Cardiovascular anticholinergic drugs

Cardiovascular Among 82717 US veterans with a new diagnosis of COPD, who were followed until they had their first hospitalization for a cardiovascular event, or died, or reached the end of the study period, there were 6234 cardiovascular events (44% heart failure, 28% acute coronary syndrome, and 28% cardiac dysrhythmias) [27. The risk of cardiovascular events was increased in those who had used ipratropium in the past 6 months (HR=1.40 95% Cl = 1.3, 1.5). Among those who had used an anticholinergic drug more than 6 months before, there did not appear to be an increased risk of a cardiovascular event. This study was limited, owing to incomplete hospital admission data and lack of data on cardiovascular risk factors and severity of COPD. 

The risk of adverse cardiovascular events during the use of inhaled anticholinergic drugs was reviewed in SEDA-32 (p. 318). Further information has come to light in this controversial area. 

Tiotropium A potential association with cardiovascular risk has been suggested for long-acting anticholinergic drugs. In a 2-year randomized controlled study of the benefits of tiotropium versus fluticasone and salmeterol in 1323 patients with severe COPD, tiotropium was associated with significantly increased mortality (3% versus 6%), with an increase in cardiac events [86 ]. However, in a case series that specifically studied stroke in relation to tiotropium, there was no association [87 ]. 

Long-term safety of long-acting beta2-adrenoceptor agonists (LABAs)—an update 357 Cardiovascular risks of inhaled anticholinergic drugs 364... 

Anthracyclines, 25.533 Antiallergic drugs, ocular treatment, 11.420 Antibacterial drugs, resistance, 31.413, 32.445 intrapartum, 32.446 Anticancer antimetabolites, 29.531 Anticholinergic drugs, 22.507, 31.273 cardiovascular risks, 32.318 Anticoagulants, oral, skin necrosis, 29.358... 

A number of medications have been associated with an increased risk of falling, including drugs affecting mental status such as antipsychotics, benzodiazepines, tricyclic antidepressants, sedative-hypnotics, anticholinergics, and corticosteroids. Some cardiovascular and antihypertensive drugs also can contribute to falls, especially those causing orthostatic hypotension.9... 

Parasympatholytics (Anticholinergic Agents) Section 4 Drugs Acting on Cardiovascular Urinary System 161... 

Patients with cardiovascular disorders or those predisposed to anticholinergic adverse effects (e.g., elderly or diabetic patients) probably do best on drugs low in these effects (e.g., an SSRI, venlafaxine, or bupropion). 

These drugs are best avoided in patients with cerebrovascular, cardiovascular and hepatic disorders. Some sympathomimetic effects may occur, mainly mild tremor and occasionally cardiac arrhythmias. Apparent anticholinergic effects may also occur but these are the result of sympathetic potentiation in tissues with dual cholinergic/adrenergic innervation, e.g. pupil. Sympatholytic effects can also occur, principally postural hypotension, because of synthesis of relatively inactive false transmitters, e.g. octopamine, in nerve terminals following inhibition of MAO and activation of alternative metabolic pathways. 

A large number of prescription and nonprescription drugs, as well as a variety of plants and mushrooms, can inhibit the effects of acetylcholine at muscarinic receptors. Some drugs used for other purposes (eg, antihistamines) also have anticholinergic effects. Many of them have other potentially toxic actions. For example, antihistamines such as diphenhydramine can cause seizures tricyclic antidepressants, which have anticholinergic, quinidine-like, and a-blocking effects, can cause severe cardiovascular toxicity. 

Early signs of tricyclic antidepressant toxicity are due to anticholinergic effects and include tachycardia, mydriasis, dry mouth, low-grade fever, diminished bowel sounds, CNS excitation, and delirium. More serious toxicity is manifested by coma, respiratory depression, seizures, and cardiovascular toxicity including conduction disturbances, hypotension, ventricular arrhythmias, and asystole. Seizures cause hyperthermia, rhabdomyolysis, and metabolic acidosis. Clinical deterioration can be rapid and catastrophic in patients with tricyclic antidepressant overdose. Death most often occurs due to dysrhythmia and circulatory collapse. The typical therapeutic dose of a tricyclic antidepressant is 2-4 mg kg day Doses of 15-20 mg kg are potentially lethal. Therapeutic drug levels for most tricyclic antidepressants range from 100 to... 

The cardiovascular, CNS, and anticholinergic symptoms of phenothiazine toxicity are similar to, but generally much less severe than, those for the tricyclic antidepressants. Phe-nothiazines are relatively safe, and few deaths have occurred when toxic doses have been ingested alone. Much more severe toxicity occurs when phenothiazines are co-ingested with tricyclic antidepressant drugs or other CNS depressant drugs, such as ethanol, opioids, barbiturates, or benzodiazepines. 

Bupropion is a well-tolerated antidepressant. It is non-sedating and lacks the cardiovascular and anticholinergic side effects of tricyclic antidepressants. Bupropion s most commonly observed adverse effects are insomnia and dry mouth. The drug is also known to be associated with a low rate of seizures however, no seizure incidents were reported in the smoking cessation clinical trials. Other less frequently occurring side effects include nervous system disturbances (mainlytremor) and skin rashes (170,182). 

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