L8 Metabolism and Drug Design

C-oxidation is involved in the dealkylation processes for various compounds, including drugs like PGE1 and Warfarin.

N- and S-oxidation reactions are facilitated by electron withdrawing properties that increase their reactivity.

Flavin mono-oxygenase is involved in oxidations, while epoxide hydrolase assists in hydrolyses.

<p>Glucuronidation increases both the reactivity and size of drugs, making them more water-soluble.</p> Signup and view all the answers

<p>Glucuronidation enhances reactivity and increases molecular size, while sulphonation primarily increases water solubility.</p> Signup and view all the answers

<p>Genetic polymorphism of drug metabolising enzymes affects drug metabolism by causing variability in enzyme activity among individuals.</p> Signup and view all the answers

<p>As individuals age, liver and heart function may decline, leading to altered drug metabolism.</p> Signup and view all the answers

<p>Variability in drug metabolism due to genetic and age factors necessitates a tailored approach in drug development.</p> Signup and view all the answers

<p>An 'ideal' drug should be readily absorbed after oral administration, not metabolized, have a high therapeutic efficacy, an extensive therapeutic window, and an optimal plasma half-life.</p> Signup and view all the answers

<p>Oral administration is preferred because it has better patient compliance compared to forms like injections or suppositories.</p> Signup and view all the answers

<p>High-affinity binding is significant because it ensures that the drug binds specifically to its pharmacodynamic target, minimizing off-target effects.</p> Signup and view all the answers

<p>Drug metabolism can lead to drug interactions as the enzymes that metabolize drugs can be influenced by other compounds, altering the drug's effectiveness or toxicity.</p> Signup and view all the answers

<p>Drug metabolizing enzymes are crucial in drug development as they help to determine the metabolic pathways and potential toxicity of new chemical entities (NCEs).</p> Signup and view all the answers

<p>Both endogenous and exogenous compounds influence metabolism as cells have evolved enzymes to detoxify and process these substances, which can affect drug efficacy and safety.</p> Signup and view all the answers

<p>A long plasma half-life implies that the drug remains in the bloodstream for an extended period, potentially leading to cumulative exposure and toxicity if not properly managed.</p> Signup and view all the answers

<p>An NCE might be particularly susceptible to drug metabolism due to the presence of various endogenous enzymes that target foreign substances for detoxification.</p> Signup and view all the answers

<p>Cytochrome P450 isoforms are responsible for more than 90% of xenobiotic oxidation reactions.</p> Signup and view all the answers

<p>A drug with an OH group can proceed directly to conjugation and may not require conjugation if it is sufficiently soluble.</p> Signup and view all the answers

<p>The main reactions include oxidation, reduction, and nucleophilic trapping processes.</p> Signup and view all the answers

<p>Glutathione protects against free radicals through nucleophilic trapping processes.</p> Signup and view all the answers

<p>Cytochrome P450 enzymes are primarily located in the smooth endoplasmic reticulum.</p> Signup and view all the answers

<p>Cytochrome P450 reductase provides the necessary electrons for the catalytic cycles of cytochrome P450 enzymes.</p> Signup and view all the answers

<p>Cofactors like PAPS, acetyl coenzyme A, UDP-glucuronic acid, and S-adenosylmethionine are involved in conjugation.</p> Signup and view all the answers

<p>They are haem-thiolate proteins that exist in multiple isoforms.</p> Signup and view all the answers

<p>*2</p> Signup and view all the answers

<p>*3</p> Signup and view all the answers

<p>Gilbert's syndrome; mild bilirubin glucuronidation deficiency.</p> Signup and view all the answers

<p>Renal function declines, leading to decreased drug excretion.</p> Signup and view all the answers

<p>Liver blood flow decreases by 0.5-1.5% per year, impacting metabolism capacity.</p> Signup and view all the answers

<p>Polymorphisms in Phase 2 - UGTs.</p> Signup and view all the answers

<p>Bilirubin buildup causes jaundice; UV treatment helps break it down.</p> Signup and view all the answers

<p>Africans</p> Signup and view all the answers

<p>Neonates exhibit 30-50% CYP activity of adults, which affects drug metabolism and clearance.</p> Signup and view all the answers

<p>Phase I and Phase II metabolic pathways reach maturity around 2 to 3 years of age.</p> Signup and view all the answers

<p>UGT1A1 is activated 24 hours after birth and plays a crucial role in bilirubin metabolism, contributing to jaundice in neonates.</p> Signup and view all the answers

<p>Prodrugs enhance drug permeability and are converted into the active form within the body, improving therapeutic effects in neonates.</p> Signup and view all the answers

<p>L-DOPA has an amino acid group that allows it to be taken up by amino acid transporters at the blood-brain barrier, where it is converted to dopamine.</p> Signup and view all the answers

<p>Neonates are more efficient at glutathione conjugation than adults, as they rely less on mitochondrial metabolism.</p> Signup and view all the answers

<p>Premature babies exhibit reduced renal clearance compared to full-term neonates, affecting drug excretion.</p> Signup and view all the answers

<p>Enalapril is an ACE inhibitor that improves oral availability, while Xeloda is an anti-cancer agent with reduced toxicity.</p> Signup and view all the answers