Pharmacology / Psychiatry

Psych pharm – Antidepressants + miscellaneous agents

by MEHLMANMEDICAL

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HY points followed by a quiz at the end

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Antidepressants

Selective serotonin reuptake inhibitors (SSRIs)

  • Be familiar with a few of these names –> fluoxetine, paroxetine, sertraline, escitalopram, citalopram

MOA of SSRIs?

  • Prevent the presynaptic reuptake of serotonin from the synaptic cleft –> increased serotonin in the synaptic cleft –> increased serotonin transmission.

What do I need to know for USMLE in terms of use?

  • First-line for many psych disorders, including depression, OCD, generalized anxiety disorder (GAD), panic disorder, PTSD.
  • Also the first medication given for premature ejaculation (because side-effect is anorgasmia, which is advantageous here).
  • Sertraline classically used for post-MI depression.

What are the HY side-effects for USMLE?

  • Anorgasmia –> major cause of non-compliance, but as mentioned before, this side-effect is advantageous if used for premature ejaculation.
  • Sleep/wake disturbance –> insomnia/somnolence.
  • Serotonin syndrome if combined with St John Wort.
  • SIADH –> high urinary osmolality + low serum sodium in someone being medicated for (usually) depression.
  • Can precipitate mania if erroneously given to patients with bipolar disorder –> if a patient with bipolar disorder is in the depressed phase and is not properly screened for history of mania or hypomania, giving an SSRI can swing the patient into the up-phase –> patients with depression need to be screened for history of mania/hypomania, and if bipolar is the diagnosis, lithium or valproic acid should be commenced, not an SSRI.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

  • Be familiar with a few of these names –> duloxetine, venlafaxine, desvenlafaxine, milnacipran

MOA of SNRIs?

  • Prevent the presynaptic reuptake of serotonin and norepinephrine from the synaptic cleft.

What do I need to know for USMLE?

  • Duloxetine and milnacipran are used first-line for fibromyalgia.
  • Can be used for depression after SSRI (e.g., in patients who’ve failed different SSRIs or who’ve experienced side-effects).
  • SNRIs classically chosen after SSRIs for conditions such as panic disorder, OCD, PTSD, etc.
  • USMLE will not make you choose between an SSRI and SNRI. You just need to be aware of the names and that they have broad application in psych.

Tricyclic antidepressants (TCAs)

  • Be familiar with a few of these names –> amitriptyline, nortriptyline, clomipramine, imipramine, doxepin

MOA of TCAs?

  • Prevent the presynaptic reuptake of serotonin and norepinephrine from the synaptic cleft (yes, similar to SNRIs).

When are TCAs used?

  • First-line for diabetic neuropathic pain.
  • Clomipramine can be used for OCD if SSRI not listed as an answer.
  • Imipramine can be used in theory as a last-line agent for nocturnal enuresis, but on the USMLE, never choose drugs for this diagnosis.
    • Tx for nocturnal enuresis: spend more time with the kid (behavioral answer) –> star chart –> enuresis alarm –> drugs such as desmopressin or TCAs (once again, drugs are always wrong on the USMLE for nocturnal enuresis); this sequence is HY for 2CK Peds forms.
  • 2CK Psych shelf likes doxepin, so be familiar with this name (i.e., don’t disregard it as a “weird TCA I probably don’t need to know.”).
    • 45M + on various meds including doxepin + has delirium; next best step in management? –> answer = “discontinue doxepin,” or “discontinue anti-cholinergic medications.” (explanation about side-effects below)
  • Nortriptyline is used in elderly (on FM shelf).
  • Only used for depression if other agents have failed first.

Side-effects are hugely HY on the USMLE:

  • CCC (the 3Cs) –> Coma, Convulsions, Cardiotoxicity (prolonged QT interval –> causes ↑ risk of precipitating torsades).
    • TCAs interfere with myocardial sodium channels.
  • Causes the “triad” –> anti-cholinergic (anti-muscarinic), anti-alpha 1, anti-H1.
    • If an agent is cholinergic, it will cause DUMBBELSS signs/symptoms –> Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, neuromuscular Excitation, Lacrimation, Salivation, Sweating. Since antipsychotics are anti-cholinergic, they cause the opposite of they will cause the opposite of DUMBBELSS –> Constipation, Urinary retention, Mydriasis, Tachycardia, Not bronchodilation (β2 agonism, but not M antagonism, will bronchodilate), Skeletal muscle relaxation, Dry eye, Dry mouth, Anhydrosis.
      • 23M + started on agent for depression + now has suprapubic mass and is hot and dry; which of the following receptor effects is most likely responsible for this patient’s condition? –> answer = anti-cholinergic (anti-muscarinic); patient has urinary retention (full bladder).
    • Anti-alpha 1 –> orthostatic hypotension + fainting (alpha 1 agonism normally constricts peripheral arterioles, maintaining BP and cerebral perfusion).
    • Anti-H1 –> sedation.
    • The “triad” is seen with TCAs, antipsychotics, and 1st gen H1 blockers (e.g., diphenydramine).

How is TCA toxicity treated?

  • Sodium bicarb (HY) –> causes decreased binding of TCA from myocardial sodium channels.
    • Do not confuse this mechanism with sodium bicarb used for aspirin (salicylate) toxicity; this mechanism is different –> increased excretion through urinary alkalinization (-COOH –> -COO–, where the kidney cannot reabsorb charged species as readily).
    • TCAs are basic (-NH3+ –> NH2), not acidic, so giving bicarb will actually decrease urinary excretion, but the effect on causing dissociation from myocardial sodium channels is how the toxicity is managed.

Monoamine oxidase inhibitors (MOAs)

  • Be familiar with a few of these names –> tranylcypromine, phenelzine, selegiline

MOA of MOAs?

  • Prevent the breakdown of neurotransmitters (mostly serotonin and NE) in the synaptic cleft.
  • Selegiline is used for Parkinson disease and is a MOAB inhibitor –> primarily prevents breakdown of dopamine.

What do I need to know for USMLE?

  • MOAs are classically associated with serotonin syndrome. The risk is particularly elevated when the patient is switching to a MOA from a different drug class (usually SSRI) and not enough time has passed. “Washout periods” upwards of 6 weeks are generally required.
    • 22F + switched to tranylcypromine + discontinued fluoxetine a week ago + now has tachycardia, diaphoresis, flushing + temperature of 105F; treatment? –> cyproheptadine (blocks serotonin receptors).
  • MOAs can precipitate serotonin syndrome if the patient is simultaneously taking St John wort, meperidine, dextromethorphan, or linezolid.
  • MOAs are considered the most effective agents for treating atypical depression (depression where the patient notably has hypersomnolence + hyperphagia + the depression is reversible with positive social affirmation), but SSRIs are still first-line.

Mirtazapine

MOA of mirtazapine?

  • Alpha 2 antagonist –> increases presynaptic release of serotonin and NE.
  • Alpha 2 is normally a negative feedback receptor on the presynaptic terminal. When NE binds to it, this results in decreased NE and serotonin release.

When is mirtazapine used?

  • Patients who have depression + anorexia –> mirtazapine stimulates appetite.

Bupropion

MOA of bupropion?

  • Inhibits reuptake of NE and dopamine, with minimal effect on serotonin reuptake.

What do I need to know for USMLE?

  • Bupropion can cause seizures (i.e., lowers seizure threshold) –> do not give to patients with history of eating disorders (because of risk of electrolyte disturbance –> further risk of seizure).
  • Does not cause sexual dysfunction –> notably can be given to patients who decline SSRIs because of the anorgasmia side-effects, or who have had history of erectile dysfunction.
  • Can be used as a smoking cessation agent (as with varenicline, mentioned below).

Miscellaneous HY agents

Lithium

MOA of lithium?

  • Called a “mood-stabilizer.”
  • Regulates the rate of phosphoinositide synthesis in neurons.

When is it used?

  • Used first-line in bipolar disorder. If lithium isn’t used, valproic acid is also considered a first-line agent for bipolar.

Why does USMLE care so much about lithium?

  • Because of its nasty side-effects. Know these well for USMLE:
  • Tremor
    • Thiazides and loop diuretics are known to cause lithium toxicity –> the diuretics lead to increased compensatory reabsorption of sodium by the PCT –> lithium and sodium are both Group 1 metals and reabsorbed by the same transporters –> increased lithium reabsorption.
    • 40F + bipolar disorder + history of calcium nephrolithiasis + started on HCTZ in order prevent recurrent stones –> develops tremor; why? –> answer = thiazide causing lithium toxicity.
  • Nephrogenic diabetes insipidus –> insensitivity of the medullary collecting duct to the effects of ADH (vasopressin).
    • 38M + bipolar disorder + started on medication + now has tremor and is peeing a lot; what are the tonicities of the urine at the PCT, JGA, and medullary collecting duct compared to the serum? –> answer = PCT isotonic; JGA hypotonic; medullary collecting duct hypotonic.
    • PCT is always isotonic no matter what; JGA is always hypotonic no matter what (connects early-DCT to afferent arterioles; the early-DCT is always hypotonic no matter what because the thick-ascending limb of Henle reabsorbs copious ions); medullary collecting duct is hypotonic in DI (and hypertonic in SIADH and dehydration).
  • Hypothyroidism
    • Do not discontinue lithium; just add levothyroxine (sounds wrong, but on USMLE).
  • Ebstein anomaly
    • Lithium is a teratogen.
    • If a woman takes lithium while pregnant, the fetal heart may develop “atrialization of the right ventricle,” where the tricuspid valve develops inferiorly, making the RV very small (essentially instead of RV, we get a bigger RA).
  • Hepatotoxicity
    • ↑LFTs (mild transaminitis) is normal and expected in patients commencing hepatotoxic agents –> do not discontinue drug or reduce dose if mild elevation of LFTs occurs.
  • Lithium notably has a narrow therapeutic window –> means the difference between the minimum dose required for therapeutic effect vs the dose which causes toxicity is very small –> in other words, lithium is notably associated with high risk of toxicity because it’s easy to overdose.

Buspirone

MOA of buspirone?

  • Serotonin (5HT1A) receptor agonist.

When is it used?

  • Second-line for generalized anxiety disorder (GAD); first-line for for GAD is SSRIs, but USMLE wants you to know the MOA and use of buspirone nevertheless.

Trazodone

MOA of trazodone?

  • Blocks reuptake of serotonin.

When is it used?

  • Treatment of insomnia

What do I need to know for USMLE?

  • Can cause serotonin syndrome as a stand-alone agent.
  • Can cause priapism.

Varenicline

MOA of varenicline?

  • Nicotinic receptor partial agonist

When is it used?

  • Used for smoking cessation.

Anything else I need to know for USMLE?

  • Varenicline causes wild/intense dreams (similar to the HIV drug efavirenz).

Opioid-detox and -relapse agents

Methadone

  • Oral opioid with long half-life used for heroin detox (i.e., helps wean patients off heroin + prevent relapses).
  • Binds to mu-receptors.

Buprenorphine

  • Sublingual opioid used for heroin detox (i.e., binds to opioid receptors and helps wean patients off heroin + prevent relapses).
  • Weak opioid with effects mostly at  kappa-receptors.

Naloxone

  • Opioid receptor antagonist used to treat heroin overdose.

Naltrexone

  • Oral opioid antagonist to prevent cravings in those who have alcohol dependence or history of heroin use.
  • When the patient is actively weaning off heroin, methadone is used because it’s an opioid receptor agonist (same as heroin), but once the patient has weaned off, antagonistic effects at kappa-receptor have been shown to decrease cravings.
  • Psych shelf for 2CK likes naltrexone as used for decreasing alcohol cravings.

Disulfiram

  • Drug used in alcoholics to decrease drinking.
  • Acetaldehyde dehydrogenase inhibitor –> produces hangover symptoms –> incentivizes non-drinking.
  • Normal ethanol metabolism is EtOH –> acetaldehyde –> acetic acid. If patient drinks EtOH, disulfiram causes a buildup of acetaldehyde, which produces hangover symptoms.

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1. Which of the following agents are SSRIs? (check all that apply)

 
 
 
 
 
 
 
 
 

2. Which of the following agents are SNRIs? (check all that apply)

 
 
 
 
 
 
 
 
 

3. SSRIs can cause which of the following? (select all that apply)

 
 
 
 
 
 

4. 23M + depressed mood + started on citalopram a week ago + now has flight of ideas and pressured speech; what happened?

5. 31F + has pain in 12 symmetric pressure points across her body + recently stressed at work + remainder of history and exam unremarkable;

a) What’s the most likely diagnosis?

b) What are two first-line pharmacologic treatments for her condition?

6. If we give a TCA to an elderly patient, which one do we normally give, and why?

7. Name two first-line agents for OCD.

8. How do we treat nocturnal enuresis (bedwetting in kids age 5+)?

9. 45M + on various meds including doxepin + has delirium; next best step in management?

10. Which of the following are TCAs? (select all that apply)

 
 
 
 
 

11. What are the HY side-effects of TCAs for USMLE?

12. a) What’s the treatment for TCA toxicity?

b) What’s the mechanism via which this works?

13. What’s the MOA of TCAs?

14. Name three monoamine oxidase inhibitors.

15. a) MOA of selegiline?

b) What’s it used for?

16. 22F + switched to tranylcypromine + discontinued fluoxetine a week ago + now has tachycardia, diaphoresis, flushing + temperature of 105F; treatment?

17. 49F + started on tranylcypromine + now has tachycardia, diaphoresis, flushing + temperature of 105F. Patient says she takes various vitamins and nature supplements at home. What’s the diagnosis?

18. a) What is atypical depression?

b) How is it treated first-line?

c) What’s the most effective treatment?

19. a) MOA of mirtazapine?

b) When’s it used?

20. a) MOA of bupropion?

b) What are three HY factoids about it for USMLE?

21. a) MOA of lithium?

b) When’s it used?

22. Name five adverse effects of lithium.

23. 40F + bipolar disorder + history of calcium nephrolithiasis + started on HCTZ in order prevent recurrent stones –> develops tremor; why?

24. 38M + bipolar disorder + started on medication + now has tremor and is peeing a lot; what are the tonicities of the urine at the PCT, JGA, and medullary collecting duct compared to the serum?

25. Patient with bipolar is started on lithium + now has low T3, low T4, and high TSH. What do we do?

 
 
 
 

26. What is Ebstein anomaly? What causes it?

27. Patient starts lithium for bipolar + now has elevated LFTs; what do we do?

 
 
 
 

28. a) MOA of buspirone?

b) When’s it used?

29. a) MOA of trazodone?

b) When is it used?

c) What are two adverse effects?

30. a) MOA of varenicline?

b) When is it used?

c) What is its notable adverse effect?

31. a) MOA of methadone?

b) What’s it used for?

32. a) MOA of buprenorphine?

b) What’s it used for?

33. a) MOA of naloxone?

b) What’s it used for?

34. MOA of naltrexone? And what’s it used for?

35. a) Name two smoking cessation agents.

b) What are their respective MOAs?

36. How is generalized anxiety disorder treated pharmacologically?

37. Which antidepressant treats patients who have both depression and anorexia?

38. Which antidepressant is notably not associated with any sexual side-effects?

39. Which agent is a monoamine oxidase type B inhibitor?

40. What’s the MOA of milnacipran?

41. What’s the pharmacologic treatment for premature ejaculation?

42. What’s the MOA of desvenlafaxine?

43. What’s the MOA of doxepin?

44. What’s the MOA of tranylcypromine?

45. Which antidepressant lowers the seizure threshold (i.e., increases the risk of seizures)?

46. Which psych drug regulates the rate of phosphoinositide synthesis in neurons?

47. Which psych drug helps curb alcohol cravings?

48. What’s the MOA of disulfiram? And what’s it used for?



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