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Kinetics > Lithium / Carbamazepine / Valproic acid / Phenobarbital > Flashcards

Lithium / Carbamazepine / Valproic acid / Phenobarbital Flashcards

1
Q

what are the mood stabilizers?

A

lithium
carbamazepine (antiepileptic)
valproic acid (antiepileptic)

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2
Q

lithium:
- indications
- mechanism of action
- blood level monitoring
- lithium serum concentrations co - relate with?
- full therapeutic response within?

A
  • bipolar disorder, acute manic episodes
  • not fully understood
  • blood level monitoring since narrow therapeutic index
  • efficacy and toxicity
  • 1 - 2 weeks
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3
Q

factors associated with increased lithium toxicity:

A
  • low sodium diet
  • dehydration
  • vomiting
  • elderly pts
  • hypothyroidism
  • thiaizide diuretics, NSAIDS, ACEI
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3
Q

dose of lithium:
maintenance dose?
goal serum concentration?
in elderly patients: maintenance dose?

A
  • 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
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4
Q

What increases the renal elimination of lithium?

A
  • theophylline
  • caffeine
  • osmotic diuretics
  • sodium supplements
  • acute mania
  • dialysis
  • late stages of pregnancy
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5
Q

what is the bioavailability of lithium?
what do we use in the equations?
dosage strengths?

A
  • IR: 0.95 - 1
    SR: 0.6 - 0.9
  • IR: 1
    SR: 0.75
  • IR: 150, 300, 600 mg
    SR: 300, 450 mg
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6
Q

Vd of lithium?
where does it distribute?
breast milk?
pregnancy?

A
  • 0.7 L/kg
  • central & peripheral compartments
  • excreted in breast milk
  • discontinue during first trimester of pregnancy
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7
Q

half life of lithium?
how is it excreted?
how is it metabolized?
lithium clearance?

A
  • alpha (distribution): 6 hours
    beta (elimination): 18 - 24 hours
  • filtration byy the kidneys
  • no hepatic metabolism
  • 0.25 x CrCl
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8
Q

Steady state equation of lithium?
Dose equation of lithium?
conversion from mg to meq and ml to meq

A
  • 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
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9
Q

acute side effects of lithium

A
  • N / D
  • polyuria, polydipsia
  • muscle weakness
  • fine tremors
  • CNS
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10
Q

moderate side effects of lithium

A

Nausea
Confusion
Coarse tremor
Slurred speech
Ataxia
Nystagmus

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11
Q

severe side effects of lithium

A
  • seizures
  • muscle fasciculations
  • irregular pulse
  • hypotension
  • respiratory complications
  • coma
  • death
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12
Q

chronic side effects of lithium

A
  • hypothyroidism
  • weight gain
  • renal damage
  • dermatological effects
  • rigidity
  • leukocytosis
  • EKG changes
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13
Q

how to monitor lithium in lab

A
  • CBC with differential
  • EKG
  • electrolytes (Na)
  • thyroid function tests (for hypothyroidism)
  • renal function tests
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14
Q

when is a steady state of lithium reached?
how do we monitor?

A
  • 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

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15
Q

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?
A
  • 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
16
Q

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?
A
  • 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
17
Q

side effects of carbamazepine

A

N / V / D
hepatotoxicity
leukopenia
hyponatremia
dermatological reaction (SJS)
dysarrhythmias
CNS effects

18
Q

when should carbamazepine blood levels (trough) be monitored?
what to monitor at baseline then what?

A

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

19
Q

interactions of carbamazepine?
what drugs increase the levels of carbamazepine?
what drugs decrease the levels of carbamazepine?
- carbamazepine increases the clearance of?

A
  • cimetidine, valproic acid, erythromycin, verapamil, grapefruit juice
  • phenobarbital, phenytoin, theophylline
  • theophylline, valproic acid, phenytoiin, warfarin, oral contraceptives
20
Q

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?

A
  • 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
20
Q

phenobarbital:
- what is it?
- duration of action
- indications
- target

A
  • barbiturate
  • long acting (Once daily dosing)
  • seizure disorders and anxiety
  • 15 - 40 mcg/ml
21
Q

phenobarbital

  • dosing
  • bioavailability
  • maintenance dose dosing
  • absorption
  • S
  • half life
A
  • 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
21
Q

phenobarbital: dosage strengths:
does it need dosing adjustment?

A

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

21
Q

phenobarbital

volume of distribution
breast milk? pregnancy?
metabolism
excretion
how long to reach steady state?
loading dose equation

A
  • 0.7 L/kg (0.9 L/kg in neonates)
  • crosses placenta and is excreted in breast milk
  • liver
  • 40% in urine
  • 2 weeks
  • CVd / S F
22
Q

phenobarbital

Css av equation
side effects
monitoring level
interactions

A
  • SF Dose / Cl x tau
  • dec calcium, dec libido, dec folic acid, CNS depression, sedation, behavioral abnormalities
  • after LD then every 3 - 4 days then every 2 - 3 weeks
  • dec levels of phenytoiin, carbamazepine, warfarin, theophylline

Kinetics (3 decks)

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