shapes and properties of drugs Flashcards
Q: What are the phases of drug metabolism?
A: Phase I metabolism modifies the drug by introducing or unmasking a functional group (e.g., -OH, -NH2), making it more polar and usually more water-soluble. Phase II metabolism involves conjugation with endogenous molecules like glucuronic acid or sulfate, further increasing solubility for excretion.
Q: What is the role of glucuronidation in drug metabolism?
A: Glucuronidation is a Phase II reaction where a drug or its metabolite is conjugated with glucuronic acid, making it more water-soluble and easier to excrete in urine or bile.
Q: What is the significance of the UGT1A1 polymorphism in drug metabolism?
A: The UGT1A1 enzyme is subject to genetic polymorphisms like *28 and *6, which can affect drug conjugation and elimination. Variants like *28 are common in some populations and can lead to increased toxicity if the enzyme’s activity is reduced.
Q: How does the pH of different body compartments affect drug ionization and absorption?
A: Drug absorption is influenced by the pH of the surrounding environment, which affects drug ionization. Only the uncharged form of a drug can pass through biological membranes efficiently. The Henderson-Hasselbalch equation helps predict the ionization state of a drug at different pH levels.
Q: How does P-glycoprotein (P-gp) affect drug disposition?
A: P-gp is an efflux transporter that pumps drugs out of cells, reducing drug absorption in the intestine and increasing drug excretion in the liver and kidney. It can affect the bioavailability and distribution of drugs in the body.
Q: What are the different routes of drug excretion in the body?
A: Drugs and their metabolites can be excreted through urine (renal excretion), bile (biliary excretion), sweat, breast milk, and saliva. The efficiency of these routes depends on factors like drug solubility and transporter proteins.
Q: What is the importance of the therapeutic window in pharmacokinetics?
A: The therapeutic window is the range of drug concentrations in the blood that provides efficacy without causing toxicity. It is critical for determining the correct dosage to achieve therapeutic effects safely.
Q: What is bioavailability, and how is it measured?
A: Bioavailability is the fraction of an administered drug that reaches the systemic circulation. It is measured by comparing plasma drug concentrations after oral administration with those after intravenous administration (AUC_oral/AUC_IV).
Q: How does drug clearance affect dosing regimens?
A: Drug clearance determines how quickly a drug is eliminated from the body, influencing the maintenance dose rate needed to maintain therapeutic plasma concentrations. Clearance is calculated using the formula Cl = Dose / AUC.
Q: What is the role of cholinesterase enzymes in drug metabolism?
A: Cholinesterase enzymes, like acetylcholinesterase (AChE) and butyrylcholinesterase, hydrolyze acetylcholine and other ester-containing drugs, terminating their action. They play a crucial role in regulating neurotransmission and drug metabolism.
Q: What are kinase inhibitors, and how do they work in cancer treatment?
A: Kinase inhibitors block kinase activity, preventing the phosphorylation of target proteins involved in cell signaling pathways. They are used in cancer treatment to inhibit the growth and survival of cancer cells by targeting specific kinases like BCR/Abl in chronic myelogenous leukemia (CML).
Q: What is the function of G-protein coupled receptors (GPCRs) in opioid signaling?
A: GPCRs, including opioid receptors, mediate the effects of opioids by activating G-proteins, which then initiate intracellular signaling cascades. This can lead to analgesic effects as well as side effects like respiratory depression and addiction.
Q: How do optical isomers of drugs differ in their effects?
A: Optical isomers (enantiomers) have the same chemical composition but different 3D orientations, affecting their interactions with biological targets. For example, the S-isomer of methacholine is more potent than the R-isomer due to its orientation.
Q: What are the different types of binding forces between drug molecules and their targets?
A: Binding forces include covalent bonds, ionic bonds, ion-dipole and dipole-dipole interactions, hydrogen bonds, cation-π and π-π interactions, and hydrophobic interactions. These forces determine the strength and specificity of drug-target interactions.
Q: What is bioisosteric replacement in drug design?
A: Bioisosteric replacement involves substituting one group in a drug molecule with another that has similar physical and chemical properties, to enhance potency, selectivity, or metabolic stability. For example, replacing a methyl group on acetylcholine with an amine to form carbachol.
