Pharmacology Exam 4

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Rx2013
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49366
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Pharmacology Exam 4
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2010-11-14 00:11:56
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Antidepressant drugs lithium
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antidepressant drugs and lithium
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  1. mental state of excessive sadness characterized by persistently low mood or extensive loss of pleasure and interest
    Major depressive disorder
  2. Tricyclic antidepressants
    • three ring core
    • similar to phenothiazines
    • most NE reuptake inhibitors
  3. Tertiary amines
    • inhibit both NE and 5HT reuptake
    • imipramine: also anticholinergic
    • amitriptyline
    • trimipramine: no inhibition at monoamine transport
    • clomipramine: most potent; also used for OCD
    • doxepin
  4. Secondary amines
    • relatively selective NE reuptake inhibitors
    • desipramine: less anti ach effect
    • nortriptyline: not selective
    • protriptyline
  5. Pharmacological action of tricyclic antidepressants in non-depressed pt
    no mood elevating effects
  6. action of tricyclic antidepressants in depressed patients
    • elevate mood
    • decrease time in REM sleep
  7. Anticholinergic actions of TCAs
    3` greater than 2`
  8. TCA alpha adrenergic blockade
    selective fore alpha 1 more than alpha 2, no affinity for beta
  9. Mechanism of action for TCAs
    inhibit neuronal uptake of biogenic amines in the CNS (NE and 5HT)
  10. Pharmacokinetic properties of TCAs
    • high protein binding
    • highly lipophilic
    • well absorbed
    • significant 1st pass metabolism
  11. Side effects of TCAs
    • anti ACH and alpha adrenergic blockade are common: GI & postural hypotension
    • weight gain
    • excessive sweating
  12. CNS side effects of TCAs
    • hypomania to mania transition
    • restlessness
    • insomnia
    • tremor/seizures
    • antihistamine effects
  13. Cardiac toxicity of TCAs
    • tachycardia
    • orthostatic hypotension
  14. Drug interactions with TCAs
    compete with antiepileptics, antipsychotics, smoking and barbituates
  15. Interaction of TCAs with antipsychotics
    prodtein binding and additive anticholinergic action
  16. interactions of TCAs with anihypertensive agents
    guanethidine
  17. interactions of TCAs with MAOIs
    • serotonin syndrome when co-treated with SSRIs
    • akathisia like restlessness
  18. Therapeutic uses of TCAs
    • used toether with lithium for BPD
    • enuresis in children and elderly
    • ADHD (NE selective)
    • Tourette's
    • Severe anxiety disorders
    • chronic pain
  19. commonly used SSRT Drugs
    • fluoxetine
    • paroxetine
    • sertraline
    • citalopram
    • fluvoxamine
  20. pharmacodynamic action of SSRIs
    high affinity for serotonin transporter 80% inhibition but not histamine, ach and alpha-adrenoceptors
  21. Pharmacokinetics of SSRIs
    • highly lipophilic
    • active metabolite is norfluoxetine
  22. potent inhibitors of CYP2D6 and TCA
    fluoxetine and paroxetine
  23. Side effects and toxicity of SSRIs
    • GI upset
    • weight gain
    • sexual function
  24. Drug interactions with SSRIS
    causes 5-HT syndrome with MAOIs
  25. Therapeutic uses of SSRIs
    • MDD
    • GAD
    • PTSD
    • OCT
    • Panic disorder
    • PMDD & bulimia
  26. SNRIs
    venlafaxin and duloxetine
  27. Drug interactions with SNRIs
    MAOI causes 5HT syndrome
  28. Therapeutic uses of SNRIs
    • panic disorder
    • social anxiety disorder
    • pain disorder
    • urinary incontinence
  29. may be used for diabetic neuropathy and fibromyalgia
    duloxetine
  30. 5HT2 antagonists
    • trazodone
    • nefazodone (hepatotoxicity)
  31. Atypical antidepressants
    bupropion mirtazapine
  32. bupropion
    • unicyclic
    • blocks NE and DA reuptake
    • increased availability of NE and DA
    • smoking cessation
  33. Mirtazapine
    • tetracyclic
    • presynaptic A2 autoreceptor antagonist
    • blocks 5HT2 and 5HT3 receptors
    • H1 antagonist
  34. Non-selective & irreversible MAOIs
    • phenelzine
    • Tranylcypromine
  35. Selective MAOIs
    • selegiline (MAO-B)
    • Clorgyline (MAO-A)
  36. Pharmacologic actions of MAOIs
    • Mood elevation in depressed patient
    • increased motor activity and appetite
    • excitement and euphoria
    • Suppression of REM sleep
  37. Mechanisms of action of MAOIs
    • inhibit oxidative deamination of monoamines (NE and 5HT)
    • Tranylcypromine: amphetamine like effects
  38. Pharmacokinetic properties of MAOIs
    • readily absorbed
    • not given parenterally
    • Hydrazide: cleaved to hydrazine then acylated
  39. Side effects and toxicity of MAOIs
    • excessive CNS stimulation
    • orthostatic hypotension
    • weight gain
    • anorgasmia
    • hepatotoxicity (especially with hydrazides)
  40. Drug and Food interactions with MAOIs
    • enhance effects of CNS depressants by interfering with metabolism
    • potentiate effects of sympathomimetics (hypertensive crisis)
    • Tyramine may lead to hypertensive crisis
    • first pass metabolism in GI tract and tyramine
  41. Therapeutic uses of MAOIs
    • secondary use for depression
    • phobic anxiety when TCA and ECT don't work
  42. uses for lithium carbonate
    • BPD (especially manic phase)
    • prevention of mania and depression
    • recurrent endogenous depression
    • schizophrenia
    • unipolar depression
  43. Mechanism of lithium
    • inhibiting sodium dependent action potentials and sodium exchange across the membrane
    • inhibition of IP3 and DAG production in neurons, GSK3 inhibition
    • Decreases NE and DA turnover
    • increases 5 HT activity amd ACH synthesis
    • blocks DA receptor supersensitivity
  44. Pharmacokinetics of lithium
    • readily absorbed
    • eliminated through urine
    • increased sodium = increased lithium excretion
    • low therapeutic index, requires monitoring
  45. Toxicity with lithium
    • acute intoxication
    • tremor (propranolol and atenolol may be used)
    • prolonged effects
    • edema & sodium retention
  46. Prolonged effects with lithium
    • ligand-GPCR uncoupling
    • hypothyroidism/increased TSH secretion
    • polydipsia
    • polyuria
    • aquired nephrogenic diabetes insipidus
  47. Drug interactions with lithium
    • diuretics (increase reabsorption of Li)
    • aspirin and acetamenophen
    • Norepinephrine (Li antagonizes NE effect on blood pressure)
    • old neuroleptics: severe extrapyramidal syndrome
  48. Act on MAO
    MAO inhibitors
  49. Act on NE reuptake
    • desipramine
    • maprotiline
  50. Acto on alpha 2 receptor
    mirtazapine
  51. act on 5-HT reuptake
    • fluoxetine
    • trazodone

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