Tricyclic antidepressants amphetamines

Because neuronal uptake is necessary for the hypotensive activity of guanethidine, drugs that block the catecholamine uptake process or displace amines from the nerve terminal (see Chapter 6) block its effects. These include cocaine, amphetamine, tricyclic antidepressants, phenothiazines, and phenoxybenzamine. 

All the major oxidative mechanisms can be illustrated by considering the metabolism of the barbiturates, benzodiazepines, amphetamines, tricyclic antidepressants, phenothiazines, and opiates. 

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. 

Cocaine and desipramine inhibit the reuptake of monoamine neurotransmitters whereas amphetamine, which is a phenylalkylamine - similar in structure to the catecholamines, see Fig. 4 - competes for uptake and more importantly, evokes efflux of the monoamine neurotransmitters. All of them exert antidepressant effects. Cocaine and amphetamine are addictive whereas tricyclic antidepressants and their modern successors are not. The corollaty of the addictive properties is interference with DAT activity. Blockade of DAT by cocaine or efflux elicited by amphetamine produces a psychostimulant effect despite the different mechanisms even the experienced individual can hardly discern their actions. Because of the risk associated with inhibiting DAT mediated dopamine clearance the antidepressant effects of psychostimulants has not been exploited. 

The amphetamines and the anorexiants should not be given during or within 14 days after administration of monoamine oxidase inhibitors (see Chap. 31) because the patient may experience hypertensive crisis and intracranial hemorrhage. When guanethidine is administered with the amphetamines or the anorexiants, the antihypertensive effect of guanethidine may decrease. Coadministration of the amphetamines or the anorexiants with the tricyclic antidepressants may decrease the effects of the amphetamines or the anorexiants. 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

The proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

The linkage of uptake to the Na+ gradient may be of physiological significance since transport temporarily ceases at the time of depolarization-induced release of catecholamines. The transport of catecholamines can be inhibited selectively by such drugs as tricyclic antidepressants and cocaine. In addition, a variety of phenylethyl-amines, such as amphetamine, are substrates for carrier thus, they can be concentrated within catecholamine-containing neurons and can compete with the catecholamines for transport. 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

Bupropion is an a-aminoketone that is structurally related to amphetamines, and it exhibits unique activity comparable to that of other antidepressants. It is believed that bupropion restores the total amount of norepinephrine in the body. This compound is a poor reuptake inhibitor of dopamine, and does not exhibit anticholinergic activity or inhibit MAO. Its efficacy as an antidepressant is comparable to that of tricyclic antidepressants, and as a serotonin uptake inhibitor it is comparable to fluoxetine. It is preferable to use amoxapine. Synonyms of bupropion are amphebutamon and wellbutrin. 

Drugs that may be affected by dronabinol include amphetamines, cocaine, sympathomimetics, anticholinergics, antihistamines, tricyclic antidepressants, alcohol, sedatives, hypnotics, psychomimetics, disulfiram, fluoxetine, and theophylline. 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

Inhibitors codeine, encainide, flecainide, fluoxetine, haloperidol, hydrocodone, 4-methoxy-amphetamine, metoprolol, mexiletine, oxycodone, paroxetine, propafenone, propoxyphene, risperidone, selegiline (deprenyl), thioridazine, most tricyclic antidepressants, timolol Fluoxetine, haloperidol, paroxetine, quinidine... 

Levodopa or dopamine agonists produce diverse dyskinesias as a dose-related phenomenon in patients with Parkinson s disease dose reduction reverses them. Chorea may also develop in patients receiving phenytoin, carbamazepine, amphetamines, lithium, and oral contraceptives, and it resolves with discontinuance of the offending medication. Dystonia has resulted from administration of dopaminergic agents, lithium, serotonin reuptake inhibitors, carbamazepine, and metoclopramide and postural tremor from theophylline, caffeine, lithium, valproic acid, thyroid hormone, tricyclic antidepressants, and isoproterenol. 

Kokkinidis, Larry, Robert M. Zacharko, and Patrick A. Predy. 1980. "Post-Amphetamine Depression of Self-Stimulation Responding from the Substantia Nigra Reversal by Tricyclic Antidepressants." Plmmmcotogy Biochemistry and Behavior 13 379-83. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

Toxicants may have three effects on pulse rate bradycardia (decreased rate), tachycardia (increased rate), and arrhythmia (irregular pulse). Alcohols may cause either bradycardia or tachycardia. Amphetamines, belladonna alkaloids, cocaine, and tricyclic antidepressants (see imi-primine hydrochloride in Figure 6.12) may cause either tachycardia or arrhythmia. Toxic doses of digitalis may result in bradycardia or arrhythmia. The pulse rate is decreased by toxic exposure to carbamates, organophosphates, local anesthetics, barbiturates, clonidine, muscaric mushroom toxins, and opiates. In addition to the substances mentioned above, those that cause arrhythmia are arsenic, caffeine, belladonna alkaloids, phenothizine, theophylline, and some kinds of solvents. 

Amphetamines and cocaine (Figure 6.11), tricyclic antidepressants (see imiprimine hydrochloride in Figure 6.12), phenylcyclidines, and belladonna alkaloids at toxic levels increase blood pressure. Overdoses of antihypertensive agents decrease blood pressure, as do toxic doses of opiates, barbiturates, iron, nitrite, cyanide, and mushroom toxins. 

Examination of the mouth provides evidence of exposure to some toxicants. Caustic acids and bases cause a moist condition of the mouth. Other toxicants that cause the mouth to be moister than normal include mercury, arsenic, thallium, carbamates, and organophosphates. A dry mouth is symptomatic of poisoning by tricyclic antidepressants, amphetamines, antihistamines, and glutethimide. 

Among the many toxicants that cause convulsions are chlorinated hydrocarbons, amphetamines, lead, organophosphates, and strychnine. There are several levels of coma, the term used to describe a lowered level of consciousness. At level 0, the subject may be awakened and will respond to questions. At level 1, withdrawal from painful stimuli is observed and all reflexes function. A subject at level 2 does not withdraw from painful stimuli, although most reflexes still function. Levels 3 and 4 are characterized by the absence of reflexes at level 4, respiratory action is depressed and the cardiovascular system fails. Among the many toxicants that cause coma are narcotic analgesics, alcohols, organophosphates, carbamates, lead, hydrocarbons, hydrogen sulfide, benzodiazepines, tricyclic antidepressants, isoniazid, phenothiazines, and opiates. 

Therefore some advertisements emphasised the sedative action of tricyclic antidepressants. Amitriptyline, for example, was frequently recommended for its sedative action. It was described in one advert as having intrinsic tranquillising properties and additional sedative action which relieves insomnia, agitation and anxiety (Tryptizol advertisement 1964). Drinamyl, the combination of amphetamine and a barbiturate... 

Drug interactions The depressant actions of morphine are enhanced by phenothiazines (see p. 127), monoamine oxidase inhibitors (see p.123), and tricyclic antidepressants (see p. 119 and Figure 14.5). Low doses of amphetamine (see p. 103) strangely enhance analgesia. Hydroxyzine (see p. 422) also enhances analgesia. 

Drugs that alter the pH of urine can significantly affect the renal excretion of other drugs. Acid urine increases the effectiveness of mercurial diuretics. It also accelerates the excretion of basic drugs such as meperidine, tricyclic antidepressants, amphetamines, and antihistamines. Acidic drugs, such as aspirin, streptomycin, phenobarbital, sulfonamides, nalidixic acid, and nitrofurantoin have been shown to increase renal clearance in alkaline urine (61). The possible effects of urine pH on the renal excretion of drugs has been illustrated by the observation that if urine is rendered sufficiently alkaline, the excretion of amphetamine is markedly delayed and effective blood levels, after a single dose, can be maintained for several days (62). 

Because tricyclic antidepressants suppress REM sleep, they have been used in the management of narcolepsy and cataplexy when amphetamines fail or abuse potential is high. Clomipramine is the most effective, possibly because it has more pronounced actions on serotonergic mechanisms (61). 

---