S7 REPASO (Clase 2)

New Section

The instructor begins the class with a second review of pharmacology, expressing gratitude to Dr. Ana Lucía for her support and welcoming students to the Zoom session for the second review.

Introduction to Pharmacology Review

• The review focuses on addressing student queries received through delegate Marita, emphasizing key points about NSAIDs, opioids, and their mechanisms.

• Basic concepts related to NSAIDs are discussed, highlighting the role of eicosanoids in prostaglandin formation mediated by cyclooxygenase enzymes (COX-1 and COX-2).

• Pain, inflammation, and fever genesis involving prostaglandins derived from arachidonic acid metabolism are explained along with the significance of COX enzymes.

• The origin of endogenous pharmacological complexes from arachidonic acid is detailed, emphasizing the pathways leading to leukotrienes and prostaglandins.

Understanding Prostaglandins

This section delves into the roles of prostaglandins in various physiological processes such as intestinal motility, vascular function, coagulation, renal function, and mucosal protection.

Roles of Prostaglandins

• Prostaglandins' impact on intestinal motility is highlighted for both contraction and relaxation processes necessary for bowel movements.

• Discussion on prostacyclin's dual role in antiplatelet aggregation and vasodilation within blood clotting mechanisms.

Impact on Vascular System

The discussion shifts towards how NSAIDs affect vascular dynamics concerning platelet aggregation and vasoconstriction.

Vascular Effects

• Explanation of how NSAIDs can disrupt beneficial effects like vasodilation while maintaining risks associated with vasoconstriction in patients with cardiac issues.

Renal Function and Gastric Mucosa Protection

Insights into the protective functions of prostaglandins in renal blood flow regulation and gastric mucosal defense mechanisms are provided.

Renal Function & Gastric Mucosa Protection

• Importance of prostaglandins in maintaining renal blood flow for proper filtration processes despite vasoconstriction challenges.

• Role of specific prostaglandins (F2 Alpha, E2) in protecting gastric mucosa by enhancing mucus production while reducing acid secretion.

Reproductive System Impact

The influence of prostaglandins on female reproductive processes like menstruation is explored alongside their involvement in ovulation and labor.

Reproductive System Functions

Prostaglandins and Their Effects

In this section, the speaker discusses the role of prostaglandins, their receptors, and the various actions they elicit in the body.

Prostaglandin Actions and Receptors

• Prostaglandin I2 acts on the IP2 receptor, leading to vasodilation and inhibition of platelet aggregation.

• Different receptors such as F1 and IP2 are associated with bronchoconstriction or bronchodilation, muscle contraction or relaxation in the digestive tract, and vasodilation.

• Prostaglandin E2 acts on the EP3 receptor to decrease gastric acid secretion, increase gastric mucus secretion, inhibit uterine contractions during pregnancy, inhibit smooth muscle contraction in the digestive tract, inhibit lipolysis, and increase autonomic neurotransmitters.

Importance of Understanding Prostaglandins for NSAIDs

• Understanding prostaglandins is crucial for discussing nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can block both Cox 1 and Cox 2 enzymes. Blocking Cox 1 leads to issues with mucosal protection and homeostasis while blocking Cox 2 reduces pain, inflammation, and fever.

• NSAIDs can reduce pain by affecting peripheral sensitization caused by prostaglandins like E2 and I2. They inhibit prostaglandin synthesis peripherally which helps in reducing sensitivity to afferent stimuli.

Mechanism of Action of Anti-Inflammatory Drugs

This part delves into how anti-inflammatory drugs work at a molecular level.

Action of Anti-Inflammatory Drugs

• COX-2 inhibitors reduce pain by decreasing prostaglandin levels resulting in less pain, inflammation, and fever without affecting other components like atheroma formation or renal filtration.

• The inflammatory response involves prostaglandins E2 & I2 causing increased local blood flow & vascular permeability along with leukocyte activation; meanwhile prostaglandin D2 triggers mast cell release leading to congestion & redness during inflammation.

Fever Regulation by Prostaglandins

• Prostaglandin E2 stimulates central neurons responsible for temperature regulation leading to fever; NSAIDs suppress this elevation centrally by inhibiting interleukin 1 production.

Insights into Cyclooxygenase Enzymes

Exploring details about cyclooxygenase enzymes including COX-3.

Understanding COX Enzymes

• COX enzymes play a vital role in inflammation regulation where two key prostaglandins (E2 & I2) contribute to increased blood flow & leukocyte activity during inflammation processes.

Understanding the Role of COX Enzymes in Pain Management

The discussion delves into the regions of the brain where the presence of COX enzymes is identified, focusing on their roles and implications in pain management.

Regions of Brain with COX Enzyme Presence

• COX enzyme presence identified in regions such as the epithalamus, hypothalamus, hippocampus, cerebellum, and spinal cord.

• COX-3 primarily found in the brain, functioning differently from COX-1 and COX-2 with protective roles.

• Acetaminophen (paracetamol) highlighted as a selective drug for pain management due to its low affinity towards Cox 1 and Cox 2.

Comparative Analysis: Ketorolac vs. Metamizole for Pain Relief

A comparison between ketorolac and metamizole regarding their potency and efficacy in pain relief post-surgery is discussed.

Ketorolac vs. Metamizole

• Debate on whether ketorolac is more potent than metamizole surfaces different opinions.

• Study comparing ketorolac (10mg) to paracetamol shows superior results in pain relief post-extraction.

Prostaglandins' Role in Pain Management

Explores the impact of prostaglandins on pain modulation and how drugs affect their synthesis for pain management.

Prostaglandins' Functionality

• Prostaglandins like thromboxane play a role in platelet activation, vasoconstriction, and proliferation.

• Inhibition of Cox 1 reduces thromboxane synthesis, platelet activity, renal prostaglandins leading to vasoconstriction.

Effects of Drugs on Prostaglandin Synthesis

Discusses how different drugs influence prostaglandin synthesis impacting various physiological functions.

Drug Impact on Prostaglandin Synthesis

• Drugs affecting Cox 2 increase thromboxane while decreasing prostacyclin levels leading to platelet activation and vasoconstriction risks.

Loss of Protective Effect in Ischemia and Infarctions

The discussion focuses on the loss of the protective effect of COX2 regulation during ischemia and infarctions, leading to sodium retention, water edema, exacerbation of renal and congestive heart failure in high-risk patients.

Effects of Aging on Renin-Angiotensin System

• Older adults experience an increase in the renin-angiotensin system, resulting in elevated levels of angiotensin (a potent vasoconstrictor), enhanced sodium and water reabsorption, heightened sympathetic activity, catecholamines release, leading to renal vasoconstriction and reduced renal function.

Cardiovascular Effects of Anti-Inflammatory Drugs

This section delves into the normalization effects induced by giving diuretics post-COX inhibitors administration. It also highlights cautionary notes regarding NSAIDs use in patients with renal issues.

Cardiovascular Impact of NSAIDs

• Diuretics can help normalize the compensatory effect induced by renal kinases after COX inhibitor administration.

• Caution is advised when using NSAIDs; while naproxen may be used cautiously, avoid selective COX inhibitors due to increased cardiovascular risks like thrombosis.

Differential Effects of Anti-Inflammatory Drugs

This part discusses the varying impacts of different anti-inflammatory drugs on cardiac health and cancer prevention.

Selective vs. Non-selective NSAIDs

• Selective COX inhibitors decrease prostacyclin levels, increasing atherothrombotic risks compared to non-selective ones that reduce prostaglandins but maintain protection against arrhythmias and cardiovascular risks.

Renal Function Impairment Due to Anti-Inflammatory Drugs

Examines how NSAIDs affect kidney function through modulation of prostaglandins levels impacting sodium excretion and blood pressure regulation.

Impact on Kidney Function

• NSAIDs reduce prostacyclin C2 levels affecting sodium elimination, leading to decreased water filtration and renal blood flow elevation causing hypertension risk.

Risk Factors Associated with Gastrointestinal Issues

Discusses gastrointestinal risk factors associated with NSAID use including history of ulcers, age over 60 years old, concurrent medication usage like antiplatelets or corticosteroids.

Gastrointestinal Risk Factors

• Factors such as previous ulcer history or concomitant use with multiple medications increase gastrointestinal complications' likelihood.

Comparative Analysis: Lesivity Levels Among Anti-Inflammatory Drugs

Compares the gastrolesivity among various anti-inflammatory drugs from least harmful (ibuprofen) to most harmful (ketoprofen).

Gastrolesivity Ranking

• Ibuprofen is less gastrolesive compared to ketoprofen which is more damaging; caution should be exercised based on drug selection for patient safety.

Impact on Blood Pressure Regulation by Anti-Inflammatory Drugs

Explores how anti-inflammatory drugs can elevate blood pressure irrespective if individuals are normotensive or hypertensive due to their inflammatory response modulation properties.

Blood Pressure Modulation

Elucidating Pharmacological Concepts

In this section, the speaker delves into various pharmacological concepts related to drug actions and interactions.

Understanding Drug Actions

• Misoprostol, an analog of prostaglandin E2, is designed to treat specific ulcers by increasing mucus production and reducing gastric secretions.

• Acute Paracetamol intoxication often necessitates antidotes like N-acetylcysteine, which transforms into glutathione to counteract toxic metabolites.

• Paracetamol metabolism primarily involves glucuronidation to prevent hepatic necrosis caused by reactive metabolites.

Drug Interactions and Metabolism

• Ethanol's induction effect on enzymes can increase the risk of toxic metabolite formation in drugs like Paracetamol.

• Ethanol acts as both an enzyme binder acutely and a potent inducer chronically, highlighting its impact on drug metabolism.

Exploring Gout Treatment Strategies

The discussion shifts towards treatment approaches for gout, focusing on medications and their mechanisms of action.

Gout Medications Differentiation

• Allopurinol reduces uric acid levels by inhibiting xanthine oxidase, while Probenecid enhances uric acid excretion through renal mechanisms.

• Colchicine's anti-inflammatory effects aid in gout management, while Probenecid and Sulfinpyrazone inhibit renal uric acid reabsorption for therapeutic benefits.

Mechanisms of Action

Clonidine and its Effects

The discussion revolves around the effects of clonidine, particularly its analgesic properties and impact on blood pressure due to its action as an alpha-2 adrenergic agonist.

Clonidine Effects

• Clonidine is considered to have analgesic effects, especially in neuropathic pain. It acts as an alpha-2 adrenergic agonist, leading to a decrease in blood pressure by reducing norepinephrine release.

Role of Chlorina in Spasticity Treatment

The conversation delves into the role of chlorina in treating spasticity, primarily through inhibiting excessive sensory transmission below the level of injury.

Chlorina for Spasticity

• Chlorina plays a role in treating spasticity by inhibiting excessive sensory transmission below the level of injury.

• Despite its efficacy, chlorina is often used as a second or third-line agent due to side effects like hypotension, bradycardia, and somnolence.

Comparison of Analgesics and Blood Pressure Effects

A comparison is made between different medications regarding their effects on blood pressure, analgesia, and muscle relaxation.

Medication Comparison

• Atenor solely reduces blood pressure. Morphine can lower blood pressure and provide analgesia but lacks muscle relaxant properties.

• Nitroprusside and prazosin induce hypotension.

Detailed Analysis of Transcript Content

In this section, the speaker discusses the concept of low-power analgesics and their role as agonists. Additionally, they touch upon the affinity for the mu sector and the potentiation of inhibitory effects.

Low-Power Analgesics and Agonists

• Low-power analgesics are crucial to avoid confusion in medication.

• Agonists have a fundamental affinity for the mu sector and enhance inhibitory effects.

Insights on Potentiation and Effects

This part delves into how adrenaline and serotonin contribute to potentiation, showcasing effects at various levels.

Adrenaline, Serotonin, and Potentiation

• Adrenaline and serotonin play a role in enhancing inhibitory effects.

• The session concludes with a note on staying updated for exams and thanking participants for their attention.