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51 Cards in this Set
- Front
- Back
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What does the lipophilic nature of drugs allow?
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-Passage through biological membranes
-Allows absorption -Access to site of action -Hinders exretion |
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Is the hydrophilic drug ionized?
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Yes, so it can be trapped in urine and excreted
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Is the lipophilic drug ionized?
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No, it is unionized so it can cross membranes and be absorbed
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If a drug is bound by a protein can it be filtered?
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No
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Will a lipophilic drug be reabsorbed?
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Yes
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What is back diffusion?
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Passive reabsorption; lipid soluble, unionized drugs are reabsorbed
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What is biotransformation?
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Biotransformation is the process by which the chemical structure of a drug is changed to another form called the metabolite
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What organ is responsible for biotransformation?
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The liver
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Name three properties of metabolites
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-More water soluble
-More easily excreted by kidneys -Frequently inactive |
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Name the sites of biotransformation in descending order of popularity
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Liver
Lung Kidney Intestine |
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The duration and intensity of a lipophilic drug is limited by what?
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Its rate of metabolism
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When does metabolism activate a drug?
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When it's a prodrug
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Examples of prodrugs?
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Codeine and anti-cancer drugs
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T/F: Metabolites are more stored in fat
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FALSE
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T/F: Metabolites are less lipid soluble
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True; there become more water soluble
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T/F: Metabolites are more ionizable at physiologic pH
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True so that they can be trapped in the urine to be excreted
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T/F: Metabolites are bound to plasma proteins
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False; less bound to plasma proteins so they can be excreted
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T/F: Metabolites are less able to penetrate cell membranes
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True
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What damage does acetaminophen do?
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Causes hepatic necrosis
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What does penicillin do?
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Allergic reactions because the reactive intermediate covalently binds to protein or DNA
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What is the major pathway in acetaminophen metabolism?
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Glucuronidation & sulfation
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What is the backup pathway for acetaminophen metabolism?
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Glutathione conjugation
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What does Phase I metabolism do?
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Alters the drug to a more polar metabolite; if polar enough it may be excreted; oxidation, reduction & hydrolysis; (generally adds -OH to drug)
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What does Phase II metabolism do?
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Conjugation; adds something to the -OH group; forms highly polar, inactive metabolite that is renally excreted
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Please list Phase II reactions (5)
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-Glucuronidation
-Acetylation -Glutathione conjugation -Glycine conjugation -Methylation |
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T/F: All drugs have to go through Phase I before Phase II
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False, some can go directly to Phase II
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Where are P450 enzymes found?
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Endoplasmic Reticulum
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What kind of protein is P450?
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Hemoprotein; contains oxygen; that's why its able to add -OH group to drug in Phase I reactions
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Why CYP metabolized ~50% of clinically used drugs?
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CYP3A4
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Where is CYP3A4 found?
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liver and intestines
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Which CYP is susceptible to drug-drug interactions?
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CYP3A4
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Most important inducer for CYP3A4?
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St. John's Wort
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Biggest inhibitor of CYP3A4 in intestines?
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Grapefruit juice; can decrease activity by ~50%
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Which CYP is involved in the metabolism of antipsychotics and antidepressants?
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CYP2D6
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Which CYP has more than 20 mutant alleles and considerable racial diversity?
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CYP2D6
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Name two drugs that result in toxic metabolites from Phase II metabolism
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NSAIDs and isoniazid
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Where are the enzymes located for Phase II reactions?
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cytosol or microsomes
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Name the substrates that can be attached to drugs in Phase II reactions
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Carbohydrates (glucuronic acid)
Amino acids Sulfates Methyl groups Acetyl groups Glutathione |
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Which metabolism phase is the most frequent?
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Phase II
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What is the name of the enzyme involved in Phase II metabolism? What does it do?
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UDP - uridine diphosphate glucuronosyl transferase;
Catalyzes transfer of glucuronic acid from UDP-glucuronic acid to a drug |
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How is morphine inactivated?
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By glucuronidation
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What type of reaction in Phase II protects cells against toxic injury?
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Glutathione conjugation
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Name of medicine given in acetaminophen overdose?
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N-Acetylcysteine
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Once the drug is metabolized by the liver into a hydrophilic, ionized metabolite, how does it get out of the hepatocyte?
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ABC transporter (P-glycoprotein)
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T/F: Glucuronidation can be increased by P450 induction
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True
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T/F: Induction involved de novo protein synthesis
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True; induction is making more protein through transcription and transclation; it is not reversible
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Can inhibition quickly reverse?
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Yes
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How long does induction take to manifest?
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Hours to days
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T/F: Inhibition decreases plasma concentration of drug
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False, it increases the concentration of a drug
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T/F: Inhibition results in reduced metabolism of produgs
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True
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T/F: Inhibition decreases the potential for drug induced toxicity
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False, inhibition increases the potential for drug induced toxicity
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