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Questions and Answers
What is the result of enzyme inducers on co-administered drugs?
Which of the following is an example of an enzyme inhibitor?
How does age affect drug metabolism in children?
What is the primary route of drug excretion in the body?
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What mechanism describes the action of ligand-gated ion channels?
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What typically happens when drugs are co-administered with enzyme inhibitors?
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Which type of receptors are directly activated by ligand binding to influence gene expression?
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What effect does female sex hormones typically have on drug metabolism?
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What is the significance of active proximal tubular secretion in renal excretion?
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What is one consequence of liver diseases, like cirrhosis, on drug metabolism?
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What is the term for the time from administration of a drug until its effect appears?
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Which type of drug transport involves moving substances against a concentration gradient using energy?
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What factor increases the absorption of a drug in the gastrointestinal tract?
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What is the effect of plasma protein binding on drug distribution?
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Which statement about weak acid drugs is true?
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The therapeutic index (TI) is calculated using which formula?
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What does an increased therapeutic index indicate about a drug?
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Which of the following transportation methods does NOT require energy?
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What is primarily affected in drug absorption by the pH of the environment?
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What happens to warfarin levels when sulfonamides or aspirin displace it from plasma proteins?
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Study Notes
Enzyme Inducers
- Enzyme inducers stimulate selected CYP isozymes, resulting in increased drug biotransformation, leading to increased plasma concentration of metabolized drugs.
- This could intensify the pharmacologic effect of the drugs.
- If inducer drugs are co-administered with other medications, the dose of the other drug might need an adjustment.
- Examples of enzyme inducers include Rifampin, Carbamazepine, Phenobarbital, and Phenytoin.
Enzyme Inhibitors
- Enzyme inhibitors suppress the activity of selected CYP metabolizing isozymes, leading to reduced drug biotransformation.
- This decrease in metabolism can result in increased plasma concentrations of metabolized drugs, potentially leading to toxicity.
- The dose of the other drug may need to be decreased.
- Examples of enzyme inhibitors include Omeprazole, Erythromycin, Ketoconazole, Ritonavir, Cimetidine, and warfarin.
Factors Affecting Drug Metabolism - Age
- Elderly individuals may have reduced enzyme activity due to aging.
- Children have immature enzymes, making them more susceptible to adverse drug effects.
- For example, Chloramphenicol can cause Gray Baby Syndrome in infants due to a deficiency in glucuronide conjugation.
Factors Affecting Drug Metabolism - Sex
- Men generally exhibit higher metabolic rates compared to women.
- Women tend to have decreased metabolism due to the influence of anabolic hormones like estrogen.
Factors Affecting Drug Metabolism - Pathological Condition
- Liver diseases, such as cirrhosis, can significantly impact drug metabolism, leading to a decrease in the rate of metabolism.
Excretion
- Excretion is the process of removing drugs from the body via various routes.
Routes of Drug Excretion
- Primary Route: Kidney (urine)
- Secondary Routes: Bile, Intestine, Lung, Sweat, Tears, Hair, Milk in nursing mothers.
Renal Excretion of Drugs
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Passive Glomerular Filtration:
- Drugs enter the kidney through the afferent renal arteriole and flow into Bowman's capsule.
- Free drugs, not bound to albumin, pass through the glomerular capillary slits into Bowman's space.
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Active Proximal Tubular Secretion:
- Drugs that haven't been filtered in the glomerulus can be actively secreted via energy-dependent transport in the proximal tubules.
- Competition between drugs for these carriers can occur due to structural similarities, influencing excretion rates.
- For example, Probenecid has a higher affinity for the carrier than penicillin, leading to prolonged duration for penicillin.
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Passive Renal Distal Tubular Reabsorption:
- Drugs can undergo passive reabsorption in the distal tubules, depending on their lipid solubility and pH of the urine
Receptors
- Receptors are specific target macromolecules located on cell surfaces or inside cells, interacting with drugs and chemicals.
- They are named according to the drug/chemical that binds best to them (e.g., histamine receptor).
Types of Receptors
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Ligand-gated Ion Channels:
- These receptors control ion movement across membranes.
- Ligand binding causes conformational changes, opening ion channels and activating secondary messengers, leading to a biological response.
- Examples: Nicotinic receptors stimulated by acetylcholine, leading to muscle contractions.
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G protein-coupled Receptors:
- Ligand binding activates a G-protein, initiating a signaling cascade that activates secondary messengers, ultimately resulting in a response.
- Signal amplification: G protein-coupled receptors amplify signals, increasing sensitivity in response to the drug, leading to a stronger and longer-lasting effect.
- Examples: α and β receptors of epinephrine.
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Enzyme (Tyrosine kinase) linked Receptors:
- Receptor activation leads to phosphorylation of tyrosine residues on target proteins.
- This phosphorylation process can modify the function of these target proteins.
- Duration: Minutes to hours.
- Examples: Insulin, Growth hormone, Platelet growth factor.
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Intracellular / Nuclear Receptors:
- Drugs must be lipophilic, enter the cell, bind to intracellular receptors, and then enter the nucleus.
- This binding activates transcription and translation, leading to increased production of specific proteins, which ultimately trigger its effects.
- Duration: Hours to days.
- Examples: Steroid hormones (corticosteroids, testosterone, estrogen, progesterone).
Enzymes
- Drugs can exert effects through chemical reactions (e.g., trimethoprim inhibits DHFR, antacids neutralize heartburn) or physical interactions (e.g., activated charcoal adsorbs other chemicals).
Pharmacology
- The study of drugs, encompassing both biochemical and physiological aspects.
Pharmacokinetics
- The study of what the body does to the drug (ADME: Absorption, Distribution, Metabolism, Excretion).
Onset
- The time it takes for a drug to start producing its intended effect.
- The rate of absorption significantly influences the onset of action.
Duration
- The time period during which the drug's effect is noticeable.
- It's influenced by the rate of metabolism and excretion.
Absorption
- The movement of a drug from its administration site into the bloodstream.
- It is considered complete (100% bioavailability) for IV administration, while other routes have partial absorption (lower bioavailability).
- Drugs can be absorbed through various routes, including passive transport, active transport, or pinocytosis.
Types of Drug Transport
- Passive Diffusion: Movement driven by concentration gradient, no carrier required, no energy consumption.
- Facilitated Diffusion: Movement along concentration gradient, requires a carrier, no energy consumption.
- Active Transport: Movement against concentration gradient, requires a carrier and energy consumption.
- Pinocytosis: Transport of large molecules via engulfment by cell membranes.
- Exocytosis: Process for cells to secrete substances.
Factors Affecting Absorption
- pH: Weak acid drugs are primarily absorbed from the stomach, while weak basic drugs are mostly absorbed from the intestine.
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Physical Factors:
- Blood flow: Higher blood flow increases absorption.
- Total surface area: Larger surface area enhances absorption.
- Contact time: Increased contact time increases absorption.
Distribution
- The reversible movement of a drug from the bloodstream to tissues and interstitial fluid.
- The state of the drug (active, inactive, bound to plasma proteins) influences distribution.
- Active form: Can be metabolized and excreted.
- Inactive form: Not metabolized or excreted, often bound to plasma proteins.
- Plasma Proteins: Act as a reservoir for drugs, providing sustained release of the drug.
Drug Safety (Therapeutic Index)
- LD50: Lethal dose 50 - dose killing 50% of animals.
- ED50: Effective dose 50 - dosage treating 50% of animals.
- Therapeutic Index (TI) = LD50 / ED50: Higher TI indicates a safer drug.
- Drug-drug interactions: Drugs like sulfonamides or Aspirin can displace Warfarin from plasma proteins, increasing free Warfarin, potentially leading to bleeding.
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Description
Test your knowledge on enzyme inducers and inhibitors, their effects on drug metabolism, and the necessary dosage adjustments for co-administered medications. This quiz covers key examples and factors like age that influence drug metabolism. Challenge yourself to understand pharmacologic implications thoroughly!
