Pharmacokinetics: Drug Action and the Body

• General pharmacology covers pharmacokinetics.
• The class should be taught by Emad Elhenawy around the year 2025.

Course Objectives

• Understand the parameters and clinical importance of drug pharmacokinetics.
• The material includes a description of the first-pass effect of drugs, bioavailability, and how that data can be used in patient care.
• Factors affecting drug absorption will be listed.
• The clinical importance of the drugs ionization constant (pKa) will be identified.
• Dose adjustments, according to associated patient diseases, will be understood.

Pharmacology

• Pharmacology is the branch of science dealing with drugs.

Subdivisions of pharmacology

• Pharmacokinetics studies the effect of the body on the drug like absorption, distribution, metabolism, and excretement.
• Pharmacodynamics studies the effect of the drug on the body and its mechanism of action and pharmacological actions.
• Pharmacodynamics includes therapeutic uses, adverse drug reactions, and contraindications.

Importance of Pharmacokinetics

• Pharmacokinetics helps tailor a dose regimen to the individual patient's requirements such as renal failure and liver disease.
• Pharmacokinetics helps to find out a possible cause of treatment failure if the drug can't reach the site of action or taken by the wrong route.
• Pharmacokinetics helps to find out a cause of drug toxicity.

Absorption

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

Factors affecting drug absorption

• Factors related to the drug include lipid solubility, degree of ionization, and stability of gastric acid and digestive enzymes.
• Factors related to the patient include route of administration absorbing surface area, and specific factors.

Drug Factors

• Lipid-soluble drugs are more readily absorbed.
• A greater degree of ionization leads to less absorption.
• Digestive enzymes destroy benzyl penicillin and insulin in the GIT.

Patient Factors

• Intravenous (IV) administration is the faster route.
• The absorbing surface area depends on the state of health of the absorbing surface.
• Intrinsic factor is needed for Vitamin B12 absorption.

PH and drug ionization

• Unionized drugs in basic media are lipid-soluble.
• Unionized drugs in acidic media is lipid-soluble.
• Ionized drugs are less lipid soluble.
• Unionized drugs (uncharged) are more lipid soluble and more easily absorbed and vice versa.
• Most drugs are weak acids or bases.
• Weak acids are better absorbed in acidic media where it is less ionized and so more lipid soluble.
• Weak bases better absorbed in alkaline media where it is less ionized and so more lipid soluble.
• pKa is the pH at which 50% of the drug is ionized and 50% is unionized; e.g., the Pka of aspirin is 3.5.
• Aspirin is an acidic drug with a Pka of 3.5, indicating that 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 and vice versa.
• Pka (of the drug) = pH (of the media) + log unionized/ionized.

Significance of pH and pKa

• Knowing the site of drug absorption is important because 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 are absorbed only when they reach the intestines.
• Ion trapping is significant because acidic drugs like aspirin are largely unionized in the gastric lumen, so aspirin passes into cells lining the stomach.
• Once entered cells finds the pH is alkaline where it is ionized and trapped
• Alkalization of urine increases renal excretion of acid drugs such as Aspirin.
• Acidification of urine increases renal excretion of basic drugs such as Ephedrine.

First-pass metabolism

• First-pass metabolism (presystemic elimination) is the metabolism of drugs at the site of administration before reaching systemic circulation.
• This occurs in the GIT or liver after oral administration.
• Gastric acidity destroys benzyl penicillin
• Digestive enzymes destroy insulin.
• Hepatic first-pass effect happens with Nitroglycerine.
• To avoid first-pass metabolism the route of administration can be changed, such as giving nitroglycerine sublingually, or increase the oral dose.

Bioavailability

• Bioavailability is the fraction of the drug that reaches the systemic circulation in the unchanged form.
• Bioavailability is 100% after IV administration.
• Bioavailability is variable after oral administration; bioavailability is 70% if 70 mg of a 100 mg dose is absorbed unchanged.
• Absorption affects bioavailability. The more the drug absorption, the higher the bioavailability
• First-pass metabolism affects bioavailability; the more first-pass metabolism, the less the bioavailability.