Pharmacokinetics & Drug Absorption

• Pharmacology is the branch of science dealing with drugs

Subdivisions of Pharmacology

• Pharmacokinetics (ADME) examines the effect of the body on the administered drug.
• Pharmacodynamics examines the effect of the drug on the body.
• Pharmacokinetics is defined as the effect of the body on the drug.

Pharmacokinetics phases include:

• Absorption
• Distribution
• Metabolism
• Excretion

Importance

• It is important to tailor a dose regimen to the individual requirements of a patient.
• Tailoring is specifically important for patients with renal failure and liver disease
• Figure out the possible cause of treatment failure if a drug cannot reach the site of action or is taken by the wrong route
• Ascertain the cause of drug toxicity

Absorption Intro

• Absorption is the transfer of a drug from the site of administration to the bloodstream.

Factors affecting drug absorption that relate to the drug:

• Lipid solubility: lipid soluble drugs are more readily absorbed
• Degree of ionization: the greater the ionization, the lesser the absorption
• Stability of gastric acid and digestive enzymes
• Benzyl-penicillin and insulin are destroyed in the GIT

Factors affecting drug absorption that relate to the patient:

• Route of administration - IV is faster
• Absorbing surface area is a factor
• Specific factors such as intrinsic factor is needed for Vitamin B12 absorption

Effect of pH, pKa on Drug Ionization, and Lipid Solubility

• Unionized-lipid and ionized- less lipid soluble pass through basic and acidic media
• pKa is the pH at which 50% of the drug is ionized and 50% is unionized.
• Aspirin has a pKa of 3.5.
• Calculation: Pka (of the drug) = PH (of the media) + log unionized /ionized.

Principles

• Unionized drugs are more lipid soluble and easily absorbed
• Most drugs are weak acids or bases
• Weak acids are better absorbed in acidic media where it is less ionized
• Weak bases are absorbed in alkaline media where it is less ionized
• Aspirin is an acidic drug with Pka 3.5, in media with PH 3.5 aspirin will be half ionized, and half unionized.
• The more acidic the medium the more the absorption of aspirin.

Clinical Significance

• Knowing the site of drug absorption helps our understanding of how drugs work in the body
• Acidic drugs, such as aspirin, are largely unionized in gastric acidic PH and are absorbed from the stomach
• Bases, such as atropine, are largely ionized and absorbed only when they reach the intestines.

Ion trapping

• Acidic drugs are largely unionized in gastric lumen, so aspirin passes into cells lining the stomach
• Once entered into the a cell find the pH is alkaline where it is ionized and trapped

Treatment of drug toxicity

• Alkalization of urine decreases renal reabsorption, so increase renal excretion of acid drugs such as aspirin
• Acidification of urine increase renal excretion of basic drugs.

First-Pass Metabolism (Presystolic Elimination)

• The metabolism of drugs at the site of administration before reaching systemic circulation
• For example, GIT or liver after oral administration

Types of first pass effect:

• Gut: Gastric acidity destroys benzyl penicillin and digestive enzymes destroy insulin
• Hepatic: Nitroglycerine is one such example

To avoid high first pass effect:

• Change the route of drug administration
• An example of this is nitroglycerine being given sublingually
• Increase the oral dose

Bioavailability

• The fraction of the drug that reaches the systemic circulation in the unchanged form
• Bioavailability is 100% after IV administration
• It is variable after oral administration
• For example, if 100 mg of a drug are administered orally and 70 mg are absorbed unchanged, the bioavailability of this drug is 70%

Factors Affecting Bioavailability

• Absorption: the more drug absorption the higher the bioavailability
• First pass metabolism: the more first pass metabolism, the less the bioavailability

Assess your knowledge of pharmacokinetics. Questions cover ionization, absorption, metabolism, and the impact of pH and pKa on drug behavior in different physiological compartments. Includes routes of administration, first-pass metabolism, and renal excretion strategies.