Neuropharmacology II Quiz

Basic Principles of Neuropharmacology II

• The image depicts a person pouring water from a bottle into a brain.
• Igor Morski's quote: "Someone is making water out of your brain."
• Learning outcomes include defining drugs and medicines, reviewing drug actions in biological systems, defining pharmacodynamics and pharmacokinetics, discussing bioavailability (admin., release, absorption, distribution, metabolism, and excretion), and discussing volume of distribution and clearance.

Basic Terms: Ligands, Drugs, and Medicines

• A ligand is any chemical that binds to a receptor (can be agonist or antagonist).
• A drug is a substance (other than food) used for prevention, diagnosis, treatment, or symptom relief of diseases or abnormal conditions. Drugs can alter brain and body function, potentially causing changes in mood, awareness, thoughts, feelings, or behavior, with opioids being a potential example of drugs that can cause addiction.
• A medicine refers to practices and procedures for preventing, treating, or relieving diseases or symptoms; it may also refer to a legal drug for the same purpose.
• Drugs affecting behavior are known as psychotropic agents, but other terms such as chemical or compound are also used.

Drugs are All Around Us

• Antidepressants, anti-anxiety, anticonvulsants, and antipsychotics are common medications.
• Some drugs can affect other organ systems and can cause unpleasant side effects.
• Common substances such as caffeine, alcohol, and nicotine also affect the central nervous system.
• In some individuals, drugs can be used compulsively, resulting in addiction.

The Action of Drugs on Neural Targets

• The initial drug target determines the cells and circuits affected, and the potential for both efficacy and side effects.
• Initial drug binding is just the beginning of a signaling cascade influencing cell behavior, neural circuits, and animal behavior.

Agonists, Antagonists, and Modulators

• Ligands can alter agonist responses.
• Competitive antagonists compete with agonists for the binding site.
• Allosteric modulators can either enhance or reduce agonist responses at separate sites.

Affinity, Potency, and Efficacy

• Affinity (Ka) is the strength of ligand binding to its target.
• Efficacy is the ability of a drug to produce a maximal biological effect at a receptor.
• Potency is the amount of ligand (agonist or antagonist) needed to elicit a specific biological effect.

Pharmacodynamics

• Pharmacodynamics describes the time course and intensity of drug effects on the body.
• Drug action is determined by affinity, efficacy, potency, and concentration-response relationships, spare receptors, and amplification.
• The ability of a drug to produce an effect depends on these underlying mechanisms.

Pharmacodynamics vs. Pharmacokinetics

• Pharmacodynamics focuses on the effects of a drug "what the drug does to the body".
• Pharmacokinetics describes the journey of a drug in the body "what the body does to the drug".
• Pharmacodynamics considers drug action at the site of action, whereas pharmacokinetics considers absorption, circulation, metabolism, excretion, etc.

Pharmacokinetics and Bioavailability

• Pharmacokinetics describes the movement/time course of a drug in the body.
• Bioavailability measures the ability of a drug to reach the target, from absorption to elimination.

Pharmacokinetics Stages

• Route of administration
• Release/liberation
• Absorption
• Distribution
• Metabolism
• Excretion

Getting Drugs into the Brain - Administration

• Enteral routes (through the intestine) include oral (slow onset), sublingual, buccal, and rectal administrations.
• Parenteral routes include intravenous, intramuscular, subcutaneous, inhalation, and intracerebroventricular or intracerebral routes.

Pros and Cons of Drug Administration Routes

• Enteral routes are convenient and non-sterile, but oral administration can have significant first-pass metabolism effects and erratic absorption.
• Parenteral routes offer faster action, complete absorption, and potentially less degradation, but some may have greater pain or risks of complications.

Oral Bioavailability - Tablet Dissolution (Release/Liberation)

• Tablet dissolution in the acidic environment of the stomach (pH 1–2) into solution (fragmentation and smaller particles) is essential for absorption.
• Several factors like pH, pepsin, food, drug formulation, and surface area affect absorption.

Oral Bioavailability - Absorption

• Most drugs are absorbed in the duodenum and jejunum of the small intestine.
• Villi increase surface area for absorption.
• Epithelial cells, capillary networks, and the portal vein system enhance absorption.
• Numerous processes like passive diffusion, convective absorption, active transport, facilitated transport, ion pair formation, and pinocytosis enable absorption.
• Drug absorption also depends on intestinal motility (influenced by time of day, exercise, disease, or food consumption).

Oral Bioavailability - First Pass Metabolism

• Most venous outflow from the stomach and intestines goes to the liver via the portal vein.
• Cytochrome P450 enzymes in the liver play a role in metabolizing endogenous substances and drugs.
• Bioavailability is reduced because of the liver, which inactivates many drugs before they reach systemic circulation.

Bioavailability Affected by Plasma Proteins

• Many drugs bind to plasma proteins, primarily albumin, which reduces their bioavailability because only free drug can act at the receptor.

Bioavailability Affected by Barriers

• Various factors, including paracellular, transcellular, transport proteins, receptor-mediated transcytosis, and adsorptive transcytosis, can potentially affect drug bioavailability, especially when crossing barriers like the blood-brain barrier.

Drugs into the Brain - Bioavailability

• Bioavailability is affected by absorption, metabolism, excretion, binding to plasma proteins, and blood-brain barrier penetration.

Drug Pharmacokinetics Decides Dosing Regimen

• Pharmacokinetic parameters such as concentration-time profiles (Cmax), time to reach Cmax (tmax), and area under the curve (AUC) help define dosing regimens.
• Unbound drug can access the receptor to exert activity.

Pharmacokinetics & Dosing Terms Used

• Describes various pharmacokinetic terms used in calculating and defining drug dosages.

Fundamentals of Pharmacokinetics

• Key concepts in pharmacokinetics, such as volume of distribution, clearance, and elimination half-life.

Pharmacokinetics - Volume of Distribution

• Volume of distribution (Vd) is a hypothetical volume that a drug would occupy if it were distributed at the same concentration as in the plasma.

Pharmacokinetics - Clearance

• Clearance (CL) describes the rate at which a drug is removed from the body.

Case Study - Fate of Ethanol in Body

• Describes the pharmacokinetic and pharmacodynamic processes of ethanol in the body, starting from administration to effects, factors influencing blood alcohol levels (BAC), and influencing factors including the administration route, absorption, distribution, metabolism, and excretion.

Case Study - Ethanol Distribution Volume

• Describes the factors of age, weight, height, and sex differences in the body composition of patients and their correlation to ethanol (alcohol) distribution volume.

Variability in Drug Response

• Drug response can vary due to aspects including appearance, philosophy, physiology/biochemistry, occupation, and genetics (genotype vs. phenotype).

Summary: Pharmacodynamics & Pharmacokinetics

• Pharmacodynamics (PD) is the study of drug effects on the body.
• The ability of a drug to produce effects depends on characteristics such as affinity, efficacy, potency, concentration-response relationships, spare receptors, and amplification.
• Pharmacokinetics (PK) is the study of a drug's movement through the body.
• Factors include absorption, distribution, metabolism, and excretion of a medicine.
• Bioavailability and the rate of clearance determine the drug effect time course.

Study Materials

• Lists books related to the subject: Psychopharmacology, Molecular Neuropharmacology, and Rang & Dale's Pharmacology.

Example Question L3

• Pharmacokinetics is the time course of a drug in the body.

Weekly Schedule

• A detailed schedule of topics related to neuropharmacology in a course.

Test your knowledge on the basic principles of neuropharmacology. This quiz covers topics like pharmacodynamics, pharmacokinetics, and the definitions of drugs and medicines. Enhance your understanding of how drugs interact within biological systems.