Aqueous diffusion by
Tight junctions
Allow large molecules 20000_30000
Not in testes or brain
Lipid diffusion depends on
1: lipid solubility
2: ionization state
3: CG
4: Mw
5: surface area
6: oil_water partition
Clinical significance of pka
1: site of absorption become known
2: treatment of toxicity
Bioavailability
Fraction of unchanged drug that reaches the circulatio
Factors reducing bioavailability
1: first pass
2: metabolism of drug by flora (digoxin)
3: gastric acid affect on stability of drug (penicillin)
4: digestion of drug (insulin)
5: intestinal wall metabolism
VD
The volume of water that accommodate all the drug in body
Factors that affect the drug distribution
1: PBP
2: tissue uptake
3: tissue barrier
4: perfusion rate
5: diseases like chf
6: plasma concentration & lipid solubility
7: ionization at physiological ph
Clinical significance of vd
Loading dose calculation
Remove the toxicity by hemodialysis or not
Albumin for
Acidic and hydrophobic drug
Alpha 1_acidic glycoprotein for
Basic drug
Hard drugs like
1: streptomycin
2: neostigmine
Inactive to active (Prodrug) like
1: Enalapril~Enalaprilat
2: Levodopa~Carbidopa
Not toxic to toxic
Isoniazid to acetyl isoniazid
UGT inhibitor
Cortisol
UGT inducer
Anthracyclin
Factors affecting biotransformation
1: estrogen inhibit while testosterone stimulate
2: metabolism reduced with age
3: lover and heart disease
4: smoking induce metabolism
5: other drugs
First order elimination
Dependent on plasma concentration Rate of elimination is not the same Exponential graph Most drugs Constant proportion is eliminated Half time is constant
Zero order elimination
Linear graph Constant amount is eliminated Rate of elimination is same Aspirin and alcohol and phenytoin Independent to plasma concentration Elimination and enzymes pump are saturated
