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