Pharm Test #3

abnormalities in serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurotransmission

• changes in nerve growth factors (ie: BDNF) play a role in cell survival and synaptic plasticity
• ex: loss of monoamines or increased glucocorticoids (stress)

• Imipramine, Amitriptyline, Desipramine
• block NE and 5-HT reuptake (increased synaptic concentrations)
• largely replaced by SSRIs
• not used for elderly

• anticholinergic effects (used for enuresis)
• strong 5-HT and NE (to lesser extent) reuptake inhibition

• less anticholinergic action
• stronger NE reuptake inhibition than 5-HT
• more effective at treating neuropathic pain

• highly anticholinergic
• high alpha blocking properties (causes orthostatic hypotension
• most sedative of TCAs

• muscarinic receptor blockers: anticholinergic (dry mouth, constipation, blurred vision)
• CNS toxicity
• cardiotoxicity: Na/Ca channel blockers
• sexual dysfunction
• weight gain

• Fluoxetine, Paroxetine, Citalopram, Escitalopram, Sertraline
• most widely prescribed
• used for other psychiatric conditions
• block reuptake of 5-HT (increased synaptic concentration)

• safest of all antidepressants
• nervousness, agitation, sweating, fatigue, GI upset
• sexual dysfunction
• serotonin syndrome (when used in combo)

• occurs when SSRI used in combo w/ another SSRI or MAOI
• early: lethargy, restlessness, confusion, diaphoresis, tremor
• untreated: hypertension, hyperthermia, rhabdomyolysis, death

• sudden discontinuation of short half-life SSRIs
• symptoms: dizziness, paresthesias
• why: clearance of drug occurs faster than re-adaptation to receptor regulation and sensitization
• switch to SSRI with longer half-life (fluoxetine)

• Mirtazapine
• blocks alpha2 receptors (increased synaptic 5-HT and NE)
• blocks 5-HT3 receptors (anti-emetic)
• effects: sedation, weight gain, no sexual

• Trazodone
• weak 5-HT reuptake blockade
• effects: sedative, priapism (peripheral A1 blocker)
• no tolerance or dependence

• Venlafaxine, Duloxetine
• block 5-HT, NE reuptake
• duloxetine- balanced inhibition (used for neuropathic pain)

• Bupropion
• DA/NE reuptake inhibitor
• effects: lowers seizure threshold

• Phenelzine, Tranylcypromine
• irreversible binding of MAO-A & B
• MAO-A: liver, brain, GI, sympathetic nerves (5-HT, NE, DA, and Tyramine neurons)
• MAO-B: brain, liver, platelets (DA neurons)

• Moclobemide
• competitive inhibition of MAO-A

• Selegiline
• competitive inhibition of MAO-B
• MAO-B not present in GI, so no tyramine restrictions needed at low doses
• high dose (patch): avoids first pass effect

• postural hypotension, dry mouth, blurry vision, weight gain, restlessness, anorgasmia
• Phenelzine- irreversible, Moclobemide- transient

• must avoid certain foods (ex: cheese, preserved meats and fish, fava beans, chianti, chocolate)
• tyramine triggers release of catecholamines, which can cause hypertensive crisis (stroke)

• 2-4 weeks to reach max benefit
• SSRIs are safer in overdose
• MAOIs, TCAs, and SSRIs should not be combined

• blocks hydrolysis of IP, inhibits NE release, enhances glutamate reuptake
• mood-stabilizing
• 60-80% success rate for achieving remission from manic phase

• subclinical hypothyroidism
• nephrogenic diabetes insipidus
• weight gain, GI upset, skin reactions, hand tremors

• Thiazide and loop diuretics diminish clearance (lead to toxicity)
• diuretics block Na reabsorption: Na and Lithium are reabsorbed from proximal tubule (elevates plasma Li [ ])

• Pentobarbital, Thiopental, Phenobarbital
• anxiolytic by virtue of sedative effects