Questions and Answers
What is the origin and meaning of the term 'pharmacology'?
The science of drugs, their origins, compositions, pharmacokinetic use, toxicology, etc.
What is the main difference between a 'drug' and a 'medicine'?
A drug is a substance with a biochemical or physiological effect, whereas a medicine is a carefully produced, tested, approved, and regulated substance used to prevent, alleviate, or cure symptoms or disease.
Give an example of a drug derived from a natural source.
Aspirin, derived from the willow tree, is used for its anti-inflammatory effects.
What are the three ways to name a drug?
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Who are the key players involved in the drug development process?
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What is the therapeutic index of a drug?
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Give an example of a drug with a narrow therapeutic index.
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What was a significant discovery in the 1920s that impacted the development of pharmacology?
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What is drug absorption, and which pathway do hydrophilic drugs use to cross the cell membrane?
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What are the two approaches to estimate drug solubility?
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What is the main difference between ABC transporters and SLC transporters?
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What is the purpose of using Caco-2 cells in vitro, and how is it done?
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What are the three in vitro approaches to investigate transporters involved in intestinal efflux of drugs?
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What are the major body compartments in drug distribution?
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How does plasma protein binding affect drug distribution, metabolism, and renal clearance?
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What are the two important plasma proteins for drug binding?
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How does lipophilicity affect drug distribution, and what is an important consideration in obese individuals?
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What is the role of blood flow in drug distribution, and how does it affect the pharmacokinetic behavior of drugs?
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What is the primary function of CYP enzymes in the human body?
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What is the difference between CYP3A4 and CYP2D6?
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What is the outcome of CYP inhibition on drug metabolism?
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What is the role of ritonavir in HIV treatment?
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What is drug excretion, and how does it differ from drug elimination?
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What is Fu, and why is it important in drug excretion?
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What is the primary mechanism of active tubular secretion in renal drug excretion?
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How does urine pH affect drug reabsorption in the kidneys?
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What is the role of CYP enzymes in vitro studies?
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What is the outcome of CYP induction on drug metabolism?
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What are the main characteristics of the blood-brain barrier that limit drug distribution into the brain?
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In which organs are barrier functions present, and what is the role of these barriers?
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What is the role of transporters in hepatic uptake and brain penetration of drugs?
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What is the volume of distribution, and how does it relate to plasma concentration and body compartments?
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Describe the main sites involved in drug metabolism and the role of first-pass metabolism.
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What are the main reactions involved in phase 1 and phase 2 metabolism, and provide examples of each?
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What are the outcomes of drug metabolism, and provide examples of each?
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What are CYP450 enzymes, and what is their role in drug metabolism?
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What is the role of efflux transporters in the blood-brain barrier, and how do they affect drug distribution?
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How do transporters contribute to the poor drug distribution into the brain?
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Describe the process of enterohepatic recirculation of a drug, using morphine as an example.
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What are the two main categories of factors that can influence individual variations in drug response?
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How do CYP single nucleotide polymorphisms (SNPs) affect the metabolism and response to a pharmacologically active parent drug or a prodrug?
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What is the difference between the fraction of excreted drug (Fe) for hepatically cleared drugs and renally cleared drugs?
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What is the approach to determine total body clearance in non-compartmental analysis (NCA)?
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What is drug bioavailability, and how is it determined for an orally administered drug?
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What is the relationship between drug clearance and the volume of plasma?
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What is the significance of hepatic metabolism in the enterohepatic recirculation of a drug?
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Study Notes
What is Pharmacology?
- Pharmacology is the science of drugs, their origins, compositions, pharmacokinetic use, toxicology, etc.
- Distinction between a "drug" and a "medicine":
- Drug: a man-made or natural endogenous molecule with a biochemical or physiological effect on the cell, tissue, or organism.
- Medicine: prevents, alleviates, or cures symptoms or diseases, carefully produced, tested, approved, and regulated.
Sources of Drugs
- Examples of drugs derived from natural sources:
- Willow tree (Salicylates)
- Belladonna (atropine)
- Sweet wormwood (antimalarial drug)
- Examples of drugs derived from synthetic sources:
- Aspirin
Drug Nomenclature
- Names of drugs can be categorized into three types:
- Chemical name
- Generic name (e.g., statin, Prazole, Oxetine, Sartan)
- Brand name
Drug Development Process
- Involves scientists, clinicians, pharmaceutical companies, and regulators
- Key milestones:
- 1920s: Banting and insulin for treatment
- 1928: Alexander discovers penicillin in mould
Key Pharmacological Concepts
- Therapeutic index: the ratio of the blood concentration at which a drug causes death or toxicity to the amount that causes a therapeutic effect
- Drug absorption:
- Process by which a drug moves from its site of administration to the systemic circulation
- Factors affecting oral absorption: physicochemical properties, biological factors, and transporters
Drug Distribution
- Reversible passage of drugs between tissues, organs, and compartments
- Major body compartments: intravascular fluid, interstitial fluid, intracellular fluid, and body fat
- Factors influencing drug distribution:
- Solubility
- Local pH
- Blood flow
- Tissue binding
- Plasma protein binding
- Important plasma proteins for drug binding:
- Alpha1 acid glycoprotein
- Human serum albumin (HSA)
Drug Metabolism
- Chemical change of a drug into one or more products in the body
- Main sites involved: liver and gut wall (first-pass metabolism)
- Phase 1 metabolism: lipophilic drugs are metabolized to become more hydrophilic
- Examples: oxidation, hydrolysis
- Phase 2 metabolism: hydrophilic drugs are converted into more hydrophilic products for renal excretion
- Examples: glucuronidation
- Outcomes of drug metabolism:
- Increase molecular size to facilitate renal excretion
- Decrease drug elimination half-life
- Alter pharmacological activity of the parent drug
- Terminate action of the drug
CYP450 Enzymes
- Important family of drug-metabolizing enzymes
- Found on the endoplasmic reticulum of hepatocytes
- Use NADPH and O2 to metabolize xenobiotics/drugs
- Two important CYP450 members:
- CYP3A4: most important enzyme with broad substrate specificity
- CYP2D6: most polymorphic enzyme
Drug-Drug Interactions
- Caused by CYP450-mediated interactions
- Examples:
- Ethanol and paracetamol
- CYP induction (phenobarbital)
- CYP inhibition (ritonavir and cobicistat)
Drug Excretion
- Irreversible physical removal of a drug and its metabolites from the body
- Factors affecting drug excretion:
- Urine pH
- Renal blood flow
- Drug concentration in plasma
- Impaired renal function
- Plasma protein binding
- Molecular size and weight
- Transporters (SLC transporters)
- Routes of drug excretion:
- Renal excretion (kidneys)
- Faeces (bile)
- Breast milk
- Fu: the fraction of drug unbound that is unbound in plasma
Renal Drug Excretion
- Three processes involved:
- Glomerular filtration
- Active tubular secretion
- Passive reabsorption
- Clinical application: importance of urine pH and transporters in renal excretion
Enterohepatic Recirculation
- The metabolizing and reabsorption of a drug back into systemic circulation via hepatic pathways
- Example: morphine
Individual Variations in Drug Response
- Affected by intrinsic and extrinsic factors
- Intrinsic factors: age, genetics, sex, disease status
- Extrinsic factors: concomitant medication, diet, and exposure to chemicals and other environmental causes
CYP Single Nucleotide Polymorphism (SNP)
- Relationship between CYP SNP, phenotype, and metabolism of a pharmacologically active parent drug or a prodrug
- Four types of phenotypes represent metabolizers in the population
Drug Clearance
- How efficiently a drug is eliminated from the volume of plasma
- Relationship between fe and hepatically cleared drugs and renally cleared drugs
- Simple approach to determine total body clearance in non-compartmental analysis (NCA)
Drug Bioavailability
- The fraction of the administered dose that reaches systemic circulation
- To calculate the bioavailability of orally administered drugs, use the formula: F = AUCoral / AUCiv
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Test your knowledge of pharmacology basics, including the origin of the term, differences between drugs and medicines, and key concepts in drug development.