pharmokinetics Flashcards
what is clinical pharmacology
science of drugs and their use in humans
what is bioavailability
the proportion of administrated drug which reaches the systemic circulation unchanged
what type of drug administration achieves 100% bioavailability
intravenous injection
what is the most common route of drug administration
oral route
in the oral route what does absorption rate depend on
GI transit
what are the mucosal routes of drug administration
nasal, eye, vaginal, rectum,
what route of administration avoids first pass metabolism
inhalation, mucosal routes, transdermal, intravenous subcutaneous and intramuscular injections
what is pharmacokinetics
study of drug movement within the body
what is pharmacodynamics
study of drug effects and metabolism of action
what are the four stages of pharmacokinetics
absorption, distribution, metabolism, excretion
For an orally- administrated drug to reach
systemic arterial circulation intact, the drug must :
- cross the GI tract
- avoid metabolism by the GI tract and liver
factors affecting GI drug absorption rates
- Surface area and blood flow
- Gastrointestinal motility
- Malabsorptive tates
- food type
what is first pass metabolism
the extent of metabolism occurring BEFORE the drug enters the systemic circulation. Occurs in gut lumen, gut wall and liver
after absorption orally-administrated drugs enter what system
portal system
rate and distribution of a drug are determined by
- the ability of the drug to pass through membranes
- lipid solubility Of the drug
- Binding of the drug to plasma proteins
- active transport across cell membranes
- Presence of other drugs in the body
what is drug distribution
process by which drugs are transferred from systemic circulation to tIssues
what is the volume of distribution, what is the effect on lipid solubility and protein-bound on VD? What are the impacts of high VD?
the amount of water h20 which the drug would have to be added to give the same concentration as in plasma
lipid solubility: increases VD
protein-bound: decreases VD
high VD , causes sequestration of fat cells = long half-life
a high Vd can indicate what
sequestration in body fat and Long drug half- life
what type of drug can transverse membranes to accesss cells and targets
non-protein bound
do drugs bind reversibly or irreversible to plasma proteins
reversible without causing damage
what are the criteria for protein binding to significantly affect drug distribution
- protein-bound proportion must constitute 90% Off total drug in the plasma
- extent Of the distribution of the drug to the tissues must be the same
- High protein binding can dramatically Increase half- Life
what is causes protein displacement
co-adminstrating drugs
protein displacement is very important to what
drug distribution, effect and quality
what organ is a major site of drug metabolism
liver
what happens during phase 1 of absorption
products produced tend to be more chemically reactive and often more toxic than the parent drug
what happens during phase 2 of absorption
drug produces chemically polar products which are cleared by the kidney
examples of factors affecting drug metabolism
Liver disease
- genetic polymorphisms in drug metabolism
- advancing age
- genetic polymorphisms in drug metabolising enzymes
- competition between different drugs for some metabolising enzymes
what are the main routes of excretion
kidney via the urine
what are elimination kinetics in the rate of elimination
amount of drug eliminated from the body/unit of time
what are first-order kinetics in drug elimination, what is an important parameter to measure this?
drug concentration decreases exponentially over time. drug elimination half-life curve
what can be determined from elimination curves
drug half-life
what is half life
the time it takes for the plasma drug concentration to halve, determined by an elimination curve
what enzymes are important in phase 1 absorption
cytochrome P450
what is protein binding, what is the affect on half-life
reversible has no effect on drug function, protein-bound however cannot cross the membrane increasing half-life
what is the half-life of paracetamol, atenolol, warfarin, chloroquine
2 hours
6 hours
2 days
6 weeks
what is the effect of liver disease on bioavailability
patients have higher bioavailability because the drug is not metabolised within the lives. Drug doses and timing calculations will need to be altered.
