Test 1 - modules 1 and 2 Flashcards
what is another term for peak concentration
Cmax
What is another term for trough
Cmin
Maintenance dose formula
dose needed to maintain a steady state concentration
MD = Css x CL MD = Css x Vd x Kel
vd = volume of distribution Css = steady state concentration kel = elimination rate constant
What would be the equation for the steady state concentration if I administered a particular dose at this dosing interval
Css = 1.5(t1/2) x dose
All divided by
Vd x dose interval
volume of distribution
Css = steady state concentration
loading dose equation
Ld= Co x Vd
Co = desired plasma concentration of drug Vd = volume of distribution
is the EC50 =/not= to the ED50?
same thing -
Effective concentration where 50% of max effect
Effective dose where 50% of the max effect
what is the difference between first-order kinetics and zero-order kinetics
in first order - constant fraction of drug is eliminated
This is where you have half-life calculated
in zero order kinetics. There is a constant amount of drug is eliminated. It does not matter how much you give (independent of concentration of drug)
in first order kinetics on a non-log scale, what kind of line?
curved
in first order kinetics on a log scale, what kind of line?
straight
Is ASA a first order kinetic drug or a zero order kinetic drug
zero order
Is Dilantin a first order kinetic drug or a zero order kinetic drug
zero order
on a non-log scale, what kind of line for zero order kinetic drug
straight
on a log scale, what kind of line for zero order kinetic drug
straight
in first order kinetic drugs the rate of drug elimination per hour is _______ on drug concentration.
dependent
The more drug in the body, the more eliminated per hour
in zero order kinetic drugs, the rate of drug elimination per hour is ______ of drug concentration.
independent
the same amount is eliminated per hour regardless of how much drug is in the body
in zero order kinetic drugs Cp decreases ______ with time
linearly
In first order kinetic drugs Cp decreases ______ with time
exponentially
gentamycin
zero order or first order
first order
Vancomycin
zero order or first order
first order
Ethanol
zero order or first order
zero order
phenytoin
zero order or first order
zero order
what is pharmacodynamics
once the drug has arrived to its site of action what is the effect on the body
formula for therapeutic index
IT = LD50/ED50
LD50 = lethal dose in 50 percent
ED - effective dose in 50%
the higher the Therapeutic index, the _____ the drug
safer
2 drugs have the same active ingredients and are identical in strength or concentration, dosage form, route of administration and F (fraction making it - how much of the drug actually makes it to the body)
they have ______
Bioequivalence
Fraction of the drug that makes it to the body
bioavailability (F)
Dosage formulation influences rate of _____
dissolution
where are drugs metbolized
liver
intestines
kidneys
What is the purpose of drug metabolism
to make active (or) inactive metabolites
and to make drug molecules more water soluble for easier elimination
what class of meds are known to significantly inhibit the metabolism of simvastatin because of inhibition of CYP3A4
Protease inhibitors
what meds will increase the levels of Warfarin via (S-warfarin due to CYP2C9)?
Amiodarone
Metronidazole
TMP/SMX
Fluconazole
increases risk of bleeding
Phenytoin brand names
Dilantin
Phenytek
Phenytoin are used for what type of seizures
primary generalized and partial seizures
what type of seizures does Phenytoin known to worsen
Absence
Dosage forms of Phenytoin
PO or IV (NO IM)
side effects for Phenytoin
Increase drugs associated with CYP3A4
Sedation and CNS depression
gingival hyperplasia (also Calcium channel blockers and Cyclosporine)
Hirsutism
coarsening of facial features
hyperglycemia
Hematologic effects
osteoporosis - due to reduction in Vit D
Rash (including DRESS) - drug reaction when eosinophils are high
Megaloblastic anemia - due to reduction in folate (macrocytosis)
Teratogenicity
labs to monitor for Phenytoin
albumin uremia (BUN) TSH Total Phenytoin level Free Phenytoin level
How does Phenytoin work
blocks Na+ channels associated with depolarization, repolarization and membrane stability.
so if you have rapid firing this is to help stop the seizure
cardiac problems in TCA overdose or when you combine TCA with phenytoin
widen QRS
ventricular tachydysrhythmias
cause seizures
if someone has overdosed on TCA, now seizing….what should you avoid
(any tox case with seizures…NEVER give…)
Phenytoin -
blocks NA channels
worsen the seizures and cardiac conduction
what is the prodrug of phenytoin
Fosphenytoin (Cerebyx)
Prodrug of phenytoin is different from phenytoin and can be given by what route
This can be given IM
does not contain propylene glycol
Caution for phenytoin and kinetics
phenytoin will go from first order kinetics to a zero order kinetics at higher doses. overall phenytoin is considered to follow non-linear kinetics
what is the max rate for phenytoin on the IV load and why?
15-20mg/kg rate at no more than 50mg/min due to the presence of propylene glycol causes hypotension and cardiac arrhythmias
Phenytoin dose adjustments are based on ____
levels
Cp < 7mg/L - increase dose by 100mg/d
Cp 7-12 mg/L: increase by 50mg/d
Cp >12 mg/L increase by 30mg/d or less
0.74 mg/kg will increase level by 1 ug/ml assuming you haven’t reached the saturation point
Free fraction is what is pharmacologically ____
active
when you give fosphenytoin IM when can you check a phenytoin level?
IV?
4 hours
2 hours
Phenytoin toxic effects
levels and effect
Total >20mg/L = nystagmus
> 30mg/L = ataxia, increased seizures
> 40mg/L = Lethargy, altered consciousness and coma
drug of choice for trigeminal neuralgia
Carbamazepine
what type of seizures will Carbamazepine treat?
Partial and secondarily generalized tonic-clonic seizures
what type of seizures will Carbamazepine make worse
absence or myoclonic
what type of mental health disorder will Carbamazepine also treat
Mood stabilizer for bipolar disorder (esp mixed or rapid cycling)
other names for Carbamazepine
Tegretol, Tegretol XR
Carbatrol
Epitol
Equetro
Mechanism of Action Carbamazepine
Blocks Na channels
partial agonist at the adenosine A2A and A2B receptors
Therapeutic range for Carbamazepine
4-12 mg/L
Phenytoin (Dilantin) level reference range (total)
10-20mg/L
Can pregnant women take Carbamazepine
no
what genetic problem Carbamazepine
HLA-B 1502 allele - > severe rash (Stevens-Johnson Syndrome or Toxic epidermal necrolysis (TEN) - they need to be sent to the burn ICU - seen mainly in patients of Asian descent (Specifically Han Chinese)
Side effects of Carbamazepine
Leukopenia - caution in pt with Bone marrow suppression
Aplastic anemia and agranulocytosis (BBW)
Hyponatremia - stimulates release of ADH (SIADH)
Drowsiness
Fatigue
Nystagmus
Oxcarbazepine is also called
Oxtellar XR
Trileptal
what drug interaction is important to note for oxcarbazepine
contains ethanol
cannot take with flagyl or antibuse
what drugs mentioned cannot be taken with flagyl or antibuse
Oxcarbazepine (antiepileptic)
ritonavir (HIV)
what is the indication for Oxcarbazepine?
Initial and/or adjunct therapy for partial seizures
MOA Oxcarbazepine
Structurally similar to carbamazepine
NOT a metabolite
Inhibit voltage sensitive Na+ channels and modulates activity of voltage activated calcium channels
pharmacokinetic difference between Oxcarbazepine and Carbamazepine
Oxcarbazepine is not metabolized by CYP450
but it does still induce CYP3A4
Oxcarbazepine and food
IR can be taken without regard to food
XR should be taken on an empty stomach (1 hr before or 2 hrs after food)
Pregnancy risk
Lactation risk
Oxcarbazepine
C
L3
Oxcarbazepine side effects
Headache dizziness nystagmus blurred vision n/v rash hyponatremia
overall lower risk
Eslicarbazepine indications
partial -onset seizures adjunct therapy
MOA Eslicarbazepine
thought to be sodium channel blocker but unknown
Eslicarbazepine pharmacokinetic
Induces CYP3A4
Inhibits CYP2C19 - problem if on plavix
Valproic Acid indications
Complex partial (mono or adjunct therapy)
Status epilepticus
Absence Seizures (alternative option for, not first line)
Bipolar Disorder
Migraine prophylaxis
Migraine abortive therapy
Valproic Acid Brand
Depakene and Stavzor - Caps/syrup
Depakote (enteric coated) - preferred due to the GI side effects
How does Valproic Acid work
Partially blocks Na currents
may increase GABA levels and its effects by inhibiting the degradation of GABA by inhibiting GABA-T enzyme on the brain
Reference range and Tox range for Valproic acid
Ref - 50-125 mg/L or mcg/mL
Toxicity starts between 150-200
Drug interactions with Valproic acid
Lamotrigine (lamictal) - inhibits metabolism - associated with a dose or concentration effect of skin reactions (Steven johnsons)
Phenytoin
phenobarbital
CBZ
Ethosuximide
AZT (zidovudine)
Valproic acid pregnancy and lactation
D - neural tube defects
L2
Side effects of Valproic Acid
GI is the most common - enteric coated will help
weight gain
hepatotoxicity
pancreatitis
tremors
thrombocytopenia
Teratogenicity - due to folate deficiency
Hyperammonemia (NH3) - consider L carnitine therapy (Carnitor) if this happens
- causes encephalopathy
how do you treat hyperammonemia from valproic acid
L carnitine therapy (Carnitor)
drug of choice for absence seizures
Ethosuximide (Zarontin)
mechanism of action for Ethosuximide (Zarontin)
blocks thalamic (T-type) Ca++ channels
reference range for Ethosuximide (Zarontin)
60-100mcg/ml (some go up to 125 mcg/ML
side effects for Ethosuximide (Zarontin)
Gastritis (primary)
fatigue
headache
neurologic (psychotic behavior)
Rash (SJS)
Leukopenia (check CBC periodically)
Lupus like syndrome
phenobarbital (luminal) indications
alternative for partial and generalized tonic clonic seizures
typically used as second line but may be preferred in pregnant women (cat B/D depending on manufacturer)
Avoid in absence seizures - can worsen like phenytoin
MOA phenobarbital (luminal)
enhances GABA via increase in cl channel opening and makes GABA work better
also decreases glutamate mediated excitation on AMPA
at higher concentrations may block Ca channels
herbal medicinals that work on GABA providing anti anxiety
GABA
Valerian root
Kava
phenobarbital (luminal) clinical issues
Inducer of CYP450 and UGT enzymes
main side effect is sedation
develop tolerance