FUNDAMENTOS DE FARMACOLOGIA - AULA 3

Summary

Course announcements

• The course’s third-week “General Knowledge Week” includes three lectures and a 10-question activity worth one point toward the course grade. Students were reminded to complete it by the 15th.
• The study activity map and General Knowledge Week materials were available on the course platform. Students could contact the mediator for help locating them.

Clinical pharmacokinetics and individualizing treatment

The lecturer reviewed how pharmacokinetic measurements help guide medication choice, dose, timing, and duration:

• Volume of distribution (Vd): Indicates how much a drug distributes into tissues versus remaining in the bloodstream.
• Clearance: Describes how quickly the body removes a drug through organs such as the kidneys, liver, and lungs.
• Half-life: The time it takes for a drug’s concentration to fall by half. It is influenced by Vd and clearance.
• Bioavailability: The portion of an administered dose that reaches the circulation and is available to act. It varies with dosage form and route. Oral medicines may also undergo first-pass metabolism in the liver before reaching systemic circulation.

Together, these measures help determine how much medicine to give, how often, and for how long. They also inform the evidence and documentation used in drug approval.

The lecturer stressed that standard doses may not suit every patient. Pregnancy, age, and illnesses such as kidney or liver impairment can change absorption, distribution, metabolism, or elimination, potentially causing toxicity or inadequate treatment.

• Pregnancy: Changes in digestion and absorption, body composition, protein binding, liver metabolism, and kidney function may alter drug concentrations and effects.
• Children: Body composition changes substantially with age, so doses should be guided by pediatric references and protocols rather than simply scaled from adult doses. The lecture defined a newborn as up to 28 days old, an infant as 1–12 months, a child as 1–12 years, and an adolescent as 13–18 years.
• Older adults: Age-related changes in digestion, body composition, liver function, and kidney function can affect drug levels and removal, sometimes increasing toxicity risk.

The overall lesson was to make care patient-centered: use the best available evidence and clinical practice while considering each person’s circumstances, needs, expectations, and characteristics. Protocols are useful guides, but treatment should be individualized.

Chronopharmacology: why medication timing can matter

• Chronopharmacology studies how biological rhythms and medication timing affect treatment response and adverse effects.
• The circadian rhythm is a roughly 24-hour cycle influenced especially by light. It affects sleep and wakefulness, hormones such as melatonin and cortisol, body temperature, blood pressure, and other functions. The lecturer identified the suprachiasmatic nucleus in the hypothalamus as a key coordinator.
• Chronopharmacokinetics asks whether timing changes a drug’s absorption, distribution, metabolism, or elimination. Chronopharmacodynamics asks whether timing changes its effects, including because receptor availability or sensitivity can vary.
• The lecturer emphasized that timing decisions should account for the patient’s routine, sleep schedule, meals, symptoms, evidence about the medication, and treatment response—not rely on a universal rule.

Examples discussed:

• Blood pressure: Many people experience a nighttime fall, while others show little fall or even a nighttime rise. A 24-hour blood-pressure monitor can identify an individual pattern, which may help clinicians consider medication timing.
• Statins: Conventional simvastatin has a shorter half-life and is commonly taken at night, when the body’s cholesterol production is active. Atorvastatin and rosuvastatin have longer half-lives and can generally be taken at different times as prescribed.
• Glucocorticoids: Morning administration may better match the body’s cortisol rhythm and help with some morning symptoms.
• Levothyroxine: Consistent timing and separation from food are important for absorption. The lecture advised taking it 30–60 minutes before eating or 2–3 hours after a meal.
• Inflammatory conditions: Symptoms can vary over the day. Adjusting dosing time or using modified-release formulations may help align a medicine’s effect with periods of greater pain or stiffness.
• Work and sleep schedules: A night-shift worker, for example, may need a different plan for sleep-inducing medication than someone who sleeps at night.

Medication toxicity and poisoning

• A medicine’s potential to help does not mean it is harmless. Over-the-counter drugs, “natural” products, vitamins, minerals, herbs, and supplements can all cause harm or interact with other substances. Some fat-soluble vitamins can accumulate in the body.
• The lecturer cited SINITOX data indicating that medicines were the largest category of reported poisoning. Drug groups discussed included central nervous system medicines, common painkillers and anti-inflammatory drugs, respiratory medicines, and cardiovascular medicines.
• In children, accidental access to medicines and administration or dosing errors were highlighted as important causes of poisoning. Improper storage and inadequate supervision were also discussed.
• Therapeutic index was used to explain safety margins: a narrow therapeutic index means the effective dose is relatively close to a harmful or lethal dose. Barbiturates were contrasted with benzodiazepines. The lecture described benzodiazepines as having a limiting effect tied to the presence of GABA, while barbiturates can cause profound central nervous system depression and respiratory danger. Benzodiazepines still carry risks.
• Possible poisoning signs mentioned included changes in heart rate, blood pressure, pupils, vision, or skin; sweating; breathing difficulty; vomiting, diarrhea, or abdominal pain; extreme drowsiness; hallucinations; and delirium. Symptom patterns can help clinicians assess a case, particularly when the substance is unknown.
• Poisoning response, as outlined in the lecture: Stabilize and monitor the person’s vital functions; try to identify the substance and exposure; consider measures to reduce absorption or increase elimination where appropriate; and use an antidote if one exists. Examples discussed included activated charcoal in selected cases, dialysis, and naloxone for opioid poisoning. Decontamination and other interventions depend on the substance and the patient; not every treatment is appropriate in every case.
• The lecturer provided the SINITOX national number for poisoning information: 0800 722 6001.

How toxic effects develop

The lecture organized toxic effects into three stages:

1. Exposure: Toxicity depends on the route, dose or concentration, duration and frequency, the substance’s properties, and the individual’s susceptibility.
2. Toxicokinetics: What the body does to the toxic substance—absorption, distribution, metabolism, and excretion.
3. Toxicodynamics and clinical effects: The substance’s interaction with its site of action and the resulting signs and symptoms.

Examples illustrated how route and duration matter. The lecture contrasted the effects of acute and chronic exposure to silica and mercury, and noted that different chemical forms of the same element can have very different toxicity.

Thalidomide and post-market safety

• Thalidomide was marketed in the late 1950s as a sedative and for pregnancy-related nausea. Its use was linked to severe birth defects, including phocomelia, and it was withdrawn from markets in the early 1960s.
• The lecturer explained that safety findings from animal studies or limited trials may not reveal all risks that emerge in a wider population. The thalidomide example showed why pharmacovigilance must continue after a medicine is approved and why a drug may be withdrawn or restricted.
• The lecture also discussed thalidomide’s mirror-image molecular forms and the possibility that the body can convert between them, meaning that isolating one form would not necessarily remove the risk.

Closing points and student questions

In response to questions, the lecturer noted that taking an antibiotic dose later than scheduled can affect treatment if drug concentrations fall below effective levels, while taking doses too close together may raise concentrations excessively. Alcohol may affect how long other substances remain in the body.

The lecturer also explained that oral administration is especially subject to first-pass metabolism, that there is no single fixed duration for how long a drug remains in everyone’s body, and that activated charcoal can bind some substances and reduce their absorption.

Speakers and sources featured

• Lecturer, addressed as Professor Jessica: Presented the pharmacology lesson; the transcript does not provide a full name.
• Course moderator/mediator: Handled announcements, chat support, and closing reminders; the name is unclear in the transcript.
• Student commenters in the chat: Vanessa, Rafa, Bia/Bianca, Suzy, Jaqueline, Maraney, Maria, and Antônio.
• Named or institutional sources mentioned: Mário Sérgio Cortella (quoted for a motivational idea); sleep researcher Altair de Sousa; SINITOX, the Brazilian National System of Toxicological and Pharmacological Information.
• Other materials referenced but not identified by title: An English-language article on biological rhythms and medication, and professional references/manuals on poisoning treatment and antidotes.