Pharmacology: Drug Metabolism and Distribution

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Questions and Answers

What happens to the elimination half-life in zero-order kinetics as drug concentration increases?

It increases (correct)

It decreases significantly

It remains constant

It fluctuates irregularly

Why is bioequivalence particularly significant for generic drugs?

It guarantees lower pricing

It ensures similar drug concentrations compared to the reference drug (correct)

It ensures faster market approval

It allows for unlimited substitutions of active ingredients

Which of the following correctly describes an antagonist?

It causes stronger biological responses than agonists

It enhances the effects of endogenous ligands

It binds to receptors and activates them

It binds to receptors but does not activate them (correct)

What characterizes a partial agonist?

It produces a weaker response than full agonists Signup and view all the answers

In pharmacodynamics, drug-receptor interactions lead to changes in which of the following?

Cellular signaling pathways and physiological responses Signup and view all the answers

How do drugs interact with carrier proteins?

By acting as substrates or inhibitors of these proteins Signup and view all the answers

What defines bioavailability?

The rate and extent of drug absorption Signup and view all the answers

What is the role of endogenous ligands in drug interactions?

They bind to receptors and produce biological responses Signup and view all the answers

What is the main division of the nervous system that consists of the brain and spinal cord?

Central Nervous System Signup and view all the answers

Which neurotransmitter is released by both preganglionic and postganglionic neurons in the parasympathetic nervous system?

Acetylcholine Signup and view all the answers

Which of the following best describes the length of preganglionic and postganglionic neurons in the sympathetic nervous system?

Short preganglionic and long postganglionic Signup and view all the answers

What branch of the autonomic nervous system is often referred to as the 'fight or flight' response?

Sympathetic nervous system Signup and view all the answers

What type of receptors are used at the ganglionic synapse of both the sympathetic and the parasympathetic nervous systems?

Nicotinic receptors Signup and view all the answers

Which part of the central nervous system plays a crucial role in integrating autonomic functions?

Hypothalamus Signup and view all the answers

What is the spinal cord division of origin for parasympathetic outflow?

Craniosacral Signup and view all the answers

Which neurotransmitter is predominantly released by postganglionic neurons in the sympathetic nervous system?

Norepinephrine Signup and view all the answers

What is a primary use of ipratropium?

Relieving bronchospasm in asthma and COPD Signup and view all the answers

Which muscarinic antagonist is selectively used for the treatment of peptic ulcers?

Pirenzepine Signup and view all the answers

What is a common adverse effect of muscarinic antagonists?

Sedation Signup and view all the answers

Which of the following is a contraindication for the use of muscarinic antagonists?

Prostatic hypertrophy Signup and view all the answers

What mechanism of action do muscarinic antagonists employ?

Blocking muscarinic receptors Signup and view all the answers

What effect do muscarinic antagonists have on pupil size?

Dilation of pupils (mydriasis) Signup and view all the answers

Which of the following is NOT a pharmacological effect of muscarinic antagonists?

Increased bowel motility Signup and view all the answers

Which of the following muscarinic antagonists is not commonly used due to safer alternatives?

Hexamethonium Signup and view all the answers

What physiological response is associated with sympathetic involvement?

Decreased gastrointestinal motility Signup and view all the answers

Which of the following drugs is classified as a reversible indirect acting cholinomimetic?

Edrophonium Signup and view all the answers

What is a common disorder resulting from abnormal autonomic nervous system activity?

Orthostatic hypotension Signup and view all the answers

Which of the following actions is NOT predominantly influenced by the parasympathetic nervous system?

Dilation of the pupils Signup and view all the answers

What effect does direct acting cholinergic drugs have on the heart rate?

Decreases heart rate Signup and view all the answers

What is the mechanism of action for anticholinesterases?

Inhibit acetylcholinesterase Signup and view all the answers

Which direct acting cholinergic drug is primarily used in ophthalmology?

Pilocarpine Signup and view all the answers

What is an effect of excessive sympathetic nervous system activity?

Bronchodilation Signup and view all the answers

What is the primary therapeutic use of Prazosin?

Treatment of hypertension Signup and view all the answers

Which mechanism of action is associated with Phenoxybenzamine?

Irreversibly blocks both alpha 1 and alpha 2 adrenergic receptors Signup and view all the answers

What adverse effect may occur due to adrenergic antagonists?

Pulmonary edema Signup and view all the answers

Which beta blocker selectively targets beta 1 adrenergic receptors?

Metoprolol Signup and view all the answers

Which of the following is a nonselective beta blocker?

Propranolol Signup and view all the answers

For which condition is Phentolamine primarily indicated?

Diagnosis of pheochromocytoma Signup and view all the answers

What therapeutic effect results from the action of alpha 1 adrenergic blockade?

Vasodilation Signup and view all the answers

What is a common therapeutic use of Propranolol?

Controlling migraines Signup and view all the answers

What does the term 'ED50' refer to?

The dose that produces a therapeutic effect in 50% of the population Signup and view all the answers

How does a competitive antagonist affect agonist activity?

It competes for the same receptor site as the agonist Signup and view all the answers

What is the role of spare receptors in pharmacology?

They allow maximum response even when some receptors are occupied Signup and view all the answers

What does 'potency' measure in drug action?

The strength at which a drug can produce a specific effect Signup and view all the answers

What happens when a partial agonist is administered after a full agonist?

The drug efficacy is generally reduced Signup and view all the answers

What is the main characteristic of a non-competitive antagonist?

It binds to a different site and alters receptor function Signup and view all the answers

Which term describes the maximum effect a drug can achieve?

Efficacy Signup and view all the answers

What is indicated by the term 'LD50'?

The dose that causes death in 50% of the population Signup and view all the answers

Study Notes

Pharmacology

Drug permeation and disposition processes include absorption, distribution, metabolism, and excretion
Factors affecting drug permeation and disposition include physicochemical properties, blood flow, protein binding, and membrane barriers
Drug permeation is also influenced by the presence of efflux transporters

First Pass Metabolism and Bioavailability

First pass metabolism is the metabolism of a drug before it reaches systemic circulation
Bioavailability is the fraction of the drug that reaches systemic circulation unchanged after administration
Factors affecting first pass metabolism and bioavailability include hepatic metabolism, gut wall metabolism, intestinal and hepatic blood flow, and interactions with other drugs or food.

Effect of Plasma Protein Binding

Plasma protein binding affects drug distribution in the body
Bound drugs have limited distribution, while unbound drugs are available for tissue uptake
Protein binding also influences drug redistribution and enterohepatic circulation

Two Main Phases of Biotransformation

Biotransformation involves enzymatic modification of drugs into metabolites
Phase I biotransformation includes oxidation, reduction, or hydrolysis reactions
Phase II biotransformation involves conjugation reactions, where metabolites are attached to endogenous compounds
Clinical significance of biotransformation includes drug inactivation or activation, formation of active or toxic metabolites, and drug-drug interactions
Variability in drug response is also a consideration

Processes Involved in Drug Excretion

Excretion refers to the elimination of drugs and metabolites from the body
Major excretion routes include renal (urine), biliary (feces), and pulmonary (breath) excretion
Factors affecting excretion include the rate of absorption, route of administration, dose, and formulation.

Definition of Pharmacokinetic Parameters

Bioavailability: Fraction of unchanged drug reaching systemic circulation
Volume of distribution (Vd): Theoretical volume required to contain the total drug amount in the body at the same plasma concentration
Clearance (CI): Rate of drug removal from the body (volume of plasma cleared per unit time)
Elimination half-life (t1/2): Time required for the drug concentration to decrease by half during elimination phase

First and Zero Order Kinetics

First-order kinetics: Elimination is proportional to drug concentration, and the elimination half-life remains constant.
Zero-order kinetics: Elimination occurs at a constant amount regardless of concentration, leading to a variable elimination half-life that increases with increasing concentration.

Bioequivalence

Bioequivalence refers to the similarity in bioavailability of two formulations of the same drug
Bioequivalent formulations show comparable rate and extent of absorption
Bioequivalence is crucial for generic drugs to ensure similar drug concentrations in the body compared to the reference drug.

Applied Pharmacodynamics

Pharmacodynamics describes how drugs exert their effects on the body
Receptors: Proteins that bind to ligands (like drugs) triggering cellular responses
Endogenous ligands: Naturally occurring substances that bind to receptors
Agonists: Drugs that bind to and activate receptors producing a biological response
Antagonists: Drugs that bind to receptors but do not activate them, blocking other molecules from activating the receptor, preventing their effects
Partial agonists: Bind to receptors producing a weaker response compared to full agonists
Inverse agonists: Bind to receptors, inducing the opposite effect to agonists or decreasing constitutive activity of the receptor

Dose-Response Curves

Dose-response curves illustrate the relationship between drug dose and the magnitude of effect
Threshold: Minimum dose eliciting a detectable response
Slope: Steepness of the curve; indicates sensitivity to dose changes
Maximum effect (Emax): Peak response at high doses
Variability: Individual differences in response

Spare Receptors, ED50, LD50, TD50

Spare receptors: Receptors present in excess, allowing for maximum response even when some are occupied
Effective dose (ED50): Dose producing a therapeutic effect in 50% of individuals
Lethal dose (LD50): Dose causing death in 50% of individuals
Toxic dose (TD50): Dose causing a toxic effect in 50% of individuals

Interpretation of Dose-Response Curves

Agonist: Dose-dependent increase in response, reaching maximum effect at high doses
Partial agonist: Dose-dependent increase in response, but maximal effect is lower than a full agonist
Antagonist: Does not produce a response but blocks or reduces agonist response

Efficacy and Potency

Efficacy: Maximum effect or response a drug can produce
Potency: Dose or concentration of a drug required to produce a specific effect

Therapeutic Index (TI)

Therapeutic index: Ratio of lethal dose (LD50) to effective dose (ED50); measures drug safety margin
Higher TI indicates a wider safety margin; conversely, a lower TI increases toxicity concern

Plasma Concentration-Time Curve

Shows the relationship between drug plasma concentration and time after administration
Factors affecting the curve include absorption rate, dose, and route of administration
Curve typically shows initial increase in plasma concentration as drug is absorbed, followed by a gradual decline

Steady State Concentration

Steady state is reached when the rate of drug administration equals the rate of elimination

Drug Toxicity and ADRs

Drug toxicity refers to harmful effects caused by drug concentration or duration of exposure
Factors influencing toxicity include dose, duration, individual variability, metabolism and elimination, and route of administration
Adverse reactions are unintended harmful effects

Tests for Toxicity

General tests: Evaluate overall toxic effects on various organs
Specific tests: Evaluate organ-specific toxicities

Adverse Drug Reactions (ADRs)

Unintended and harmful effects of drug therapies
Classification includes type A (augmented), type B (bizarre), type C (chronic), type D (delayed), type E (end-of-treatment), and type F (failure)

Risk Factors for ADRs

Individual factors (age), conditions, and concurrent medications
Drug properties, dosing, and route

Pregnancy Risk Categories

Classify drugs based on potential fetal risks during pregnancy

Autonomic Nervous System (ANS)

ANS subdivisions include central and peripheral nervous systems, further categorized as the somatic and autonomic nervous systems
Divides into parasympathetic and sympathetic branches

Neurotransmitters and Receptors

Sympathetic and parasympathetic systems use different neurotransmitters and receptors
Acetylcholine (ACh) is a key neurotransmitter in both systems
Different receptors determine specific physiological responses

Direct Acting Cholinergic Drugs and Anticholinesterases

Direct-acting drugs: Exert their effects by activating cholinergic receptors
Anticholinesterases: Inhibit acetylcholinesterase, increasing acetylcholine levels
Therapeutic uses: For myasthenia gravis, post-operative urinary retention, and to counter the effects of organophosphate poisoning

Cholinergic Antagonists

Block cholinergic receptors, preventing acetylcholine from activating them
Muscarinic antagonists: Block muscarinic receptors (ex. atropine, scopolamine)
Ganglion-blocking agents: Block ganglion transmission reducing autonomic nerve activity (hexamethonium)

Neuromuscular Blockers

Act at the neuromuscular junction, interfering with acetylcholine signaling
Two types: Depolarizing (ex. succinylcholine) and non-depolarizing (ex. tubocurarine)
Therapeutic uses: Muscle relaxation during surgery; clinical testing

Adrenergic Agonists

Activate adrenergic receptors (alpha and beta) leading to varied effects
Alpha-1 agonists: Vasoconstriction blood vessel restriction
Alpha-2 agonists: Reduced sympathetic output
Beta-1 agonists: Increase heart rate and contractility
Beta-2 agonists: Bronchodilation
Non-selective agonists: Affect multiple adrenergic receptor subtypes
Uses: Treating hypertension, asthma, glaucoma, and other conditions

Adrenergic Antagonists

Block adrenergic receptors, reducing the effects of norepinephrine and epinephrine
Alpha-blockers: Block alpha-receptors, reducing vasoconstriction
Beta-blockers: Block beta-receptors, reducing heart rate and contractility
Specific use for some beta blockers: Treating hypertension, angina, arrhythmias, and other conditions

Autocoids

Locally-acting substances produced in the body, affecting nearby tissues
Examples include prostaglandins, histamine, serotonin, and leukotrienes
Important roles in inflammation, pain, immune responses, and others
Pharmacological uses for modifying actions.

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Description

This quiz covers key concepts in pharmacology related to drug permeation, metabolism, and bioavailability. Understand how factors like first pass metabolism and plasma protein binding influence drug disposition in the body. Test your knowledge on the processes affecting how drugs enter and move through the system.