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amitriptyline, imipramine, and nortriptyline
- tricyclic antidepressant
- use depends on tolerance to side effects and duration of action
- blocks reuptake of NE and 5-HT
- also blocks muscarinic, adrenergic, and histamine receptors (underlies side effects)
- oral, readily absorbed in small intestine
- therapeutic effects requires > 2 weeks
- long half life, highly lipid soluble, high binding to plasma proteins
- P450 metabolism, renal excretion
- adverse effects: antimuscarinic effects, CV overstimulation, orthostatic hypotension, sedation, metabolic-endocrine (weight gain, sexual dysfn), neurologic (seizures), psychiatric (mania, delirium, aggravation)
-
citalopram, fluoxetine, sertraline
- selective serotonin-reuptake inhibitors (SSRIs)
- most widely rx'ed AD in the US
- fewer side effects than TCAs (fewer anticholinergic, no significant cardiotoxic effects)
- also rx anxiety disorder, OCD, PTSD, some eating disorders
- orally active
- sertraline has high first-pass effect
- long half life (fluoxetine is demethylated to active metabolite norfluoxetine, half life up to 30 days)
- high binding to plasma proteins
- blocks P450 enzymes (2D6, 1A2, 3A4)
- eliminated via kidneys
- adverse effects (much safer than TCA): early onset - nausea, anxiety, sleep disturbance; late - anorexia, sex. dysfn, induction of mania
-
venlafaxine, duloxetine
- serotonin-NE reuptake inhibitors
- fewer side effects than TCAs
- oral
- half life 11-12 hrs
- venlafaxine - 27% bound to plasma proteins
- - CYP2D6 metabolism
- duloxetine - highly bound to plasma proteins
- - 1A2 and 2D6 metabolism
- eliminated via kidneys
- adverse effects: nausea, anxiety, sleep disturbance, sex. dysfn, at higher doses - inc blood pressure and heart rate (NE effect)
-
buproprion
- atypical antidepressant
- inhibits dopamine and NE reuptake
- useful for rx'ing rapid-cycling bipolar disorder
- can be used in combination with TCAs
- fewer side effects than TCAs
- common side effects: nausea, headache, insomnia, nervousness, tinnitus
-
trazadone
- atypical antidepressant
- inhibits reuptake of 5-HT and blocks 5-HT2 receptors
- can be used in combination with TCAs
- fewer side effects than TCAs
- common side effects: nausea, headache, insomnia, nervousness, tinnitus
-
mirtazapine
- atypical antidepressant
- increases NE and serotonin release by blocking α2 receptors
- can be used in combination with TCAs
- fewer side effects than TCAs
- common side effects: nausea, headache, insomnia, nervousness, tinnitus
-
phenelzine and tranylcypromine
- monoamine oxidase inhibitors (MAO-A and B)
- 3rd line drug for depression
- limited due to severe and unpredictable side effects
- MAO-A deaminates NE, 5HT, DA
- MAO-B deaminates DA
- oral
- therapeutic effect reqs 2-4 weeks
- eliminated via kidneys
- blocks MAO irreversibly, meaning loss of MAO activity persists long after drugs are metabolized and eliminated (several weeks to synthesize new MAO)
- adverse effects: CNS (agitation, psychoses, restlessness), CV (ortho hypo, tachycard), serotonin syndrome (when combined with SSRIs - cognitive coma; autonomic, and somatic effects), tyramine (cheese effect can lead to stroke, headache, tachycard, htn, seizures; elevated tyramine in GI can lead to release of large amounts of catecholamines - from chicken, cheese, liver, beer, red wine)
-
selegiline
- MAOI (MAO-B specific)
- 3rd line drug for depression
- limited due to severe and unpredictable side effects
- transdermal patch
- therapeutic effect reqs 2-4 weeks
- eliminated via kidneys
- blocks MAO irreversibly, meaning loss of MAO activity persists long after drugs are metabolized and eliminated (several weeks to synthesize new MAO)
- adverse effects: CNS (agitation, psychoses, restlessness), CV (ortho hypo, tachycard), serotonin syndrome (when combined with SSRIs - cognitive coma; autonomic, and somatic effects), tyramine (cheese effect can lead to stroke, headache, tachycard, htn, seizures; elevated tyramine in GI can lead to release of large amounts of catecholamines - from chicken, cheese, liver, beer, red wine)
-
lithium salts
- drug of choice for maintenance rx of bipolar illness
- can be used as prophylactic
- sometimes combines with antidepressants, neuroleptics, antiepileptics
- onset 3-4 weeks
- will substitute for Na+ (undesirable effects)
- VERY toxic - extremely low therapeutic index
- mechanism: blocks hydrolysis of inositol phosphate, blocks GSK-3β kinase, inhibits 5-HT1A and 5-HT1B, enhances glutamate reuptake
- oral - available as carbonate and citrate salts
- soluble ion
- eliminated by kidneys (reduced kidney fn associated with greater Li toxicity)
- adverse effects: CNS (tremors, confusion, convulsions, coma), CV (arrhythmias), thyroid dysfunction, renal (polydipsia, polyuria, diabetes insipidus), teratogenic effects, interaction with thiazide diuretics and NSAIDs
-
dextroamphetamine
- amphetamine stimulant
- prevents narcolepsy, rx ADHDoral, liver metabolized, excreted in urine
- smoking or via IV by abusers
- increase release of DA and NE in brain
- - vesicular monoamine transporter
- - inhibit MAO
- - reverse transporter direction (instead of removing from cleft, adds to it)
-
methylphenidate (Ritalin)
- amphetamine stimulant
- prevents narcolepsy, rx ADHD
- oral, high conc in brain, de-esterified product (ritalinic acid) excreted in urine
- increase release of DA and NE in brain
- - vesicular monoamine transporter
- - inhibit MAO
- - reverse transporter direction (instead of removing from cleft, adds to it)
-
methamphetamine
- amphetamine
- no clinical use
- psychomotor stimulant
- abused widely, cheap, easily synthesized
- increase release of DA and NE in brain
- - vesicular monoamine transporter
- - inhibit MAO
- - reverse transporter direction (instead of removing from cleft, adds to it)
-
atomoxetine
- rx ADHD
- NE reuptake inhibitor
- NOT a psychostimulant
- NOT habit forming, not controlled substance
-
amphetamine (Adderall)
- amphetamine stimulant
- prevents narcolepsy, rx ADHD
- oral, high conc in brain, de-esterified product (ritalinic acid) excreted in urine
- increase release of DA and NE in brain
- - vesicular monoamine transporter
- - inhibit MAO
- - reverse transporter direction (instead of removing from cleft, adds to it)
-
modafinil
- narcolepsy treatment
- mechanism unclear - likely NE and DA systems involved
- new drug with fewer psychoactive and euphoric effects, as well as effects on mood and thinking
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