Adrenergic Side Effects

Antipsychotics block aj-adrenergic receptors, which can result in orthostatic hypotension and dizziness. Administration of epinephrine, which stimulates both a- and P-adrenergic receptors, will result in a paradoxical decrease in blood pressure because of the stimulation of P-adrenergic receptors in the presence of aj-adrenergic receptor blockade. 

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Olanzapine is metabolized by several pathways and is therefore unlikely to be affected by concurrent administration of other medications. Because olanzapine does not appear to inhibit any cytochrome P450 enzymes, it should not increase the availability of other medications through inhibition of such enzymes. Additive pharmacodynamic effects are expected if olanzapine is combined with medications that also have anticholinergic, antihistaminic, or aj-adrenergic side effects. 

Quetiapine is metabolized by hepatic CYP 3A3/4. Concurrent administration of cytochrome P450-inducing drugs, such as carbamazepine, decreases blood levels of quetiapine. In such circumstances, increased doses of quetiapine are appropriate. Quetiapine does not appreciably affect the pharmacokinetics of other medications. Pharmacodynamic effects are expected if quetiapine is combined with medications that also have antihistaminic or a-adrenergic side effects. Because of its potential for inducing hypotension, quetiapine also may enhance the effects of certain antihypertensive agents. 

Because of the widespread nature of adrenoceptors, nonselective P-agonists can produce many undesirable side effects. Therefore, before adrenergic agonists could become widely used in the treatment of asthma, some selectivity in action was needed. Whereas epinephrine and ephedrine have significant agonist activity at both a and P adrenoceptors, isoproterenol is a selective agonist at the P receptor (39). However, isoproterenol does not distinguish between the P and receptors and it is not active orally. 

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

Some of the side effects due to beta blockers such as the slowing of heart rate can be counteracted by administration of drugs which antagonize the alpha adrenergic receptors. The... 

Preventive measures for patients who may be prone to hypotension include accurate determination of the dry weight and maintaining a constant ultrafiltration rate. Midodrine is an a-adrenergic agonist that is effective in reducing hypotension in patients with autonomic dysfunction that is taken with each dialysis session or as chronic therapy. Midodrine can be administered at doses of 2.5 to 10 mg prior to HD or 5 mg twice daily for chronic hypotension. Side effects of midodrine include pruritus and paresthesias. 

The answer is c. (Hardman, pp 414-4163) Unwanted pharmacologic side effects produced by phenothiazine antipsychotic drugs (e.g., perphenazine) include Parkinson-like syndrome, akathisia, dystonias, galactorrhea, amenorrhea, and infertility. These side effects are due to the ability of these agents to block dopamine receptors. The phenothiazines also block muscarinic and a-adrenergic receptors, which are responsible for other effects. 

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. 

Amitriptyline, doxepin, and nortriptyline are effective, but side effects include anticholinergic effects, adrenergic blockade, and cardiac conduction prolongation. 

Trazodone, 25 to 100 mg, is often used for insomnia induced by selective serotonin reuptake inhibitors or bupropion. Side effects include serotonin syndrome (when used with other serotonergic drugs), oversedation, a-adrenergic blockade, dizziness, and rarely priapism. 

Clinical reports on minoxidil indicate that the drug is effective, particularly in cases which are refractory to other drugs (21. 22). It has the typical side-effects of a vasodilator and co-administration of a diuretic and a p-adrenergic blocker is recommended in many of the reported studies (21-28). 

Bretylium (L) showed selective adrenergic blocking activity in animals and man but erratic absorption and other side effects limited its utility in hypertension (61). 

Mirtazapine (Remeron) is a newer antidepressant that also blocks 5-HT reuptake, but additionally has antagonistic effects at adrenergic o2, 5-HT2, and 5-HT3 receptors (Stahl 1998). Mirtazapine appears to have indirect agonistic effects on 5-HTlA receptors, which may contribute to its antidepressant effect (Berendsen and Broekkamp 1997). Nefazodone, as well, has SSRI and 5-HT2 antagonist effects. The 5-HT2 antagonist effects of these antidepressants is believed to be responsible for their lower incidence of sexual side effects (Nutt 1997). 

The net result is that low potency antipsychotics cause more histamine-blocking, acetylcholine-blocking, and a-1 adrenergic blocking side effects. The high potency antipsychotics are more likely to produce dopamine-blocking side effects. Now, let s take a brief look at each of the specific medications. 

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