Drug Metabolism and Elimination Flashcards
Which type of reactions take place in phase I metabolism?
Oxidation, reduction, hydrolysis
What is achieved by phase I metabolism?
Introduction/revelation of functional group
More reactive products
What type of reactions take place in phase II metabolism?
Synthetic, conjugative reactions
What results from phase II metabolism?
Hydrophilic, inactive compounds generated
Which type of drugs are easily excreted by the kidneys in urine?
Hydrophillic
What happens to hydrophobic drugs in the liver?
Converted to hydrophillic metabolite
Conjugated and excreted in bile
What happens to drugs excreted in bile?
Pass to intestines and out in faeces
De-conjugated and taken back up by liver
Describe the CYP450 enzymes
Microsomal enzymes
Composed of CYP450, NAPDH-CYP450 reductase and lipid
Require NADPH and oxygen
Describe the reaction of aspirin to salicyclic acid
Spontaneous, non-enzymatic conversion when in the plasma - rapid process (phase I metabolism)
How is salicylic acid metabolised?
Oxidised (phase I)
Glucoronidation and glycination (phase II)
Which molecules are responsible for transfer of drugs from plasma to bile?
Organic cation transporters (OCTs)
Organic anion transporters (OATs)
P-glycoproteins (P-GP)
Why may oral antibiotics make the contraceptive pill less effective?
They disrupt the microbiota of the gut, reducing enterohepatic recirculation of oestrogen which is required to keep oestrogen levels high and prevent ovulation
Describe enterohepatic recirculation?
Drug in blood is conjugated in liver and excreted into the intestines in bile
Drug is then reabsorbed into the blood from the intestine and enters the liver again to be conjugated and excreted in bile again
When are lipophilic drugs not filtered in the glomerulus?
When they are bound to albumin
Which molecules are responsible for tubular secretion of drugs in the kidney?
OATs and OCTs
Describe the diffusion of different types of drugs in the renal tubule
Lipophillic drugs are mostly reabsorbed so poorly excreted
Polar drugs remain in the lumen so are more readily excreted
Urinary pH can affect this
How does pH of urine affect drug excretion?
Weak acids are more rapidly excreted if urine is alkaline
Weak bases are more rapidly excreted if urine is acidic
Why can bicarbonate be used in aspirin overdose?
Urine becomes more alkaline resulting in drugs that are weak acids to become more ionised meaning they cannot be reabsorbed and therefore are more rapidly excreted
Give an example of a drug which exhibits 0 order kinetics
Alcohol - 1 unit per hour
Alcohol dehydrogenase becomes saturated
What is zero order kinetics?
Rate of metabolism is constant
Rate doesn’t vary with amount of drug present
What is first order kinetics?
Constant fraction of drug metabolised per unit time
Increases proportionately to drug (more drug, faster metabolism)
What is clearance?
The volume of plasma cleared of the drug per hour
What is the volume of distribution?
The total amount of drug in the body / blood plasma concentration of drug
How do you calculate half life?
Ln2xVd/CL
How does Vd affect half life?
Higher Vd, higher half life
How does CL affect half life?
Higher clearance, lower half life
