Pharm For Depression And Mania

Question 1

Antidepressants by class

Answer 1

TCAs, SSRIs, SNRIs, MAOIs, atypicals, drugs fro bipolar disorder

Question 2

TCAs

Answer 2

Imipramine

Question 3

SSRIs

Answer 3

Escitalopram, fluoxetine, paroxetine, sertraline

Question 4

SNRIs

Answer 4

Venlafaxine, duloxetine

Question 5

MAOIs

Answer 5

Phenelzine

Question 6

Atypicals

Answer 6

Buproprion, mirtazapine

Question 7

Drugs for bipolar disorder

Answer 7

Lithium, carbamazepine, valproic acid, lamotrigine, quetiapine

Question 8

Mechanism of TCAs

Answer 8

Inhibition of reuptake of NE pump
Side effects- increased HR, BP, and fight or flight
(Same as MAOIs but happens by having more NE in vesicles to then get more NE released in synapse)

Question 9

Not explained by the monoamine hypothesis

Answer 9

Therapeutic lag- MAOIs and TCAs affect their targets within hours, but full therapeutic effect requires weeks-months (possibly changes in receptor density or birth of new neurons)
25-50% of patients fail to respond to the first antidepressant or even several
Not all inhibitor of reuptake pumps are antidepressants
Several drugs are clinically effective antidepressants, but do not affect MAOs or reuptake pumps for NE or 5-HT at therapeutic doses

Question 10

Long-term adaptations in NT by anti-depressants- another explanation for therapeutic lag

Answer 10

Acutely, antidepressants increase synaptic levels of monoamine NTs
Initial changes in monoamine function lead to numerous changes in the functional state of the target neurons related to alterations of intracellular signal transduction pathways
These changes may in turn result in alterations in gene expression that develop slowly and become increasingly prominent with continued drug administration
Increased levels of CREB
Changes in gene expression result in altered levels of specific neuronal proteins, which subsequently underlie long-term changes in the functional properties of neurons

Question 11

Long term antidepressant administration increases

Answer 11

BDNF expression in hippocampus and prevents the down regulation of BDNF that occurs in response to stress
Enhances dendritic sprouting in contrast to the effects of stress
Antidepressant induced up-regulation of BDNF helps repair stress induced damage to hippocampus neurons and may protect vulnerable neurons from further damage

Question 12

SNRIs inhibit

Answer 12

Both 5-HT and NE reuptake pumps

Question 13

What inhibits tyrosine hydroxylase and NE synthesis

Answer 13

AMPT

Question 14

What inhibits tryptophan hydrolase and serotonin synthesis

Answer 14

PCPA

Question 15

Safety vs. efficacy of anti-depressants

Answer 15

TCA, MAOIs, and SSRIs all have the same efficacy
But SSRIs are much safer

TCAs affect many targets in many systems- notably stimulate the autonomic systems. They also affect Na and Ca channels. Significant cardiac arrhythmia risk
MAOIs have many drug-drug and drug-food interactions. By inhibiting metabolism of amines in diet or medications, they have a risk of hypertensive crisis
SSRIs have adverse effects, but not acutely life-threatening

Question 16

What FDA drug class are antidepressants

Answer 16

Category C or D
Animal studies demonstrate a risk, but no human studies performed. Potential benefits outweighs risk
Human studies demonstrate some risk

Question 17

Most common side effects of SSRIs/SNRIs

Answer 17

GI and sexual effects are very common

No life threatening risks

Question 18

Adverse events of tricyclics

Answer 18

Sedation
Sympathomimetic-tremor, insomnia
Anti muscarinic- blurred vision, constipation, urinary hesitancy, confusion
CV- orthostatic hypotension, conduction defects, arrythmias
Psychosis
Seizures
Weight gain, sexual disturbances

Question 19

SSRIs adverse effects

Answer 19

Insomnia, tremor, GI, rashes, deceased libido, sexual dysfunction

Question 20

MOAIs adverse effects

Answer 20

Sleep disturbances, weight gain, postural hypotension, sexual disturbances

Question 21

Buproprion adverse events

Answer 21

Dizziness, dry mouth, sweating, tremor, aggravation of psychosis, potential for seizures at high doses

Question 22

One future prospect to separate the therapeutic lag time from clinical efficacy

Answer 22

NMDA glutamate receptors targeted

Ketamine (antagonist)

Question 23

Drugs for mania and bipolar disorder- mood stabilizers

Answer 23

Lithium
Anticonvulsants- carbamazepine, valproic acid, lamotrigine
Atypical antipsychotics- quetiapine, aripiprazole

Question 24

Iithium MOA

Answer 24

Narrow therapeutic window
Lag time
Rapidly absorbed, widely distributed, moved by Na transporters- low sodium makes lithium more toxic*
AES- nausea, diarrhea, weight gain, tremor, nephrotoxicity, arrythmias
Drug drug interactions especially with renal drugs
Teratogenic*

Question 25

Carbamazepine MOA

Answer 25

Inhibits voltage sensitive sodium channels, giving enhanced inhibitory action to GABA
Medium therapeutic lag, wide therapeutic window
Induces hepatic CYP3A4 metabolism of itself and other drugs
AES- neuro effects, GI, decreased blood cells, risk of serious skin reactions in HLA-B58 patients
Teratogenic

Question 26

Valproic acid

Answer 26

Inhibits sodium and calcium channels giving enhances inhibitory action to GABA
Little therapeutic lag, wide therapeutic range compared to others
AES- GI complaints, rare hepatic problems, tremor, sedation, drug-drug interactions due to high serum protein binding
Teratogenic