What are the major organs involved in ADME?
1. GI Tract(Absorption) 2. Liver(Metabolism) 3. Kidney(Excretion) 4. Lungs( Absorption and excretion of volatile anaesthetic gases)
How does the biological membrane impact on drugs?
Small, uncharged and lipid soluble drugs are distributed faster than ionised, bulky and lipid insoluble drugs.
What are the 4 mechanisms of transport across the membrane?
1. Transcellular diffusion 2.Facilitated diffusion 3. Active transport 4. Endocytosis
What are the properties of passive diffusion?
-Most important mechanism for lipid soluble drugs(ie non-polar) - Concentration gradient is the driving force -No energy is required
What are the properties of facilitated diffusion?
-Depends on a carrier protein -Depends on concentration gradient -No energy required -Usual substrates=sugars and amino acids
What are the properties of active transport?
- can proceed against a conc. gradient -Requires energy - can become saturated -Organs= Liver, Kidney, blood-brain barrier, gut epithelium
What does active transport achieve?
1 Accumulates compounds essential for growth 2. Removes waste products 3. Protects against toxins
What are the main properties of Endocytosis?
-Internalisation of large molecules -MW>1000 -3 steps involved 1.Substrate binds to receptor 2.Invagination of receptor-substrate complex 3. Budding off and delivery of vesicle into cell.
What does filtration help with?
For drugs that cannot pass through cells to cross biological membranes
Where does filtration occur?
Blood capillaries Glomerular capillaries (Kidney)= extremely porous which allow passage of all plasma constituents except >30,000.
Summarise the path of drug deposition in the body?
Drug dosage⇒ Free drug concentration in exracellular water⇒Metabolism, Binding to proteins and storage in tissues, AND Biliary and Renal excretion⇒Drug conc at site of action(small)⇒Receptor occupancy⇒Intensity of pharmacological effect