Week 10 - Chapter 32 Antidepressant Drugs Flashcards Preview

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Flashcards in Week 10 - Chapter 32 Antidepressant Drugs Deck (29):
1

Biogenic Amines

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2

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.

3

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.

4

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.

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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)

6

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).

7

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.

8

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).

9

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.

10

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.

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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.

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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 )

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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.

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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.

15

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

16

Fluoxetine


Mechanism of Action

>Produce selective inhibition of serotonin reuptake
>Produce central nervous system (CNS) excitation

17

Fluoxetine

Adverse affects

>Serotonin syndrome
-Begins 2 to 72 hours after treatment
-Altered mental status (for example, agitation, confusion, disorientation, anxiety, hallucinations, and poor concentration)
-Incoordination, myoclonus, hyperreflexia, excessive sweating, tremor, and fever
-Deaths have occurred
-Syndrome resolves spontaneously after discontinuing the drug
-Risk increased by concurrent use of MAOIs and other drugs
>Withdrawal syndrome
>Neonatal effects when used during pregnancy
>Teratogenesis
>Extrapyramidal side effects
>Bruxism
>Bleeding disorders
>Sexual dysfunction
>Weight gain

18

Venlafaxine [Effexor]

Classification & Indications

Serotonin/Norepinephrine Reuptake Inhibitors

Indications
-Major depression
-Generalized anxiety disorder
-Social anxiety disorder (social phobia)

19

Venlafaxine [Effexor]

Mechanism of action

>Blocks NE and serotonin uptake
>Does not block cholinergic, histaminergic, or alpha1-adrenergic receptors
>Serious reactions if combined with MAOIs

20

Venlafaxine [Effexor]


Adverse effects

-Nausea
-Headache
-Anorexia
-Nervousness
-Sweating
-Somnolence
-Insomnia
-Weight loss/anorexia
-Diastolic hypertension
-Sexual dysfunction
-Hyponatremia (in older adult patients)
-Neonatal withdrawal syndrome

21

Imipramine

Classification & Uses

Tricyclic Antidepressants

Therapeutic Uses: Depression, Bipolar disorder, Fibromyalgia syndrome
Drugs of first choice for many patients with major depression

22

Imipramine

Mechanism of action

MOA: Block neuronal reuptake of two monoamine transmitters, NE and Serotonin

23

Imipramine

Adverse effects

Primarily from anticholinergic and cardiotoxic actions:
-Orthostatic hypotension
-Diaphoresis
-Sedation
-Cardiac Dysrhythmias: Major serious adverse effect
-Seizures
-Hypomania

24

Phenylzine

Classification & Uses

Monoamine Oxidase Inhibitors
-Second or third choice antidepressants for most patients
-As effective as TCAs and SSRIs but more hazardous
-Risk of triggering hypertensive crisis if patient eats foods rich in tyramine
-Drug of choice for atypical depression
>Subtype of major depression, appetite, sleep, volatile to short-term environmental circumstances (e.g. hypersensitive to rejection)

>Therapeutic uses
-Depression
-Other uses
-Bulimia nervosa
-Agoraphobia
-Attention-deficit/hyperactivity disorder
-Obsessive-compulsive disorder
-Panic attacks

25

Phenylzine

Mechanism of action

>Inhibition of MAO
--Two forms of MAO in the body: MAO-A, MAO-B
--MAO inactivates NE, serotonin, dopamine neurotransmitters in brain, tyramines in G-I system (tyramines stimulate NE release)
--Increased NE accumulation in vesicles, increase transmission

26

Phenylzine

Adverse effects

>CNS stimulation
>Orthostatic hypotension
>Hypertensive crisis from dietary tyramine
-Tyramine: Promotes the release of NE from sympathetic neurons
-Hypertensive crisis: Increased vesicle NE + Systemic tyramine (normally degraded at gut wall by MAO), ---> stimulation to release the NE-engorged vesicles ---> super sympathetic stimulation
-Severe headache, Tachycardia, Hypertension, Nausea and vomiting, Confusion, Profuse sweating, Stroke, Death

27

Bupropion [Wellbutrin]

Actions and uses

Atypical Antidepresent
Bupropion [Wellbutrin]

Actions and uses
-Acts as stimulant and suppresses appetite
-Antidepressant effects begin in 1 to 3 weeks
-Does not affect serotonergic, cholinergic, or histaminergic transmission
-Does not cause weight gain

28

Bupropion [Wellbutrin]

Adverse effects

Adverse effects
-Seizures
-Agitation
-Tremor
-Tachycardia
-Blurred vision
-Dizziness
-Headache
-Insomnia

29

Nonconventional Drugs for Depression

1. St. John’s wort (Hypericum perforatum)
>Efficacy may approach TCAs, Mild to Moderate Depression
>Problem w purity in OTC preparations

2. S-adenosylmethionine
>Severe depression, need more clinical data to warrant recommended usage.

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