problems, but will also have tremendous effects in the oral cavity (xerostomia).

Chronic Obstructive Pulmonary Disease (asthma, bronchitis) will be spoken about later when we turn to the handout. In the bronchial tree there is dual innervation; with regard to the adrenergic side of the pulmonary innervation we have a lot of beta2 receptors, commonly we’ll give a beta2 agonist to produce bronchodilation. On the other hand bronchial smooth muscle also has muscarinic effectors, stimulation of these receptors causes bronchoconstriction, the opposite effect. So clearly the rationale of using an anticholinergic drug that would be very selective for the pulmonary tree would be good. One of the most commonly prescribed drugs for this is Ipatropium bromide (brand name Atrovent). This is an anticholinergic drug and is inhaled, it acts as a bronchodilator but is totally unrelated to beta2 agonists that are prescribed for COPD. Atrovent is also prescribed for rhinorrhea (runny nose).

The antidote for mushroom poisoning is Atropine. Its also an effective antidote for anticholinesterase pesticides. These organo-phospate anticholinesterase pesticides aren’t used any more. Also, there are muscarinic receptors in the heart, so atropine and other drugs can be used to manage arrhythmias or dysrrhythmias. So the cholinergic antagonists are used for a wide number of things.

Ganglionic blockers affect ganglionic transmission. Used to have a role in tx of HTN. Trimethaphan is given via injection for fast acting malignant HTN by interfering with sympathetic ganglionic transmission. Basically, these drugs are only of historical interest. Ganglionic receptors work at the ganglia!

Category: Pharmacology Notes