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Questions and Answers
What effect does ionisation have on weak bases like morphine in acidic brain environments?
What effect does ionisation have on weak bases like morphine in acidic brain environments?
Which of the following phases of drug metabolism involves the transformation of lipophilic drugs into more hydrophilic substances?
Which of the following phases of drug metabolism involves the transformation of lipophilic drugs into more hydrophilic substances?
Which characteristic of a drug primarily affects its renal excretion?
Which characteristic of a drug primarily affects its renal excretion?
What role do liver enzymes play in drug interactions during metabolism?
What role do liver enzymes play in drug interactions during metabolism?
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What type of drug metabolism is mainly associated with genetic polymorphism?
What type of drug metabolism is mainly associated with genetic polymorphism?
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What is the primary determinant of drug absorption in the gastrointestinal tract?
What is the primary determinant of drug absorption in the gastrointestinal tract?
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Which route of administration is least affected by first-pass metabolism?
Which route of administration is least affected by first-pass metabolism?
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What effect does food have on the bioavailability of sparingly lipid-soluble drugs?
What effect does food have on the bioavailability of sparingly lipid-soluble drugs?
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Which type of drug primarily binds to α1-acid glycoprotein?
Which type of drug primarily binds to α1-acid glycoprotein?
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Which of the following drugs has the highest bioavailability after oral dosing?
Which of the following drugs has the highest bioavailability after oral dosing?
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Which barrier is NOT typically associated with drug distribution in the body?
Which barrier is NOT typically associated with drug distribution in the body?
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Which factor affects glomerular filtration most significantly?
Which factor affects glomerular filtration most significantly?
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What is commonly the result of first-pass metabolism on drugs administered orally?
What is commonly the result of first-pass metabolism on drugs administered orally?
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How does active secretion in the proximal tubule differ from glomerular filtration?
How does active secretion in the proximal tubule differ from glomerular filtration?
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Which body compartment is primarily affected by protein binding of drugs?
Which body compartment is primarily affected by protein binding of drugs?
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What is the effect of lipid solubility on drug excretion?
What is the effect of lipid solubility on drug excretion?
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Which of the following factors does NOT affect drug excretion?
Which of the following factors does NOT affect drug excretion?
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Which type of drugs are primarily cleared by forming active secretion pumps?
Which type of drugs are primarily cleared by forming active secretion pumps?
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Which condition is likely to reduce glomerular filtration rate?
Which condition is likely to reduce glomerular filtration rate?
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What does the phrase 'one dose for all' imply in pharmacokinetics?
What does the phrase 'one dose for all' imply in pharmacokinetics?
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Which of the following factors is least likely to influence renal function?
Which of the following factors is least likely to influence renal function?
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Which of the following are considered poor metabolizers according to genetic polymorphism involving CYP2D6?
Which of the following are considered poor metabolizers according to genetic polymorphism involving CYP2D6?
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What is the main role of CYP2D6 in drug metabolism?
What is the main role of CYP2D6 in drug metabolism?
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Which of the following drugs is listed as an inhibitor of Cytochrome P450?
Which of the following drugs is listed as an inhibitor of Cytochrome P450?
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What is the consequence of combining midazolam with erythromycin based on drug interactions?
What is the consequence of combining midazolam with erythromycin based on drug interactions?
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What type of compounds are formed during N-dealkylation and hydroxylation processes?
What type of compounds are formed during N-dealkylation and hydroxylation processes?
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What is the relationship between a pro drug and its hydrolyzed metabolite?
What is the relationship between a pro drug and its hydrolyzed metabolite?
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Which enzyme is primarily involved in the hydrolysis of ramipril to its active form?
Which enzyme is primarily involved in the hydrolysis of ramipril to its active form?
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Which of the following best describes the effect of rifampicin when co-administered with midazolam?
Which of the following best describes the effect of rifampicin when co-administered with midazolam?
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Study Notes
Pharmacokinetics (ADME)
- Pharmacokinetics is the study of how drugs are absorbed, distributed, metabolized, and excreted.
1. Absorption
- Absorption is how drugs enter the bloodstream
- Includes oral cavity, pharynx, esophagus, stomach, small intestine, and other sites.
- Different drug delivery methods have different rates of absorption.
- Factors affecting absorption include the drug's properties (lipid solubility, ionization), the route of administration, and physiological conditions.
2. Distribution
- Distribution is how drugs are transported throughout the body
- Drugs are transported in the blood via the circulatory system.
- Factors affecting distribution include blood flow, drug binding to proteins, and the presence of barriers to the drug's passage (e.g. Blood Brain Barrier).
3. Metabolism
- Metabolism of drugs involves their chemical alteration in the body.
- Primarily occurs in the liver.
- Liver enzymes change drug structure
- Lipid-soluble drugs get converted to water-soluble forms(hydrophilic)
- This process can make a drug safer or more effective.
- Factors affecting metabolism include the presence of other drugs (drug interactions), genetic factors, and liver function.
4. Excretion
- Excretion is the removal of the drug or its metabolites from the body.
- Primarily occurs in the kidneys.
- Can also occur in the liver, lungs, sweat glands, etc.
- Two main routes: glomerular filtration and tubular secretion
- Drugs are filtered out through the nephron of the kidney.
Routes of Administration
- Various methods include intravenous, intramuscular, subcutaneous, topical, and oral among others.
- Factors like rapid or sustained effect, first-pass metabolism, and targeted delivery play a role.
- Oral administration may involve first-pass metabolism (50%). First-pass metabolism is when a drug is absorbed from the intestines and then goes through the liver, before reaching systemic circulation.
1. Drug Absorption
- Gastrointestinal tract is the primary site for oral drug absorption.
- First-pass metabolism can decrease bioavailability and the amount of drug reaching systemic circulation.
- Bioavailability is the proportion of administered drug reaching the systemic circulation.
(i) Gastrointestinal Tract
- Drugs can be absorbed via sublingual and oral routes using different forms.
- Rectal administration of suppositories and foams is another way of administration.
Gastric Emptying and Intestinal Surface Area
- Gastric emptying rate is a key factor in drug absorption from the gastrointestinal tract.
- The large surface area of the small intestine is important for drug absorption.
(ii) First-Pass Drug Metabolism
- Drugs absorbed from the gut enter the hepatic portal system and are metabolized by liver enzymes.
- Some drugs, therefore, lose potency or are rendered ineffective following this first pass through the liver. This is an important consideration during drug development and use.
(iii) Bioavailability
- Bioavailability of a drug is the fraction of a dose reaching systemic circulation.
- Factors affecting bioavailability include drug absorption, first-pass metabolism, and other factors.
- Food can influence bioavailability by affecting absorption.
2. Drug Distribution
- Protein Binding: Drugs can bind to proteins in the blood or in tissues, influencing their distribution and activity.
- Blood Flow: Blood flow to tissues affects the rate at which drugs reach target locations.
- Body Compartments: Drug distribution varies across different body compartments.
- Blood-Brain Barrier: The blood brain barrier limits certain drugs’ access to the brain
- Placental Barrier: The placental barrier limits drug entry into the fetus.
- Cell Membrane: Drug movement through cell membranes is crucial for drug action
(i) Protein Binding
- Acidic drugs bind primarily to albumin proteins in the blood.
- Basic drugs bind mainly to a₁-acid glycoprotein.
(ii) Blood Flow
- Rate of perfusion and membrane permeability will determine the rate at which drugs are deposited in specific tissues.
- Higher perfusion rate will cause faster distribution of drug.
(iii) Body Compartments
- Drugs accumulate in certain body compartments more than others.
- Blood-brain barrier prevents drugs’ penetration into the central nervous system.
- Acidic drugs can be ‘trapped’ in acidic regions.
(iv) Body Compartments: Placental Barrier
- The placental barrier affects the entry of certain drugs from the mother to the fetus.
- The lipid solubility of a drug relates to its ability to cross membrane barriers.
(iii) Cell Membrane
- Factors like the drug's lipid solubility, and properties affect the crossing of cell membranes.
- Drugs cross membrane barriers by passive diffusion/active transport etc.
3. Drug Metabolism
- Lipid solubility: Fat-soluble drugs need to be converted to water-soluble forms to be excreted.
- Phase I drug metabolism: Oxidation, reduction, or hydrolysis reactions that chemically alter the drug molecule to make it more hydrophilic or to facilitate further metabolism, mostly in the liver.
- Phase II drug metabolism: Conjugation reactions such as glucuronidation, sulfation, etc., further modify the drug to increase its water solubility and make it easier for excretion.
- Liver enzymes: Drug interactions occur involving liver enzymes that metabolise drugs.
- Genetic polymorphism: Variations in genes encoding liver enzymes can affect drug metabolism.
- Prodrugs: These are inactive drugs that are converted to active forms by the body.
4. Drug Excretion
- Kidneys are the main organs for drug excretion.
- Processes include glomerular filtration, active tubular secretion, and passive reabsorption.
- Factors like drug solubility and renal function influence the removal of drugs.
(i) Glomerular Filtration
- Drugs are filtered out through glomeruli in the kidneys.
- Lipid solubility and molecular size affect the filtering process.
- Unbound filtered drugs are excreted in the urine and unbound drugs are best filtered.
(ii) Active Tubular Secretion
- Drug molecules are actively pumped into the tubule of a nephron.
- This process clears drugs and their metabolites from the bloodstream
- Drug specificity will depend on their structure and properties.
(iii) Passive Tubular Diffusion
- Passive flow of drugs across gradients across the tubes in a kidney, depending on their lipid solubility.
Response to Drugs
- Drug response can vary greatly among patients and will depend on their characteristics.
- Genetic, age, and lifestyle factors influence drug responses.
- "One dose for all" is therefore not suitable in all cases.
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Description
Explore the critical concepts of pharmacokinetics, focusing on the processes of absorption, distribution, metabolism, and excretion of drugs. Understand how various factors influence these processes and their significance in medicine. This quiz will test your knowledge on how drugs interact within the body.
