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Psychopharmacology What you should know to survive the LMCC and Internship

Psychopharmacology What you should know to survive the LMCC and Internship. Dr. Kate Huntington khunting@rohcg.on.ca April 2011. Objectives. To review: indications for mechanism of action side effects (remember not everyone gets these) monitoring parameters

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Psychopharmacology What you should know to survive the LMCC and Internship

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  1. PsychopharmacologyWhat you should know to survive the LMCC and Internship Dr. Kate Huntington khunting@rohcg.on.ca April 2011

  2. Objectives To review: • indications for • mechanism of action • side effects (remember not everyone gets these) • monitoring parameters for the major classes of psychotropic medications

  3. Which of the following is not a common side effect of SSRI’s? • a. Nausea • b. Headache • c. Rigidity • d. Anxiety • e. Sleep disruption

  4. Which of the following receptors does Mirtazepine not block? • a. Histamine • b. 5HT1 • c. 5HT2 • d. 5HT3 • e. Alpha 2

  5. At which dose level does Venlafaxine typically begin to have a noradrenergic effect? • a. 75mg • b. 150mg • c. 225mg • d. 300mg

  6. Which is not an indication for the use of Benzodiazepines? • a. Catatonia • b. Long term hypnotic • c. Mania • d. Alcohol withdrawal • e. Anxiety

  7. How are the novel hypnotics different from Benzodiazepines? • a. Do not cause falls • b. Do not lead to tolerance • c. Used as long term hypnotics • d. More selective for the alpha one subtype of GABA-A receptor

  8. Which of these is the most prominent side effect of atypical antipsychotics? • a. Rigidity • b. Dystonia • c. Dyskinesia • d. Akathisia

  9. Which of the following is an example of a low potency typical antipsychotic? • a. Haldol • b. Pimozide • c. Olanzapine • e. Clomipramine • f. Chlorpromazine

  10. Which class of cognitive enhancers is indicated in mild to moderate Alzheimer’s Disease? • a. Cholinesterase inhibitor • b. NMDA receptor antagonist

  11. Which mood stabilizer can reduce the risk of suicide in Bipolar Disorder? • a. Valproic Acid • b. Lamotrigene • c. Lithium • d. Carbamazepine

  12. What is the most common excitatory neurotransmitter in the brain? • a. Serotonin • b. Glutamate • c. Norepinephrine • d. GABA • e. Dopamine

  13. SSRI’s: Indications • MDD • Premenstrual Dysphoric Disorder • GAD • Social phobia • PTSD • OCD • Panic Disorder

  14. SSRI: Mechanism of Action • In depression, the serotonin neuron has a relative deficiency of serotonin and the autoreceptors and postsynaptic receptors are increased in number & sensitivity • When the reuptake pump is blocked, the level of serotonin increases in the somatodendritic area, causing autoreceptors (the brakes) to decrease in number & sensitivity • This turns off the brake on the serotonin neuron and electrical impulses flow down the axon, releasing more serotonin at the axon terminal • Increased levels of serotonin in the synapse leads to down regulation (decreased number and sensitivity) of postsynaptic receptors & other downstream changes

  15. SSRI: Side Effect Profile • Headache • Anxiety (limbic projections) and Agitation (basal ganglia projections) • Nausea (chemoreceptor trigger zone) • Diarrhea (peripheral GI 5HT3 & 5HT4 receptors) • Sexual dysfunction (spinal projections) and Sleep disruption or Somnolence (Brainstem sleep centre)

  16. SSRI: Rare but Dangerous Side Effects • UGI bleeding (platelet dysfunction) • SIADH • SSRI discontinuation syndrome (slow taper) • Flu like symptoms • Insomnia • Nausea • Imbalance • Sensory disturbance • Hyperarousal (anxiety/agitation) • Serotonin syndrome

  17. Norepinephrine & Dopamine Reuptake Inhibitor:Mechanism of Action (Bupropion/Wellbutrin) • Blockade of norepinephrine and dopamine reuptake pumps, leads to similar cascade as with SSRI’s

  18. NDRI: Side Effect Profile • Seizures (not with extended release formulations & following correct dosing; contraindicated with Bulimia or electrolyte disturbances) • Headache, Hypertension (SNS activation) • Agitation (frontal and limbic projections) and Anticholinergic (relative decrease in parasympathetic tone) • Rash • Emesis, decreased appetite and weight loss (SNS activation) • Sleep disruption, Shaking and Sweating (sleep center and cerebellar projections and SNS activation)

  19. Serotonin & Noradrenergic reuptake Inhibitors: Mechanism of Action(Venlafaxine/Effexor, Desvenlafaxine/Pristiq, Duloxetine/Cymbalta) • Blockade of serotonin reuptake at lower dose range • Blockade of serotonin and norepinephrine reuptake in mid dose range • Blockade of serotonin, norepinephrine and dopamine reuptake at very high dosages

  20. SNRI: Side Effect Profile • As with SSRI’s in lower to mid dose range • As with NDRI in mid to high dose range

  21. SNRI: Rare but Dangerous Side Effects • As with SSRI’s

  22. NaSSA: Mechanism of Action • Blocks Alpha 2 autoreceptors on norepinephrine neurons & heteroreceptors on Serotonin neurons, causing more NE & 5HT to be released (puts the brakes on the brakes) • NE neurons from the locus coeruleus innervate midbrain raphe 5HT neurons. Therefore, increased NE causes a further increase in 5HT release • Blocks 5HT2 receptors, having an anxiolytic effect & blocking sleep & sexual side effects • Blocks 5HT3, blocking GI side effects from peripheral receptors & from brainstem chemoreceptor trigger zone • Blocks H1 histamine receptors, causing sedation & weight gain

  23. NaSSA: Side Effect Profile • Weight gain (H1 blockade) • Anticholinergic: constipation, urinary retention, dry mouth, blurred vision, drowsiness, sinus tachycardia, confusion/delirium, fever (red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare; bowel & bladder lose their tone & the heart goes off alone) • Drowsiness (H1 blockade) • Equilibrium

  24. NaSSA: Rare but Dangerous Side Effects • Neutropenia • Serotonin syndrome • Hepatotoxicity • SIADH

  25. SARI: Mechanism of ActionSerotonin 2A antagonists/reuptake inhibitors (Trazadone/Desyrel) • Primarily blocks 5HT2A, reducing sexual dysfunction & sleep disruption & increasing effect of 5HT1A stimulation (5HT2A & 5HT1A oppose one another) • Weak 5HT reuptake inhibitor, increasing 5HT stimulation of 5HT1A (therapeutic effects) • H1 blockade causes sedation • Alpha One blockade leads to orthostatic hypotension

  26. SARI: Side Effect Profile • Orthostatic hypotension • Sedation

  27. SARI: Rare but Dangerous Side Effects • Serotonin syndrome

  28. TCA: Mechanism of ActionTricyclic antidepressants: 3° amines (eg amitriptyline, imipramine, doxepine) 2° amines (eg nortriptyline, desipramine) • Therapeutic effects and side effects from blocking Serotonin, Norepinephrine & Dopamine Reuptake • Some also have 5HT2 blocking ability (blocks sex & sleep side effects) • Side effects from blocking H1 histamine receptors, muscarinic receptors, alpha one adrenergic receptors & sodium channels in the heart & brain

  29. Antihistamine – weight gain & sedation Anticholinergic – (remember toxidrome from NaSSA) Anti-alpha adrenergic – dizziness, orthostatic hypotension Blockade of fast sodium channels – prolongation of QTc (risk of Torsades) TCA: Side Effect Profile

  30. TCA: Rare but Dangerous Side Effects • Torsades de Pointes • EKG – rule out bradycardia and prolonged QTc • Lytes – rule out electrolyte imbalance • Make sure not on type 1 or 3 antiarrythmic drugs • SIADH • Serotonin Syndrome

  31. MAOI: Mechanism of ActionMonoamine oxidase inhibitors: “the classics” (phenylzine/nardil, tranylcypromine/parnate)Reversible inhibitor: (moclobemide/mannerix) • Irreversibly bind MAO (2 wks) & destroy its function, therefore decrease monoamine breakdown, increasing 5HT, NE & DA

  32. MAOI: Side Effect Profile • Side effects related to increase in serotonin norepinepherine & dopamine (see SSRI’s & NDRI’s) • Orthostatic hypotension

  33. MAOI: Rare but Dangerous Side Effects • Hyperthermia i.e.Serotonin Syndrome • even more susceptible than with other serotonergic antidepressants; need to avoid anything that has serotonergic effects such as such as antidepressants and opioids) • When you see an MAOI, get a pharmacy consult, the patient should consult their pharmacist about any over - the – counter medications • Hypertensive crisis • Consult the dietician Re: MAOI diet • Patients need to avoid all foods with tyramine (aged foods such as aged cheeses and wines or tap beer) and any medications with noradrenergic effects (cold remedies, stimulants etc) • Hepatotoxicity • Teratogenicity • Blood dyscrasias

  34. Serotonin Syndrome: HARMED • Hyperthermia • Agitation/Autonomic instability • Rigidity/Reflexes increased • MyoClonus/tremors • Encephalopathy • Diaphoresis

  35. For reference only

  36. Hypertensive Crisis • Norepinephrine is the amine most closely linked with control of blood pressure • MAO normally inactivates norepinepherine • Tyramine, an amine present in aged foods, causes release of norepinepherine • In the presence of MAOI, this increased NE cannot be broken down, resulting in a hypertensive crisis

  37. Starting Antidepressants: General Guidelines • Start with a reuptake inhibitor or mirtazepine (not a TCA or MAOI) • Start at lowest possible dose (half of this with anxiety and in the elderly and medically frail) • Increase by this increment about every five half lives (or about once a week) until one of the following endpoints: • Intolerable side effects • Full response • Maximum dose • Continue to monitor for therapeutic effects, side effects and safety

  38. Treatment choices in children • Concerns were raised about the safety of antidepressants (Paroxetine and Venlafaxine) in children and youth in 2004 • Further metaanalyses and epidemiologic studies now confirm that antidepressants in children and youth are safe with close (weekly) monitoring. • Problems with Venlafaxine and Paroxetine may have been related to poor adherence and discontinuation symptoms

  39. Choice of Initial Treatment in children/youth • Mild to moderate depression: • Start with psychotherapy or non-medication interventions as first line • Second line is to add medication; best evidence is for Fluoxetine; other SSRI’s could be considered next • Moderate to severe depression: • First line is to consider medication but depending on patient/family preference, may also start with psychotherapy or monitoring • Note that the clinical presentation in children and youth can change quickly; they may appear severely depressed one week then by the next week be in a new relationship and everything is better…

  40. Choice of Initial Antidepressant in Adults • There is comparable efficacy between and within classes of medication, therefore, initial selection is based on: • Symptom profile • Side effect profile in relation to the individual patient • Patient preference • Cost • History of previous response of the patient or family members • Comorbid psychiatric or medical illnesses • Potential drug-drug interaction • The BEST antidepressant is the one that a patient will actually take acutely and for the long haul

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