Lithium
Antiepileptics
P450 interactions
Potpourri I
Potpourri II
100
Describe early signs of lithium toxicity and at what level you are likely to begin to see these symptoms.
1.2+ worsened nausea and diarrhea, worsened polyuria/polydipsia, increasing tremor, mild ataxia, more severe cognitive difficulties (note: may see these symptoms below 1.2 in elderly)
100
Name the three black box warnings associated with valproic acid.
teratogenicity, hepatotoxicity, pancreatitis
100
List four antidepressants that are P450 2D6 inhibitors
Prozac, Paxil, Zoloft (high doses), bupropion (milder inhibition effects), duloxetine
100
List several medications that are heavily protein bound.
benzodiazepines (e.g. diazepam), warfarin, aspirin, valproic acid, phenytoin
100
The concurrent administration of phenelzine and meperidine may produce a potentially hypermetabolic reaction secondary to what type of drug interaction?
pharmacodynamic (serotonin)
200
Name at least three medications that INCREASE lithium levels.
NSAIDs thiazide diuretics ACE inhibitors Ca channel blockers
200
Which mood stabilizer is associated with carnitine deficiency?
Valproic acid Description: Hypocarnitinemia results both in impaired mitochondrial fatty acid oxidation for energy production and impaired VPA metabolism. Microvesicular steatosis is a subsequent histological finding. Although the patterns of liver injury secondary to certain medications may vary, VPA is particularly known to cause microvesicular steatosis, in which small fat droplets are present within the hepatocytes and do not displace the nucleus. VPA-induced hyperammonemia and hepatotoxicity maybe mediated in part by carnitine deficiency (LePane et al, 2007)
200
Which P450 enzymes are inhibited with fluoroquinolones? Bonus: Which antipsychotics MAY be affected by this drug class?
1A2, 3A4 inhibition Bonus: clozapine, olanzapine (1A2 substrates); aripiprazole, haldol, ziprasidone (3A4 substrates); note also tertiary TCAs may be affected
200
Alprazolam 0.5 mg is roughly equivalent to what dose Lorazepam?
Lorazepam 1 mg
200
Which of the SSRIs has an increased chance for anticholinergic effects due to some affinity at the muscarinic receptors?
Paroxetine
300
List at least two medications that DECREASE lithium levels.
caffeine acetazolamide theophylline
300
What are some common signs/symptoms of valproate toxicity?
MOST common: nausea and vomiting Other common symptoms: confusion, somnolence, headache, atrial tachyarrhythmias
300
Fluvoxamine is an inhibitor of which P450 enzymes?
1A2, 3A4, 2C9/19
300
What cardiac problems may be associated with lithium?
(caused by displacement of intracellular potassium by the lithium ion) T wave flatteneing or inversion (benign), sinus dysrhythmias, heart block, syncope, rarely CHF and ventricular arrhythmias. Li cardiotoxicity more prevalent in those on low-salt diet, on diuretics or ACE inhibitors, renal insufficiency. Li treatment C/I in those with sick sinus syndrome.
300
Which antiepileptics are associated with hyponatremia?
trileptal, carbamazepine
400
Describe the management of lithium toxicity at levels deemed inappropriate for dialysis.
labwork (lithium level, BMP, EKG) gastric lavage polyethylene glycol/polystyrene sulfonate bowel irrigation IV fluids! follow lithium level q 6 hours
400
Describe the basis of the following drug interaction: lamotrigine + valproic acid
Valproic acid: inhibitor glucuronidation 1A4 Lamotrigine: substrate glucuronidation 1A4 Addition of adjunctive valproic acid leads to INCREASED lamotrigine half-life and blood levels due to valproic acid’s inhibition of glucuronidation
400
What psychotropic medications might affect the level/metabolism of methadone?
Methadone metabolized at 3A4, 2D6, 2C9; antiepileptics (inducers) may result in decreased levels and subsequent withdrawal symptoms, 2D6 antidepressants have potential to increase levels
400
Psoriasis is associated with which mood stabilizer medication?
lithium
400
Describe the mechanism involved in hypertensive crisis/tyramine reaction associated with MAO-Is.
tyramine in the diet causes release of NE (and other sympathomimetic amines) from storage vesicles into extracellular space leading to dangerous rise in NE levels and hypertensive crisis when in environment of irreversible MAO-I
500
Describe the challenges relating to dialysis management of lithium toxicity. In what situations might dialysis be reasonable?
risk of "rebound phenomenon"--rise in Li levels post-dialysis due to slow equilibration across cellular membranes requiring repeat dialysis most useful in levels at least >2.5, some say even 4+, may consider if symptoms very severe or in the elderly
500
Which antiepileptic has the following black box warning: risk of TENS/SJS (associated with HLA-B 1502 allele in Asian populations)
Carbamazepine
500
Describe the nature of the following interaction: valproic acid + carbamazepine (e.g. which med may have increased
DECREASED valproic acid level INCREASED valproic acid metabolite 4-ene-valproic acid (hepatotoxic) INCREASED carbamazepine 10,11 epoxide (neurotoxic) (mildly) INCREASED carbamazepine level
500
What is the treatment of choice for seizures associated with acute porphyria?
Gabapentin (benzodiazepines can also be used); avoid antiepileptics as they may lead to porphyria crises (e.g. ramp up demand for oxidative processes/P450 enzymes)
500
Name the precursor to catecholamines.
Tyrosine
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