Introduction to Pharmacology

Introduction to Pharmacology

• Galala University, powered by Arizona State University
• Pharmacology I, taught by Assoc. Prof. Mohamed Hamzawy

Nature of Drugs

• To interact chemically with its receptor, a drug molecule must have appropriate size, electrical charge, shape, and atomic composition.
• A diagram illustrates the drug interacting with the receptor to form a drug-receptor complex, triggering a response or pharmacological effect.

Drug Action and Distance

• Drugs are often administered at a location distant from their intended site of action.
• Examples include oral medication to relieve headaches.
• A useful drug must possess properties enabling transport from the site of administration to its targeted site of action.
• This process is described as Pharmacokinetics, which includes the processes of absorption, distribution, metabolism (and excretion) of a drug.

Drug Action and Practical Considerations

• A practical drug should be inactivated or excreted by the body at a rate appropriate for maintaining a needed duration of action.

Divisions of Pharmacology

• Two main divisions of pharmacology are: pharmacokinetics and pharmacodynamics.
• Pharmacokinetics describes what the body does to the drug (ADME)
• Pharmacodynamics describes what the drug does to the body.

Pharmacokinetics (ADME)

• Absorption: How the drug moves from the administration site to the bloodstream.
• Distribution: How the drug moves to various body tissues and organs.
• Metabolism: How the drug is altered or broken down.
• Excretion: How the drug is removed from the body.
• Diagrams show the relationships between these processes, highlighting drug administration, absorption, distribution to the blood, metabolism, excretion, and the site of action.

Routes of Drug Administration

• Enteral: Oral, sublingual/buccal.
• Parenteral: Intramuscular (IM), intravenous (IV), subcutaneous (SC), Intrathecal
• Other: Oral Inhalation, Nasal inhalation, Topical, Transdermal, Rectal

Oral Route of Administration

• Advantages: Easy self-use, safe, convenient, cheap, no need for sterilization.
• Disadvantages: Slow effect, incomplete absorption (low bioavailability), destruction by gastrointestinal tract (GIT), first pass effect, GIT irritation, food-drug interactions, and drug-drug interactions. The route is not suitable for patients experiencing vomiting, unconscious, or for emergency situations.

First Pass Metabolism

• Oral drugs are first metabolized by the liver (via portal circulation) before entering the systemic circulation which significantly reduces the effective dose of the drug.
• This results in low bioavailability and short duration of action.
• The process involves the liver gut wall and gut lumen.

Sublingual Administration

• Advantages: Rapid effect (emergency), no first-pass metabolism, high bioavailability.
• Disadvantages: Not suitable for irritant drugs.

Parental Administration

• Advantages: High bioavailability, rapid action (emergency), no first-pass metabolism
• Disadvantages: Infection risk, sterilization required, pain, skill needed, anaphylaxis, and expensive.

Inhalation Administration

• Advantages: Rapid absorption, rapid effects, local action, less side effects, no first pass effect
• Disadvantages: Only a few drugs suitable for this route.

Rectal Administration

• Advantages: Suitable for vomiting or unconscious patients, irritant, and bad taste drugs.
• Disadvantages: Irregular absorption, low bioavailability, rectal mucosa irritation, not a well-accepted route.

Transdermal Administration

• Advantages: Bypasses first-pass effect, convenient, painless, ideal for lipophilic drugs.
• Disadvantages: Allergies to patches, drug must be highly lipophilic, delayed delivery, and limited to small doses.

Topical Application

• Produces local effects like topical anesthesia.
• Absorption rate varies based on skin properties and drug solubility.

Absorption

• Absorption is the drug transfer from the administration site to the bloodstream.
• The process involves cell membranes containing water-loving and/or water-fearing regions and interspersed transport proteins.

Mechanisms of Drug Absorption

• Simple diffusion
• Active transport
• Facilitated diffusion
• Pinocytosis (endocytosis).

Characteristics of Simple Diffusion

• It follows a concentration gradient.
• It is non-selective.
• It is not saturable.
• It does not require energy.
• There is no need for a carrier protein.
• It depends on the drug's lipid solubility.

Water vs Liquid Soluble Drug Absorption

• Water-soluble drugs are absorbed through aqueous channels.
• Lipid-soluble drugs are absorbed through the lipid cell membrane.

Active Transport

• It occurs against the concentration gradient.
• It requires specific carrier proteins.
• It requires energy.

Facilitated Diffusion

• It occurs along the concentration gradient.
• It requires carriers.
• It is selective.
• It is saturable.
• It does not require energy.

Phagocytosis or Pinocytosis

• Endocytosis is the uptake of membrane-bound particles (such as high-molecular-weight or lipid-insoluble drugs).
• Exocytosis is the expulsion of membrane-bound particles.

Factors influencing absorption

• Effect of pH on drug absorption
• Blood flow to the absorption site
• Total surface area available for absorption
• Contact time at the absorption surface
• Expression of P-glycoprotein.
• P-glycoprotein reduces drug absorption and involved in transportation of drugs from tissues to blood.

Effect of pH on Drug Absorption

• Drugs exist in ionized and non-ionized forms (in equilibrium).
• Non-ionized forms have better membrane permeability.
• pH affects the ionized/non-ionized ratio.
• Acidic drugs are best absorbed in the stomach, while basic drugs are best absorbed in the intestine.

Blood Flow to Absorption Site

• Intestinal blood flow is higher than stomach flow; therefore, intestinal absorption is favoured.

Total Surface Area

• Intestinal surface area is much larger than that of the stomach, leading to significantly higher absorption efficiency.

Contact Time

• Longer contact time at the absorption surface results in greater absorption.
• Conversely, rapid movement through the GI tract reduces absorption.

Expression of P-glycoprotein

• P-glycoprotein is a transmembrane transporter that reduces drug absorption, pumping drugs out of cells into the blood.
• It can be found in various tissues like the liver, kidneys, placenta, intestines and brain.