Opioids and Their Effects

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Questions and Answers

What is the primary therapeutic use of morphine?

Pain relief (correct)

Gut motility increase

Mood elevation

Cough suppression

Which effect is commonly associated with opioid use?

Heightened anxiety

Sleeplessness

Increased gut motility

Respiratory depression (correct)

Which of the following substances is classified as an opioid agonist?

Aspirin

Methadone (correct)

Ibuprofen

Paracetamol

What is a common unwanted effect of opioid treatment?

Constipation Signup and view all the answers

What role do endogenous opioids, like endorphins, play in the human body?

They help regulate pain perception and mood. Signup and view all the answers

What process involves the engulfing of fluid or particles by a cell?

Pinocytosis Signup and view all the answers

What is the absolute bioavailability of a drug administered intravenously?

1 Signup and view all the answers

Which transport mechanism requires energy expenditure and plays a small role in drug transport?

Pinocytosis Signup and view all the answers

Which of the following is NOT a factor affecting bioavailability?

Heart rate Signup and view all the answers

Which statement accurately describes the absorption of drugs delivered via routes other than intravenous?

They usually have an absolute bioavailability of less than 1 Signup and view all the answers

What is the primary effect of agonists on receptors?

They stimulate receptor activity. Signup and view all the answers

Which drug is an example of a beta-receptor antagonist?

Metoprolol Signup and view all the answers

What does the term 'first-pass metabolism' refer to?

The metabolism of drugs by the liver before systemic circulation. Signup and view all the answers

Which administration route allows a drug to enter systemic circulation without passing through the gastrointestinal tract?

Intravenous Signup and view all the answers

What is the main purpose of drug absorption?

To ensure therapeutic effect. Signup and view all the answers

Which mechanism involves the movement of drugs against a concentration gradient?

Active transport Signup and view all the answers

What is meant by bioavailability?

The proportion of a drug that enters systemic circulation unchanged. Signup and view all the answers

What happens when beta-receptors in the lungs are blocked?

Bronchoconstriction may occur in asthmatics. Signup and view all the answers

What primarily establishes the impermeability of the blood-brain barrier (BBB) to most water-soluble drugs?

Tight junctions between endothelial cells Signup and view all the answers

Which of the following statements about drug binding to plasma proteins is true?

Bound drugs are limited in their distribution in the body Signup and view all the answers

What characteristics allow a drug to cross the blood-brain barrier effectively?

Low molecular weight and lipophilic nature Signup and view all the answers

What is the first phase of drug metabolism known for?

Adding or unmasking functional groups to increase polarity Signup and view all the answers

Which of the following is NOT a typical reaction involved in drug metabolism?

Protein synthesis Signup and view all the answers

What is the main purpose of drug metabolism in the liver?

To facilitate renal excretion by making drugs more water-soluble Signup and view all the answers

What is a consequence of a drug's strong binding to plasma proteins?

Decreased efficacy of the drug Signup and view all the answers

Which component of the blood-brain barrier is involved in forming the tight junctions that limit drug diffusion?

Endothelial cells Signup and view all the answers

What is the primary site of drug metabolism in the body?

Liver Signup and view all the answers

Which CYP enzyme is involved in the majority of human drug oxidation?

CYP3A4 Signup and view all the answers

What is the main function of phase I drug metabolism?

Preparation for enzyme action in phase II Signup and view all the answers

Which phase II reaction is the most common in drug metabolism?

Glucuronidation Signup and view all the answers

What effect does conjugation generally have on drugs?

Makes them more easily excreted Signup and view all the answers

Which of the following is NOT a conjugation reaction involved in drug metabolism?

Oxidation Signup and view all the answers

What major issue can arise from rapid drug metabolism?

Ineffective blood concentrations Signup and view all the answers

What role does renal excretion play in drug elimination?

Eliminates polar drug metabolites Signup and view all the answers

Which of the following factors could affect the activity of CYP450 enzymes?

All of the above Signup and view all the answers

Which process is critical for eliminating unwanted substances from the body?

Excretion Signup and view all the answers

Study Notes

Opioids and their History

Heroin, methadone and pethidine have been used for both therapeutic and recreational purposes
In 1970s, pharmacologists discovered endogenous opioids (enkephalins and endorphins) that play a role in pain perception, mood and numerous physiological functions
Opioid receptors were found in key areas of the body including the brain, spinal cord, gut and eye

Opioid Agonists

Opioid receptors bind only to substances with a chemical structure similar to morphine
Opioid agonists trigger certain responses when they attach to opioid receptors

Effects of Opioids

Opioids (like morphine), are primarily used for pain relief
Opioids also have mood-elevating, sedative, pupil constricting, anti-tussive (cough suppression) and gut motility reducing (constipation) effects
Repeated doses can lead to tolerance and dependence in individuals
Opioid overdose can cause respiratory depression and death

Opioid Receptor Challenges

Due to the variety of opioid receptors in different parts of the body, it can be difficult to separate desirable and unwanted effects from morphine and other opioid medications
Constipating effects from morphine and codeine are unavoidable in cancer patients
These drugs can also be used to slow down the gut and treat diarrhea

Agonists vs. Antagonists

Agonists are drugs that stimulate receptors
Antagonists are drugs that block receptors
Salbutamol (Ventolin®) is a beta-receptor agonist that stimulates beta-receptors in the lungs causing bronchodilation
Metoprolol (Betaloc®) is a beta-receptor antagonist that blocks beta-receptors in the heart, slowing heart rate and providing cardioprotection
Metoprolol can also cause bronchoconstriction in asthmatics due to its blocking effect on lung beta-receptors

Pharmacokinetics: ADME

Pharmacokinetics studies how a drug is processed in the body
This includes absorption, distribution, metabolism, and excretion (ADME)

Routes of Drug Administration

Parenteral: Injection (Intravenous, intramuscular, subcutaneous), topical, respiratory
Enteral: Rectal, oral

Absorption

Process of drug moving from administration site to the bloodstream
Necessary for therapeutic effect
Most drugs undergo gastrointestinal absorption
Intravenous (IV) drug administration is an exception

Drug Absorption Pathways

Drugs absorbed through the skin, mouth, lungs, or muscle go directly into the systemic circulation
IV injections deliver 100% of the drug directly into the bloodstream for distribution
Oral drugs must be absorbed from the GI tract into the portal circulation

First-Pass Metabolism

Drugs absorbed via the portal circulation are processed first by the liver
The liver is the primary site of drug metabolism (biotransformation)
Some drug is metabolized before reaching the systemic blood, reducing bioavailability to less than 100%

IV vs. Oral Administration

IV administration bypasses first-pass metabolism
Oral administration has the potential for lower bioavailability due to first-pass metabolism

Mechanisms of Drug Absorption

Simple diffusion: passive diffusion, no energy required
Active transport: requires energy to move drugs from low to high concentration
Facilitated diffusion: similar to active transport but doesn't require energy
These mechanisms are used to absorb drugs from specific sites in the small intestine

Pinocytosis

Cells engulf fluid or particles
Cell membrane encloses the substance, fuses, and forms a vesicle that moves to the cell interior
Requires energy
Plays a minor role in drug transport, except, for protein drugs

Bioavailability

Fraction of the administered dose that reaches the systemic circulation
Bioavailability can be reduced by:
- Drug destruction in the gut
- Incomplete drug absorption
- Drug destruction by the gut wall
- Drug destruction by the liver

Determining Bioavailability

Intravenous drugs have an absolute bioavailability of 1 (100%)
Bioavailability of drugs administered through other routes is typically less than 1.

Capillary Structure

Most capillaries are "leaky" and allow for easy diffusion of drugs
The blood-brain barrier (BBB) is formed by tight junctions between cells in the brain
The BBB is impermeable to most water-soluble drugs

Protein Binding

Many drugs bind to plasma proteins in the bloodstream, limiting drug distribution
The most important binding proteins are: albumin, alpha-1 acid glycoprotein, and lipoproteins
Drugs travel in blood as both free drug and bound drug
Plasma protein binding reduces drug diffusion

Blood-Brain Barrier

Drugs reach the central nervous system (CNS) via brain capillaries and cerebrospinal fluid
The BBB consists of brain capillary endothelium and astrocytic sheath
Tight junctions between endothelial cells in the BBB limit diffusion of water-soluble drugs
Lipophilic, positively-charged, and low-molecular weight drugs (under 400-600 Da) can cross the BBB

Elimination

Irreversible removal of parent drugs from the body
Includes drug metabolism (biotransformation) and excretion

Drug Metabolism

Liver is the main site of drug metabolism
Chemical modifications of drugs to facilitate their removal from the body
Enzymes typically catalyze drug metabolism
Metabolism processes include: oxidation, reduction, hydrolysis, hydration, conjugation, condensation, and isomerization

Liver as Site of Drug Metabolism

The liver receives all the blood from the body, making it the primary site for drug metabolism

Cytochrome P-450 (CYP450)

The most important enzyme system for phase I metabolism
A superfamily of microsomal isoenzymes responsible for the oxidation of many drugs
Can be induced or inhibited by interactions with other drugs or substances, affecting drug levels

CYP Enzyme Family

Located in the liver, small intestine, lungs, kidneys, and placenta
Consists of more than 50 isoforms
Responsible for most drug oxidation
6 main enzymes: CYP1A2, CYP2D6, CYP2C9, CYP2E1, CYP2C19, CYP3A4
CYP oxidase activity varies significantly between individuals

Phase II Metabolism

Prepares chemicals for phase II metabolism and excretion via conjugation
Detoxication step in drug metabolism
Glucuronidation is the most common phase II reaction and the only one that occurs in the liver's microsomal enzyme system

Conjugation Reactions

Glucuronidation, sulfation, acetylation, amino acid conjugation, glutathione conjugation, fatty acid conjugation, and condensation reactions

Phase I & II Summary

Drug metabolites are typically more water-soluble
Conjugation aids in renal excretion
Drug metabolism rates vary significantly between individuals
Rapid metabolizers may not reach therapeutic levels
Slow metabolizers can experience toxic effects at normal doses

Excretion

Process of removing unwanted substances from the body
Most common routes: biliary or renal
Other routes: lungs (exhalation), skin (perspiration)
Lipophilic drugs may require several metabolism steps before excretion

Renal Excretion

Kidneys are the most important organs for drug excretion
Glomerular filtration removes about one-fifth of plasma, with water and electrolytes reabsorbed
Most polar compounds and metabolites are not reabsorbed and are excreted
Blood cells, platelets and plasma proteins are retained in the blood

Active Tubular Secretion

Active tubular secretion in the proximal tubule is important for drug elimination
Energy-dependent process and can be inhibited by metabolic inhibitors
Secretion capacity has a transport maximum

ADME Summary

Describes the comprehensive processes of drug absorption, distribution, metabolism, and excretion (ADME)

Drug Research and Development

Develops a new medicine over 10-15 years
Success rate is approximately 10%
Costs between $800 million and $1 billion dollars

Reasons for Drug Failure

Drugs may not be effective or safe for clinical use

Importance of Pharmacokinetic Studies

Essential for ensuring:
- Appropriate dosing to avoid accumulation of toxic drugs
- Effective drug doses for therapeutic benefit
- Efficient drug delivery considering rapid metabolism

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Description

This quiz explores the history and effects of opioids, including heroin and morphine. It examines the roles of opioid receptors and the consequences of opioid use, such as pain relief and the risks of dependence. Test your knowledge on this important topic in pharmacology and pain management.