Gen/multisys Flashcards
INR range on warfarin
2 - 3
CyP450 inducers
Dec efficacy of warfarin by inc elimination
» CRAP GPS MaN « Carbamazepine Rifampin Alcohol, chronic Phenytoin
Griseofulvin
Phenobarbital
St. John’s wort
Modafinil
Nevirapine
CyP450 inhibitors
Inc warfarin effect
» ABCG «
Amiodarone Azole antifungal antiBiotics (metronidazole. Macrolides) Cimetidine Grapefruit juice
CyP450 subtypes
CYP1A2:
CYP2E1:
CYP2C9:
CYP2D6:
CYPEA4:
CYP1A2: Acetaminophen
CYP2E1: Ethanol
CYP2C9: Warfarin
CYP2D6: Cardiac drugs
CYPEA4: #MC
MAB elimination
- Against cell surface Ag undergo internalization (receptor mediated encpdocytosis) : bind to target, removed from circulation
- NS : taken up by RES macrophages (Fc receptor) + vasc endoth cella (pinocytosis)
Catabolized into AA within lysosomes
Inhibition of which efflux pump improves drug delivery to brain?
P-glycoprotein
efflux pump on brain capillary endoth cells, part of BBB
Sustained release preparations of drugs
- Reduced SE d/t dampening of peak levels
- Longer duration of therapeutic effect due to prolonged absorption of the drug
- Improved patient compliance due to less frequent administration
- useful for drugs with short half-lives (ie, allowing prolonged effect without need for multiple doses) or narrow therapeutic windows (ie, maintaining effective drug levels while minimizing absorption peaks).
Enterohepatic cycling of drugs
Drugs excreted into bile undergo enterohepatic cycling which inc drug’s effect longer than its t1/2
Compared to adults, which of the following neonatal factors is the most likely cause of the difference in drug effectiveness?
- ↑ Proportion of body water (↑ Distribution of water-soluble drugs may necessitate higher mg/kg dose)
- Blood-brain barrier immaturity (↑ CNS toxicity)
- ↓ CYP enzyme activity + ↓ Hepatic glucuronidation (↑ Sensitivity to hepatically metabolized drugs)
- ↓ Renal blood flow & GFR
- ↑ TBW : ↑ Vd : ↓ plasma concentration
Changes in log dose-response curve
- Full agonist + Rev comp antag
- Full ag + Noncomp antag
- Full agonist + Rev comp antag :
- parallel shift to right, inc in ED50
- no change in Emax - Full ag + Noncomp antag:
- shift down d/t dec Emax
- no change in ED50
» Competitive = change ED50 = shift right;
Noncompetitive = change Emax = shift down. «
Drug conc mg/L =
Drug conc mg/L = drug dose (mg) / Vd (L)
Vd (L)
Vd (L) = amount of drug given (mg) / plasma concentration of drug (mg/L)
Zero vs First order kinetics
Zero-order:
Same AMOUNT of drug metabolized per unit time independent of serum levels/ dose
First-order:
Same FRACTION/ PROPORTION of drug metabolized
TBW
TBW ~ 41L
- ECF ~ 14L or 1/3 TBW
- Plasma ~ 3L
- Interstitial fluid ~ 10L
- ICF ~ 25L or 2/3 TBW
Vd based on properties of drugs
Low Vd(3-5L): since remains in plasma/ bloodstream - plasma protein bound - highly charged (hydrophilic) - large molecular weight ❗️renal elimination
High Vd (14-16L) - small molecular wt, but -highly charged (hydrophilic) Drug in plasma + interstitial fluid ❗️most affected by body weight!
Highest Vd (41L)
- small molecular weight
- uncharted (hydrophobic or lipophillic) since can cross cell memb n reach into intracellular compartment n bound to tissues
- highest conc in skeletal muscle, bone, adipose tissue
❗️ hepatic elimination into bile + urine
Bioavailability
Bioavailability is the fraction of an administered drug that reaches the systemic circulation unchanged.
- decreases with oral administration due to incomplete absorption and first-pass metabolism compared to parenteral administration.
Why’s dosing based on body weight required?
To improve safety, efficacy,
For meds w narrow therapeutic index eg. Heparin, Aminoglycosides, Anesthetics
🌟 dosing based on adjusted/ lean body wt in obese pts which includes only a portion (~40%) excess adipose mass. Usually for hydrophilic drugs that do not distribute in adipose tissue.
What is drug clearance based on?
Lean body weight (wt of nonadipose tissue: muscle, liver, kidney)
Lean body mass req for?
- Vd
2. Drug clearance
Loading dose req for?
Lipophilic drugs eg. Phenytoin
- sequestered w/in adipose, : loading dose req to saturate fat stores to achieve adequate serum levels
How is drug toxicity of a drug reduced?
Frequent small dosing : lower peak, lower avg drug conc
❗️Drug toxicity = peak/ avg plasma drug levels
Serum trough conc of a drug
Lowest conc level before next dose
Drug clearance
Cl = amt of plasma cleared of the drug / time (mL/min)
Therapeutic window
range of drug dosages that have an appropriate clinical effect.
From the lowest dose at which the drug is effective to the highest dose without significant toxic effects.
❗️narrow TI drugs : frequent dose age to prevent peak/ toxicity of drug
