Pharmacokinetics Flashcards
What is ADME?
Absorption
Distribution
Metabolism
Excretion
What is the permeability coefficient?
Permeability coefficient = the number of molecules crossing the membrane per unit area.
What are the consequences of pH partition?
pH partition is the tendency for acids to accumulate in basic fluid compartments and vice versa. Drugs are absorbed from the membranes by passive diffusion depending on the fraction of un-ionized form of the drug at the pH of that biological membrane.
Urinary acidification accelerates excretion of weak bases and retards that of weak acids.
Urinary alkalisation has the opposite effect.
Increasing plasma pH causes weakly acidic drugs to be extracted from the CNS into the plasma.
Free base trapping of some antimalarial drugs in the acidic environment in the food vacuole of the malaria parasite -> disruption of hemoglobin digestion pathway -> toxic effect of the parasite.
Where are drugs taken orally usually absorbed?
villi and microvilli of small intestine
What is the first pass effect?
when the concentration of a drug is greatly reduced before it reaches the systemic circulation.
How can the first pass effect be avoided?
Sublingual and rectal absorption avoid this phenomenon.
Glyceryl trinitrate, used in angina, is effective sublingually but not when swallowed.
What is bioavailability?
Measurement of the extent with which a therapeutically active drug reaches the systemic circulation.
What is transcutaneously?
delivered through the skin by a patch.
Which tissues tend to show the highest and lowest concentrations of a drug?
Well perfused tissues, lungs, kidneys, show the highest concs.
Poorly perfused tissues such as adipose show lowest concs.
What is volume distribution (Vd)?
The volume of fluid which the drug will occupy if it were evenly distributed through that volume at the concentration measured in the plasma.
What are 2 types of transporters?
SLC = solute carrier transporters
Facilitate passive movement of solutes down their electrochemical gradient
ABC = ATP-binding cassette transporters
Active pumps fuelled by ATP.
What are 3 processes of kidney excretion?
Glomerular filtration, tubular secretion, tubular reabsorption
All occur in nephron
What are features of tubular secretion?
Saturation can occur. zero order kinetics.
Secretion into proximal tube is active.
Competition for transport of physicochemically similar drugs might occur. This reduces renal clearance -> can cause toxicity.
Drugs bound to plasma protein can be actively secreted in proximal tubular.
What are the features of glomerular filtration?
Drug conc in filtrate identical to plasma conc. Drugs bound to plasma protein not efficiently filtrated eg warfarin
20% of blood entering is filtered. Passive process.
What are the features of tubular reabsorption?
Occurs in distal convoluted tubule.
Water from glomerular filtration reabsorbed in proximal tubule. High drug conc in proximal tubular. Lipid soluble drugs can readily be reabsorbed.
Acidic urine results in increased reabsorption of weak acidic drugs.
