Antimuscarinic agents

Motilium contains domperidone, v/hich is a dopamine antagonist and acts on the chemoreceptor trigger zone. It is ineffective in motion sickness. Stugeron contains cinnarizine Avomine and Phenergan contain promethazine and Kwells contains hyoscine hydrobromide. Cinnarizine and promethazine are antihistamines, which are indicated in motion sickness and hyoscine hydrobromide is an antimuscarinic agent that is also used in motion sickness. 

Buscopan is a branded preparation containing hyoscine butylbromide, an antimuscarinic agent that reduces gastrointestinal motility. Antimuscarinic agents are contraindicated in cases of angle-closure glaucoma as they may aggrevate the condition. Hyoscine butylbromide is a quaternary ammonium compound, unlike atropine, which is a tertiary ammonium compound. 

Ipratropium bromide is an antimuscarinic agent indicated in asthma and in chronic obstructive pulmonary disease but it is more effective in the latter. The drug is available only for inhalation because of the potential side-effects if given orally. 

Co-careldopa is a combination of levodopa and the peripheral dopadecar-boxylase inhibitor. Co-careldopa is indicated in Parkinson s disease to improve bradykinesia and rigidity rather than tremor. Orphenadrine is an antimuscarinic agent indicated in patients with Parkinson s disease where tremor predominates. Trifluoperazine is a piperazine antipsychotic that should be used with caution in patients with Parkinson s disease as its use may exacerbate the condition. 

Pharmacology Trospium is an antispasmodic, antimuscarinic agent. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium increases maximum cystometric bladder capacity and volume at first detrusor contraction. 

Pharmacology Tiotropium is a long-acting, antimuscarinic agent, which is often... 

The control of access to muscarinic receptors in the central nervous system (CNS) by a tertiary amine versus quaternary ammonium group is fundamentally important in selecting among antimuscarinic agents. 

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. 

B. Although scopolamine effectively combats motion sickness, it is an antimuscarinic agent, not an antihistamine. Dimenhydrinate is an antihistamine with signihcant antimuscarinic properties that are likely to contribute to its anti-motion sickness activity. Chlorpheniramine, fexofenadine, and tripelennamine are antihistamines without signihcant efficacy in the treatment of motion sickness. 

Prostatic hyperplasia Antimuscarinic agents Urinary retention... 

Quaternary amine antimuscarinic agents (Figure 8-2) have been developed to produce more peripheral effects with reduced CNS effects. 

Most blood vessels receive no direct innervation from the parasympathetic system. However, parasympathetic nerve stimulation dilates coronary arteries, and sympathetic cholinergic nerves cause vasodilation in the skeletal muscle vascular bed (see Chapter 6). Atropine can block this vasodilation. Furthermore, almost all vessels contain endothelial muscarinic receptors that mediate vasodilation (see Chapter 7). These receptors are readily blocked by antimuscarinic drugs. At toxic doses, and in some individuals at normal doses, antimuscarinic agents cause cutaneous vasodilation, especially in the upper portion of the body. The mechanism is unknown. 

Imipramine, a tricyclic antidepressant drug with strong antimuscarinic actions, has long been used to reduce incontinence in institutionalized elderly patients. It is moderately effective but causes significant CNS toxicity. Propiverine, a newer antimuscarinic agent, has been approved for this purpose. 

Antimuscarinic agents have also been used in urolithiasis to relieve the painful ureteral smooth muscle spasm caused by passage of the stone. However, their usefulness in this condition is debatable. 

Hyperhidrosis (excessive sweating) is sometimes reduced by antimuscarinic agents. However, relief is incomplete at best, probably because apocrine rather than eccrine glands are usually involved. 

Because the antimuscarinic drugs slow gastric emptying, they may increase symptoms in patients with gastric ulcer. Nonselective antimuscarinic agents should never be used to treat acid-peptic disease (see Chapter 62). 

Short-term relief is thus most effectively achieved by agents that relax airway smooth muscle, of which B-adrenoceptor stimulants (see Chapter 9) are the most effective and most widely used. Theophylline, a methylxanthine drug, and antimuscarinic agents (see Chapter 8) are also used for reversal of airway constriction. 

Observation of the use of leaves from Datura stramonium for asthma treatment in India led to the discovery of atropine, a potent competitive inhibitor of acetylcholine at postganglionic muscarinic receptors, as a bronchodilator. Interest in the potential value of antimuscarinic agents increased with demonstration of the importance of the vagus nerves in bronchospastic responses of laboratory animals and by the development of a potent atropine analog that is poorly absorbed after aerosol administration and that is therefore relatively free of systemic atropine-like effects. 

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