FUNDAMENTOS DE FARMACOLOGIA - AULA 2

Summary

The lecture introduces pharmacokinetics and explains how a medicine moves through the body, what can affect that journey, and why treatment and dosing need to be tailored to the patient.

1. Medication use is a chain of steps

A successful treatment depends on more than choosing a drug. The lecture distinguishes several connected stages:

• Pharmaceutical/biopharmaceutical phase: The dosage form disintegrates and the active ingredient dissolves, making it available for absorption.
• Pharmacokinetics: The body absorbs, distributes, metabolizes, and eliminates the drug—often abbreviated ADME.
• Pharmacodynamics: The drug interacts with targets such as receptors at its site of action and produces an effect.
• Pharmacotherapeutic outcome: The care team assesses whether the treatment is achieving its intended benefit.

Errors can occur at prescribing, formulation selection, or administration. The lecturer emphasizes that an individual mistake may reveal a weakness in the wider process, so protocols and safety checks should help catch errors before they harm patients. Communication among health professionals and careful listening to patients can also reveal problems such as difficulty swallowing, missed doses, or interactions with food and other medicines.

2. Formulation and route affect how a drug becomes available

A solid tablet generally needs to break apart and dissolve before its active ingredient can be absorbed. A liquid formulation may skip some of those steps, but its absorption is not automatically faster in every case.

Different formulations serve different purposes. Coatings may mask taste or protect a drug from light or stomach acid; modified-release formulations release the active ingredient gradually. Tablets should not be crushed or altered unless the product information or a qualified professional confirms it is safe, since some coatings and release mechanisms are essential.

The route also affects how much drug reaches the bloodstream and how quickly:

• Intravenous: Enters the circulation directly; the lecture describes this as having 100% bioavailability.
• Intramuscular or subcutaneous: Must be absorbed from the injection site before reaching the circulation.
• Oral: Convenient, but bioavailability can vary because of absorption barriers and first-pass metabolism in the gut and liver.
• Rectal: Bioavailability varies; the first-pass effect may be less pronounced than with oral administration.
• Inhaled: Can act quickly because the lungs have a large surface area and close contact with blood vessels.
• Transdermal: Often absorbs slowly and can provide prolonged delivery.

3. What pharmacokinetics studies

Pharmacokinetics examines how drug and metabolite concentrations change over time. Absorption, distribution, metabolism, and elimination are commonly taught in that order, but the processes can overlap rather than occurring as a strict sequence.

The lecture uses topical lidocaine to illustrate that route selection matters: a drug may be unsuitable by one route if it is broken down before reaching its intended site. It also contrasts topical treatment of a nail fungus with oral treatment, explaining that the appropriate approach depends on the treatment goal and the tissue involved.

4. Absorption and bioavailability

Bioavailability is the fraction of an administered dose that reaches systemic circulation. The area under the blood-concentration-versus-time curve represents the extent of exposure, while the curve’s rise and peak help describe how quickly the drug is absorbed. A drug can reach a similar overall exposure more slowly, or reach a lower exposure despite being absorbed at a similar rate.

Absorption can be influenced by:

• The route and dosage form, including whether the drug is dissolved.
• Food and other substances in the gastrointestinal tract.
• Gastric emptying, intestinal movement, and gut conditions.
• Age, pregnancy, nutritional state, and illness.
• Drug properties, including solubility, membrane permeability, and ionization.
• Interactions with other medicines.
• Genetic differences that affect metabolism.

The lecture explains that uncharged (non-ionized) molecules generally cross cell membranes more readily than charged molecules. The relationship between a drug’s pKa and the pH of its surroundings affects how much of it is ionized. A drug also needs an appropriate balance of solubility and permeability: dissolving in body fluid is not enough if it cannot cross membranes, and membrane permeability is of limited use if the drug does not dissolve adequately.

5. Distribution, volume of distribution, and clearance

After absorption, a drug distributes between blood and tissues. The volume of distribution (Vd) is an apparent measure relating the amount of drug in the body to its concentration in plasma; it is not the size of a particular organ. A relatively low Vd suggests more of the drug remains in plasma, while a higher Vd suggests more is present outside the plasma, such as in tissues.

Drug characteristics matter: lipid-soluble drugs may enter tissues more readily, while some water-soluble drugs remain more restricted to the bloodstream. Binding to circulating proteins such as albumin can also affect how much drug is available to reach its target. The lecturer stresses that patient physiology and disease can change drug distribution.

Clearance (CL) describes the body’s capacity to remove a drug in relation to its concentration. Total clearance can reflect elimination by multiple organs. The kidneys commonly excrete drugs or their metabolites; the liver commonly transforms drugs, and the lungs and other tissues can also contribute to elimination.

6. Metabolism and first-pass effect

Biotransformation is a set of enzyme-driven changes to a drug or other foreign substance (a xenobiotic). It often makes the substance more water-soluble so it can be eliminated, though metabolism can also activate a drug. A medicine given in an inactive form that becomes active after metabolism is called a prodrug.

The lecture describes phase 1 and phase 2 metabolic reactions and highlights the liver as a major site, while noting that metabolism can also occur in the kidneys, lungs, skin, and other tissues. Oral drugs may pass from the intestine to the liver before entering general circulation; this is the first-pass effect, which can reduce the amount of active drug reaching the rest of the body.

Enzyme activity varies with genetics, age, health, diet, gut microbiota, and drug interactions. The lecturer distinguishes:

• Enzyme induction: Increased enzyme activity can speed the metabolism of another drug and lower its concentration.
• Enzyme inhibition: Reduced enzyme activity can slow metabolism and alter the other drug’s concentration.

7. Half-life, dosing intervals, and steady state

A drug’s half-life is the time required for its concentration or amount in the body to fall by half during elimination. It is related to both volume of distribution and clearance. Half-life helps inform dosing intervals, but the appropriate schedule also depends on the drug, the condition being treated, and the patient.

With repeated doses, drug can accumulate until the amount administered over time balances the amount eliminated. This is called steady state. Some treatments may use a loading dose to reach a target concentration sooner, followed by maintenance doses. The lecture compares continuous infusion with dosing at intervals: longer intervals can produce larger rises and falls in concentration. A suitable regimen must keep concentrations effective while avoiding excessive exposure; it cannot be generalized from one medicine or patient to another.

8. Individualized dosing and patient safety

Standard doses are generally developed from studies involving healthy participants and patients with typical drug-handling capacity. They may not suit everyone. Age, pregnancy, newborn development, and liver, kidney, or heart conditions can alter absorption, distribution, metabolism, or elimination.

Reduced kidney function, for example, can slow elimination and allow some medicines to accumulate. The lecture urges particular care at the extremes of age and for people taking many medicines. Medication reconciliation—reviewing a patient’s full medication list and coordinating with prescribers—can help identify duplication, interactions, and opportunities for dose adjustment. Patients should consult their care team rather than changing doses themselves.

9. Other points raised in the question period

• The lecturer cautions that package inserts list possible adverse effects; a listed effect is a possibility, not a guarantee that it will occur.
• She describes the placebo effect as an expectation of benefit and the nocebo effect as expectations or fear contributing to negative experiences. She cites an unnamed study in connection with reported vaccine side effects.
• She explains that antibiotics can disrupt beneficial gut microorganisms as well as target harmful bacteria; this is not the same as directly suppressing the immune system.
• Whether a medicine should be taken with food or on an empty stomach depends on drug-specific effects on absorption and interactions. The lecture gives mineral-containing products and thyroid medication as examples where food or other substances may interfere with absorption.
• The interval between doses is informed by pharmacokinetic studies and the medicine’s properties; the lecturer discourages treating one schedule as interchangeable with another without professional guidance.

Speakers and sources featured

• Professor Jéssica Bonato — moderator and course host; introduces the session, monitors the chat, and relays questions.
• Professor Bárbara — main lecturer, presenting the pharmacokinetics lesson and answering questions.
• Audience members asking questions: Eduarda, William, Patricia, Augusto, Anete, Letícia, Juan, Daniela, Elinete, Jessica, Mari, and Felipe. The subtitles also contain a possibly mistranscribed name, “Juan O”/“Guan.”
• Sources and materials mentioned: Clinical guidelines and professional-society protocols; pharmacology textbooks; the course’s conceptual lesson, book, and library materials; medicine package inserts; pharmacokinetic and clinical studies, including drug-registration research associated with Anvisa; and an unnamed study cited in the discussion of nocebo effects.
• Examples discussed: A medication-administration error involving the wrong route, and medicines including lidocaine, ibuprofen, cephalexin, theophylline, gentamicin, phenobarbital, and warfarin.