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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
What stages of bipolar disorder is valproate useful for?
Acute mania
26
What is trazodone?
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
27
How does lamotrigine work?
Blocks voltage-dependent Na+ channels -> decreased glutamate release Modulates monoamine reuptake (5-HT, dopamine) Inhibits depolarization of glutaminergic presynaptic membrane -> inhibits glutamate release
28
How does carbamazepine work?
Stabilizes inactivated state of Na+ channels, meaning fewer of these channels are available to subsequently open, making brain cells less excitable Potentiate GABA receptors
29
What do you see in SSRI withdrawal?
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
30
What is a potentially toxic metabolite of carbamazepine?
Carbamazepine-10,11 epoxide
31
Which SSRI has the longest half life?
Fluoxetine - bad for side effects; good for patients who aren't good at taking their meds (less withdrawal symptoms)
32
How much of valproate is protein bound?
80-90% Will compete with other bound drugs and may kick them off (unbound is active)
33
What stage of bipolar disorder is lamotrigine useful for?
Maintenence
34
Why do antidepressants have strict diets that patients need to follow?
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
35
What is desipramine?
Secondary amine tricyclic antidepressant (TCA)
36
What are monoamine oxidase inhibitors used for?
Atypical depression Treatment-resistant depression, panic disorder, or social anxiety disorder
37
What is duloxetine?
SNRI - Serotonin norepinephrine reuptake inhibitor Similar affinity at all doses 1% get hepatic toxicity BP monitoring recommended
38
Are MAOIs mostly reversible or irreversible?
Irreversible - need at least 2 weeks for enzyme levels to recover following cessation
39
What is the effect of overdosing on TCAs?
Death
40
What are first-line treatments for anxiety disorders and major depressive disorder?
SSRIs
41
What are SNRIs used for?
MDD Anxiety disorder Neuropathic pain Fibromyalgia Painful symptoms of depression Stress urinary incontinence Vasomotor symptoms
42
What are side effects of lamotrigine?
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
43
What are the classes of antidepressants?
Monoamine Oxidase Inhibitors Tricyclinc antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) Antidepressants with multiple receptor targets
44
What is sertraline?
SSRI (zoloft)
45
How is lamotrigine excreted?
Renal
46
What are uses of carbamazepine?
Epilepsy (partial and tonic-clonic seizures) Trigeminal neuraliga Manic and mixed episodes of bipolar disorder
47
What is citalopram?
SSRI (Celexa)
48
What are side effects of TCAs (tricyclic antidepressants)?
paste-3440268804538.jpg
49
Which SSRIs have the least drug interactions?
Citalopram and escitalopram
50
What antidepressant is absolutely contraindicated in a patinet wiht an eating disorder?
Buproprion
51
How do we define a mood stabilizer?
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
What are side effects of lithium?
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
What is tranylcypromine?
Monoamine oxidase inhibitor Antidepressant
54
What are the three classes of mood stabilizers?
Lithium Anticonvulsants Antipsychotics
55
What is a serious side effect/complication of lamotrigine?
Stevens Johnson Syndrome
56
What is carbamazepien helpful for in bipolar disorder?
Mania +/- maintenence +/- rapid cycling
57
What is lamotrigine helpful for in bipolar disorder?
Maintenence +/- depression +/- rapid cycling
58
What stages of bipolar disorder is lithium useful for?
Acute mania Maintenence
59
What are the main side effects to be aware of with lithium?
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
What is a unique consideration of fluoxetine?
May cause insomnia
61
What are common side effects of SSRIs?
GI - nausea, upset stomach Weight gain Sweating Sexual dysfunction (decrease libido, delays to orgasm) Akathisia/Tremor Headache paste-6210522710440.jpg
62
What is a complication that can be seen when you give MAOIs and the patient takes noradrenergic drug?
Hypertensive crisis (Diastolic BP > 120) (for instance, decongestants, stimulants, appetite suppressants, antidepressants)
63
What are side effects of mirtazapine?
Somnolence Increased appetite Weight gain Dry mouth Constipation (often given for these reasons too!)
64
What is an advantage of transdermal selegiline?
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
What is important to know about the therapeutic range of lithium?
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
What are carbamazepine drug-drug interactions?
Notably decreases levels of oral contraceptives paste-14856291877282.jpg
67
What are drug-drug interactions of valproate?
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
Which MAOI selectively blocks MAO-B and not MAO-A?
Selegiline
69
Which SSRIs have the most drug interactions?
Fluvoxamine and fluoxetine
70
What is imoprtant about the dosing regimen of lamotrigine?
Slow escalation of doses (increase over ~5 weeks to final dose)
71
What are the SSRIs?
fluoxetine sertraline paroxetine citalopram escitalopram
72
What stage of bipolar disorder is carbamazepine useful for?
Acute mania
73
What are the two major important side effects that can be seen with MAOIs?
Serotonin Syndrome - when MAO + serotonergic drug Hypertensive crisis - when MAOI + noradrenergic drugs
74
What is lamotrigine useful for?
Partial complex and generalized seizures Lennox-Gastaut Syndrome Maintenence of bipolar 1 disorder
75
Which tricyclic antidepressants have fewer side effects?
Secondary amines (lesser anticholinergic, lesser α1 blockade)
76
How long do antidepressants take to work?
~4-8 weeks; perhaps has to do with downregulation of receptors Serotonin is not the answer
77
What is buproprion?
Used for MDD, smokinc cessation, ADHD Weak norepinephrine and dopamine reuptake inhibitor; inhibitor of nicotine acetylcholine receptor No sexual dysfunction or weight gain
78
What are important drug-drug interactions of lamotrigine?
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
How is lamotrigine metabolized?
Hepatic
80
What is the mechanism of valproate metabolism?
Liver - CyP450 (oxidation), and glucoronidation
81
What are major indications for SSRIs?
Major depressive disorder Generalized Anxiety Disorder Panic Disorder Post Traumatic Stress Disorder Obsessive Compulsive Disorder Premenstrual Dysphoric Disorder Bulimia Nervosa
82
What dosing regimen do you follow for tricyclic antidepressants?
Once daily at night, usually
83
What are important features of SSRI metabolism?
Significant 1st pass metabolism Fluvoxamine and Fluoxetine have the most drug interactions
84
How do you choose an antidepressant?
They all work pretty well (placebo resopnse is significant) Choose based on side effect profile; patient needs/desires; comorbid conditions; etc...
85
Why are people reluctant to give valproate to young women?
Polycystic ovarian syndrome monitor closely for development of weight gain, hirsutism, menstrual irregularities, acne
86
What foods must you avoid with MAO-Is?
Soy, beer, red wine, aged cheese, dried sausage, fava beans, liver, smoked fish, sauerkraut
87
What is nortriptyline?
Secondary amine tricyclic antidepressant (TCA)
88
What is the bioavailability of lamotrigine?
100% (close)
89
What is a unique consideration of fluvoxamien?
not FDA approved for MDD, often used for OCD
90
What is an SNRI?
Serotonin norepinephrine reuptake inhibitor
91
How do SSRIs work?
Bind to serotonin transporter and inhibit the reuptake of serotonin into presynaptic nerve terminals paste-6004364280118.jpg
92
What are side effects of carbamazepine?
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
What is valproate helpful for in bipolar disorder?
Mania +/- maintenence +/- rapid cycling
94
What is important about young women and the use of carbamazepine?
Need to use secondary method of contraception as it will decrease levels of oral contraceptives
95
How is lithium proposed to work?
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
What is mirtazapine?
Noradrenergic and specific serotonergic antidepressant α2 receptor antagonsit that enhances adrenergic neurotransmission Causes weight gain, sedation Used for depresison, insomnia, appetite stimulation
97
What is Phenelzine?
Monoamine oxidase inhibitor Antidepressant
98
What is valproate used for?
Epilepsy (simple and complex absence attacks, partial seizures) Migraine prophylaxis Acute mania
99
Where is MAO-A found?
Brain, gut, liver, placenta, skin
100
What are the effects of anticholinergic toxicity?
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
What is venlafaxine?
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
What is important about lithium with respect to drug-drug interactions?
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
What is selegiline?
Monoamine oxidase B inhibitor Antidepressant
104
What is amitriptyline?
Tertiary amine tricyclic antidepressant
105
When are tricyclic antidepressants indicated?
Depression and treatment resistant depression Childhood enuresis (imipramine) Generalized anxiety disorder Panic disorder OCD (clomipramine) Insomnia Neuropathic pain Migraine Cataplexy Syndrome Fibromyalgia
106
How do tricyclic antidepressants work?
Inhibit presynaptic reuptake of norepinephrine Some inhibit the serotonin reuptake pump as well (tertiary amines) Neurotransmitters accumulate in the synaptic cleft
107
What is paroxetine?
SSRI (paxil)
108
What is important about the pharmacokinetics of carbamazepine?
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
What is a class adverse effect of antiepileptics (black box warning)?
Increased suicidality
110
What is escitalopram?
SSRI (lexapro)

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