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NU 624

Exam 2 - Metabolic Pathways

What are three types of reactions in Phase I metabolism? Oxidation, reduction, hydrolysis
In pharmaceutical metabolism, the word "substrate" refers to the ______________. Drug
What happens in a Phase I reaction? The original architecture of the drug is changed in preparation for Phase II metabolism.
Phase I metabolism is also referred to as ____________. Biotransformation
What types of enzymes are employed in Phase I metabolism Hepatic microsomal enzymes
What is the major enzyme system of Phase I reactions? CYP450 enzymes
What occurs in an oxidation reaction? Oxygen is added to a molecule, or its oxidative state is changed so the oxygen content is increased
Molecular oxygen contains how many atoms? 2
In an oxidation reaction, the molecule of oxygen is split. What happens to each oxygen atom? One atom oxidizes each molecule of a drug while the other is incorporated into a molecule of water
The loss of an electron is referred to as _____________. Oxidation
Phase I reactions require a (donor/acceptor) electron along with molecular __________. Donor, oxygen
The donor electron in a Phase I reaction occurs in the form of ______________. Reduced nicotinamide adenine dinucleotide
What types of enzymes catalyze both oxidation and reduction reactions in drug metabolism? CYP450
What change occurs when insufficient amounts of oxygen are available to compete for electrons? CYP450 enzymes donate electrons to substrates instead of oxygen
A reduction reaction results in the ___________ of an electron. Gain
What does the reduction of a drug create? Free radicals that can attach to cells
True/False: The reductive metabolism of drugs is not capable of producing harmful products. False - the reduction of drugs creates free radicals that can attach to cells to cause toxic outcomes
What occurs in a hydrolysis reaction? Water is added to an ester or an amide to break a bond and form two smaller molecules
Adding water to an ester creates what two products? Alcohol, acid
Adding water to an amide creates what two products? Amine, acid
True/False: Amide-type drugs are frequently metabolized via hydrolysis. False - Amides rarely undergo hydrolysis
Name 6 commonly used drugs in anesthesia that undergo hydrolysis. Succinylcholine, cocaine, neostigmine, esmolol, remifentanil, cisatracurium
BONUS: Succinylcholine is utilized in __________ for patients who are categorized as ___________. RSI, full stomach
BONUS: What effect does succinylcholine have on vocal cords? Causes relaxation
BONUS: What purpose is neostigmine serve in anesthesia? Reversal of nondepolarizing NMBDs
BONUS: The cholinergic side effects of neostigmine is offset with the use of what two medications? Atropine or glycopyrrolate
BONUS: Which neuromuscular blockers can have their effects reversed? nondepolarizing NMBDs
After undergoing a Phase I reaction, a drug is now (more/less) polar. More
The addition of _______ or _________ groups in Phase I metabolism allows for Phase II reactions to occur. Carboxy, hydroxy
Give 5 examples of oxidation reactions. Hydroxylation, deamination, desulfuration, dealkylation, dehalogenation
What is hydroxylation? Process that introduces one or more hydroxy groups (OH-) into a compound
Give an example of a hydroxylation reaction. A minor metabolite of phenobarbital undergoes aliphatic hydroxylation to turn it into an alcohol
Phenobarbital is converted to an acid by what metabolic process? Aliphatic hydroxylation
What occurs in a deamination reaction? An amino radical is removed from a compound
Give two examples of deamination reactions. 1)Cytosine deaminates to uracil 2)d-methylcytosine deamintes to thymine
What is the process by which epinephrine and norepinephrine are metabolized? Deamination
What is the end metabolite of epinephrine and norepinephrine deamination? Vanyllyl mandelic acid (VMA)
What occurs in a desulfuration reaction? A sulfur atom is removed from a molecule and replaced by an oxygen atom
What types of medications undergo desulfuration reactions? Thiobarbiturates
What does the prefix "thio" indicate in a medication? It contains sulfur
What does the desulfuration of a thiobarbiturate yield? oxybarbiturate
What do oxybarbiturates further break down into? Inactive metabolites
What is the only halogenated alkane? Halothane
What are the methods of metabolism that break down halothane? Oxidation, dehalogenation, reduction
What does the oxidation of halothane produce? TFA
What does the dehalogenation of halothane produce? Inorganic bromine and chlorine
What does the reduction of halothane produce? Fluoride and volatile byproducts
What two conditions must exist for halothane hepatitis to occur? Enzyme induction, hepatocyte hypoxia
What do the volatile byproducts of the reductive metabolism of halothane cause? Hepatoxicity and halothane hepatitis
Phase II reactions are referred to as _____________ reactions. Synthesis
What does the body do in a Phase II reaction? Synthesizes a new compound by donating a functional group
The donated functional group in a Phase II reaction is usually derived from what type of molecule? Endogenous acid
The new compound formed as a result of a synthesis reaction is referred to as a __________. Conjugate
Give examples of common molecules that synthesize with drugs to form compounds that can be eliminated by the body. (5) Glucuronic acid, sulfuric acid, acetic acid, glycine, methyl group
True/False: The products of Phase II metabolism usually have high levels of bioactivity. False
Conjugation yields a (more/less) polar compound. More
The compound produced in a Phase 2 reaction is highly (ionized/nonionized) at physiologic pH and therefore easily extractable by the kidneys. ionized
The hepatic microsomal enzymes responsible for biotransformation reside in the ________________. Smooth endoplasmic reticulum
What does the name “mixed-function oxidase system” refer to? CYP450 enzymes include both oxidation and reduction reactions
How many CYP iso-enzymes in body are responsible for drug metabolism? 6
What are the 6 CYP iso-enzymes that metabolize drugs? 1A2, 2C9, 2C19, 2D6, 2E1, 3A
What accounts for the variability of drug metabolism between individuals? Differences in the amino-acid sequence of CYP iso-enzymes
How is hepatic enzyme activity determined? Genetics and lifestyle habits
What is enzyme induction? The increased activity of hepatic enzymes
What is the usually cause of enzyme induction? Prolonged exposure to drugs or certain chemical compounds
What is one substance that can lead to enzyme induction after repeated exposure? ETOH
What are 4 different drugs that have the ability to cause enzyme induction? Phenobarbital, dilantin, rifampin, carbamazepine
Hepatic enzymes can not only be induced, they can also be __________. Inhibited
What antibiotic inhibits CYP enzyme activity? Erythromycin
What are 2 medications affected by the enzyme inhibiting effects of erythromycin? theophylline, cimetidine
Created by: philip.truong
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