Drug Distribution Flashcards
Many drugs bind to proteins in the plasma. Give two examples of plasma proteins which may bind to a drug
Albumin and alpha1-glycoprotein (phenytoin)
What kind of drug is the only active form?
Unbound
The amount of bound drug can be altered by what factors?
- Renal failure
- Hypoalbuminaemia
- Pregnancy
- Other drugs
- Saturability of binding
Explain why protein binding is important
Maths and shit
What is the Apparent Volume of Distribution (Vd)?
It is defined as the volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration
The greater the Vd…
The greater the ability of a drug to diffuse into and through membranes
What is clearance?
It is defined as the theoretical volume of fluid from which a drug is completely removed over a period of time - a measure of elimination
What are the units of clearance?
Units of time (ml/min)
What is the half life of a drug?
It is defined as the time taken for the drug concentration to decrease by half
What will prolongation of a drugs half life do?
Increase the toxicity of the drug
Knowledge of half lives will help us to determine what about a given drugs administration?
How often it needs to be administered
Plasma levels of a drug take many doses before they stabilise, usually 4-5 half-lives. What might this necessitate?
A loading dose (initially higher dose)
What is drug elimination?
The removal of active drug and metabolites from the body - determining the length action of a drug and comprised of drug metabolism and drug excretion
What is the primary excretory organ for drugs?
The kidneys
What three principle mechanisms are used in the kidneys for drug excretion?
Glomerular filtrate, passive tubular reabsorption and active tubular secretion
Renal damage therefore is important in causing what?
Drug toxicity
Where and how are all unbound drugs filtered out of the blood?
The glomerulus in the kidneys as long as they aren’t too big
How are some acidic and basic compound drugs filtered out of the blood?
Actively secreted into the proximal convoluted tubule
Active tubular secretion is the most important process in elimination of what drugs?
Protein bound cationic and anionic drugs
What kind of drugs are reabsorbed and where?
Un-ionised weakly acidic drugs at the distal tubule and collecting duct
How are drugs secreted into bile?
Both actively and passively
Many drugs are absorbed from the bile back into circulation; what is this called?
Entero-heaptic circulation
For how long does enter-hepatic circulation continue for?
Until the drug is metabolised in the liver or excreted in the kidneys
Metabolism of a drug often leads to what?
Conjugation of the drug
What happens to the conjugated drug in the liver?
It is not reabsorbed from the intestine
