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98 Cards in this Set
- Front
- Back
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What is currently thought to account for the delayed therapeutic effects of antidepressant drugs?
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Down regulation of beta adrenergic or 5-HT2 receptors
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What is the most important biochemical effect of the tricyclic antidepressants?
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Potentiation of biogenic amine effects by inhibiting biogenic amine uptake at the nerve terminal
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Name 3 tertiary amine tricyclic antidepressants:
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Imipramine, Amitriptyline, Doxepin
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Name 2 secondary amine tricyclic antidepressants:
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Desipramine, Nortriptyline
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Contrast the selectivity of secondary vs tertiary inhibition of NT uptake.
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Secondary: inhibit NE uptake
Tertiary: inhibit serotonin uptake |
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What are the AE of tricyclic antidepressants?
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• Cardiovascular: arrhythmias, conduction defects
• Muscarinic blockade: dry mouth, constipation, dizziness, tachycardia, urinary retention, memory impairment/confusion • Alpha adrenergic blockade: orthostatic hypotension • Histamine blockade: sedation, weight gain |
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What are the tricyclic antidepressant toxicities?
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Convulsions, coma, cardiotoxicity (Tri Cs), respiratory depression, hyperpyrexia
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For what conditions are MAOIs used?
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Major depression, panic disorder, social phobia
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For what condition is MAO-B used?
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Parkinson's disease
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What are the most common side effects of MAOIs?
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Dizziness, HA, dry mouth, insomnia, constipation, blurred vision, nausea, peripheral edema, forgetfulness, fainting, hesitancy of urination, myoclonic jerks, elevation of liver enzymes
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Name 4 MAOIs:
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Phenelzine, Isocarboxazid, Tranylcpromine, Selgiline Transdermal System
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What is the mechanism of action of MAOIs?
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they form stable complexes with the enzyme monoamine oxidase and irreversibly inactivate it leading to increased stores of NE, serotonin & dopamine which then diffuse into the synaptic space
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What is the main limitation to the widespread use of MAOIs?
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drug drug and drug food interactions;specifically tyramine (found in many foods) is inactivated by MAO in the gut but MAOIs inhibit that action resulting in large amts of stored catecholamines in the nerve leading to occipital HA, stiff neck, tachycardia, nausea, HTN, cardiac arrhythmias, seizures, or stroke
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What combination of drugs causes you to worry about serotonin syndrome?
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MAOIs & SSRIs
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What are the side effects of MAOIs?
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drowsiness, orthostatic hypotension, blurred vision, dysuria, contipation
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What is the most widely prescribed class of antidepressants?
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SSRIs
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Name some common SSRIs:
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Fluoxetine, Sertaline, Paroxetine, Citalopram, Fluvoxamine, S-Citalopram
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What are the most common side effects of SSRIs?
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Altered GI motility, nausea, agitation, anxiety, sleep distrubance, tremor, HA, sexual dysfunction
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Which antidepressants are approved for pediatric patients?
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• Fluoxetine -depression
• Fluoxetine, sertraline, fluvoxamine, clomipramine-OCD |
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Name 2 SNRIs:
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Venlafaxine, Duloxetine
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For what is Duloxetine approved?
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MDD, diabetic peripheral neuropathic pain
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What is the only non serotoninergic antidepressant?
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Bupropion
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Buproprion inhibits the uptake of what neurotransmitters?
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DA & NE
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What patients is bupropion contraindicated in?
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Patients with a hx of seizures, severe head injury, or eating disorders
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What are the side effects of Mirtazapine?
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Weight gain, sedation
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Bupropion assists in decreasing the the craving and attentuating the withdrawal of what drug?
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nicotine
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Mirtazapine blocks what presynaptic receptors?
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alpha 2
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Which serotonin receptors does Mirtazapine block?
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5-HT2 & 5-HT3
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What are the main affects of Mirtazapine?
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antidepressant & sedation
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What is the mechanism of action of Trazadone?
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Mixed 5-HT agonist/antagonist
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What are the side effects of Trazadone?
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Significant orthostatic hypotension and sedation (caused by alpha 1 and H1 antagonist effects)
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What is the black box warning on Nefazodone?
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Liver necrosis
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What is the mechanism of action of Nefazodone?
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5-HT2 antagonist
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What is Nefazodone an analog of?
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Trazadone
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What is Aripipazole?
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An atypical antipsychotic used for depression. It's a D2 partial agonist)
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For what other indications are antidepressants used?
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Panic disorder, Social Phobia, PTSD, Premenstrual Dysphoric Disorder, Chronic pain syndromes, OCD (SSRIs & Clomipramine only)
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What are the indications for Lithium?
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Acute mania, long term prophylaxis of bipolar disorder (reduce both severity & frequency of profound mood cycles)
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What are the side effect of Lithium?
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Tremor, increased thirst, diarrhea, weight gain, cystic acne, hypothyroidism
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What is the mechanism of action of Lithium?
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Enhances 5-HT neurotransmission, diminishes neostriatal dopamine activity, facilitates release of NE; however, no clear mechanism explains its therapeutic effectiveness
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Why is a benzodiazepine or antipsychotic added in the early stages of Lithium treatment?
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There is a 5-10 day latency of response in Lithium treatment; the benzo/antipsychotic are tapered when acute symptomatology is stabilized
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How is Lithium excreted?
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Lithium is not metabolized but is excreted via the kidneys; it reversibly reduces the kidney's ability to concentrate the urine via its effects on renal tubular function, often resulting in polyuria
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What is the main difficulty of using Lithium?
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Lithium maintenance requires high concentration in the blood but it has a low therapeutic index and thus requires regular monitoring. Lithium levels can be increased by dehydration, vomiting, fever, & diarrhea. Signs of toxicity include: delirium, ataxia, coarse temor
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How is Lithium overdose treated?
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Hemodialysis
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What are the main drug drug interactions with Lithium?
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Diuretic & NSAIDs
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For what condition is valproate FDA approved?
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Acute manic episodes associated with bipolar disorder
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What are the theorized mechanisms of action of valproate?
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Decreases catabolism & turnover or and increases release of GABA; increases GABAB receptor density
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What are the side effects associated with valproate use?
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GI distress, benign elevations in hepatic transaminases, sedation, tremor, weight gain
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What is the indication for lamotrigine?
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Treatment and maintenance of bipolar disorder
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The risk of what side effect is reduced through the slow titration of lamotrigine?
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Rash & Stevens-Johnson syndrome
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Name some atypical antipsychotics:
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Olanzapine, quetiapine, aripiprazole, risperidone, ziprasidone
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What are the adverse effects of the atypical antipsychotics?
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Weight gain, glucose intolerance, hypercholesterolemia
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What are the atypical antipsychotics indicated for?
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Treatment of acute mania
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What effect do you have to be especially careful of when using antidepressants for bipolar disease?
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Rapid cycling or inducing switching to mania; antidepressants must be used in conjunction with a mood stabilizer; lamotrigine does NOT induce switching or rapid cycling
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What are the clinical applications of anxiolytics?
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Alleviate anxiety prior to procedures, generalized anxiety disorders, panic disorder phobias, PTSD, psychosomatic complaints, anxiety secondary emotional crises, physiological dependence, anesthesia, following cerebral ischemia resulting from MI or stroke
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What are the clinical applications of anxiolytics?
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Alleviate anxiety prior to procedures, generalized anxiety disorders, panic disorder phobias, PTSD, psychosomatic complaints, anxiety secondary emotional crises, physiological dependence, anesthesia, following cerebral ischemia resulting from MI or stroke
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Where are the barbituates metabolized?
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The liver
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What are the adverse effects of barbituates?
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Respiratory depression, can lead to coma or death
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Do barbituates produce pharmacokinetic or pharmacodynamic tolerance?
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both
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Phenobarbital + what drugs leads to increased phenobarbital levels?
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Cimetidine, erythromycin, clarithromycin, fluconazole
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Phenobarbital + what drug leads to decreased phenobarbital levels?
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rifampin
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For what reasons have barbituarates been replaced by benzodiazepines?
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barbituarates induce tolerance, drug metabolizing enzymes, physical dependence, are associated with severe withdrawal symptoms
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What is the mechanism of action of barbituarates?
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bind to distinct site on GABAa receptor and potentiate GABA action on choloride entry into the neuron by prolonging duration of chloride channel opening
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What is the action of barbituarates on liver enzymes?
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barbituarates induce P450 so chronic barbituarate use can lead to diminished action of other drugs that are dependent on P450 metabolism to reduce their concentration
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What are the clinical properties of benzodiazepines?
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anxiolytic, muscle relaxant, anticonvulsant, sedative/hypnotic-decreased sleep latency, decreased stage 4 & REM sleep, increased stage 2 sleep, increased total sleep time
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What is the common structure of all benzodiazepines?
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• 1,4-BZ ring system
• Chlorine in position 7 • Phenyl group in position 5 Modification of the ring leads to different properties |
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Where are the benzodiazepine receptors found?
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GABAa receptors are postsynatpic receptors found only in the brain and spinal cord. They are coupled to chloride ion channels and stimulation of the receptor results in increased inward chloride ion conductance which hyperpolarizes the membrane. BDZs potentiate the action of GABA at GABAa receptors.
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What is the mechanism of GABAb receptors?
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GABAb receptors are G protein coupled receptors found on the presynatpic terminals of neurons in the CNS. Stimulation of GABAb receptors induces increased outward K+ conductance (hyperpolarization) and block inwards Ca++ movement (inhibit transmitter release) via action of a second messenger.
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What is the mechanism of action of BDZs?
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BDZs bind to distinct site from GABA on GABAa and potentiates the action of GABA: increases chloride ion conductance by enhancing the frequency of chloride channel opening events
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What is the mechanism of action of barbiturates?
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Barbiturates bind to a distinct site from GABA on GABAa and potentiate the action of GABA by prolonging the duration of chloride channel opening events
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What drug is used to reverse the CNS side effects of BDZs and how does it work?
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Flumazenil is a selective competitive antagonist against BDZs; can induce withdrawal syndrome in pts on chronic BDZ tx
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What are the short acting BDZs and what are they used for?
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Triazolam: sleep
Midazolam: anesthesia |
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What are the intermediate acting BDZs?
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Lorazepam, alprazolam, temazepam
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What are the long acting BDZs?
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Diazepam, flurazepam, chlordiazepoxide, chlorazepate
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Which drug class, barbiturates or BDZs are more dangerous in the event of an acute overdose?
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Barbiturates
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What side effects are associated with BDZ use?
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Drowsiness, confusion, impairment of motor coordination and memory
Effects are dose dependent |
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What toxicity is associated with BDZ use?
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Confusion, slurred speech, ataxia, drowsiness, dyspnea, hyporeflexia
Incidence & intensity of CNS toxicity increases with age |
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What symptoms are associated with withdrawal from BDZs?
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Increased anxiety, tremor, dizziness, convulsions
Symptoms have slower and less intense onset than with barbiturates |
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What are the risk factors for toxicity?
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Impaired liver function, age, COPD, sleep apnea, hx of substance abuse, cognitive disorders, renal disease, CNS depression, myasthenia gravis
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What are the indications for BDZ use?
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GAD, panic disorder, social anxiety disorder, PTSD, acute stress disorder, adjustment disorder with anxiety, anxiety assoc with life events, bipolar disorder (adjunctive tx), akathesia
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What are the advantages and disadvantages of the long 1/2 life BDZs?
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Advantages: less frequent dosing, less variable plasma [], less severe withdrawal
Disadvantages: daytime psychomotor impairment, increased daytime sedation, accumulation of drug/metabolites in blood |
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What are the advantages and disadvantages of the short 1/2 life BDZs?
Advantages: no drug accumulation, less daytime sedation Disadvantages: more frequent dosing, earlier & more severe withdrawal symptoms, rebound insomnia, anterograde amnesia |
Advantages: no drug accumulation, less daytime sedation
Disadvantages: more frequent dosing, earlier & more severe withdrawal symptoms, rebound insomnia, anterograde amnesia |
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What is the main advantage of buspirone over BDZs?
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Relieves anxiety without producing significant sedation, drowsiness, amnesia or impaired motor coordination
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What indication is buspirone used for?
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GAD
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Which patients are the most satisfied with buspirone: those with prior BDZ use or those without prior buspirone use?
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Those without prior buspirone use
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That is the mechanism of action of buspirone?
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Partial agonist for serotonin receptors of 5-HT1a
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TCAs were the gold standard for the treatment of what prior to the emergence of SSRIs?
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Panic disorders
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Which TCA is the only TCA effective for OCD?
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Clomipramine
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What are SSRIs effective for?
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Depression, panic disorder, OCD, social anxiety disorder
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What are SNRIs effective for?
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Panic disorder, GAD, PTSD
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What classes of medications have been shown to effectively treat panic disorder?
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TCAs, SSRIs, SNRIs, BDZs, MAOIs
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What class of drugs are the 1st line treatment for PTSD?
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SSRIs; treats co-morbid disorders & shows improvement in all three symptom clusters
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What is the role of trazodone in the treatment of PTSD?
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Reverses SSRI induced insomnia, promotes sleep thru sedative properties, reduces the nightmares associated with PTSD
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What symptoms of PTSD do a2 agonists decrease?
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Autonomic hyperactivity, nightmares, hypervigilance, startle reactions, outbursts of rage
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What is the first line treatment for social anxiety disorder?
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SSRIs
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What are the side effects of H1 Histamine blockade?
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Sedation & weight gain
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What are the side effects of 5HT2C blockade?
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Weight gain
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What are the side effects of muscarinic receptor blockade?
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Anticholinergic side effects
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What are the side effects of hERG blockade?
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Q-T interval prolongation
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