Phenothiazines Clonidine

A. G. Gallanosa, D. A. Spyker, J. R. Shipe and D. L. Morris, Human xylazine overdose a comparative review with clonidine, phenothiazines, and tricyclic antidepressants, J. Toxicol. Clin. Toxicol., 1981,18, 663-678. 

Medications (analgesics, anticholinergerics, calcium channel blockers, clonidine, diuretics, phenothiazines, tricyclic antidepressants, iron supplements, calcium- and aluminum-containing antacids)... 

Drugs that may be affected by beta blockers include flecainide, gabapentin, haloperidol, hydralazine, phenothiazines, anticoagulants, benzodiazepines, clonidine, disopyramide, epinephrine, ergot alkaloids, lidocaine, nondepolarizing muscle relaxants, prazosin, sulfonylureas, and theophylline. 

Uses Endogenous depression Action TCA T synaptic CNS levels of serotonin /or norepinephrine Dose Adults. 25 mg PO tid-qid >150 mg/d not OK Elderly. 10-25 mg hs Peds. 6-7 y 10 mg/d 8-11 y 10-20 mg/d >11 y 25-35 mg/d, 4- w/ hepatic insuff Caution [D, +/-] NAG, CV Dz Contra TCA allergy, use w/ MAOI Disp Caps, soln SE Anticholinergic (blurred vision, retention, xerostomia) Interactions T Effects W/ antihistamines, CNS depressants, cimetidine, fluoxetine, OCP, phenothiazine, quinidine, EtOH T effects OF anticoagulants T risk of HTN W/clonidine, levodopa, sympathomimetics T effects W/barbiturates, carbamazepine, rifampin EMS Concurrent use w/ MAOIs have resulted in HTN,... 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

If these measures fail, clonidine, fluphenazine, clonazepam, or carbamazepine should be tried. The pharmacologic properties of these drugs are discussed elsewhere in this book. Clonidine reduces motor or vocal tics in about 50% of children so treated. It may act by reducing activity in noradrenergic neurons in the locus coeruleus. It is introduced at a dose of 2-3 mcg/kg/d, increasing after 2 weeks to 4 mcg/kg/d and then, if required, to 5 mcg/kg/d. It may cause an initial transient fall in blood pressure. The most common adverse effect is sedation other adverse effects include reduced or excessive salivation and diarrhea. Phenothiazines such as fluphenazine sometimes help the tics, as do dopamine... 

Some toxicants that affect body temperature are shown in Figure 6.11. Among those that increase body temperature are benzadrine, cocaine, sodium fluoroacetate, tricyclic antidepressants, hexachlorobenzene, and salicylates (aspirin). In addition to phenobarbital and ethanol, toxicants that decrease body temperature include phenothiazine, clonidine, glutethimide, and haloperidol. 

Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA concentrations Cimetidine may increase plasma concentrations of TCAs and cause anticholinergic symptoms Phenothiazines or haloperidol may raise TCA blood concentrations May alter effects of antihypertensive drugs may inhibit hypotensive effects of clonidine Use of TCAs with sympathomimetic agents may increase sympathetic activity Methylphenidate may inhibit metabolism of TCAs... 

Clinically important, potentially hazardous interactions with albuterol, alcohol, clonidine, corticosteroids, danazol, diuretics, epinephrine, estrogens, isoniazid, lithium, oral contraceptives, pentamidine, phenothiazines, propranolol, somatropin, terbutaline, thyroid... 

Although phenothiazines, clonidine, carbamazepine, y-hydroxybutyric acid, and valproic acid may reduce symptoms of alcohol withdrawal, their ability to prevent seizures or delirium tremens has yet to be proven, and in fact, the phenothiazines may lower the seizure threshold. Other drugs used to treat symptoms of alcohol withdrawal include other barbiturates, alcohol itself, sympatholytics such as atenolol, thiamine, magnesium, and other neuroleptics such as haloperidol. At the time of this writing, gabapentin is being compared to lorazepam for acute alcohol withdrawal in a phase II clinical trial. 

Sympatholytic syndrome. Blood pressure and pulse rate are both decreased (peripheral alpha blockers may cause hypotension with reflex tachycardia). The pupils are small, often of pinpoint size. Peristalsis is often decreased. (Examples centrally acting alpha-2 agonists [clonidine and methyidopa], opiates, and phenothiazines.)... 

Opioids (especially methadone and heroin) are the most common cause of serious neonatal drug withdrawal symptoms. Other dmgs for which a withdrawal syndrome has been reported include phencyclidine (POP), cocaine, amphetamines, tricyclic antidepressants, phenothiazines, benzodiazepines, barbiturates, ethanol, clonidine, diphenhydramine, lithium, meprobamate, and theophylline. A careful dmg history from the mother should include illicit drugs, alcohol, and prescription and over-the-counter medications, and whether she is breast-feeding. 

The hypotensive adverse effects of the phenothiazines, and possibly haloperidol may be additive with the antihypertensive effects of clonidine. Patients may feel faint and dizzy if they stand up quickly. 

The increased hypotension and orthostasis that can occur if phenothiazines are used with antihypertensive drugs such as clonidine is established. Note that, of the phenothiazines, levomepromazine is particularly associated with postural hypotension. One report suggests that haloperidol may interact similarly. Monitor, particularly during the initial stages of concurrent use, and warn patients that if they feel faint and dizzy they should lie down, and that they should remain lying down until symptoms abate completely. Dosage adjustment may be necessary. 

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