21) Therapeutic drug monitoring Flashcards
4 parts of pharmacokinetics
Absorption
Distribution
Metabolism/Biotransformation
Excretion
Drugs are absorbed from the gastrointestinal tract by either ——– or ———-.
passive diffusion
active transport
how does pH affect drug absorption
A drug that is uncharged tends to pass through membranes more readily than a charged drug.
Indicates the fractional extent to which a dose of drug reaches its site of action.
bioavailability
Metabolism or biliary excretion may occur before it reaches the systemic circulation.
first-pass effect
PO disadvantages
Limited absorption because of solubility, vomiting, destruction by digestive enzymes, and low gastric pH that may inactivate the drug
counteract disadvantages of PO administration
controlled-release drugs
how can first-pass effect work on parenteral meds?
- Partitioning into the lipids located in liver tissue
- Filtration
- Elimination as a volatile substance
aqueous solutions or specialized depot preparations in ethylene glycol or peanut oil
IM meds
50% of the drug absorbed will bypass the liver; avoids first-pass effect
rectal meds
topical anesthetics
Tetracaine and lidocaine
applied to eye to induce vomiting
atropine
Initially, most of the drug goes to the…
Then, to…
liver, kidneys, brain, and other well-perfused organs
muscles, skin, fat, and viscera
tissue distribution of a drug depends on…
- Partitioning of drug between blood and the particular tissue
- Lipid solubility
- pH gradients between intracellular and extracellular fluid
2 forms of drug circulating
bound and unbound
albumin alpha 1-acid glycoprotein
plasma protein that binds drugs
how does hypoalbuminemia affect drug levels?
protein binding is reduced, ↑ free drug level
Metabolism of a drug into more hydrophilic metabolites is essential for…
- Elimination of these compounds from the body
- Cessation of their biological activity
Reactions generate more polar, inactive metabolites that are readily excreted from the body.
biotransformation of drugs
2 types of biotransformation
Phase I (functionalization)
Phase II (conjugation)
phase I biotransformation reactions
Hydrolysis
Reduction
Oxidation
may be rapidly excreted into the urine, or they can react with endogenous compounds to form highly water-soluble conjugates
Products of phase I reactions
phase II biotranformation reactions
Leads to formation of covalent linkage between a functional group on the parent compound with an endogenously derived:
Glucuronic acid
Sulfate
Glutathione
Amino acid
Or acetate group
concentration of drug < MM constant
1st order kinetics
rate of drug metabolism is directly proportional to the concentration of free drug
concentration of drug > MM constant
zero-order kinetics
rate of metabolism remains constant over time
drugs that lead to zero order kinetics
aspirin
ethanol
Enzymes involved in biotransformation are found mainly in the ——-
liver
biotransformation phases location
Phase I: Endoplasmic reticulum
Phase II: Cytosol
Major enzyme system that metabolizes drugs
cytochrome P450 (CYP) monooxygenase system
most important organs for excretion of drugs and their metabolites
kidneys
——- compounds are more efficiently excreted than ——- ones.
polar
nonpolar
Measure of the body’s efficiency in eliminating drugs
Clearance (CL)
clearance (CL)
amount of renal plasma flow multiplied by the extraction ratio
extraction ratio
C2/C1
a function of clearance (mL/ min) times plasma drug concentration (mg/mL)
Excretion rate (mg/min)
Sum of the clearances from the various body organs that metabolize and eliminate drugs
total body clearance
CLtotal =
CL hepatic + CL renal + CL pulmonary + CL other
Clearance of a drug indicates…
the volume of biological fluid from which a drug would have to be completely removed to account for elimination
Measure of the apparent space the body has available to contain the drug
volume of distribution
volume of distribution (Vd) =
D/C
units: L
C = plasma conc; D = total drug in body
Takes —— half-lives to achieve steady state
5-7
A parameter that changes as a function of both clearance and volume of distribution
elimination half-life
elimination half-life =
0.693(Vd/CL)
conditions that alter half-life of drug
- Decreased renal blood flow
- Addition of a second drug that may displace the first drug from its carrier protein
- Decrease in metabolism because of hepatic insufficiency
Point when the total amount of drug in a human does not change over multiple loading dose intervals.
steady state
dosing rate (mg/min) =
CL(mL/min) x Css (mg/mL)
Css = the concentration at steady state
MEC
MTC
minimum effective conc.
minimim toxic conc.
between them –> therapeutic range
C maxss
minimum steady-state conc
Fraction of drug dose reaching the systemic circulation following administration by any route.
bioavailability
used to maintain the steady-state concentration of the drug associated within the therapeutic window
maintenance dose
Usually results in the attainment of target drug concentration in a shorter period of time
loading dose
Occurs more frequently in long-term treatments of diseases antihypertensive, antiretroviral, and anticonvulsant drugs
pt non-compliance
Fundamental action(s) of drugs
pharmacodynamics
The formation of a ——– leads to a biologic response or effect.
drug-receptor complex
The probability that a drug molecule will interact with its receptor to form the drug-receptor complex
drug affinity
The measurement of biological effectiveness of a drug-receptor complex
intrinsic affinity
Least amount of drug required to produce the maximum effect
potency