Farmacocinética: ABSORÇÃO | Aula 3 | Farmacologia rápida e fácil | Flavonoide

Introduction to Pharmacokinetics: Absorption

Overview of Absorption in Pharmacokinetics

• The video introduces the topic of pharmacokinetics, focusing on the first stage: absorption. A bonus video discussing administration and bioavailability will be released next week.

• Absorption refers to the process by which a drug passes from its site of administration into the bloodstream, allowing it to reach systemic circulation.

• Some medications, like topical treatments, do not require absorption as they are applied directly at their site of action (e.g., eye drops for ocular issues).

Pathway of Blood Flow and Drug Administration

• Blood flows from the intestines to the liver via the hepatic portal system before reaching the heart and then circulating through various tissues.

• Medications can be administered at different points along this blood flow pathway; oral medications must be absorbed into circulation first.

Challenges in Drug Absorption

Membrane Permeability

• The primary challenge for drugs is crossing cell membranes, as most cells have a plasma membrane that acts as a barrier.

• There are four main mechanisms for drugs to cross these membranes: passive diffusion, facilitated diffusion, active transport, and endocytosis.

Mechanisms of Membrane Crossing

• Passive diffusion is commonly used by many drugs; it relies on concentration gradients without energy expenditure.

• For passive diffusion to occur effectively, drugs need to be minimally lipophilic (fat-soluble), enabling them to traverse hydrophobic regions within membranes.

Types of Diffusion Mechanisms

Passive Diffusion

• While passive diffusion is energy-efficient and straightforward for lipophilic drugs, hydrophilic drugs may still cross membranes under certain conditions with assistance.

Facilitated Diffusion

• Facilitated diffusion also utilizes concentration gradients but requires carrier proteins in the membrane for larger or less lipophilic molecules that cannot passively diffuse.

Understanding Drug Transport Mechanisms

Passive Diffusion and Saturable Transport

• The concept of facilitated passive diffusion is introduced, emphasizing that specific proteins have binding sites for certain molecules. Drugs must closely resemble these molecules to pass through.

• It is noted that this transport mechanism is saturable; once all available proteins are occupied, no further drug can pass through until they are freed.

Active Transport Mechanisms

• Active transport does not rely on concentration gradients and requires energy, typically derived from ATP breakdown. Membrane proteins act like revolving doors to facilitate drug passage.

• Larger molecules can be engulfed by the membrane in a process requiring energy, classifying it as another form of active transport.

Factors Influencing Absorption

• Drug absorption is influenced by both the properties of the drug and the biological environment. Lipid solubility and molecular weight are critical factors for passive diffusion.

• High molecular weight drugs face challenges crossing membranes; smaller drugs can navigate tighter junctions found in structures like the blood-brain barrier.

Role of Molecular Charge and pH

• The electrical charge of a molecule significantly impacts its ability to cross membranes. Many effective drugs are weak acids or bases due to their ionization properties.

• Ionization affects solubility: ionized forms tend to be water-soluble while non-ionized forms are more lipid-soluble, facilitating membrane passage.

Impact of Environmental pH on Drug Formulation

• The surrounding hydrogen ion concentration (pH level) determines whether a weak acid or base will be in an ionized or non-ionized state, influencing absorption rates across membranes.

• Weak acids absorb better in acidic environments while weak bases fare better in basic conditions due to their respective solubility states.

Concentration Effects on Drug Absorption

Absorption of Medications: Key Factors

Dissolution and Absorption Speed

• Compressed medications must first dissolve to release their active molecules, which takes time. In contrast, liquid forms of medication do not require this process, leading to faster absorption and quicker effects.

Area of Absorption

• The area available for absorption is crucial; a larger area increases the likelihood of drug molecules colliding with absorptive surfaces, enhancing absorption rates.

• The stomach has a significantly smaller absorption area compared to the intestines, which have approximately 200 square meters due to villi. This explains why weakly acidic drugs are often better absorbed in the intestines despite its more basic environment.

Influencing Factors on Absorption

• Gastric emptying time, intestinal motility, and food intake are important factors that influence how long a drug remains in the stomach or intestines and thus affect its overall absorption.

• Vascularization plays a critical role; more blood vessels increase the chances of drugs entering circulation. Additionally, various pathological conditions related to the gastrointestinal system can impact drug absorption.

Conclusion and Further Learning