Basic Principles of Pharmacotherapy

By

Mohammad H. Farjoo

Pharmacotherapy• Why is it necessary ?• Preadministration factors:

• Bioequivalency • Absolute (oral to IV)• Relative (test to standard)

• Patient compliance• Chronopharmacology

• Used in cancer therapy• Applies to CsA , Aspirin & propranolol

What does it depend on ?1. Pharmacokinetic : Dose– Concentration

relationship1. Absorption (How rapidly?)2. Distribution (What concentration?)3. Elimination (How long?)

2. Pharmacodynamy : Concentration–Effect relationship1. Drug concentration at receptor site2. Drug – Receptor affinity3. Post receptor efficiency

Pharmacotherapy

Sensitivity

Disposition

Absorption • Definition • Poor for too hydrophobe/hydrophil drugs• May vary with protein/lipid content of food

Eg:CsA , Sirolimus• AUC measures extent of absorption & tmax

measures its rate• Sometimes is Ph dependent• First pass effect• Enterohepatic cycle

Disposition • What is it ?• Categorized to :

• Distribution• Volume of distribution• Loading dose

• Elimination (clearance)• Excretion• metabolism

Volume of distribution

• Definition• Vd = Amount of drug / concentration

• High Vd means drug escape from vessels & vice versa

• Vd is a balance between protein binding in tissue and that of blood

• Varies in pathological conditions• Vd of more than 42 Lit. reflects tissue

binding

Loading dose

• What is it ?• When is it necessary ?• Loading dose = Vd X concentration• Not only amount but rate of

administration is important

Elimination (clearance)

• What is it ? And why should it occur?

• First order :– Elimination rate = CL x Concentration– Depends on drug Concentration (Not

CL)– Not saturable – Applies to most of the drugs

• Zero order (many other names)– Elimination rate is non linear (so it is

dangerous)– Applies to Aspirin , Ethanol , Phenytoin

• Good correlation between renal (But not liver) dysfunction & clearance

• Affected by “Inducers & Inhibitors”– Drugs– Smoking & Alcoholism– Food !!

• Not all the excretions cause elimination!

Elimination (clearance)

Other important factors :

• Half life• Protein binding• Drug interactions• Therapeutic drug monitoring

(TDM)