Antidepressants

Question 1

What are the tricyclic antidepressants (2)?

Answer 1

Imipramine, Amitryptiline

Question 2

What are the heterocyclic antidepressants (3)?

Answer 2

Mirtazapine, Venlafaxine, Bupropion

Question 3

What are the SSRIs (3)?

Answer 3

Fluoxetine, Paroxetine, Sertraline

Question 4

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

Answer 4

Phenelzine

Question 5

What is the therapeutic mechanism of antidepressants?

Answer 5

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

Question 6

Does relief of depression happen right away?

Answer 6

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

Question 7

What is the biogenic amine hypothesis?

Answer 7

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.

Question 8

What does chronic stress cause?

Answer 8

Increase of coritosteroids, decreased hippocampal volume, depression

Question 9

What happens with long term treatment with antidepressants?

Answer 9

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.

Question 10

Do antidepressants affect normal mood?

Answer 10

No. (no euphoria)

Question 11

How do tricyclic antidepressants work?

Answer 11

they block NE and 5HT uptake

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

What are some side effects of tricyclics? Why?

Answer 14

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

Question 15

How does Venlafaxine work?

Answer 15

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

Question 16

What are the side effects of venlafaxine?

Answer 16

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

Question 17

How does Mirtazapine work?

Answer 17

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

Question 18

What are the side effects of Mirtazapine?

Answer 18

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

Question 19

How does Bupropion work?

Answer 19

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

Question 20

What is a special indication for Bupropion?

Answer 20

smoking cessation

Question 21

How do SSRI’s work?

Answer 21

Specific in blocking reuptake of serotonin 5HT

Question 22

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

Answer 22

2-3 weeks

Question 23

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

Answer 23

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

Question 24

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

Answer 24

True. they alter the plasma levels of concomitant medications

Question 25

Which SSRI has the longest half life?

Answer 25

Fluoxetine (they differ in their hald lives)

Question 26

How do the MAO inhibitors work?

Answer 26

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

Question 27

What do MAO inhibitors do to psychomotor activity?

Answer 27

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

Question 28

How long before therapeutic effect in MAO inhibitors?

Answer 28

several weeks

Question 29

What is central serotonin syndrome?

Answer 29

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

Question 30

toxicities of MAOI (6)?

Answer 30

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

Question 31

drug interactions of MAOIs?

Answer 31

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

Question 32

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

Answer 32

hypertensive crisis

Question 33

What causes hypertensive crisis?

Answer 33

MAOIs potentiate CV effects of sympathomimetic amines, especially tyramine.

Question 34

What foods contain tyramine?

Answer 34

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

Question 35

What are the additional potential applications for antidepressants (13)

Answer 35

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)

Question 36

Other side effects and toxicity of antidepressants (6)

Answer 36

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

Question 37

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

Answer 37

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

Question 38

What drugs are used for Bipolar Disorder (3)?

Answer 38

mood stabilizers: lithium and Anticonvulsants Lithium, Divalproex, Carbamazepine

Question 39

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

Answer 39

high concentration range. many brain systems may be affected.

Question 40

Why does lithium accumulate in active neurons?

Answer 40

permeability through sodium channels and synaptic ion channels

Question 41

Does lithium have a high or low therapeutic index?

Answer 41

very low.

Question 42

lithium toxicity? how to avoid?

Answer 42

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!

Question 43

side effect of lithium administration?

Answer 43

polyuria (disruption of distal tubular reabsorption in kidney)