Monoamine oxidase blockers

Figure 10.22. Hypothetical mechanism of the antihypertensive effect of monoamine inhibitors. This mechanism does not fit the observation of the cheese reaction , in which tyramine contained in fermented food causes hypertensive episodes in patients receiving monoamine oxidase blockers.

Serious adverse effects of epinephrine potentially occur when it is given in an excessive dose, or too rapidly, for example, as an intravenous bolus or a rapid intravenous infusion. These include ventricular dysrhythmias, angina, myocardial infarction, pulmonary edema, sudden sharp increase in blood pressure, and cerebral hemorrhage. The risk of epinephrine adverse effects is also potentially increased in patients with hypertension or ischemic heart disease, and in those using (3-blockers (due to unopposed epinephrine action on vascular Ui-adrenergic receptors), monoamine oxidase inhibitors, tricyclic antidepressants, or cocaine. Even in these patients, there is no absolute contraindication for the use of epinephrine in the treatment of anaphylaxis [1,5,6]. 

Blockers are contraindicated in patients with decompensated heart failure unless it is caused solely by tachycardia (high output). Other contraindications include sinus bradycardia, concomitant therapy with monoamine oxidase inhibitors or tricyclic antidepressants, and patients with spontaneous hypoglycemia. Side effects include nausea, vomiting, anxiety, insomnia, lightheadedness, bradycardia, and hematologic disturbances. 

Listing of antidepressants grouped by principal mechanism of action in the synapse. Abbreviations MAOI—irreversible = irreversible monoamine oxidase inhibitor MAOI—reversible = reversible monoamine oxidase inhibitor NDRl = norepinephrine/ dopamine reuptake inhibitor NRI = norepinephrine reuptake inhibitor NSRl = norepinephrine/serotonin reuptake inhibitor NSSA = norepinephrine/specific serotonin agonist SRI = serotonin reuptake inhibitor SRl/serotonin-2 blocker = serotonin reuptake inhibitor and serotonin-2 receptor antagonist. 

A host of medications have been nsed to treat TD including medications that block norepinephrine activity (clonidine and propranolol), dopamine-activating medications (bromocriptine), benzodiazepines, acetylcholine-activating medications, calcium channel blockers, and monoamine oxidase inhibitors. In addition, vitamin E supplementation and atypical antipsychotics including clozapine have been used to treat TD. 

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). 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

Although behavioral treatments for social phobia have been well studied, there are very limited data on its pharmacological management, b- Blockers (propranolol, atenolol) have been recommended, but available evidence indicates their effect may be no different than that of placebo ( 78). In a controlled study, the monoamine oxidase inhibitor (MAOl) phenelzine has been shown to be more effective than placebo (78, 79). Anecdotal reports have also described efficacy with alprazolam, clonidine, and fluoxetine, but systematic data are lacking (80, 81, 82 and 83). 

The positive effects of the monoamine oxidase inhibitor isoniazid and the amine reuptake blocker imipramine were both discovered by accident. Isoniazid was being used as an antitubercular drug when patients reports of elation led Nathan Kline to test and to demonstrate its antidepressant power. Ronald Kuhn had synthesized imipramine, a tricyclic molecule, as a possible me-too analog of chlorpromazine. When Kuhn found that it had little or no antipsychotic potential, he tried it out on depressives, and voila They got better. After a while, that is. As with isoniazid, imip-ramine s antidepressant action was evident only after one to four weeks of administration. 

L-deprenyl (selegiline), a monoamine oxidase B inhibitor, clonidine and guanfacine, a2-adreno-receptor agonists, and levodopa (L-dopa) have been reported to improve cognitive function in some subjects. Zimeldine, citaloprani, and alaproclate — selective serotonin uptake blockers — have no beneficial effects. 

MAO inhibitors can cause bradycardia. A report of two cases of interactions of monoamine oxidase inhibitors with beta-blockers (nadolol and metoprolol) is of interest, and several possible mechanisms were discussed (14). 

Action on receptors provides numerous examples. Beneficial interactions are sought in overdose, as with the use of naloxone for morphine overdose (opioid receptor), of atropine for anticholinesterase, i.e. insecticide poisoning (acetylcholine receptor), of isoproterelol (isoprenaline) for overdose with a P-adrenoceptor blocker (p-adrenoceptor), of phentolamine for the monoamine oxidase inhibitor-sympathomimetic interaction (a-adrenoceptor). 

Interactions. With nonselective monoamine oxidase inhibitors (MAOI), the monoamine dopamine formed from levodopa is protected from destruction it accumulates and also follows the normal path of conversion to noradrenaline (norepinephrine), by dopamine (J-hydroxylase severe hypertension results. The interaction with the selective MAO-B inhibitor, selegiline, is possibly therapeutic (see below). Tricyclic antidepressants are safe. Levodopa antagonises the effects of antipsychotics (dopamine receptor blockers). Some antihypertensives enhance hypotensive effects of levodopa. Metabolites of dopamine in the urine interfere with some tests for phaeochromocytoma, and in such patients it is best to measure the plasma catecholamines directly. 

The antidepressants, generally, produce their therapeutic effects by blocking the reuptake of one or more catecholamines (norepinephrine, serotonin, and dopamine), which leads to a decrease (down-regulation) of the number of post-synaptic receptors—generally within seven to twenty-one days, coinciding with the onset of clinical effect (see chapter 3). The MAOIs block monoamine oxidase, which metabolizes the catecholamines stored at the nerve ending of the presynaptic neuron—thereby making more catecholamine available. Stimulants increase the release of catecholamines. Buspirone is a 5-HT lA receptor blocker. 

Antidepressants (tricyclics, monoamine oxidase inhibitors) Antihypertensives (calcium channel blockers, methyidopa, reserpine)... 

They must be avoided by patients taking monoamine oxidase inhibitors or beta-blockers, as they can interact to cause potential large rises in blood pressure. 

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