Pharm: Antidepressants Flashcards
Citalopram
- SSRI -
MOA: selective seratonin reuptake inhibitor: inhibit seratonin transporter (SERT), thus increasing concentration of seratonin in cleft
Escitalopram
- SSRI
MOA: selective seratonin reuptake inhibitor: inhibit seratonin transporter (SERT), thus increasing concentration of seratonin in cleft
Sertraline
- SSRI
MOA: selective seratonin reuptake inhibitor: inhibit seratonin transporter (SERT), thus increasing concentration of seratonin in cleft
Selegiline
MAOI
MOA: monoamine oxidase inhibitors prevnt metabolism of NE and 5-HT and DA:
= selective irreversible MAO-B inhibitor at low doses (useful in Parkinson’s disease) and nonselective MAO-A/B inhibitor at higher doses (used to treat refractory depression)
monoamine hypothesis
i) Depression is caused by a decrease in biogenic amines (primarily NE and 5-HT, but also DA); excess biogenic amines results in mania and psychotic states
ii) All currently available antidepressant drugs are classified as having as their primary mechanism of actions on the metabolism, reuptake, or selective receptor antagonism of serotonin, norepinephrine, or both
iii) Depletion of biogenic amines with reserpine, which blocks vesicular uptake of monoamines and depletes their concentration in nerve endings, can induce depression in normal individuals
iv) LSD is a 5-HT2A receptor agonist that causes hallucinations and altered mental states
v) Anti-adrenergic drugs can induce depression
receptor hypothesis
i) Some antidepressants decrease NE and/or 5-HT receptor density in particular brain regions or decrease the sensitivity of these receptors to stimulation
ii) Antidepressants may take 1-4 weeks to produce any improvement and 6-8 weeks to achieve substantial benefit; The acute pharmacological effects of these drugs on neurotransmitter levels and subsequent receptor activation are immediate (minutes)
iii) This lag in onset of clinical efficacy implies that dynamic changes in neural circuits must occur before benefits can be realized; This probably involves regulation of receptor signaling, cellular sensitivity to signals, and trophic factor-induced changes in neuronal plasticity
Fluoxetine
- SSRI
MOA: selective seratonin reuptake inhibitor: inhibit seratonin transporter (SERT), thus increasing concentration of seratonin in cleft
USE: depression, eating disorders, OCD
Fluvoxamine
- SSRI (labeled for OCD)
MOA: selective seratonin reuptake inhibitor: inhibit seratonin transporter (SERT), thus increasing concentration of seratonin in cleft
USE: depression, OCD
Paroxetine
- SSRI
MOA: selective seratonin reuptake inhibitor: inhibit seratonin transporter (SERT), thus increasing concentration of seratonin in cleft
USE: depression, OCD
receptor hypothesis
i) Some antidepressants decrease NE and/or 5-HT receptor density in particular brain regions or decrease the sensitivity of these receptors to stimulation
ii) Antidepressants may take 1-4 weeks to produce any improvement and 6-8 weeks to achieve substantial benefit; The acute pharmacological effects of these drugs on neurotransmitter levels and subsequent receptor activation are immediate (minutes)
iii) This lag in onset of clinical efficacy implies that dynamic changes in neural circuits must occur before benefits can be realized; This probably involves regulation of receptor signaling, cellular sensitivity to signals, and trophic factor-induced changes in neuronal plasticity
first line MMD and anxiety?
SSRIs- fewer antimuscarinic side effects and are less cardiotoxic in overdose
SNRI’s, bupropion and Mirtazapine as well
tx for patient who can’t tolerate sexual dysfunction, weight gain, and sedation that may occur with other antidepressants?
bupropion - but generally is not effective for treatment of anxiety
second and third choice for MMD tx?
x) TCAs and MAOIs are relegated to second- or third-line treatments for MDD; they are potentially lethal in overdose, require titration to achieve therapeutic dose, have serious drug interactions, and have many adverse effects; However, these drugs remain valuable alternatives for patients with moderate to severe depression who do not respond to an SSRI or SNRI
suicidality?
all antidepressants increase risk of suicidal ideation and gestures - however decrease the risk of completed suicides
SNRI’s AEs?
** have the serotonergic side effects exhibited by SSRIs but also have noradrenergic SE’s: insomnia, anxiety, and agitation
** Elevated blood pressure and heart rate are sometimes an issue
- Discontinuation syndrome like that seen with SSRIs
TCA AE’s?
- Anticholinergic effects : drowsiness, dry mouth, constipation, urinary retention, blurred vision, and confusion
- Orthostatic hypotension due to α-adrenergic receptor blockade, especially in the elderly
- Weight gain and sedation due to H1 histamine receptor antagonism
- Cardiotoxicity, arrhythmias and heart block; Convulsions; hepatic dysfunction; Hyponatremia, which may lead to confusion in the elderly
- Hematological abnormalities (e.g., leucopenia, thrombocytopenia and agranulocytosis)
- Sexual side effects similar to those seen with SSRIs
- Discontinuation syndrome like that seen with SSRIs
Contraindications: Arrhythmias, recent myocardial infarction, liver disease, glaucoma, mania
Selegiline
MAOI
MOA: monoamine oxidase inhibitors prevnt metabolism of NE and 5-HT and DA:
= selective irreversible MAO-B inhibitor at low doses (useful in Parkinson’s disease) and nonselective MAO-A/B inhibitor at higher doses (used to treat refractory depression)
AE’s:
- Orthostatic hypotension and weight gain
- Highest rates of sexual side effects of all the antidepressants; anorgasmia is common
- May cause dangerous interactions with certain tyramine-containing foods and with serotonergic drugs (see “Drug Interactions” below)
- Sudden discontinuation syndrome manifested in delirium-like presentation with psychosis, excitement, and confusion
TCA AE’s?
- Anticholinergic effects : drowsiness, dry mouth, constipation, urinary retention, blurred vision, and confusion
- Orthostatic hypotension due to α-adrenergic receptor blockade, especially in the elderly
- Weight gain and sedation due to H1 histamine receptor antagonism
- Cardiotoxicity, arrhythmias and heart block; Convulsions; hepatic dysfunction; Hyponatremia, which may lead to confusion in the elderly
- Hematological abnormalities (e.g., leucopenia, thrombocytopenia and agranulocytosis)
- Sexual side effects similar to those seen with SSRIs
- Discontinuation syndrome like that seen with SSRIs
Contraindications: Arrhythmias, recent myocardial infarction, liver disease, glaucoma, mania
which antidepressants seen more often in OD?
- TCAs are the most toxic of all the antidepressants, particularly amitriptyline, especially when taken in overdose, which can lead to arrhythmias, altered mental status, and seizures
- MAOIs are also potentially lethal in overdose producing autonomic instability, hyperadrenergic symptoms, psychotic symptoms, confusion, delirium, fever, and seizures
Tyramine effect
- Tyramine is a naturally occurring monoamine compound that acts as a catecholamine releasing agent
- In foods, it is often produced by decarboxylation of tyrosine during fermentation or decay
Foods containing considerable amounts of tyramine include:
- pickled, aged, smoked, marinated, or meats that are potentially spoiled;
- chocolate; alcoholic beverages;
- fermented foods, such as most cheeses, etc.
Tyramine is normally metabolized by MAO; when large amounts of tyramine are ingested and MAOIs reduce metabolism, hypertensive crisis can occur – tyramine induces NE release from peripheral nerve terminals and subsequent dramatic (and potentially fatal) rise in heart rate and blood pressure
dopamine
imp. in attention, motivation, pleasure, reward
** bupropion = only drug thats dopamine selective
NE
imp. in alertness and energy (also seen in anxiety)
serotonin
imp. in obsessions and compulsions
Trazodone
- 5-HT2 antagonist
MOA: Deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients, suggesting that postsynaptic 5-HT2A overdensity is involved in the pathogenesis of depression
ADR’s:
- most common adverse effects are sedation and gastrointestinal disturbances
- Sexual side effects are uncommon (priapism!)
- Orthostatic hypotension due to α-adrenergic receptor blockade
USE: infrequently used!
