Pharmacology in Dentistry - Drug abs & distribution

Question 1

What is the Drug Disposition of Absorption, Distribution, Metabolism and Excretion?

Drug distribution refers to the movement of a drug to and from the blood and various tissues of the body (for example, fat, muscle, and brain tissue) and the relative proportions of drug in the tissues

Answer 1

Absorption - drug enters the body from its site of administration and enters the general circulation.

Distribution - the transport of drug by the general cicrulation. Drugs most often leave the bloody and enter perfused tissues. Once within a tissue further, reversible, distribution dictated by a concentration gradient, may occur by diffusion

Metabolism - the process by which tissue enzymes catalyze the chemical conversion of a frequently lipid soluble drug to an often less active and more polar from that is more readily excreted from the body

Excretion - the processes that remove the drug, or its metabolites, from the body

Question 2

What are the 3 Physicochemical factors controlling drug absorption from the G.I. Tract?

Answer 2

1. Solubility - the drug must dissolve in an aqueous enviroment in order to be absorbed
2. Chemical Stability - some drugs are destroyed by acid in the stomach, or enzymes in the G.I. tract
3. Lipid to water partition coefficient - For a given drug concentration gradient across a membrane, the rate of diffusion increases with the lipid solubility of the drug.

• the Partition coefficient is the ratio of the drug concentration in the membrane and concentration in water at equilibrium
  4. Degree of ionisation - many drugs exist as weak acids or weak bases existing in both ionised and unionised forms. Only unionised forms readily diffuse across the lipid bilayer

Question 3

What are some more facts about Degree of ionisation controlling drug absorption from G.I. tract?

Answer 3

• Degree of ionisation depends upon pKa of the drug and local pH
• pKa = pH at which 50% of drug is ionised and 50% unionised
• Proportions of inonised and unionised drugs can be calculated by the Henderson-Hasselbalch equation.
• Weak acids and weak bases are well absorbed. Strong acids and strong bases are poorly absorbed

Question 4

What is oral availability and systemic availability?

Answer 4

Oral availability is the fraction of drug that reaches the systemic circulation after oral ingestion

Systemic availability is the fraction that reaches the systemic circulation after absorption