Pharmacology basics and definitions – Easy [Part 2]

To find part one please click here .. :biggrin:

We mentioned in the previous part two steps of Pharmacokinetics ( Absorption and Distribution ) in this part we will continue the two steps of pharmacokinetics ( Metabolism & Excretion ).

3.  Biotransformation (Metabolism) :

The step where the drug structure changed thus its properties also changed. The most influenced organ for metabolism is the liver , also some drugs may have first pass metabolism in liver like nitroglycerin.

Drugs that have a high rate of metabolism have a low degree of bioavailability , the route of administration of those drugs plays an important role for example  we can’t give nitroglycerin PO , as about 90% of its dose will be eliminated by first pass metabolism leaving the body with no effect !

Another example morphine dose when given as tablet is higher than morphine when given as injection , this is due to first pass metabolism effect.

Phases of metabolism : Phase I and Phase II

Phase I aims to convert the lipid soluble drugs to more water soluble , then Phase II aims to conjugate the drug with another compound to form water soluble complex.

The phase I reactions occur in the cytochrome P450 system , phase II reactions occur in the cytosol. In conjugation reaction many substrates form a complex with the drug like : Glucuronate ( the most important one ), Acetic acid , Glutathione & sulfate.

Factors affecting drug biotransformation :

• Age and Gender.
• Disease : specially in liver may affect drug metabolism , for liver diseased patients dose adjustment needed.
• Induction of Cytochrome P450 system : increase the rate of metabolism.
• Inhibition of Cytochrome P450 system : enzyme inhibitors or competition between two drugs for example may lead to decrease the rate of biotransformation.
• Genetic difference : Groups or even individuals are different for example rapid and slow acetylators; the slow acetylators can’t rapidly inactivate the drug therefor  dose adjustment needed.

Drugs will be biotransformed by a predictable rates described by two principles :

1. Zero Order Kinetics :

Rare , described as constant amount of drug eliminated by time regardless the drug concentration (linear ) ex: Ethanol, phenytoin & aspirin.

Cp : Plasma Concentration.

2. First Order Kinetics :

More common , the decline in plasma concentration varies depending on the concentration , thus the higher concentration , the higher biotransformation rate. The concentration declines ex- ponentially with time.

4. Excretion :

Describe the process by which the drug or biotransformed drug is eliminated from the body. The major routes of excretion  are :

• Renal ; the most common route of excretion for hydrophilic compounds , the pH controls the excretion rare in which acidic urine enhance excretion of weak bases while alkaline urine enhance the excretion of weak acids.
• Fecal.
• Skin.
• Respiration ( exhaled air ).
• Breast milk.

Drug Clearance :

drug clearance defined as the rate of which drug is eliminated from your body, it means the volume of blood cleared from drug per unit time L/h ;  for every drug in any organ has a clearance like renal clearance , hepatic clearance .. etc

Total clearance is the summation of every organ clearance.

Total body clearance  ( CL )= CL (hepatic) + CL (renal) + CL(x)

The rate of drug elimination is directly proportional with plasma concentration Cp , Thus :