pharmacokinetics Flashcards
Pharmacodynamics
The effects of drugs and their mechanisms of action
-“The effect of the drug on the body”
Pharmacokinetics
The movement of drugs through the body
“The effect of the body on the drug”
Pharmacotherapeutics
The clinical (therapeutic) use of drugs "Using drugs to treat disease"
Therapeutic Index (Ratio)
The amount of drug that brings about the therapeutic effect compared to the amount that causes toxicity or death
“effective dose vs. harmful dose”
ADME
- Absoption: mvmt of a drug from the site of administration into blood
- Distribution: movement of drugs throughout the body (in blood)
- Metabolism: “biotransformation”- important for lipid soluble to water soluble; enzymatic alteration of drug - (in liver)
- Elimination: the removal of drugs from the body, either by excretion into bile or urine.
Bioavailability
The fractional extent to which a dose of drug reaches the blood stream and its site of action.
Dependent on several factos—ROUTE OF ADMINISTRATION
Other less common routes of administration
- Sublingual: oral mucosa (bypasses the liver)
- Transdermal: lipid soluble
- Rectal: 50% bypass the liver, can irritate mucosa.
- Intra-Arterial: localize effects (bypasses the liver)
- Intrathecal: CSF (bypasses BBB)
- Inhaled (pulmonary absorption): almost instantaneous, bypasses liver
- Topical application: mucous membranes (nasopharynx, oropharynx, vagina, colon, urethra, bladder, eye, etc…)
Metabolism of Drugs
- mostly inactivation (activation = prodrugs)
- biotransformation rxns that generate more polar inactive metabolites that are more readily excreted
- enzyme systems primarily in liver.
- (others GI tract, kidneys, and lungs)
Fundamental tenet of pharmacokinetics and
4 parameters
- relationship between the pharmeffect of a drug and the accessible blood or plasma concentration of the drug. (blood conc. of drug and effect on body)
4 Parameters
-Bioavailability
-Volume of distribution: space to contain drug
-Clearance: efficiency in eliminating
-Elimination half-life: time for plasma conc to decrease by half
enteral vs parental
absorbed by the GI tract or not
factors affecting movement (how/what they effect)
- lipid solubility: membrane diffusion, ADME
- ionization: rate and location of absorption
- protein binding: D, M, E (rate!)
first pass effect
large % of conc will be metabolized by liver in 1st pass, may have to increase dosage
portal circulation
portal vein carries blood that went through GI tract (while in liver, drugs will be metab or neutralized) - blood flow leaves via hepatic vein to vena cava
common routes of administration
- oral: most convenient, absorption can be affected by food
- IV: bypasses absorption, immediate effects; able to titrate for individual doses
- SubQ: slower than IM, affected by tissue perfusion, self admin
- IM: 15-30min, affected by tissue perfusion, self-admin; contraindicated with anti-coagulants
factors of distribution
- physiological: cardiac output, regional blood flow, capillary perm, tissue volume
- chem prop of drug: lipid solubility, pH partitioning, binding to plasma proteins/tissue macromolecules
sequestration
- drugs get into the tissue and stay there until blood conc decreases - can move back into blood stream (redistribution)
(fat soluble and high bone affinity)
special considerations for distribution
- to CNS and CSF: site of action brain - mechanism is impt
- placental transfer of drugs
cytochrome P-450 superfamily
- responsible for biotransformation
- basis for drug - drug interactions (effect activity of ENZYME)
- inhibitors: decrease enzyme activity, drug stays in body, need lower dose
- activators: increase enzyme activity - metabolized faster; need higher dose
(inter-individual variation
excretion of drugs
- mainly by kidney
- biliary and fecal
- less common: sweat, saliva, tears, breast milk, lungs
renal excretion
- kidneys filter from blood stream to tubules (upper or lower end of tubule)
- substances can move back into blood stream.. especially lipid-soluble (biotransformation impt)
- rate affected by impaired function
drug dosing/steady state
- keep drug in therapeutic range; know conc it needs to be at and how long it will last
- with each dose blood conc will increase; steady state reached after 3-5 half-lives
