Lithium / Carbamazepine / Valproic acid / Phenobarbital Flashcards
what are the mood stabilizers?
lithium
carbamazepine (antiepileptic)
valproic acid (antiepileptic)
lithium:
- indications
- mechanism of action
- blood level monitoring
- lithium serum concentrations co - relate with?
- full therapeutic response within?
- bipolar disorder, acute manic episodes
- not fully understood
- blood level monitoring since narrow therapeutic index
- efficacy and toxicity
- 1 - 2 weeks
factors associated with increased lithium toxicity:
- low sodium diet
- dehydration
- vomiting
- elderly pts
- hypothyroidism
- thiaizide diuretics, NSAIDS, ACEI
dose of lithium:
maintenance dose?
goal serum concentration?
in elderly patients: maintenance dose?
- 600 - 900 mg/day in 2 -3 divided doses
- 900 - 1800 mg/day
- 0.6 - 1.2 mEq / L
- lower doses in elderly patients (MD = 900 - 1200 mg/day) due to increased risk of toxicity
What increases the renal elimination of lithium?
- theophylline
- caffeine
- osmotic diuretics
- sodium supplements
- acute mania
- dialysis
- late stages of pregnancy
what is the bioavailability of lithium?
what do we use in the equations?
dosage strengths?
- IR: 0.95 - 1
SR: 0.6 - 0.9 - IR: 1
SR: 0.75 - IR: 150, 300, 600 mg
SR: 300, 450 mg
Vd of lithium?
where does it distribute?
breast milk?
pregnancy?
- 0.7 L/kg
- central & peripheral compartments
- excreted in breast milk
- discontinue during first trimester of pregnancy
half life of lithium?
how is it excreted?
how is it metabolized?
lithium clearance?
- alpha (distribution): 6 hours
beta (elimination): 18 - 24 hours - filtration byy the kidneys
- no hepatic metabolism
- 0.25 x CrCl
Steady state equation of lithium?
Dose equation of lithium?
conversion from mg to meq and ml to meq
- SS = SFDose / Cl (lithium)x tau (24 hours)
- Css x Cl (li) x tau / S F
- 300 mg lithium carbonate = 8.12 meq lithium
5 ml lithium citrate = 8 meq lithium
acute side effects of lithium
- N / D
- polyuria, polydipsia
- muscle weakness
- fine tremors
- CNS
moderate side effects of lithium
Nausea
Confusion
Coarse tremor
Slurred speech
Ataxia
Nystagmus
severe side effects of lithium
- seizures
- muscle fasciculations
- irregular pulse
- hypotension
- respiratory complications
- coma
- death
chronic side effects of lithium
- hypothyroidism
- weight gain
- renal damage
- dermatological effects
- rigidity
- leukocytosis
- EKG changes
how to monitor lithium in lab
- CBC with differential
- EKG
- electrolytes (Na)
- thyroid function tests (for hypothyroidism)
- renal function tests
when is a steady state of lithium reached?
how do we monitor?
- within 3 - 5 days
- every week for 1 month then every 6 - 12 months
monitor more frequently when changes in renal function, elderly, dosage changes, or concurrent medications that may affect lithium clearance
Carbamazepine
- indications
- target level
- PK parameters show?
- dose? maximum dose?
- how to administer?
- absorption of carbamazepine is ____. it follows a ____.
- solubility of carbamazepine?
- bioavailability (F)?
- dosage strengths?
- dosage forms available?
- volume of distribution?
- is i bound to any proteins or no?
- pregnancy + breast milk?
- seizure disorders, neuralgias, bipolar disorder
- 4 - 12 **mcg / mL **
- variability between patients –> blood level monitoring
- 10 - 15 mg/kg/day in 2 or 3 divided doses (max: 1200 mg/day).
- with food (food increases its absorption)
- highly variable –> follows a 0 order process
- poorly soluble drug and has anticholi properties
- F = 0.8
- IR: (100, 200 mg)
CR: 100, 200, 400 mg
SR: 200, 300 mg - IR, SR, CR, oral suspension 100 mg/5 ml
not available in IV form - 0.8 - 3 L /kg
- yes: albumin and alpha acid glycoprotein
- excreted in breast milk; pregnancy category D
Carbamazepine
- metabolism
- half life? (single dose vs chronic dose)
- usually we need how much time to reach steady state?
- is it an enzyme inhibtor or inducer?
- Css equation?
- when can we use Css av?
- metabolized in the liver
induces its own metabolism => 3 - 5 days after starting therapy and up to 2 - 4 weeks. - enzyme inducer
- 35 hours (single dose); 11 - 27 hours (chronic dose).
- inducer
- Css av = S F Dose / Cl x tau
- once auto - induction is over
side effects of carbamazepine
N / V / D
hepatotoxicity
leukopenia
hyponatremia
dermatological reaction (SJS)
dysarrhythmias
CNS effects
when should carbamazepine blood levels (trough) be monitored?
what to monitor at baseline then what?
every 1 - 2 weeks for 2 - 3 months then every 4 - 6 months
- CBC, sodium, LFTs at baseline then every 6 - 12 months in stabilized patients
interactions of carbamazepine?
what drugs increase the levels of carbamazepine?
what drugs decrease the levels of carbamazepine?
- carbamazepine increases the clearance of?
- cimetidine, valproic acid, erythromycin, verapamil, grapefruit juice
- phenobarbital, phenytoin, theophylline
- theophylline, valproic acid, phenytoiin, warfarin, oral contraceptives
valproic acid:
- indications
- target level
- dose
- administration
- when do we give a LD?
- how is it absorbed
- bioavailability
- dosage strengths
- volume of distribution
- plasma protein binding
- saturation at conc of?
- how is it excreted?
- metabolism
- Css av equation
- half life?
- side effects (most imp)
- when do we check blood trough levels?
- how to monitor and what
- goal of free:
- goal of total (bound + unbound)
- drug interactions of valproic acidd:
a. what decreases its concentrations
b. what does it decrease the concentraton of?
- seizure disorders (generalized, partial, and absence seizures), bipolar disorder, migraine prophylaxis.
- target level = 50 - 100 mcg/ml
- start dose at 5 - 10 mg/kg/day, then gradually titrated upward 250 - 500 mg every 3 days to a max of 60 mg/kg/day.
- administered in divided doses (BID - TID) since it’s short acting
- in acute seizures (25 mg/kg)
- rapid absorption from the GI tract
- 1 but for ER = 0.9
- (125, 250 mg capsules), (125, 250, 500 tablets), (500 mg tablets); valproate sodium (injection 500 mg/5 ml), oral solution (250 mg/5 ml)
- 0.1 - 0.5 L/kg
- highly bound to plasma proteins
- saturation of plasma protein binding at concentrations > 50 mcg/ml
- minimal excretion in the urine
teratogenic but compatible with breast feeding- metabolized by liver enzymes: toxic metabolite 4 - ene leading to hepatotoxicity / inhibits the metabolism of other drugs
- Css av = S F Dose / Cl x tau
- 4 - 17 hours
- thrombocytopenia, hepatotoxicity (esp in children), inc in pancreatic enzymes.
- every 1 - 2 weels for 2 months then every 3 - 6 months in stabilized pts
- LFTs and platelets monthly for 3 months then every 3 - 6 months
- ↓ levels of valproic acid : phenytoin,
phenobarbital, carbamazepine, rifampin
- Valproic acid decreases the clearance of:
phenytoin, phenobarbital, carbamazepine
phenobarbital:
- what is it?
- duration of action
- indications
- target
- barbiturate
- long acting (Once daily dosing)
- seizure disorders and anxiety
- 15 - 40 mcg/ml
phenobarbital
- dosing
- bioavailability
- maintenance dose dosing
- absorption
- S
- half life
- adults: 1 - 3 mg /kg/day
children: 2 - 5 mg/kg/day - 1 after oral, rectal, and IM
- start the patient on 1/4 of the maintenance dose for the first week then gradually inc over 3 weeks (25% of the dose each week)
- bioavailability = 1 for IM, oral rectal
- 0.9 after IV and IM (sodium salt)
- 5 days
phenobarbital: dosage strengths:
does it need dosing adjustment?
tablets: 15, 30, 60, 100 mg
sodium salt and IV: 30, 60, 65, 130 mg/ml
- no need for dosage adjustment in mild renal / hepatic impairment since elim is by both routes
- 50% bound to albumin
