Pharmacokinetics Flashcards
Ways the body impacts the drug
Absorption into the body
Distributed throughout the body
Eliminated from the body
Standard drug dose
Does the elicits the average therapeutic to the normal “healthy” individual
Therapeutic window
Increases the effectiveness of drug without reaching adverse effects.
Intrathecal administration
Drug directly injects into CSF (avoids BBB)
Charged form of drug
pKa < pH
Can’t move out of area
Uncharged drug form
PKa> pH
Can move out of area
1st-pass Metabolism
Oral drugs are absorbed from GIT and harried to liver via hepatic portal vein
- helps reduce the amount of drug reaching the target tissue by inactivating unneeded amounts.
- can in special circumstances activate pro-drugs
Bioavailability
Quantity of drug reaching the systemic circulation/ quantity of drug administered
Rated 0 (all of it is inactivated) to 100 (all of it is activated)
Hepatic extraction ratio
Percentage of drug absorbed by 1st pass metabolism (not entered systemic circuit).
Loading dose
Initial doses that accounts for low distribution of a drug.
- drugs with high Vd use loading doses to get distribution quickly and remain in therapeutic range.
Maintenance dose
Maintains steady stet by using subsequent doses to replace drug concentration lost through metabolism.
- amount is dependent on clearance fo a drug (high clearance = high maintenance dose)
Volume of distribution
Fluid volume required to contain total amount of absorbed drug in body at uniform concentration
.
Measured by amount of drug in body/ plasma drug concentration
Types of binding proteins
Albumin (acidic drug binding)
Alpha 1 acid glycoprotein (basic drug binding)
Iipoprotein (lipid drug binding)
High protein binding
Drug has lower Vd since less drug volume is “free” and remains locally bound to proteins.
Low protein binding
Drug has higher Vd since most of the drug is in the “free” form
Special neonate and infant information
Higher percentage of “free” drug
Lower Vd for lipid soluble drugs
Special elderly information
Vd for hydrophillic drugs decreases
Vd for lipophillic Cruz’s increase
During acute illness, has lower plasma proteins
5 outcomes of drug metabolism
Active -> inactive metabolite
Unexcretable drugs -> excretable metabolite
Active -> active metabolite
Inactive prodrug -> active
Active -> toxic metabolite
Types of metabolism reactions
Phase 1: oxidation/reduction reactions
Phase 2: conjugation/hydrolysis reactions
Usually occur sequentially and are used to reduce lipid solubility
what are phase 1 reactions mediated by?
Cytochrome P450 Enzymes
Three conjugation reactions
Glucuronidation
Acetylation
Sulfation
ALL increase the polarity of a drug and metabolites
Cytochrome P450 system
Transfer oxygen atoms onto drugs
- found in SER in hepatocytes
- roughly 75% of drugs are metabolized
Specific cytochromes (CYPs) for drug metabolism
CYP3A4
CYP2D6
CYP2C19
CYP2C9
CYP2E1
CYP1A2
Inhibitors of CYP 3A4
Grapefruit and Cimetidine
Inducer of CYP 3A4
St. John’s Wort
Inducer of CYP 2E1
Ethanol
Inducer of CYP 1A2
Tobacco smoke
Inducer vs inhibitor
An inducer allows the specific P450 enzyme for itself to clear its substrate faster
-decrease drug efficacy
An inhibitor allows the specific P450 enzyme for itself to clear its substrate slower
- Increases drug toxicity
Major route of drug excretion?
Renal excretion
First order elimination kinetics
Constant fraction of drug does lost every half life
- exponential decay
- (95% of drugs)
Zero order elimination kinetics
Constant amount of the drug is lost per half life
- linear decay
4 drugs that undergo zero order elimination kinetics
Alcohol, warfarin, aspirin, theophylline
Clinical significance of zero-order elimination
Small increases of doses cause large increase in blood levels.
Volume of distribution equation
(Bioavailability x Dose) / plasma concentration
Clearance equation
dose / (dosing interval x concentration)
Half-life equation
(0. 69 x Vd) / CL
- usually 4-5 half life’s causes a drug to be officially removed from a patients system
Loading dose equation
(Volume of distribution x target concentration) / bioavailability
