1 and 2. Pharmacokinetics Flashcards
What is pharmacokinetics?
The study of a drug into and out of the body considering 4 main mechanisms (absorption, distribution, metabolism, and elimination).
What are the four main mechanisms in pharmacokinetics?
Absorption, distribution, metabolism, elimination.
What can affect peak plasma concentration of a drug in oral administration?
Rate of uptake of the drug and first pass metabolism.
What can affect the systemic entry of a drug?
GI motility, splanchnic blood flow, molecule size, pH levels, presence of active transport systems.
What is first pass metabolism?
Metabolism occurring before a drug enters the systemic circulation. Mostly in liver and portal venous system.
What is the effect of first pass metabolism?
Significantly reduced amounts of available drug in systemic circulation.
What is bioavailability?
Amount of drug which reaches the systemic circulation in an unchanged form relative to if administered via IV.
How is bioavailability calculated?
Amount of drug reaching systemic circulation/total amount of drug administered.
What is bioavailability affected by?
Drug preparation, intestinal motility, food, age, and first-pass metabolism.
What is drug distribution?
Ability of a drug to dissolve in the body.
What are the main factors affecting distribution throughout the body?
Lipophilicity/hydrophilicity and protein binding.
How does lipophilicity/hydrophilicity affect drug distribution?
If more lipophilic, more partitions out of the blood plasma into tissues with higher lipid content so if lipid-insoluble, then confined to plasma and interstitial fluid.
How does protein binding affect drug distribution?
Most drugs have to be unbound to have effect but most drugs are protein bound in circulation.
How do object and precipitant drugs differ?
Object - numbers of drugs less than binding site numbers.
Precipitant - number of molecules administered higher than binding sites.
How do precipitant drugs affect object drugs?
They displace molecules so free concentration of object drug increases.
How can protein binding be changed?
Hypoalbuminaemia, pregnancy, renal failure, displacement by other drugs.
When is changes to protein binding a problem?
If high protein binding normally, low volume of distribution, and narrow therapeutic ratio.
What are the two main separate body compartments?
Extracellular fluid compartment and intracellular fluid compartment.
What does the ECF compartment comprise of?
Plasma, interstitial fluid, transcellular fluid, and fat.
What does the apparent volume of a drug depend on?
Binding capacity there is for a given drug.
What is the volume of distribution?
Measure to see how well a drug distributed throughout body systems.
How is volume of distribution calculated?
Total amount of drug in the body/plasma concentration of drug (at time = 0).
What is the effect of being lipid soluble on volume of distribution?
It can leave plasma into other fluid compartments so volume of distribution is higher.
What is volume of distribution proportional to?
Half life.
What is volume of distribution affected by?
Lipid solubility, protein binding, disease states, regional blood flow, specific receptor sites in tissues.
When are acute increases in volume of distribution seen?
In sepsis, concurrent drugs, hypoalbuminaemia.
What are the phases of metabolism?
1 - catabolic reactions -> products that are chemically active.
2 - anabolic reactions with conjugation -? inactive products.
How do the phases of metabolism affect lipid solubility and therefore renal elimination?
Decreases lipid solubility so increases renal elimination.
Where do the phases of metabolism mainly occur?
Liver.
What enzyme family does phase 1 of metabolism depend on?
Cytochrome P450.
What affects CYP450 activity?
Drugs, age, liver disease, hepatic flow.
What are CYP enzymes?
Haem protein in the liver.
What induces CYP enzymes?
PCBRAS - phenytoin, carbamazapine, barbiturates, rifampicin, alcohol, sulphonylureas.
What inhibits CYP enzymes?
O-DEVICES - omeprazole, disulfiram, erythromycin, valproic acid, isoniazid, cimetidine, ethanol, sulphonamides.
What is the main route of drug elimination?
Via the kidney.
What are minor routes of drug elimination?
Lungs, breast milk, sweat, tears, genital secretions, bile, and saliva.
What are the three processes determining rate of renal excretion of drugs?
GFR, passive tubular reabsorption, and active tubular secretion.
What is clearance a measure?
Hepatic clearance and renal clearance.
How do organic anion and cation transporters contribute to drug elimination?
Act as renal transporters and transport drugs from plasma to nephron lumen, they’re in the PCT.
What affects clearance rate?
Heart (CVS affects blood flow to main organs of elimination), renal (affects renal elimination), hepatic (affects hepatic elimination).
What is the half life of a drug?
The amount of time over which the concentration of a drug in plasma decreases to one half of the concentration value it had when measured.
What affects the half life of a drug?
Cardiovascular factors, renal elimination, and hepatic metabolism.
What is 1st order kinetics?
Rate of elimination is proportional to drug level so a constant fraction of drug is eliminated in unit time.
What is zero order kinetics?
Rate of elimination is constant and no half life can be defined.
How can steady state concentration in plasma be calculated?
CpSS = dose rate/clearance.
When is CpSS reached?
4-5 half lives.
What is the purpose of a loading dose?
A clinician wants to achieve a CpSS within the therapeutic window quickly.
How is loading dose calculated?
DoseL = Vd x CpSS.
