Nervous system drugs anticholinergics

III. Clinical presentation. Major toxicity is manifested in the cardiovascular and central nervous systems. Also, anticholinergic intoxication (see p 84) may occur as a result of ingestion of benztropine (Cogentin) or other co-administered drugs. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

Clinical trials of some of the more potent tertiary amines revealed these to exhibit marked psychotomimetic activity.11 Much subsequent work thus dealt with the quaternary salts which do not reach the central nervous system. Many of the uses of anticholinergic drugs involve "topical" application (e. g., interior of the stomach, intestine or bronchi) ... 

AChE, acetylcholinesterase CNS, central nervous system COPD, chronic obstructive pulmonary disease. PREPARATIONS AVAILABLE Antimuscarinic Anticholinergic Drugs ... 

Imipramine Mixed and variable blockade of NET and SERT Like SNRIs plus significant blockade of autonomic nervous system and histamine receptors Major depression not responsive to other drugs chronic pain disorders incontinence obsessive-compulsive disorder (clomipramine) Long half-lives CYP substrates active metabolites Toxicity Anticholinergic, G.-blocking effects, sedation, weight gain, arrhythmias, and seizures in overdose Interactions CYP inducers and inhibitors... 

Anticholinergic Drugs that decrease activity at acetylcholine synapses. These agents are often used to diminish activity in the parasympathetic nervous system (SYN parasympatholytic). 

Tertiary-amine muscarinic receptor antagonists gain access to the central nervous system and are therefore the anticholinergic drugs used to treat parkinsonism and the extrapyramidal side effects of antipsychotic drugs. Specific agents used primarily for these conditions include benztropine mesylate (Cogentin) and trihexyphenidyl hydrochloride (Artane, others). 

Central nervous system depressants include the barbiturates, such as phenobarbital, and the antianxiety drugs, including diazepam (VaUum), chlordiazepoxide Odbrium), oxazepam (Serax), flurazepam hydrochloride (Dalmane), and lorazepam (Ativan). The benzodiazepines, including diazepam, occasionally cause mydriasis, presumably because of their anticholinergic side effects. 

Two Japanese primigravidae, aged 25 and 28 years, developed the HELLP syndrome, a severe variant of preeclampsia in which there is Hemolysis, Elevated Liver enzymes, and a Low Platelet count (4). They were given parenteral hyoscine butylbromide for abdominal pain and had seizures 60-90 minutes later. One died from intracerebral hemorrhage some days later and the other survived after a cesarean section soon afterward. The authors speculated that anticholinergic drugs may enhance sympathetic nervous system activity, and in particular vasoconstriction, and should be avoided in pre-eclampsia. It is not clear how widespread their use is... 

Also note that the potential for an interaction between drugs does not preclude their concurrent use. Certain combinations are routinely prescribed without problems in many patients (as with lithium and antipsychotics), whereas others are contraindicated due to the severity of the interaction (for example, MAOIs and SSRIs). However, whenever psychiatric medications are coadministered, the additive potential of central nervous system depression and anticholinergic effects must be considered. 

Terfenadine binds to peripheral H-1 receptors. Receptor affinity for muscarinic, a, and /i-adrenergic receptors is low. Poor penetration of terfenadine across the blood-brain barrier limits central nervous system effects. Therefore, terfenadine is classified as nonsedating and lacks anticholinergic side effects. However, accumulation of the parent drug, terfenadine, results in prolongation of the QT interval by blocking the delayed rectifier potassium current in the heart. Prolongation of the QT interval can lead to torsade de pointes and death. 

Note Physostigmine is used to reverse the effect upon the nervous system caused by clinical or toxic dosages of drugs and herbs capable of producing the anticholinergic syndrome. 

---