EXAM #3: ANTIDEPRESSANTS Flashcards
What is the “delay of therapeutic response” in antidepressant therapy?
Weeks to months are required for therapeutic benefit
What generally limits the use of antidepressants?
Side effects
What is the monoamine/ biogenic amine hypothesis?
Depression is caused by a lack of:
- 5-HT
- NE
- DA
What is the neurotrophic hypothesis of depression?
Changes in nerve growth factors play a role in depression
What is the mechanism of action of currently available antidepressants?
Increase in 5-HT and/or NE in the synapse
What is the general function of neurotrophic factors e.g. BDNF?
“Brain fertilizer” for neuronal growth and survival
How do antidepressants alter BDNF?
Increase
What is the general mechanism of MAOIs?
Monoamine oxidase inhibitors block the degradation of monoamines (5-HT and NE)
What classes of drugs block reuptake of monoamines?
SSRIs
TCAs
SNRIs
SNRI= 5-HT and NE reuptake inhibitors*
What is the function of autoreceptors on the pre-synaptic terminal?
Agonism of autoreceptors decreases NT release
What class of antidepressant is commonly used to treat PTSD?
SSRI
What is the role of antidepressants as anxiolytics?
Long-term anti-anxiety effects at LOW doses
What class of antidepressants is used commonly to treat chronic pain?
TCAs
What is the mechanism of action of the MAOIs?
Antagonism of MAO to increase availability of 5-HT and NE in the synaptic cleft
What is the difference between MAO-A and MAO-B inhibitors?
A= Tyramine, NE, 5-HT, and DA
B= DA
What is the clinical use of MAOIs?
1) Treatment of resistant depression
2) Atypical depression
3) Anxiety states i.e. social anxiety and panic disorder
What are the most common side effects associated with MAOIs?
1) Orthostatic hypotension
2) Weight gain
3) Sexual dysfunction
What causes orthostatic hypotension with MAOI use?
Inhibition of alpha-1 receptors in the CNS
What is the important food interaction associated with MAOIs?
Tyramine ingestion with MAOIs can cause a hypertensive crisis
(wine and cheese phenomenon)
What is the mechanism of action of the tricyclic antidepressants?
Block reuptake of 5-HT and NE by inhibition of SERT and NET
How are TCAs used clinically?
1) 2nd line for major depression
2) CHRONIC PAIN (first line)
What TCA is used to treat bedwetting? Why?
Imparamine b/c of anticholinergic effects
What TCA is used to treat neuropathic pain?
Desipramine
What TCA has the most sedative effects?
Amitriptyline
What are the side effects of the TCAs?
1) Orthostatic hypotension (elderly = “hip breakers”)
2) Delerium in elderly
3) Sexual dysfunction
4) Cardiac toxicity–> LETHAL CARDIAC ARRHYTHMIA
What are the 3 Cs of TCA overdose?
- Convulsions
- Coma
- Cardiac arrhythmia
What is the mechanism of action of the SSRIs?
Selective inhibition of SERT; block 5-HT reuptake into the pre-synaptic terminal
What is the clinical use of SSRIs?
First line for depression
What is important to remember clinically about SSRIs?
Much safer than MAOIs or TCAs
What are the short term side effects of SSRIs?
Nausea
Dyspepsia
Diarrhea
What are the long-term side effects of SSRIs?
Sexual Dysfunction*
Number 1 reason to switch SSRIs
What precipitates Serotonin Syndrome with SSRIs?
1) Combination use with other antidepressants
2) Switching SSRIs (allow time for previous drug to clear)
What is Serotonin Syndrome?
Classically, a triad of:
1) mental status changes
2) autonomic hyperactivity
3) neuromuscular abnormalities
What is SSRI Discontinuation Syndrome?
Sudden d/c of short half-life SSRIs can can cause adverse effects in some patients in 1-7 days of cessation
How do SNRIs differ from TCAs?
SNRIs and TCAs both inhibit SERT and NET, but SNRIs have much LESS AFFINITY for other receptors i.e. have less side effects
What is the mechanism of Venlafaxine?
1) Major: SERT inhibitor
2) Minor: NET inhibitor
What is the clinical indication for Venlafaxine?
Severe depression
What is the mechanism of action of Duloxetine?
Balanced 5-HT and NE reuptake blockade
What is Duloxetine inidicated for?
Increasingly prescribed for chronic pain over TCAs
What is the mechanism of action of Trazadone?
H1 receptor antagonist
What is Trazadone indicated for?
Unlabeled hypnotic i.e. treatment for insomnia
What is the major side effect associated with Trazodone?
Priapism
What is the mechanism of action of Buproprion?
1) Blocks NE and DA reuptake
2) Increases presynaptic release of catecholamines
What is Bupropion indicated for?
1) Major depression
2) Smoking cessation
What is the mechanism of action of Mirtazapine?
1) Alpha-2 blocker
2) Increases release of 5-HT and NE
3) H1 blocker
4) 5-HT2 and 3 blocker
What do you need to remember about prescribing MAOIs, TCAs, and SSRIs?
DO NOT COMBINE–can be FATAL
What antidepressants are potent CYP2D6 inhibitors?
- Paroxetine
- Fluoxetine
- Fluvoxamine
What is the drug of choice for Bipolar Disorder?
Lithium
What anticonvulsants are used to treat Bipolar Disorder?
Valproic acid
Carbamazepine
What is the clinical utility of Lithium?
Maintenance treatment
What is the clinical utility of Valproic acid and Carbamazepine?
Treatment of acute mania
What is the mechanism of action of Lithium?
Stabilization of the postsynaptic membrane
What are the side effects of Lithium?
1) Tremor
2) Hypothyroidism
3) Nephrogenic Diabetes Insipidus
4) Skin reactions
What is the important drug interaction to remember with Lithium?
Thiazide and loop diuretics diminish Li+ clearance; thus, combination therapy can cause Lithium toxicity
