Drugs antimuscarinic

The antimuscarinic drug atropine, and its derivative ipratropiumbromide, can also be used for antiarrhyth-mic treatment. Muscarinic receptors (M2 subtype) are mainly present in supraventricular tissue and in the AV node. They inhibit adenylylcyclase via G proteins and thereby reduce intracellular cAMP. On the other hand, activation of the M2 receptor leads to opening of hyperpolarizing Ik.acii and inhibits the pacemaker current If probably via the (3y-subunit of the Gi protein associated with this receptor. The results are hyperpolarization and slower spontaneous depolarization. Muscarinic receptor antagonists like atropine lead to increased heart rate and accelerated atrioventricular conduction. There are no or only slight effects on the ventricular electrophysiology. 

Antimuscarinic drugs such as atropine have been used to modest effect in the treatment of PD for more than a century attenuating tremor and rigidity but with little effect on akinesia. Currently benzhexol and benztropine are sometimes added to levodopa therapy but peripheral effects such as dry mouth, blurred vision and constipation are unpleasant. They are also often used to counteract neuroleptic-induced extrapyramidal effects. 

It has been known for many years that antimuscarinic drugs like hyoscine, which enter the brain, cause amnesia when used clinically, e.g. pre-operatively, to reduce bronchial secretions. In experimental studies in both humans and animals they disrupt both the acquisition and the performance of learned behaviour. Anti-cholinestrase drugs have the opposite effect. It is by no means certain, however, that the memory defects induced by antimuscarinics are identical to those seen in AzD. 

Which of the following antimuscarinic drugs is used by inhalation in the treatment of bronchial asthma ... 

The answer is c. (Hardman, pp 156-158.) A wide variety of clinical conditions are treated with antimuscarinic drugs. Dicyclomine hydrochloride and methscopolamine bromide are used to reduce Gl motility, although side effects—dryness of the mouth, loss of visual accommodation, and difficulty in urination—may limit their acceptance by patients. Cyclopentolate hydrochloride is used in ophthalmology for its mydriatic and cycloplegic properties during refraction of the eye. Trihexyphenidyl hydrochloride is one of the important antimuscarinic compounds used in the treatment of parkinsonism. For bronchodilation in patients with bronchial asthma and other bronchospastic diseases, ipratropium bromide is used by inhalation. Systemic adverse reactions are low because the actions are largely confined to the mouth and airways. 

Overton DA (1969) Control of T-maze choice by nicotinic, antinicotinic, and antimuscarinic drugs. 

Digoxin (cardiac glycoside) and trihexyphenidyl (antimuscarinic drug) must be used with caution in elderly patients. Low doses are recommended in elderly patients to avoid toxicity. Lactulose may be safely administered to elderly patients with constipation. 

Sympathomimetics, such as dobutamine and isoprenaline, mimic the sympathetic system. Orphenadrine is an antimuscarinic drug acting as an antagonist to the parasympathetic system. 

Furthermore, central-acting antimuscarinic drug are effective in the treatment of motion sickness. In this indication the alkaloid scopolamine has been shown to be effective. It can be applied orally, intra venously or via a transdermal therapeutic system. 

Antimuscarinic drugs block contraction of the iris sphincter and ciliary muscles of the eye produced by ACh. This results in dilation of the pupil (mydriasis) and paralysis of accommodation (cycloplegia), responses that cause photophobia and inability to focus on nearby objects. Ocular effects are produced only after higher parenteral doses. Atropine and scopolamine produce responses lasting several days when applied directly to the eyes. 

Antimuscarinic drugs are widely used in ophthalmology to produce mydriasis and cycloplegia. These actions permit an accurate determination of the refractive state of the eye, and the antimuscarinics are also useful in treating specific ocular diseases and for the treatment of patients following iridectomy. 

Atropine, scopolamine, cyclopentolate Cyclogyl, AK-Pentolate, and others) and tropicamide Mydriacyl, Tropicacyl, and others) are among the antimuscarinic drugs used in ophthalmology. All of these agents are tertiary amines that reach the iris and ciliary body after... 

Nonselective antimuscarinic drugs have been employed in the therapy of peptic ulcers (see Chapter 40) because they can reduce gastric acid secretion they also have been used as adjunctive therapy in the treatment of irritable bowel syndrome. Antimuscarinic drugs can decrease the pain associated with postprandial spasm of intestinal smooth muscle by blocking contractile responses to ACh. Some of the agents used for this disorder have only antimuscarinic activity (e.g., propantheline), while other drugs have additional properties that contribute to their antispasmodic action. Dicyclomine (Bentyl) and oxybutynin (Ditropan) at therapeutic concentrations primarily have a direct smooth muscle relaxant effect with little antimuscarinic action. 

Antimuscarinic poisoning can result from the intake of excessive doses of belladonna alkaloids, synthetic antimuscarinic drugs, and drugs from other pharmacological groups that have significant antimuscarinic activity (Table 13.2). 

CASE Study The Risks of Treating Peptic Uicers with Antimuscarinic Drugs... 

A 55-year-old man who works in the furnace room at a steel foundry has developed chronic peptic ulcer disease that has not responded to treatment with antibiotics and H2 receptor blockers. You are considering giving him an antimuscarinic drug to block gastric acid secretion as adjunctive therapy. What are your concerns regarding the suitability of this treatment for this worker ... 

Signs of parkinsonism—akinesia, tremor, rigidity— can develop gradually, but this reaction usually responds favorably to central antimuscarinic agents. As with dystonia, parkinsonism may subside, permitting withdrawal of the antimuscarinic drug. 

If muscarinic effects of such therapy are prominent, they can be controlled by the administration of antimuscarinic drugs such as atropine. Frequently, tolerance to the muscarinic effects of the cholinesterase inhibitors develops, so atropine treatment is not required. 

Structures of some semisynthetic and synthetic antimuscarinic drugs. 

Natural alkaloids and most tertiary antimuscarinic drugs are well absorbed from the gut and conjunctival membranes. When applied in a suitable vehicle, some (eg, scopolamine) are even absorbed across the skin (transdermal route). In contrast, only 10-30% of a dose of a quaternary antimuscarinic drug is absorbed after oral administration, reflecting the decreased lipid solubility of the charged molecule. 

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