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| 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). |
