Drug distribution IA % + Flashcards
1
Q
Distribution
A
- Once a drug has been absorbed it must be available for biological action and distribution to the tissues.
- To be active a drug must then leave the blood stream and enter the inter or intracellular spaces.
- Drug Distribution refers to the Reversible Transfer of a Drug between the Blood and the Extra Vascular Fluids and Tissues of the body (for example, fat, muscle, and brain tissue).
2
Q
Tissue distribution terms
A
- Plasma protein binding
- Tissue perfusion
- Membrane characteristics
•Blood-brain barrier, Placental, Testis►
- Blood-testes/ovary barrier
- Lipid soluble drugs
- Actively transported
- Transport mechanisms
- Diseases and other drugs (esp renal failure, liver disease, obesity)
- Elimination
3
Q
Plasma protein binding
A
- Many drugs bind to proteins in the plasma such as albumin or a1-glycoprotein & lipoproteins► (eg phenytoin).
- Only unbound drug is biologically active.
- Binding is reversible.
Amount of bound drug can be changed by:
- Renal failure
- Hypoalbuminaemia (low blood albumin)
- Pregnancy
- Other drugs
- Saturability of binding
4
Q
Volume of ditribution
A
- The volume of plasma that would be necessary to account for the total amount of drug in a patient’s body, If that drug were present throughout the body at the same concentration as found in the plasma.
- The result are expressed in terms of litres per kilogram.
5
Q
Clearance
A
- Clearance is defined as the theoretical volume from which a drug is completely removed over a period of time.
- Measured in units of time (ml/min).
- Measure of elimination.
- Dependent on concentration and urine flow rate for renal clearance.
- Dependent on metabolism and biliary excretion for hepatic clearance.
6
Q
Half life
A
- The time taken for the drug concentration in the blood to decline to half of the current/initial value.
- e.g if it takes 4 hours for the concentration of a drug in the blood stream to drop from 10mg/L to 5 mg/L then the half life is 4 hours
- Half life depends on the volume of distribution and rate of clearance.
7
Q
Chronic administration
A
- To have a therapeutic benefit most drugs needed to be given chronically.
- Plasma levels of a drug take many doses before they stabilise, usually 4-5 half-lives.
- This may necessitate a loading dose.
- It is important to know how a particular drug will build up in the body.
8
Q
Drug elimination
A
- This term covers the removal of active drug and matabolites from the body.
- This determines the length of action of the drug.
Made up of 2 parts:
- Drug Metabolism (usually in the liver)
- Drug Excretion (usually in the kidney but also biliary system/gut, lung, milk)
9
Q
Excretion
A
-The kidneys are the primary organ for drug excretion.
Three principal mechanisms are used:
- Glomerular filtration
- Passive tubular reabsorption
- Active tubular secretion
-Renal damage is therefore important in causing drug toxicity.
10
Q
Glomerular filtration
A
- The glomerulus filters 190 litres of fluid a day.
- All unbound drugs will be filtered at the glomerulus as long as their molecular size, charge or shape are not excessively large.
- Factors that affect the glomerular filtration rate will reduce the clearance of a drug.
11
Q
Active Tubular Secretion
A
- Some drugs are actively secreted into the proximal tubule (acidic and basic compounds).
- This is the most important system for eliminating protein-bound cationic and anionic drugs.
12
Q
Passive tubular reabsorption
A
- As the filtrate moves down the renal tubule any drug present is concentrated.
- Passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation.
- Passive diffusion occurs in the distal tubule and collecting duct.
- Only un-ionised drugs such as weak acids are reabsorbed.
- Can also be affected by renal failure.
13
Q
Biliary secretion 1
A
- The liver secretes 1 litre of bile a day.
- Drugs may be passively or actively secreted into the bile.
- Biliary secretion accounts for 5-95% of drug elimination for many drugs.
- Many drugs are then reabsorbed from the bile into the circulation. This is called entero-hepatic circulation.
- It continues until the drug is metabolised in the liver or excreted by the kidneys.
14
Q
Biliary secretion 2 Ø
A
- Metabolism in the liver often leads to conjugation of the drug.
- The conjugated drug is not reabsorbed from the intestine.
- Damage to the liver may reduce the rates of conjugation and biliary secretion and so allow the build up or reabsorption of the drug with resultant toxicity.
15
Q
Steady state concentration graph
A