Pharm Test #3

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  1. Monoamine/ Biogenic Amine Hypothesis
    abnormalities in serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurotransmission
  2. Neurotrophic Hypothesis
    • changes in nerve growth factors (ie: BDNF) play a role in cell survival and synaptic plasticity
    • ex: loss of monoamines or increased glucocorticoids (stress)
  3. Tricyclic Antidepressants
    • Imipramine, Amitriptyline, Desipramine
    • block NE and 5-HT reuptake (increased synaptic concentrations)
    • largely replaced by SSRIs
    • not used for elderly
  4. Imipramine
    • anticholinergic effects (used for enuresis)
    • strong 5-HT and NE (to lesser extent) reuptake inhibition
  5. Desipramine
    • less anticholinergic action
    • stronger NE reuptake inhibition than 5-HT
    • more effective at treating neuropathic pain
  6. Amitriptyline
    • highly anticholinergic
    • high alpha blocking properties (causes orthostatic hypotension
    • most sedative of TCAs
  7. TCA side effects
    • muscarinic receptor blockers: anticholinergic (dry mouth, constipation, blurred vision)
    • CNS toxicity
    • cardiotoxicity: Na/Ca channel blockers
    • sexual dysfunction
    • weight gain
  8. Specific Serotonin Reuptake Inhibitors (SSRIs)
    • Fluoxetine, Paroxetine, Citalopram, Escitalopram, Sertraline
    • most widely prescribed
    • used for other psychiatric conditions
    • block reuptake of 5-HT (increased synaptic concentration)
  9. SSRI side effects
    • safest of all antidepressants
    • nervousness, agitation, sweating, fatigue, GI upset
    • sexual dysfunction
    • serotonin syndrome (when used in combo)
  10. Serotonin Syndrome
    • occurs when SSRI used in combo w/ another SSRI or MAOI
    • early: lethargy, restlessness, confusion, diaphoresis, tremor
    • untreated: hypertension, hyperthermia, rhabdomyolysis, death
  11. Discontinuation Syndrome
    • 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)
  12. Atypical: Alpha Blocker
    • Mirtazapine
    • blocks alpha2 receptors (increased synaptic 5-HT and NE)
    • blocks 5-HT3 receptors (anti-emetic)
    • effects: sedation, weight gain, no sexual
  13. Atypical: 5-HT2 antagonist
    • Trazodone
    • weak 5-HT reuptake blockade
    • effects: sedative, priapism (peripheral A1 blocker)
    • no tolerance or dependence
  14. Atypical: SNRIs
    • Venlafaxine, Duloxetine
    • block 5-HT, NE reuptake
    • duloxetine- balanced inhibition (used for neuropathic pain)
  15. Atypical: DA/NE blocker
    • Bupropion
    • DA/NE reuptake inhibitor
    • effects: lowers seizure threshold
  16. Monoamine Oxidase Inhibitors (MAOIs): irreversible
    • 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)
  17. Monoamine Oxidase Inhibitors (MAOIs): MAO-A competitive
    • Moclobemide
    • competitive inhibition of MAO-A
  18. Monoamine Oxidase Inhibitors (MAOIs): MAO-B competitive
    • 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
  19. MAOI's side effects
    • postural hypotension, dry mouth, blurry vision, weight gain, restlessness, anorgasmia
    • Phenelzine- irreversible, Moclobemide- transient
  20. MAO-A inhibitors and Tyramine
    • 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)
  21. Antidepressant Treatment Notes
    • 2-4 weeks to reach max benefit
    • SSRIs are safer in overdose
    • MAOIs, TCAs, and SSRIs should not be combined
  22. Lithium
    • blocks hydrolysis of IP, inhibits NE release, enhances glutamate reuptake
    • mood-stabilizing
    • 60-80% success rate for achieving remission from manic phase
  23. Lithium side effects
    • subclinical hypothyroidism
    • nephrogenic diabetes insipidus
    • weight gain, GI upset, skin reactions, hand tremors
  24. Lithium drug interactions
    • Thiazide and loop diuretics diminish clearance (lead to toxicity)
    • diuretics block Na reabsorption: Na and Lithium are reabsorbed from proximal tubule (elevates plasma Li [ ])
  25. CNS depressant: Barbiturates
    • Pentobarbital, Thiopental, Phenobarbital
    • anxiolytic by virtue of sedative effects
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Pharm Test #3
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