Week 10 - Chapter 32 Antidepressant Drugs Flashcards
Biogenic Amines
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Electroconvulsive Therapy
ECT is a valuable tool for treating depression. This procedure is safe and effective, and benefits develop more rapidly than with drugs or psychotherapy. Accordingly, ECT is especially appropriate when a rapid response is necessary. Candidates for ECT include (1) severely depressed, suicidal patients; (2) older-adult patients at risk of starvation because of depression-induced lack of appetite; and (3) patients who have not responded to antidepressant drugs (50% to 60% will respond to ECT).
A single treatment consists of delivering an electrical shock to the scalp that is sufficient to induce a generalized seizure lasting 20 to 30 seconds. Success requires a series of these treatments, typically 2 to 3 per week for a total of 6 to 12 treatments.
Monoamine Oxidase Inhibitors
Description
The MAOIs are second- or third-choice antidepressants for most patients. Although these drugs are as effective as the SSRIs and TCAs, they are more hazardous. The greatest concern is hypertensive crisis, which can be triggered by eating foods rich in tyramine. At this time, MAOIs are drugs of choice only for atypical depression. Three MAOIs—isocarboxazid [Marplan], phenelzine [Nardil], and tranylcypromine [Parnate]—are administered orally, and one—selegiline [Emsam]—is administered by transdermal patch.
Monoamine Oxidase Inhibitors
Mechanism of Action
MAO is an enzyme found in the liver, the intestinal wall, and terminals of monoamine-containing neurons. The function of MAO in neurons is to convert monoamine neurotransmitters—NE, 5-HT, and dopamine—into inactive products. In the liver and intestine, MAO serves to inactivate tyramine and other biogenic amines in food. In addition, these enzymes inactivate biogenic amines administered as drugs.
The body has two forms of MAO, named MAO-A and MAO-B. In the brain, MAO-A inactivates NE and 5-HT, whereas MAO-B inactivates dopamine. In the intestine and liver, MAO-A acts on dietary tyramine and other compounds. All of the MAOIs used for depression are nonselective.
Monoamine Oxidase Inhibitors
Therapeutic uses
-Depression
-Other Psychiatric Uses
(bulimia nervosa, agoraphobia, attention-deficit/hyperactivity disorder, and obsessive-compulsive disorder. Like SSRIs and TCAs, MAOIs can reduce panic attacks in patients with panic disorder)
Monoamine Oxidase Inhibitors
Adverse effects
-CNS stimulation (anxiety, insomnia, agitation, hypomania, and even mania).
-Orthostatic Hypotention
(and dizziness, lightheadedness)
-Hypertensive Crisis from Dietary Tyramine (avocados, bananas, aged meat, aged fish, dairy products, etc)
(severe headache, tachycardia, hypertension, nausea, vomiting, confusion, and profuse sweating—possibly leading to stroke and death).
Selective Serotonin Reuptake Inhibitors
These drugs are indicated for major depression as well as several other psychologic disorders (Table 32–2). Characteristic side effects are nausea, agitation/insomnia, and sexual dysfunction (especially anorgasmia). The SSRIs can interact adversely with MAOIs and other serotonergic drugs, and hence these combinations must be avoided. In addition, when used late in pregnancy, SSRIs can lead to a withdrawal syndrome and persistent pulmonary hypertension in the infant. Like all other antidepressants, SSRIs may increase the risk of suicide. Compared with the TCAs and MAOIs, SSRIs are equally effective, better tolerated, and much safer. Death by overdose is extremely rare.
Serotonin/Norepinepherine Reuptake Inhibitors
Four drugs—venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran —block neuronal reuptake of serotonin and NE, with minimal effects on other transmitters or receptors. Pharmacologic effects are similar to those of the SSRIs, although the SSRIs may be better tolerated. The SNRIs are indicated for major depression as well as other disorders (OCD, Panic disorder, PTSD, social phobia, etc).
Tricyclic Antidepressants
Despcription
The structure of imipramine, a representative TCA, is very similar to the structure of the phenothiazine antipsychotics. Because of this similarity, TCAs and phenothiazines have several actions in common. Specifically, both groups produce varying degrees of sedation, orthostatic hypotension, and anticholinergic effects.
Tricyclic Antidepressants
Mechanism of Action
The TCAs block neuronal reuptake of two monoamine transmitters: NE and 5-HT. As a result, TCAs increase the concentration of these transmitters at CNS synapses, and thereby intensify their effects. As indicated in Table 32–4, some TCAs block reuptake of NE and 5-HT, whereas others only block reuptake of NE. As with the SSRIs, biochemical effects (blockade of transmitter reuptake) occur within hours, whereas therapeutic effects (relief of depression) develop over several weeks. This delay suggests that antidepressant effects are due to adaptive changes brought on by prolonged reuptake blockade, and not to reuptake blockade directly.
Tricyclic Antidepressants
Pharmicokinetics
The half-lives of TCAs are long and variable. Because their half-lives are long, TCAs can usually be administered in a single daily dose. Because their half-lives are variable, TCAs require individualization of dosage.
Tricyclic Antidepressants
Therapeutic uses
- Depression
- Bipolar Disorder
- Fibromyalgia Syndrome.
- Other (neuropathic pain, chronic insomnia, attention-deficit/hyperactivity disorder, and panic disorder or obsessive-compulsive disorder )
Tricyclic Antidepressants
-Adverse effects
The most common adverse effects are orthostatic hypotension, sedation, and anticholinergic effects. The most serious adverse effect is cardiotoxicity. These effects occur because, in addition to blocking reuptake of NE and 5-HT, TCAs cause direct blockade of receptors for histamine, acetylcholine, and NE.
Withdrawal Syndrome
Abrupt discontinuation of SSRIs can cause a withdrawal syndrome. Symptoms include dizziness, headache, nausea, sensory disturbances, tremor, anxiety, and dysphoria. These begin within days to weeks of the last dose, and then persist for 1 to 3 weeks. Resumption of drug use will make symptoms subside. The withdrawal syndrome can be minimized by tapering the dosage slowly. Of the SSRIs in use today, fluoxetine is least likely to cause a withdrawal reaction. Because fluoxetine has a prolonged half-life, plasma levels decline slowly when dosing is stopped. When SSRIs are discontinued, it is important to distinguish between symptoms of withdrawal and return of depression.
Fluoxetine
Classification & Indications
> Most widely prescribed SSRI in the world
-Bipolar disorder, OCD, Panic, Bulimia
-Premenstrual dysphoric disorder
Off-label uses: Post-traumatic stress disorder, social phobia, alcoholism, attention-deficit/hyperactivity disorder, Tourette’s syndrome, and obesity
