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USMLE - Pharm

Kaplan Section 4 Chapter 1 CNS Pharm - Antidepressants

What is the pathological basis of major depressive disorders Amine hypothesis: depletion/deficiency of NE and/or 5HT in brain
What is the basic mechanism of anti-depressant medications increase NE and/or 5HT
Why wouldn't you give reserpine to someone at risk of depressive episodes? depletes brain amines and cauess depression
Phenelzine Inhibits both MAO type A (liver; metabolizes NE, 5HT, tyramine) and MAO type B (brain; metabolizes DA)
Tranylcypromine Inhibits both MAO type A (liver; metabolizes NE, 5HT, tyramine) and MAO type B (brain; metabolizes DA)
What are the side effects of phenelzine and tranylcypromine? orthostatic hypotension, weight gain
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!
What drugs do MAO inhibitors interact with? (2) Meperidine (narcotic analgesic), dextromethorphan (cough suppressant) ==> hyperthermia!
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
Serotonin Syndrome diaphoresis, rigidity, myoclonus, hyperthermia, ANS instability, and seizures
Name three tricyclic antidepressants I'm Ami Clom: Imipramine Amitriptyline, Clomipramine.
What is the mechanism of tricyclic antidepressants? block reuptake of both NE and 5HT --> inc adrenergic and serotonergic neurotransmission
How are TCA's similar to phenothiazines? Phenothiazines are anti-psychotic drugs. Both classes have M block, a block, sedation, and dec seizure threshold.
What is the major reason people who OD on TCA's die? quinidine-like cardiotoxicity
What is the triad of TCA-adverse side effects? 3 C's: coma, convulsions, cardiotoxicity.
Other TCA side effects 1. autonomic, 2. additive sedation with other CNS depressants, 3. weight gain
What would you use TCA's for? 1. major depressions, 2. phobic and panic anxiety states, 3. neuropathic pain, 4. enuresis, 5. OCD
Do patients experience withdrawal upon discontinuance of TCA's? yes: nausea headache, vertigo, malaise, nightmares
What drugs do TCA's interact with? MAO inhibitors --> hyperthermia, seizures, coma, death
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
What drugs do TCA's interact with? prevent anti-HTN effect of guanethidine (prevents NE release) and a2 agonists (prevent NE release)
Name the drugs that block the reuptake of serotonin SSRI's (selective serotonin reuptake inhibitors), TCA's, trazodone, nefazodone
Name the drugs that block the reuptake of NE TCA's, cocaine, amoxapine, atomoxetine, maprotiline
What is atomoxetine specifically used for? ADHD
Name 3 SSRI's -- what do they do? fluoxetine, paroxetine, sertraline. They selectively block the reuptake of 5HT --> inc serotonin activity
What is special about the effectiveness of fluoxetine? forms a long-acting metabolite, norfluoxetine, that contributes to its effects
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)
What would you use SSRI's for? major depressions, anxiety states (panic, phobias, social), premenstrual dysphoric disorder (severe PMS), bulimia, OCD, alcoholism
Do patients experience withdrawal upon discontinuance of TCA's? yes, but usually when used for depression: nausea headache, vertigo, malaise
what drugs do SSRI's interact with? MAO inhibitors, TCA's, meperidine (narcotic analgesic), dextromethorphan (cough suppressant) ==> serotonin syndrome
Name 4 types of antidepressants 1. MAOi's, 2. TCA's, 3. heterocyclic antidepressants, 4. SSRI's
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)
What drug would you use for smoking cessation? bupropion
What SSRI is a P450 inhibitor? nefazodone
Which SSRI is associated with priapism? trazodone
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
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
What is the DOC for bipolar disorder? lithium (stabilizes mood), but also need antidepressants to improve depressive phases
What is the onset for the DOC in bipolar disorder? 2 weeks
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
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.
Name some adverse side effects of Lithium. tremor, ataxia, choreoathetosis, acne, edema visual dysfunction, seizures, goiter
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.
How does lithium affect the thyroid? causes hyPOthyroidism because it inhibits 5' deiodinase (enzyme in conversion of T4 to T3)
How does lithium affect the V2 receptors? uncouples the vasopressin V2 receptors --> nephrogenic diabetes insipidus
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
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.
What happens when pregnant pts use Li? Neonatal toxicity: lethargy cyanosis, hepatomegaly. Teratogenicity remains to be confirmed.
Name 2 backup drugs for bipolar disorder. Valproic acid (affects GABA) and carbamazepine (stabilizes inactive state of Na channels - make brain less excitable).
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).
Created by: christinapham



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