Drug Distribution Flashcards
Why is plasma protein binding important in drug distribution?
Many drugs bind to plasma proteins like albumin. Only the unbound drug is biologically active. Binding is reversible.
Important as small changes of free drug can have massive changes on the plasma levels of free drug.
What factors can affect the amount of drug bound to plasma proteins?
Pregnancy Renal failure Hypoalbuminaemia Other drugs Saturability of binding
What is warfarin?
An anticoagulant drug to reduce thrombosis. It has a narrow therapeutic range and is monitored by INR.
What is volume of distribution?
Vd
Theoretical volume of plasma that would be necessary to contain the the total amount of an administered drug at the same concentration that is seen in the blood plasma. In theory the Vd should be 42L but changes on nature of the drug.
What is clearance of a drug and what is this dependent on in the kidneys and liver?
Cl measured in ml/min)
Theoretical volume from which a drug is removed completely from the body over a period of time.
Dependant on concentration and urine flow rate for renal clearance.
Dependant on metabolism and biliary excretion for hepatic clearance.
What is half life of a drug?
T1/2
The time taken for the drug concentration in the blood to decline to half the current value.
Half life depends on the volume of distribution and rate of clearance.
T1/2=0.693Vd/Cl
Prolongation of the half life will increase the toxicity of the drug.
What is drug elimination?
Removal of active drug and metabolites from the body. This determines the length of action of the drug.
Drug metabolism happens in the liver.
Drug excretion happens in the kidneys as well as the biliary system, gut, lung and milk.
What three mechanisms are used for excretion of drugs?
Glomerular filtration
Passive tubular reabsorption
Active tubular secretion
What kinds of drugs will be filtered by the glomerulus?
Most drugs are filtered by the glomerulus as long as their molecular size, charge or shape are not excessively large.
What kind of drugs are actively secreted into the proximal tubule?
Acidic and basic compounds.
Most important system for eliminating protein bound cationic and anionic drugs.
What kind of drugs are reabsorbed in passive tubular reabsorption?
Only un-ionised drugs such as weak acids are reabsorbed.
What is entero-hepatic circulation of drugs?
Drugs can be secretes in the bile but can be reabsorbed from the bile into the circulation. It continues until the drug is metabolised in the liver or excreted by the kidneys.
What is a conjugated drug?
A drug that has been metabolised by the liver and can’t be reabsorbed. If there is liver damage this process could be affected.
