Pharmacokinetics Flashcards
State the five stages of the journey of a drug through the body.
Administration Absorption Distribution Metabolism Excretion (Voiding)
What is the difference between enteral and parenteral administration?
Enteral – using the GI tract
Parenteral – everything except the GI tract
What are the advantages of intravenous administration?
It gives rapid systemic exposure and a high bioavailability
State the two ways in which drug molecules move around the body.
Bulk Flow Transfer – in the bloodstream it will move in bulk to the tissues
Diffusion Transfer – molecule by molecule over short distances
State six methods by which drugs can cross lipid membrane barriers.
Passive diffusion (most common – pH PARTITION HYPOTHESIS)
Facilitated diffusion
Active transport (more important in drug excretion)
Pinocytosis (phagocytosis-mechanisms – liposomes)
Filtration (small water soluble molecules)
Paracellular transport (around cells, often overlooked
Chemically what are most drugs?
Weak acids or weak bases
Which factors affect the ratio of ionized to non-ionized drug?
pKa of the drug
pH of the environment
Describe and explain the difference in absorption of aspirin in the stomach and the small intestine.
Aspirin has a pKa of 3.4 The stomach has a pH of around 1, as this is lower than the pKa of aspirin, the aspirin equilibrium is shifts to unionised, which is rapidly absorbed.
Eventually, aspirin reaches the small intestines which has a higher pH than the pKa of aspirin, shifting equilibrium to ionised, slowing down aspirin absorption.
What is ion trapping?
Some ionized aspirin will enter the systemic circulation, which is an aqueous environment. As it is ionized it is unable to move into the tissues.
State four factors affecting drug distribution.
Regional blood flow
Extracellular binding (plasma-protein binding)
Capillary permeability
Localisation in tissue
In which state can albumin bind to drugs? Ionized or non-ionized?
Both
State three types of capillary.
Continuous
Fenestrated
Discontinuous
Give a broad example of localization of a drug in tissue.
Lipophilic drugs tend to localise in fatty tissues e.g. brain and testes
What are the two main routes of drug excretion?
Kidneys (main route)
Liver
What types of molecule tend to get excreted via the biliary route?
Large molecule weight molecules
The liver allows concentration of large molecular weight molecules that are very lipophilic
Via what form of molecular movement do most drugs tend to get excreted into urine?
Active secretion
What happens to drug-protein complexes at the glomerulus?
Too large to enter filtrate
Where does active secretion of acids and bases occur in the nephron?
Proximal convoluted tubule
What can happen to lipid soluble drugs in the proximal and distal convoluted tubules?
Reabsorption
Why might treatment with I.V. sodium bicarbonate increase aspirin excretion?
IV sodium bicarbonate will increase blood pH,
increasing ionised aspirin at equilibrium, raising water solubility so the kidneys can excrete more of it and less aspirin is reabsorbed in the proximal and distal tubules .
What is the main purpose of the active transport systems that secrete drugs into bile?
They are meant to be for the active transport of glucuronides and bile acids into the bile but drugs can hitch a ride on this mechanism
What is a potential problem with biliary excretion of xenobiotics?
Enterohepatic cycling – it can become reabsorbed and return to the liver via the enterohepatic circulation
leading to drug persistence.
Define bioavailability.
The proportion of the administered drug that is available within the body to exert its pharmacological effect
Define apparent volume of distribution.
The volume in which a drug appears to be distributed – an indicator of pattern of distribution
Define biological half-life.
The time taken for the concentration of a drug (in blood/plasma) to fall to half its original value
Define clearance.
The volume of plasma cleared of a drug per unit time
Define First-Order kinetics.
Rate of drug excretion is proportional to the concentration of drug remaining within the body (most drug removal is this.)
T1/2 = Vd x log(2)/Cl
Vd = volume of distribution
Cl = clearance
Define Zero-Order kinetics.
Constant amount of drug removed from body per unit time, implying that the enzymes responsible for drug removal are saturated.
