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1
Q

What is serotonin syndrome??

A

Abdominal pain, diarrhea, sweating, tremor, hyperthermia, tachycardia, hypertension, myoclonus, irritability, delirium, death (basically, the result of excess serotonin in your system) Caused by MAOIs in combination with other serotonergic drugs

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2
Q

What is a unique consideration fo paxil?

A

In vetro evidence of NE reuptake blockade and anticholinergic activity More sedation, dry mouth, weight gain

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3
Q

How do you treat lithium toxicity?

A

Stop drug IV hydration May need dialysis

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4
Q

What is the bioavailability of valproate?

A

close to 100%

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5
Q

What is a downside of TCAs (tricyclic antidepressants)?

A

Dirty drugs. Many side effect

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6
Q

What is lithium used for?

A

FDA Approved:Acute mania Bipolar maintenence treatment Other: Episodic rage and irritability Augmentation, treatment resistant major depressive disorder Schizophrenia spectrum treatments Anti-suicide

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7
Q

What are advantages of SSRIs over other agents?

A

Standard dosing, easy to titrate Clinical response with starting dose Not lethal in overdose No arrhythmias, disturbance of BP, seizures, coma, respiratory depression, or special diet Fewer drug-drug interactions

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8
Q

What is desvenlafaxine?

A

Serotonin norepinephrine reuptake inhibitor (SNRI)

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9
Q

What is a black box warning for all antidepressants?

A

Suicidality - must be careful

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10
Q

How do anticonvulsants work?

A

Promote inactivated state of Na+ channel

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11
Q

What is fluoxetine?

A

SSRI Prozac

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12
Q

What are important pharmacokinetic considerations of lithium?

A

GI absorption, but not protein bound nor metabolized Excreted unchanged in urine (95%) Filtered at glomerulus, reabsorbed at proximal tubule, loop of Henle, and early distal nephron Long halflife Monitor levels and renal function

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13
Q

Which anticonvulsants are approved for use in bipolar disorder?

A

Carbamazepine Valproate Lamotrigine

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14
Q

How do MAOIs work?

A

Inhibit degradation of biogenic amines in the presynaptic terminals Get increased 5HT, norepinephrine, and dopamine in presynaptic terminals and synaptic cleft Inhibition is generally irreversible - requires 2 weeks for recovery after discontinuation of drug

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15
Q

What pharmacokinetic issues must you consider with tricyclic antidepressants?

A

Undergo extensive hepatic metabolism via p450 Tertiary amines are metabolized to secondary amines Half lives vary Usually dose once daily (at night)

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16
Q

Where is MAO-B found?

A

Brain, platelets, lymphocytes

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17
Q

What drug do you not let patients on lithium take?

A

NSAIDs Also: paste-12330851107056.jpg

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18
Q

What is a unique consdieration of citalopram and escitalopram?

A

Escitalopram is the most selective SSRI and therefore possibly has fewest side effects

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19
Q

What is imipramine?

A

Tertiary amine tricyclinc antidepressant (TCA)

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20
Q

What are side effects of MAOIs?

A

Orthostatic hypotension Weight gain Insomnia Sexual dysfunction Hepatotoxicity (rare) Serotonin Syndrome Hypertension or hypertensive crisis

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21
Q

How does Valproate work?

A

Enhances GABA function (increases glutamate to GABA conversion) Inhibits voltage-dependent Na+ channels Downregulates PKC Inhibits GSK3β may have neurotrophic effects

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22
Q

What is a unique consideration of sertraline?

A

Mild DA reuptake inhibitor - activating

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23
Q

What are side effects of buproprion?

A

Seizures Anxiety, headaches, insomnia, nausea, irritability, restlessness, psychosis (Rare) Avoid in eating disorders, seizures, recent alcohol or benzodiazepine withdrawal Hypertensive crisis if given with MAOIs

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24
Q

What are side effects of valproate?

A

GI - N/V, cramps, diarrhea Pancreatitis Hepatotoxicity CNS: sedation, tremor, ataxia Weight gain Hematological: Thrombocytopenia and platelet dysfunction Derm: alopecia Polycystic ovarian syndrome Teratogenicity

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25
Q

What stages of bipolar disorder is valproate useful for?

A

Acute mania

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26
Q

What is trazodone?

A

5HT2A receptor antagonist; mild SNRI, α1 and H1 antagonist Sedating, so used as a sleep aid only Side effects include orthostatic hypotension, sedation, and priapism

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27
Q

How does lamotrigine work?

A

Blocks voltage-dependent Na+ channels -> decreased glutamate release Modulates monoamine reuptake (5-HT, dopamine) Inhibits depolarization of glutaminergic presynaptic membrane -> inhibits glutamate release

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28
Q

How does carbamazepine work?

A

Stabilizes inactivated state of Na+ channels, meaning fewer of these channels are available to subsequently open, making brain cells less excitable Potentiate GABA receptors

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29
Q

What do you see in SSRI withdrawal?

A

Seen after at least 6 weeks of treatment Symptoms include dizziness, weakness, nausea, headache, anxiet, insomnia, paresthesias, flu-like symptoms, muscle aches Resolves within 3 weeks Least likely is fluoxetine (long half life); Most likely fluvoxamine, paroxetine

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30
Q

What is a potentially toxic metabolite of carbamazepine?

A

Carbamazepine-10,11 epoxide

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31
Q

Which SSRI has the longest half life?

A

Fluoxetine - bad for side effects; good for patients who aren’t good at taking their meds (less withdrawal symptoms)

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32
Q

How much of valproate is protein bound?

A

80-90% Will compete with other bound drugs and may kick them off (unbound is active)

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33
Q

What stage of bipolar disorder is lamotrigine useful for?

A

Maintenence

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34
Q

Why do antidepressants have strict diets that patients need to follow?

A

Tyramine induced hypertensive crisis, which can be triggered by tyramine-rich foods in the presence of MAOI Tyramien is catecholamien releasing agent. Intestinal wall MAO-A breaks down tyramine before absorption If you inhibit it, you can’t handle dietary tyramine, you release norepinephrine witn no MAO-A to destroy it Causes increased blood pressure

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35
Q

What is desipramine?

A

Secondary amine tricyclic antidepressant (TCA)

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36
Q

What are monoamine oxidase inhibitors used for?

A

Atypical depression Treatment-resistant depression, panic disorder, or social anxiety disorder

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37
Q

What is duloxetine?

A

SNRI - Serotonin norepinephrine reuptake inhibitor Similar affinity at all doses 1% get hepatic toxicity BP monitoring recommended

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38
Q

Are MAOIs mostly reversible or irreversible?

A

Irreversible - need at least 2 weeks for enzyme levels to recover following cessation

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39
Q

What is the effect of overdosing on TCAs?

A

Death

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40
Q

What are first-line treatments for anxiety disorders and major depressive disorder?

A

SSRIs

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41
Q

What are SNRIs used for?

A

MDD Anxiety disorder Neuropathic pain Fibromyalgia Painful symptoms of depression Stress urinary incontinence Vasomotor symptoms

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42
Q

What are side effects of lamotrigine?

A

Dermatological black box warning: uncomplicated rash in up to 10%; serious in 0.1% adults; 1% children CNS: dizziness, headache, diploplia, unsteadiness, sedation Less associated with weight gain or cognitive side effects Stevens Johnson Syndrome

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43
Q

What are the classes of antidepressants?

A

Monoamine Oxidase Inhibitors Tricyclinc antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) Antidepressants with multiple receptor targets

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44
Q

What is sertraline?

A

SSRI (zoloft)

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45
Q

How is lamotrigine excreted?

A

Renal

46
Q

What are uses of carbamazepine?

A

Epilepsy (partial and tonic-clonic seizures) Trigeminal neuraliga Manic and mixed episodes of bipolar disorder

47
Q

What is citalopram?

A

SSRI (Celexa)

48
Q

What are side effects of TCAs (tricyclic antidepressants)?

A

paste-3440268804538.jpg

49
Q

Which SSRIs have the least drug interactions?

A

Citalopram and escitalopram

50
Q

What antidepressant is absolutely contraindicated in a patinet wiht an eating disorder?

A

Buproprion

51
Q

How do we define a mood stabilizer?

A

A drug effective in treating acute mania and depression in a person with bipolar disorder A drug effective in preventing the recurrence of mania and depression (in a person with bipolar disorder) A drug effective in extended treatment of mania or depression without worsening the other pole of the illness

52
Q

What are side effects of lithium?

A

Apart from renal considerations, Tremor GI: N/V Hypothyroidism Cardiac: depression of sinus node, sick sinus syndrome and flatting of T waves Hematological: benign leukocytosis Cognitive: dulled, slowed, impaired memory Teratogenicity: Ebstein’s anomaly, hypotonia Dermatological: psoriasis, exacerbation of acne

53
Q

What is tranylcypromine?

A

Monoamine oxidase inhibitor Antidepressant

54
Q

What are the three classes of mood stabilizers?

A

Lithium Anticonvulsants Antipsychotics

55
Q

What is a serious side effect/complication of lamotrigine?

A

Stevens Johnson Syndrome

56
Q

What is carbamazepien helpful for in bipolar disorder?

A

Mania +/- maintenence +/- rapid cycling

57
Q

What is lamotrigine helpful for in bipolar disorder?

A

Maintenence +/- depression +/- rapid cycling

58
Q

What stages of bipolar disorder is lithium useful for?

A

Acute mania Maintenence

59
Q

What are the main side effects to be aware of with lithium?

A

Renal! - tubular funciton (collecting tubule): interfere with reabsorption of water (polyuria with polydipsia; nephrogenic diabetes insipidus) - Glomerular function: minimal change glomerulopathy, leading to nephrotic syndrome - Tuberointerstitial Nephritis/Lithium Induced Nephropathy (rare)

60
Q

What is a unique consideration of fluoxetine?

A

May cause insomnia

61
Q

What are common side effects of SSRIs?

A

GI - nausea, upset stomach Weight gain Sweating Sexual dysfunction (decrease libido, delays to orgasm) Akathisia/Tremor Headache paste-6210522710440.jpg

62
Q

What is a complication that can be seen when you give MAOIs and the patient takes noradrenergic drug?

A

Hypertensive crisis (Diastolic BP > 120) (for instance, decongestants, stimulants, appetite suppressants, antidepressants)

63
Q

What are side effects of mirtazapine?

A

Somnolence Increased appetite Weight gain Dry mouth Constipation (often given for these reasons too!)

64
Q

What is an advantage of transdermal selegiline?

A

Bypass gut Also selegiline is MAO-B selective inhibitor, so you do not need to have dietary restrictions as strictly as for other MAOIs

65
Q

What is important to know about the therapeutic range of lithium?

A

Narrow Has neurological side effects if above therapeutic range: choreoathetosis, ataxia, tremor, dysarthria, aphasia, confusion, may progess to coma and death Irreversible kidney damage Stop drug, IV hydration, may need dialysis

66
Q

What are carbamazepine drug-drug interactions?

A

Notably decreases levels of oral contraceptives paste-14856291877282.jpg

67
Q

What are drug-drug interactions of valproate?

A

Inhibitor of both oxidation and glucoronidation - can double levels of lamotrigine and increase risk of rashes Inhibited hepatic enzymes increase valproate levels; vice versa Plasma protein displacement increases valproate levels

68
Q

Which MAOI selectively blocks MAO-B and not MAO-A?

A

Selegiline

69
Q

Which SSRIs have the most drug interactions?

A

Fluvoxamine and fluoxetine

70
Q

What is imoprtant about the dosing regimen of lamotrigine?

A

Slow escalation of doses (increase over ~5 weeks to final dose)

71
Q

What are the SSRIs?

A

fluoxetine sertraline paroxetine citalopram escitalopram

72
Q

What stage of bipolar disorder is carbamazepine useful for?

A

Acute mania

73
Q

What are the two major important side effects that can be seen with MAOIs?

A

Serotonin Syndrome - when MAO + serotonergic drug Hypertensive crisis - when MAOI + noradrenergic drugs

74
Q

What is lamotrigine useful for?

A

Partial complex and generalized seizures Lennox-Gastaut Syndrome Maintenence of bipolar 1 disorder

75
Q

Which tricyclic antidepressants have fewer side effects?

A

Secondary amines (lesser anticholinergic, lesser α1 blockade)

76
Q

How long do antidepressants take to work?

A

~4-8 weeks; perhaps has to do with downregulation of receptors Serotonin is not the answer

77
Q

What is buproprion?

A

Used for MDD, smokinc cessation, ADHD Weak norepinephrine and dopamine reuptake inhibitor; inhibitor of nicotine acetylcholine receptor No sexual dysfunction or weight gain

78
Q

What are important drug-drug interactions of lamotrigine?

A

Doesn’t induce or inhibit hepatic enzymes Via effects on glucoronidation: Valproate doubles serum levels Carbamazepine reduces 25% of levels Phenobarbital and primidone decrease levels by 40%

79
Q

How is lamotrigine metabolized?

A

Hepatic

80
Q

What is the mechanism of valproate metabolism?

A

Liver - CyP450 (oxidation), and glucoronidation

81
Q

What are major indications for SSRIs?

A

Major depressive disorder Generalized Anxiety Disorder Panic Disorder Post Traumatic Stress Disorder Obsessive Compulsive Disorder Premenstrual Dysphoric Disorder Bulimia Nervosa

82
Q

What dosing regimen do you follow for tricyclic antidepressants?

A

Once daily at night, usually

83
Q

What are important features of SSRI metabolism?

A

Significant 1st pass metabolism Fluvoxamine and Fluoxetine have the most drug interactions

84
Q

How do you choose an antidepressant?

A

They all work pretty well (placebo resopnse is significant) Choose based on side effect profile; patient needs/desires; comorbid conditions; etc…

85
Q

Why are people reluctant to give valproate to young women?

A

Polycystic ovarian syndrome monitor closely for development of weight gain, hirsutism, menstrual irregularities, acne

86
Q

What foods must you avoid with MAO-Is?

A

Soy, beer, red wine, aged cheese, dried sausage, fava beans, liver, smoked fish, sauerkraut

87
Q

What is nortriptyline?

A

Secondary amine tricyclic antidepressant (TCA)

88
Q

What is the bioavailability of lamotrigine?

A

100% (close)

89
Q

What is a unique consideration of fluvoxamien?

A

not FDA approved for MDD, often used for OCD

90
Q

What is an SNRI?

A

Serotonin norepinephrine reuptake inhibitor

91
Q

How do SSRIs work?

A

Bind to serotonin transporter and inhibit the reuptake of serotonin into presynaptic nerve terminals paste-6004364280118.jpg

92
Q

What are side effects of carbamazepine?

A

CNS: sedation, dizziness, ataxia, diploplia, nystagmus GI: Nausea, increased liver enzymes, hepatotoxicity Cardiac: Slows conduction Dermatological: rash, Stevens-Johnson Syndrome Hematological: Aplastic anemia, thrombocytopenia, agranulocytosis, leukopenia Teratogenicity: neural tube defects

93
Q

What is valproate helpful for in bipolar disorder?

A

Mania +/- maintenence +/- rapid cycling

94
Q

What is important about young women and the use of carbamazepine?

A

Need to use secondary method of contraception as it will decrease levels of oral contraceptives

95
Q

How is lithium proposed to work?

A

Neurotransmitter signaling - enhances serotonergic transmission; modulates balance between excitatory and inhibitory effects of various neurotransmitters Second messengers - cAMP/Adenylyl Cyclase; Phosphatidylinositol system - PKC Neuroprotective effects - increases resilience of neurons; increases plasticity; inactivates NMDA receptors; decreased apoptosis

96
Q

What is mirtazapine?

A

Noradrenergic and specific serotonergic antidepressant α2 receptor antagonsit that enhances adrenergic neurotransmission Causes weight gain, sedation Used for depresison, insomnia, appetite stimulation

97
Q

What is Phenelzine?

A

Monoamine oxidase inhibitor Antidepressant

98
Q

What is valproate used for?

A

Epilepsy (simple and complex absence attacks, partial seizures) Migraine prophylaxis Acute mania

99
Q

Where is MAO-A found?

A

Brain, gut, liver, placenta, skin

100
Q

What are the effects of anticholinergic toxicity?

A

Red as a beet Dry as a bone Blind as a bat Mad as a hatter Hot as a hare Full as a flask Can see this in a patient who is overdosing on TCAs (tricyclic antidepressants)

101
Q

What is venlafaxine?

A

Serotonin norepinephrine reuptake inhibitor (SNRI) SSRI at < 150 mg daily doses (SNRI at higher) May increase diastolic BP at doses > 300 mg daily; tachycardia

102
Q

What is important about lithium with respect to drug-drug interactions?

A

Can increase or decrease excretion of lithium Lithium has a very narrow therapeutic window. Don’t want to get renal damage paste-12335146074352.jpg

103
Q

What is selegiline?

A

Monoamine oxidase B inhibitor Antidepressant

104
Q

What is amitriptyline?

A

Tertiary amine tricyclic antidepressant

105
Q

When are tricyclic antidepressants indicated?

A

Depression and treatment resistant depression Childhood enuresis (imipramine) Generalized anxiety disorder Panic disorder OCD (clomipramine) Insomnia Neuropathic pain Migraine Cataplexy Syndrome Fibromyalgia

106
Q

How do tricyclic antidepressants work?

A

Inhibit presynaptic reuptake of norepinephrine Some inhibit the serotonin reuptake pump as well (tertiary amines) Neurotransmitters accumulate in the synaptic cleft

107
Q

What is paroxetine?

A

SSRI (paxil)

108
Q

What is important about the pharmacokinetics of carbamazepine?

A

Metabolized by CyP450 3A3/4 enzyme and can be increased by drugs that inhibit this; vice versa Induces glucoronidation Induces its own metabolism which increases clearance, shorter halflife Potentially toxic metabolite: carbamazepin-10,11 epoxide

109
Q

What is a class adverse effect of antiepileptics (black box warning)?

A

Increased suicidality

110
Q

What is escitalopram?

A

SSRI (lexapro)

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