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Board Review > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

The combination of haloperidol with _____ can cause an encephalopathic syndrome mimicking neuroleptic malignant syndrome (NMS) in some patients.

A

Lithium

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2
Q

Diazepam is metabolized by what CYP450 enzyme? What agents are inhibitors/inducers of the enzyme that you should be mindful if co-prescribed.

A

CYP3A4. Strong inhibitors of CYP3A4 include the “-azole” antifungals and many antiretrovirals. Strong inducers include antiepileptics, barbiturate’s, and rifampin.

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3
Q

Mechanism(s) of action of Lithium

A

1) Interferes with sodium, potassium, and calcium channel function.
2) Inhibits inositol monophosphatase, modulating 2nd messenger system changes

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4
Q

What is a target lithium level?

A

0.8 (average dose of 1500 mg/day)

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5
Q

Organized by the levels at which they present, what are the signs of lithium toxicity?

A

1.2: Tremors, nausea, diarrhea, ataxia, cognitive slowing, drowsiness
1.5-2: Seizures
>2: Acute renal failure (requires dialysis)
>2.5: Coma, death

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6
Q

What are mild, but common, side effects of Lithium?

A

Sedation, cognitive difficulties, tremor, increased appetite, weight gain, polydipsia, polyuria, diarrhea, nausea, acne, dry mouth

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7
Q

Of the benzodiazepines FDA approved for sleep onset and sleep maintenance, which two agents have the highest half lives (up to 100 hrs) and have the highest risk of daytime sedation.

A

Flurazepam and Quazepam

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8
Q

What are the hypnotic agents that are ONLY indicated for sleep ONSET (not sleep maintenance)?

A

Triazolam, Zolpidem, Zaleplon (Sonata), and Ramelteon

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9
Q

T/F: Women with schizophrenia are more susceptible to side effects from atypical antipsychotics?

A

True!

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10
Q

What are the two medications used to treat moderate-to-severe psychosis associated with Parkinson’s Disease OR NCD due to LBD?

A

1) Pimavanserin (Nuplazid) - FDA indication for hallucinations AND delusions in Parkinson’s. Works as a combination of inverse agonist and antagonist activity at the serotonin 2A receptors (5-HT2A)

2) LOW DOSE CLOZAPINE (NOT risperidone)

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11
Q

Mechanism of action of Acamprosate? Contraindication?

A

Analog of GABA, acts on calcium channels and modifies transmission along GABA and glutamine pathways resulting in decreased positive reinforcement from alcohol intake and decreased withdrawal cravings. Contraindicated if GFR below 30.

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12
Q

What are the only indicated medications for treatment of nocturnal enuresis in children?

A

Imipramine and desmopressin

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13
Q

Serotonin receptors implicated in atypical antipsychotic weight gain? Timeline of weight gain? Options for adjunctive agents to mitigate weight gain?

A

1) 5-HT2A and 5-HT2C
2) Early in treatment course - esp first 6 months - then plateaus
3) Aripiprazole, metformin, liraglutide, topiramate

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14
Q

What TCA is the most likely to cause parkinsonian symptoms?

A

Amoxapine. This is because its metabolites have dopamine blocking activity. It can also cause akathesia or dyskinesia.

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15
Q

Why should TCAs be stopped before elective surgery?

A

Risk of hypertension when TCAs are given concomitant with anesthetics

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16
Q

What are the only two pharmacologic agents that act as agonists at the GABA-B receptor? What are their indications?

A

1) Sodium oxybate (gamma-hydroxybutyrate; Xyrem, “date rape” drug); FDA approved for narcolepsy and cataplexy
2) Lioresal (a POTENT antispasticity agent)

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17
Q

What is the name given to the group benzodiazepines that are directly metabolized by glucuronidation and therefore have NO ACTIVE metabolites? What are the specific benzodiazepines?

A

1) 3-hydroxy benzodiazepines
2) Lorazepam, oxazepam, temazepam (L-O-T)

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18
Q

Why do the 2-keto benzodiazepines have such long half-lives (some of the LONGEST)? What are some specific agents?

A

1) They have multiple active metabolites that can keep working in the body from 30 to 200 hours (in patients who are slow metabolizers)
2) Chlordiazepoxide, diazepam, prazepam

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19
Q

What is the TCA that is the most serotonergic AND has the highest seizure risk?

A

Clomipramine (Used in OCD)

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20
Q

What is the most noradrenergic TCA?

A

Desipramine

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21
Q

What is the therapeutic plasma range for TCAs?

A

50-150 ng/mL

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22
Q

What is the gap between stopping an MAO-I and starting another anti-depressant? What is the exception?

A

2 week gap / 5 weeks for fluoxetine

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23
Q

Aside from food restrictions and avoiding SSRIs/clomipramine, what are serious drug-drug interactions to avoid with MAOIs?

A

Meperidine, anesthetics (lidocaine is OK), asthma medication or OTC drugs containing dextromethorphan, sympathomimetics (epinephrine, amphetamines, cocaine).

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24
Q

What drugs will increase clozapine levels (5)?

A

Cimetidine, SSRIs, TCAs, valproic acid, erythromycin

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25
Q

What drugs will decrease clozapine levels (2)?

A

Phenytoin, carbamazepine

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26
Q

Therapeutic range for valproic acid

A

50 – 100 ng/mL / At 125 ng/ML side effects may occur (including thrombocytopenia)

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27
Q

Lab monitoring parameters for LFTs in patients on valproic acid

A

Obtain at start of treatment and every 6-12 months after

28
Q

What AED has a black box warning for idiosyncratic liver failure and aplastic anemia?

A

Felbamate

29
Q

What are the P450 enzymes involved in the following substance metabolism: caffeine, nicotine, codeine, cocaine

A

1) Caffeine –> 1A2
2) Nicotine –> 2A6
3) Codeine –> 2D6
4) Cocaine –> 3A4

30
Q

What prescription immunodulatory cytokine has a strong correlation with increased incidence of depression and suicide attempts in patients who have been taking the agent for long periods of time? Who would we avoid prescribing it to?

A

Interferon alpha (avoid in patients with severe histories of depression and suicide)

31
Q

What is the mechanism of action of Riluzole? What is it approved for?

A

1) Glutamate antagonist
2) Amyotrophic lateral sclerosis (ALS)

32
Q

What is the LEAST anticholinergic TCA?

A

Desipramine

33
Q

What is the mechanism of Mirtazapine’s effect on norepinephrine levels?

A

Blocks presynaptic alpha-2 receptors –> stops feedback inhibition on the release of NE into the synaptic cleft –> resulting in more NE release into the synapse

34
Q

Pimozide is FDA approached for treatment of what? What is its mechanism of action?

A

1) Tourette’s syndrome
2) Dopamine receptor antagonist

35
Q

In addition to its antidopaminergic profile, how does ziprasidone affect 5-HT and NE?

A
  • Inhibits re-uptake of NE and 5-HT
  • Agonist at 5-HT1A
  • Antagonist at 5-HT 1D, 2A, and 2C
36
Q

Treatment of choice for urinary retention?

A

Urecholine (bethanechol)

37
Q

Smoking (cigarettes) induces which CYP450 enzyme? What medications would you worry about in smokers?

A

1) 1A2
2) Clozapine, olanzapine

38
Q

Risperidone is metabolized (substrate of) by what CYP450 enzyme?

A

2D6

39
Q

What HLA is the basis for the Carbamazapine’s black box warning regarding SJS?

A

HLA-B*1502

40
Q

What SSRI’s are the most potent 2D6 inhibitors?

A

Fluoxetine and paroxetine (sertraline is a moderate inhibitor)

41
Q

What are common 1A2 inducers?

A

carbamazapine, tobacco/smoking

42
Q

What are common 1A2 inhibitors?

A

Cimetidine, ciprofloxacin, fluvoxamine, citalopram

43
Q

What is the criteria for TMS enrollment set by the FDA?

A

One ADEQUATE failed antidepressant trial

44
Q

What electrolyte abnormality can be caused by carbamazepine?

A

Hyponatremia (due to its vasopressin-like effect)

45
Q

What is an antipsychotic that is primarily metabolized by the kidney and safe in hepatic impairment?

A

Paliperidone (80% excreted by kidneys, careful if renal impaired)

46
Q

What is the level of mild to moderate lithium toxicity and what are the correlated symptoms?

A

1) 1.5 to 2
2) Nausea/vomiting, abdominal pain, ataxia, nystagmus, dizziness, slurred speech, dry mouth

47
Q

What is the level of moderate to severe lithium toxicity and what are the correlated symptoms?

A

1) 2.0 - 2.5
2) Fasciculations, clonic limb movements, hyperactive DTRs, choreoathetoid movements, seizures, delirium, stupor/coma, circulatory failure (arrhythmia, hypotension)
3) Dialysis indicated at levels above 2 due to risk for acute renal failure

48
Q

What is a lethal lithium level?

A

Levels above 2.5

49
Q

At what lithium level do tremors start to appear?

A

1.2

50
Q

Trazodone is metabolized by what CYP450 enzyme?

A

3A4

51
Q

What SSRIs cause the highest rates of GI side effects? GI side effects are mediated through what receptor?

A

1) Sertraline, Fluvoxamine
2) 5-HT3

52
Q

What is the most common cardiac side effect of SSRIs?

A

Bradycardia

53
Q

What are some common neurologic and behavioral side effects from lithium?

A

Dysphoria, lack of spontaneity, slowed reaction time, memory difficulties, “altered creativity”

54
Q

Lab findings in nephrogenic diabetes insipidus?

A

Low urine Osm, increased urine output, High plasma Osm

55
Q

What is the routine lab monitoring recommended when starting carbamazepine and why?

A

1) CBC every 3 months for the first year, then decrease frequency
2) Risk of severe blood dyscrasias (aplastic anemia, agranulocytosis)

56
Q

What is the mechanism of action of phentolamine and what can it be used to treat?

A

Alpha1 antagonist, hypertensive crisis

57
Q

In addition to its antidopaminergic profile, how does ziprasidone affect 5-HT and NE?

A
  • Inhibits re-uptake of NE and 5-HT
  • Agonist at 5-HT1a
  • Antagonist at 5-HT1D, 2a, and 2c
58
Q

Treatment of choice for urinary retention?

A

Urecholine (bethanechol)

59
Q

What is the mechanism of action of reserpine? How does this explain its therapeutic effect and adverse effects?

A

1) Interferes with teh VMAT dependent uptake of biogenic amines (No HADES) in the presynaptic vesicles –> resulting in depletion of DA, NE, and 5-HT
2) Can relieve symptoms of dystonia —> however also causes depression, sedation, and a Parkinson’s like syndrome

60
Q

What is a TCA with strong D2 antagonistic properties?

A

Amoxapine (it is a chemical derivative of loxapine, watch out for Parkinson’s)

61
Q

Describe the cardiac affects seen in TCA overdose

A

1) Termination of ventricular fibrillation –> increase collateral blood supply to ischemic tissue (anti-arrhythmic effect at non-toxic levels)
2) Decreased myocardial contractility
3) Tachycardia and hypotension
4) Increased myocardial irritability

62
Q

What is the therapeutic range for TCAs?

A

50 - 150

63
Q

How does mirtazapine decease nausea?

A

5-HT3 antagonism (similar to ondansetron)

64
Q

What is the mechanism of carbidopa in carbidopa-levodopa?

A

Inhibits DOPA decarboxylase, thereby preventing the peripheral metabolism of levodopa to dopamine before it can cross the BBB.

65
Q

What is the mechanism of action of pimvanserin? What is it indicated for?

A

1) Inverse agonist at the 5-HT2A receptor
2) Hallucinations and delusions in the setting of Parkinson’s disease

66
Q
A

Board Review (8 decks)

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