Antidepressants Flashcards
what are the types of depression
reactive, major depressive disorder and bipolar affective
what are the physiological features of Depression?
decreased sleep appetite changes fatigue and psychomotor dysfunction can also cause menstrual irregularities palpitations constipation headaches and nonspecific body aches
what are the psychological features of depression?
dysphoric mood worthlessness excessive guilt loss of interest/pleasure in all or most activities
what are the cognitive features of depression?
decreased concentration suicidal ideation
what antihypertensive and cardiovascular drugs cause depression
reserpine, methyldopa, propranolol, metoprolol, prazosin,
clonidine, digitalis
what sedative-hypnotic drugs cause depression
alcohol, benzodiazepines, barbiturates, meprobamate
what Anti-inflammatory and analgesic drugs cause depression
indomethacin, phenylbutazone, opiates, pentazocine
what steroids can cause depression
corticosteroids, oral contraceptives, estrogen withdrawal
Other drugs that induce depression
anti-parkinson, anti-neoplastic, neuroleptics
what is the BIOGENIC AMINE” HYPOTHESIS OF DEPRESSION
Reserpine causes depression by depleting NE and 5HT from vesicles
Agents that increase 5HT and NE are effective for treating depression
Genetic polymorphisms in SERT promoter
Alterations in 5HT1A/2C and a2 receptors
What is the NEUROENDOCRINE HYPOTHESIS OF DEPRESSION
Changes in Hypothalamic-Pituitary-Adrenal (HPA) Axis
Stress causes hypothalamus to release CRF,
CRF promotes release of ACTH from pituitary,
ACTH promotes release of cortisol from adrenal
Overactivity of HPA and elevated CRF found in almost all depressed patients
Overactivity of HPA may desensitize feedback response in hypothalamus and pituitary
Elevated CRF causes insomnia, anxiety, and decreased appetite and libido
Antidepressants and ECT reduce CRF levels
What is the NEUROTROPHIC HYPOTHESIS OF
DEPRESSION
Brain-derived neurotrophic factor (BDNF) is critical in Neural plasticity, resilience, neurogenesis
Stress and pain decrease BDNF levels in animals
Decrease in volume (5-10%) of hippocampus (memory and regulates HPA)
BDNF has “antidepressant” activity in animals
Depressed patients have reduced BDNF levels
Antidepressants increase BDNF levels and may increase hippocampal volume
(however, some animal studies have provided opposing evidence, BDNF knock out animals and increase BDNF following stress)
what is the integration of hypotheses of depression
HPA and steroid abnormalities regulate BDNF levels
Hippocampal glucocorticoid receptors are activated by cortisol during stress (decreasing BDNF)
Chronic activation of monoamine receptors increases BDNF signaling (> 2 weeks)
Chronic activation of monoamine receptors leads
to a down regulation of the HPA axis
What are the main classes of drugs
MAOIs = Monoamine Oxidase Inhibitors
TCAs = Tricyclic Antidepressants; tertiary and secondary amines (a.k.a. SNRIs, see below)
SSRIs = Selective-Serotonin Reuptake Inhibitors
SNRIs = Serotonin-Norepinephrine Reuptake Inhibitors
5-HT2 Antagonists
Tetracyclic and Unicyclic Antidepressants
What are the targets of Antidepressants
MAO, 5HT reuptake, NE reuptake and a2 receptors
some block transporters to increase neurotransmitters
Why does therapy take 4-8 weeks
Neuroadaptive responses?
Antidepressants cause the amount of neurotransmitter in the intrasynaptic space to increase.
Is the delay in clinical effect due to…
Activation of presynaptic receptors?
Presynaptic adaptation?
Postsynaptic adaptation?
→ No one really
knows!
What is the mechanism of action for MAOIs
NE and serotonin usually degraded by MAO when inhibited there is an increase amount of NE and 5HT packaged in vesicles so more NE and 5HT end up being released from vesicles into the synapse
What are non-selective MAO inhibitors
phenelzine (nardil) and Tranylcypromine (parnate)
what are MAO-B selective
selegline (eldepryl/ensam) and safinamide (xadago)
What are MAO-A selective
moclobemide (manerix)
What are MAO inhibitor side effects
Severe SE: headache drowsiness dry mouth weight gain orthostatic hypotension and sexual dysfunction
HTN crisis: avoid certain foods and drugs
interactions with OTC cold preparation diet pills
avoid foods with tyramine
Herbal products for depression St. John wort
what are tricyclic antidepressants
used to treat major depression panic disorder chronic pain and enuresis can be extremely dangerous depressed patient more likely to be suicidal (2 weeks into treatment)
What are tertiary amines
Inhibit both NE and 5HT reuptake via NET and SERT
Also act as receptor antagonists:
Antihistamine (H1)
Antimuscarinic
Antiadrenergic (a1)
Major Side Effects: These agents cause the most sedation, autonomic side effects, and weight gain
Other Side Effects: Conduction disturbances of heart
What is Imipramine (tofranil)
tertiary amine is metabolized to desipramine used for enuresis and ADHD
