Orthostatic antagonism

Orthostatic hypotension and resultant syncope, a common and potentially serious adverse effect of the TCAs, occurs as a result of cq-adrenergic antagonism. Additional side effects include cardiac conduction delays and heart block, especially in patients with preexisting conduction disease. 

Adrenergic Alpha lA receptor ADRAIA Agonism Smooth muscle contraction (prostate in particular, effects on the lower urinary tract) and cardiac positive ionotropy, arrhythmia. Antagonism Orthostatic hypotension and other blood pressure related adverse effects and impact on various aspects of sexual function. 

The TCA drugs have lost their place as first-line therapy for depression because of their bothersome side effects (Table 33.2) at therapeutic doses and lethal effects in toxic doses. In addition to their presynaptic effects on the neuronal uptake of norepinephrine and serotonin, they block several postsynaptic receptors. They are potent cholinergic muscarinic receptor antagonists, resulting in symptoms such as dry mouth, constipation, tachycardia, blurred vision and urinary retention. Blockade of histamine receptors (Hi) often results in sedation and weight gain. Antagonism of aj-adrenoceptors in the vasculature can cause orthostatic hypotension. 

Histamine blockade is responsible for the sedation associated with trazodone. Furthermore, priapism and orthostatic hypotension are mediated by a-adrenergic antagonism. There have been over 200 case reports of priapism (Thompson et ah, 1990). Prevalence estimates of priapism suggest that 1/6000 men treated with trazodone will be affected. Other side effects include dry mouth, nausea, and vomiting. Because of trazodone s wide therapeutic window, it is relatively safe in overdosage. There are case reports of patients surviving intentional overdoses of up to 9 (Gamble and Peterson,... 

Cardiovascular effects. Given aj-adrenergic receptor antagonism, quetiapine may induce orthostatic hypotension and concomitant symptoms of dizziness, tachycardia, and syncope. The risk of symptomatic hypotension is particularly pronounced during initial dose titration. Quetiapine should be used with caution in patients with cardiovascular disease, cerebrovascular disease, or other illnesses predisposing to hypotension. 

Diphenhydramine Competitive antagonism at Hi receptors Reduces or prevents histamine effects on smooth muscle, immune cells also blocks muscarinic and adrenoceptors highly sedative IgE immediate allergies, especially hay fever, urticaria some use as a sedative, antiemetic, and antimotion sickness drug Oral and parenteral t duration 4-6 h Toxicity Sedation when used in hay fever, muscarinic blockade symptoms, orthostatic hypotension Interactions Additive sedation with other sedatives, including alcohol some inhibition of CYP2D6, may prolong action of some 13 blockers... 

Reuptake Antagonism Norepinephrbie Serotonin Anticholinergic Effects Sedation Orthostatic Hypotension Seizures" Conduction Abnormalities"... 

Second-generation agents include prazosin, terazosin, doxazosin, and alfuzosin. These differ in terms of duration of action and dosing schedule. Whereas prazosin requires dosing two to three times a day, terazosin, doxazosin, and alfuzosin offer more convenient once-daUy dosing. Prazosin, terazosin, and doxazosin antagonize peripheral vascular ai-adrenergic receptors, in addition to those in the prostate, at the usual doses used to treat BPH. As a result, first-dose syncope, orthostatic hypotension, and dizziness are... 

I. Mechanism of toxicity. PNU is believed to antagonize the actions of nicotinamide and, in a manner similar to that of alloxan and streptozocin, injure pancreatic beta cells. The mechanisms of autonomic neuropathy and central nervous system effects are unknown. Adrenergic neurons acting on blood vessels but not the heart are affected. As a result, orthostatic hypotension associated with an intact reflex tachycardia is the usual picture. 

The manufacturers of clonidine note that a reduced antihypertensive effect may occur with antipsychotics with alpha-blocking properties (e.g. ehlorpromazine), as well as mentioning the risk of orthostatic hypotension.Consider also Clonidine + Tricyclic and related antidepressants% p.884. Although antagonism of the antihypertensive effect of clonidine has been seen in animals given ehlorpromazine, there appear to be no clinical reports. 

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