Kaplan Section 4 Chapter 1 CNS Pharm - Antidepressants
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| What is the pathological basis of major depressive disorders | Amine hypothesis: depletion/deficiency of NE and/or 5HT in brain
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| What is the basic mechanism of anti-depressant medications | increase NE and/or 5HT
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| Why wouldn't you give reserpine to someone at risk of depressive episodes? | depletes brain amines and cauess depression
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| Phenelzine | Inhibits both MAO type A (liver; metabolizes NE, 5HT, tyramine) and MAO type B (brain; metabolizes DA)
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| Tranylcypromine | Inhibits both MAO type A (liver; metabolizes NE, 5HT, tyramine) and MAO type B (brain; metabolizes DA)
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| What are the side effects of phenelzine and tranylcypromine? | orthostatic hypotension, weight gain
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| What drugs do MAO inhibitors interact with? (1) | tyramine, NE uptake blockers (cocaine, TCA's), a agonists (phenylephrine, methoxamine, clonidine, methyldopa), L-dopa ==> HTN crises!
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| What drugs do MAO inhibitors interact with? (2) | Meperidine (narcotic analgesic), dextromethorphan (cough suppressant) ==> hyperthermia!
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| What drugs do MAO inhibitors interact with? (3) | SSRI's (selective serotonin reuptake inhibitors) ==> serotonin syndrome (serotonin toxicity; excess serotonergic activity at central nervous system (CNS) and peripheral serotonin receptors, overstimulation of 5-HT1A (CNS) receptors in central grey nuclei
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| Serotonin Syndrome | diaphoresis, rigidity, myoclonus, hyperthermia, ANS instability, and seizures
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| Name three tricyclic antidepressants | I'm Ami Clom: Imipramine Amitriptyline, Clomipramine.
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| What is the mechanism of tricyclic antidepressants? | block reuptake of both NE and 5HT --> inc adrenergic and serotonergic neurotransmission
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| How are TCA's similar to phenothiazines? | Phenothiazines are anti-psychotic drugs. Both classes have M block, a block, sedation, and dec seizure threshold.
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| What is the major reason people who OD on TCA's die? | quinidine-like cardiotoxicity
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| What is the triad of TCA-adverse side effects? | 3 C's: coma, convulsions, cardiotoxicity.
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| Other TCA side effects | 1. autonomic, 2. additive sedation with other CNS depressants, 3. weight gain
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| What would you use TCA's for? | 1. major depressions, 2. phobic and panic anxiety states, 3. neuropathic pain, 4. enuresis, 5. OCD
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| Do patients experience withdrawal upon discontinuance of TCA's? | yes: nausea headache, vertigo, malaise, nightmares
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| What drugs do TCA's interact with? | MAO inhibitors --> hyperthermia, seizures, coma, death
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| What drugs do TCA's interact with? | SSRI's (selective serotonin reuptake inhibitors) ==> serotonin syndrome (serotonin toxicity; excess serotonergic activity at central nervous system (CNS) and peripheral serotonin receptors, overstimulation of 5-HT1A (CNS) receptors in central grey nuclei
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| What drugs do TCA's interact with? | prevent anti-HTN effect of guanethidine (prevents NE release) and a2 agonists (prevent NE release)
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| Name the drugs that block the reuptake of serotonin | SSRI's (selective serotonin reuptake inhibitors), TCA's, trazodone, nefazodone
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| Name the drugs that block the reuptake of NE | TCA's, cocaine, amoxapine, atomoxetine, maprotiline
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| What is atomoxetine specifically used for? | ADHD
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| Name 3 SSRI's -- what do they do? | fluoxetine, paroxetine, sertraline. They selectively block the reuptake of 5HT --> inc serotonin activity
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| What is special about the effectiveness of fluoxetine? | forms a long-acting metabolite, norfluoxetine, that contributes to its effects
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| What are the adverse effects of SSRI's? | anxiety, agitation (may need sedative), bruxism (gnashing of teeth), sexual dysfxn (anorgasmia), seizures (OD), weight loss (regained after 12 mo on Rx)
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| What would you use SSRI's for? | major depressions, anxiety states (panic, phobias, social), premenstrual dysphoric disorder (severe PMS), bulimia, OCD, alcoholism
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| Do patients experience withdrawal upon discontinuance of TCA's? | yes, but usually when used for depression: nausea headache, vertigo, malaise
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| what drugs do SSRI's interact with? | MAO inhibitors, TCA's, meperidine (narcotic analgesic), dextromethorphan (cough suppressant) ==> serotonin syndrome
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| Name 4 types of antidepressants | 1. MAOi's, 2. TCA's, 3. heterocyclic antidepressants, 4. SSRI's
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| Name 6 heterocyclic antidepressants | amoxapine and maprotiline (block NE reuptake); nefazodone and trazodone (block 5HT reuptake); mirtazapine - blocks presynaptic a2 receptors --> prevent feedback inhib --> more NE release; bupropion (affects DA transmission)
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| What drug would you use for smoking cessation? | bupropion
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| What SSRI is a P450 inhibitor? | nefazodone
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| Which SSRI is associated with priapism? | trazodone
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| What is priapism? | persistent, usually painful, erection that lasts for more than four hours and occurs without sexual stimulation. The condition develops when blood in the penis becomes trapped and unable to drain
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| What is bipolar disorder? | category of mood disorders defined by the presence of one or more episodes of abnormally elevated mood, mania; also commonly experience depressive episodes or symptoms; episodes are separated by periods of nl mood
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| What is the DOC for bipolar disorder? | lithium (stabilizes mood), but also need antidepressants to improve depressive phases
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| What is the onset for the DOC in bipolar disorder? | 2 weeks
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| Talk about Li's therapeutic window and toxicity | narrow therapeutic window; elim by kidney like Na, so if low Na (or chornic diuretic treatment) --> less drug eliminated --> greater toxicity
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| What is the mechanism of Li for mood stabilization? | inhibition of dephosphorylation of IP2 --> IP1 and IP1 to IP. These dephosphorylation steps are required in recycling of inositol --> dec PIP2 availability --> less effects on Ach/NE/5HT levels. Also, dec cAMP fxns as 2nd messenger.
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| Name some adverse side effects of Lithium. | tremor, ataxia, choreoathetosis, acne, edema visual dysfunction, seizures, goiter
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| What is choreoathetosis? | Choreoathetosis is a movement of intermediate speed, between the quick, flitting movements of chorea and the slower, writhing movements of athetosis. Worsens with intended movement.
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| How does lithium affect the thyroid? | causes hyPOthyroidism because it inhibits 5' deiodinase (enzyme in conversion of T4 to T3)
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| How does lithium affect the V2 receptors? | uncouples the vasopressin V2 receptors --> nephrogenic diabetes insipidus
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| How would you treat the adverse effects of Li? | Give amiloride -- K sparing diuretic that inhibits the ENaC channels --> inhibit Na reabsorption --> loss of Na and H2O from body, clears Li
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| How would you treat nephrogenic diabetes insipidus? | Give a thiazide diuretic, but this may cause increased reabsorption of Li. WHY?? So thiazide is not best choice.
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| What happens when pregnant pts use Li? | Neonatal toxicity: lethargy cyanosis, hepatomegaly. Teratogenicity remains to be confirmed.
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| Name 2 backup drugs for bipolar disorder. | Valproic acid (affects GABA) and carbamazepine (stabilizes inactive state of Na channels - make brain less excitable).
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| What would you give pregnant pts with bipolar disorder? | Clonazepam (BZ - enhances GABA action -- more brain inhib) or gabapentin (bind to voltage-gated Ca channel in CNS).
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