Physiology Flashcards
Variables affecting drug absorption
Blood flow- high flow faster absorption
Nature of absorbing surface- bigger surface area faster absorption
Solubility if drug- lipid soluble=faster as cell membrane have fatty bilayer
Ionisation- drugs are chemically weak acids or bases and are ionised it’s non-ionised in the body. Ionised (charged polar) is water soluble/lipid insoluble and doesn’t diffuse through cell membrane easily. Un-ionised (neutral/non-polar) is lipid soluble and can cross cell membrane. An acidic drug is relatively un-ionised in an acidic environment but a basic drug tends to ionised in the same environment. Vice versa a basic drug is less ionised in a less acidic environment (small intestines) and acidic drugs tend to ionised in less acidic environments
Formulation- can put coating on to delay release of drug or prevent breakdown in stomach etc
Eliminations of drugs
Elimination =clearance (CL) x plasma drug concentration (C)
Clearance of drugs
Ability of individual organs or whole body systems to eliminate drugs
=elimination rate/plasma drug concentration
Hepatic clearance (Cl-h) depends on liver blood flow (Q-h) and is the product of hepatic extraction ratio (E-h) and liver blood flow. Cl-h= E-h x Q-h or E-h=Cl-h/Q-h
Low hepatic clearance is <20 L/h or E-h <0.2
Intermediate is 20-60 or 0.2-0.67
High is >60 or >0.67
Bioavailability (F=1-E-h)
Renal clearance- kidneys are major organs to eliminate polar water soluble drugs.
Renal clearance is net glomerular filtration , active secretion and passive reabsorption
Cl-r=CL-gf=fu (fraction of unbound drug in plasma) x GFR
If kidney function is less than 50% drug dose must be reduced
Maintenance dose calculation
Maintenance dose rate (DR) = CL x target steady-state plasma drug concentration (C-ss)
Drug has Cl of 8L/h and steady state of 12.5. Maintenance dose rate = 8 x 12.5 which is 100mg/h
For oral tablets- maintenance dose=DR/F (bioavailability) x dosing interval.
100mg/h x 8h/0.8=1000mg
