Scientific Medicine & Pharmacokinetics

Scientific Medicine & Humoral Theory

• Scientific thought, as we know it today, truly flourished around the 1200s CE, with the 18th century marking a significant rise in scientific approaches across various fields.
• Scientific methods were applied to medicine, particularly in the 19th century, leading to a shift from the traditional humoral theory of disease.
• Humoral theory's limitations became evident as it lacked measurable evidence.
• New scientific approaches focused on identifying measurable causes of diseases, their patterns, durations, and responses to specific treatments, making medicine more effective and less risky.

Pharmacokinetics: How the Body Processes Drugs

• Pharmacology involves studying how drugs interact with the body.
• Pharmacokinetics (PK) focuses on the movement of drugs within the body, including absorption, distribution, metabolism, and excretion (ADME).
• Pharmacodynamics (PD) focuses on how the drug affects the body.
• A drug's specific properties determine its PK and PD profiles.
• Understanding drug concentrations in blood over time (plasma concentration-time profile) is crucial for determining the "therapeutic window," the range where the drug effectively treats the condition without causing harm.

Absorption: How Drugs Enter the Body

• The oral route is the most common method of drug administration.
• Drug absorption involves the movement of ingested drug molecules from the gastrointestinal (GI) tract into the portal blood.
• The oral bioavailability (F) refers to the fraction of the ingested dose that reaches the systemic circulation.
• Factors like the drug's size, lipophilicity (greasiness), and charge can impact its bioavailability.
• Larger molecules, hydrophilic drugs, and ionized drugs tend to have poor bioavailability due to their difficulty crossing lipid-rich cell membranes in the gut wall .

Metabolism: How the Body Modifies Drugs

• The body uses drug-metabolizing enzymes (DMEs) to convert drugs into water-soluble metabolites for easier excretion.
• DMEs are found in various tissues, including the gut wall, liver, kidney, and other tissues.
• Metabolism often reduces a drug's activity by altering its structure, but some metabolites retain pharmacological activity.
• Some drugs are inactive until metabolized (pro-drugs) whereas some drug metabolites can be toxic.

Alcohol: Pharmacokinetic Considerations

• Ethanol, the alcohol in alcoholic beverages, exhibits amphipathic properties, meaning it has both water-loving (hydrophilic) and fat-loving (lipophilic) characteristics.
• These properties contribute to its rapid absorption and wide tissue penetration.
• Alcohol is absorbed primarily from the upper intestine and stomach.
• Food can delay gastric emptying and alcohol absorption.
• The peak blood alcohol concentration (BAC) depends on the type of beverage and the amount consumed.
• Alcohol is distributed throughout the body via the bloodstream with a greater presence in the total body water (TBW) due to its high water solubility.
• Women tend to have higher peak BACs than men due to their smaller body size, lower proportion of TBW, and potentially lower levels of EtOH metabolizing enzymes.

Alcohol: Metabolism & Elimination

• Alcohol metabolism primarily occurs in the liver via enzymes like alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
• This metabolism requires the cofactor NAD (nicotinamide adenine dinucleotide).
• Under normal conditions, alcohol metabolism is saturated due to limited liver NAD capacity, resulting in a fixed rate of alcohol metabolism, approximately 8g/hr in a 70kg person.
• Genetic variations in ADH and ALDH genes, like the ALDH2*2 polymorphism in East Asians, can influence alcohol metabolism and acetaldehyde levels.
• Small amounts of alcohol are excreted directly in the urine and breath.