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Pharmacology Test 4 > Antidepressants > Flashcards

Antidepressants Flashcards

1
Q

What are the tricyclic antidepressants (2)?

A

Imipramine, Amitryptiline

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2
Q

What are the heterocyclic antidepressants (3)?

A

Mirtazapine, Venlafaxine, Bupropion

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3
Q

What are the SSRIs (3)?

A

Fluoxetine, Paroxetine, Sertraline

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4
Q

What are the MAO (monoamine oxidase) inhibitors (1)?

A

Phenelzine

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5
Q

What is the therapeutic mechanism of antidepressants?

A

either block NE and/or 5HT uptake or slow the breakdown of them. Therefore, they increase the synaptic concentrations of NE and serotonin

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6
Q

Does relief of depression happen right away?

A

No! 2-3 week delay even though pharmacological effects occur rapidly

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7
Q

What is the biogenic amine hypothesis?

A

5-HT1A receptors on presynaptic neurons inhibit firing of serotonin neurons, and both presynatpic alpha 2 adrenoreceptors and presynaptic 5-HT receptors act to inhibit release of serotonin. initially, the transmitters on the receptors of the presynaptic cells provide negative feedback which ooposes the increase in serotonin tone. i.e. in the initial phase of tx, effects of drugs are compensated for by inhibitory elements (less serontonin is released due to inhibition of presynaptic cell!). After extended tx, inhibitory elements desensitize, allowing drugs to have increased post-synaptic effects.

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8
Q

What does chronic stress cause?

A

Increase of coritosteroids, decreased hippocampal volume, depression

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9
Q

What happens with long term treatment with antidepressants?

A

upregulation of cAMP signaling through the activation of 5-HT and NE receptors, which produces increased levels of Brain Derived Neurotrophic Factor which reverses the effects of chronic stress.

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10
Q

Do antidepressants affect normal mood?

A

No. (no euphoria)

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11
Q

How do tricyclic antidepressants work?

A

they block NE and 5HT uptake

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12
Q

How long does it take to see improvement in mood with tricyclic antidepressants?

A

2 weeks of tx (risk of suicide during this time). tx should be at least 6-8 weeks.

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13
Q

Do all patients respond to antidepressants? Why/why not?

A

No. variations in pharmacokinetics, noncompliance, some people just don’t respond (heterogeneous disease)

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14
Q

What are some side effects of tricyclics? Why?

A

atropine-like sxs: dry mouth, blurred vision, constipation, mild sedation, hypotension and fatigue. these can affect compliance. side effects because they block muscarinic-cholingergic, histaminergic, and alpha-1 adrenergic receptors

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15
Q

How does Venlafaxine work?

A

inhibits NE and 5HT reuptake without blocking muscarinic-cholinergic, histaminergic, or alpha1 adrenergic receptors like in tricyclics.

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16
Q

What are the side effects of venlafaxine?

A

tolerated well - side effects similar to SSRI’s: nausea, vomiting, HA, sexual dysfunction

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17
Q

How does Mirtazapine work?

A

enhances neurotransmission at serotonin receptors by blocking alpha2 adrenergic receptors and presynaptic serotonin receptors. also anxiolytic.

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18
Q

What are the side effects of Mirtazapine?

A

similar to SSRI’s but no nausea: vomiting, HA, sexual dysfunction

19
Q

How does Bupropion work?

A

monoamine uptake blocker (NE, 5HT, and DA).

20
Q

What is a special indication for Bupropion?

A

smoking cessation

21
Q

How do SSRI’s work?

A

Specific in blocking reuptake of serotonin 5HT

22
Q

How long does it take for onset of antidepressant effect with SSRIs?

A

2-3 weeks

23
Q

What is the side effects profile of SSRIs? How are they different than TCAs? One more thing?

A

nausea, vomiting, HA, sexual dysfunction. Do not cause cardiac problems like TCAs. Also less toxic in cases of suicidal overdose

24
Q

True or False: SSRIs inhibit cytochrome-P450 enzymes in the liver

A

True. they alter the plasma levels of concomitant medications

25
Q

Which SSRI has the longest half life?

A

Fluoxetine (they differ in their hald lives)

26
Q

How do the MAO inhibitors work?

A

deaminate monoamines including catecholamines (NE and DA), serotonin 5HT, and other amines such as tyramine.

27
Q

What do MAO inhibitors do to psychomotor activity?

A

reverse psychomotor retardation of depressed patients, may also increase the psychomotor activity to a hypomanic or manic state

28
Q

How long before therapeutic effect in MAO inhibitors?

A

several weeks

29
Q

What is central serotonin syndrome?

A

can happen with combo of MAOI and SSRIs. can lead to hyperpyrexia, confusion, and death

30
Q

toxicities of MAOI (6)?

A

hepatotoxicity, tremors, insomnia, hyperhidrosis, convulsions, peripheral neuropathy

31
Q

drug interactions of MAOIs?

A

can interfere with metabolism (degradation) of other drugs including general anesthetics, sedatives, antihistamines, alcohol, analgesics, anticholinergic drugs, and tricyclic antidepressants

32
Q

What is the most serious toxicity from interaction of MAOI with other substances?

A

hypertensive crisis

33
Q

What causes hypertensive crisis?

A

MAOIs potentiate CV effects of sympathomimetic amines, especially tyramine.

34
Q

What foods contain tyramine?

A

cheeses, beer, wine, yeast, coffee, chicken livers, pickled herring, canned figs

35
Q

What are the additional potential applications for antidepressants (13)

A

1) depression with psychotic features (combo with antipsychotic)
2) depressed phase of bipolar disorder (combo with mood stabilizer)
3) atypical depression (SSRIs or MAOIs)
4) panic disorder
5) bulimia
6) neuropathic pain (tricyclics)
7) enuresis (Imipramine)
8) OCD
9) ADD/ADHD
10) cataplexy due to narcolepsy
11) dysthmia (chronis low grade depression)
12) organic mood disorders (caused by brain injury)
13) smoking cessation (bupropion)

36
Q

Other side effects and toxicity of antidepressants (6)

A

1) orthostatic hypotension (all but SSRIs)
2) anticholinergic properties (tricyclics and most heterocyclics): dry mouth, blurred vision, constipation, urinary hesitancy or retention, potentially confusion, agitation, delirium, tachycardia
3) sedation due to H1 antagonism. tertiary amines are more sedating and anticholinergic than secondary amines. Nortriptline has least of these side effects.
4) cardiac toxicity: quinidine-like effect slowing intracardiac conduction (tricyclics)
5) risk of death with overdose
6) generally need to monitor blood levels for therapeutic range

37
Q

many antidepressants, including the SSRIs, cause sexual dysfunction. which two don’t?

A

Mirtazapine, Bupropion. Unique mechanisms (presynaptic receptors, more direct reinforcing effects)

38
Q

What drugs are used for Bipolar Disorder (3)?

A

mood stabilizers: lithium and Anticonvulsants

Lithium, Divalproex, Carbamazepine

39
Q

what concentration range is lithium therapeutically effective in? what does this mean?

A

high concentration range. many brain systems may be affected.

40
Q

Why does lithium accumulate in active neurons?

A

permeability through sodium channels and synaptic ion channels

41
Q

Does lithium have a high or low therapeutic index?

A

very low.

42
Q

lithium toxicity? how to avoid?

A

anorexia, nausea, vomiting, diarrhea, thirst and dry mouth, ataxia, blurred vision, slurred speech, mucular weakness, convulsions, coma, death. avoid with adequate sodium intake. I.e. low sodium diet and lithium tx are contraindicated!

43
Q

side effect of lithium administration?

A

polyuria (disruption of distal tubular reabsorption in kidney)

Pharmacology Test 4 (10 decks)

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