SM_145b: GI Absorption and Metabolism / Pharmacology Review Flashcards
____ is the main criterion for choosing the route of administration
Bioavailability is the main criterion for choosing the route of administration
____, ____, and ____ are best routes for administration of drugs
Intravenous, intraosseous, and endotracheal are best routes for administration of drugs
Most drugs in clinical use are ____ and ____
Most drugs in clinical use are weak acids and bases
- Exist in ionized and non-ionized forms
- Non-ionized form is more lipid soluble -> preferentially penetrates lipid membranes
Proportion of ionized to non-ionized forms of a drug can be determinated by the ____
Proportion of ionized to non-ionized forms of a drug can be determinated by the Henderson-Hasselbach equation
pH = pKa + log ([conjugate base] / [acid])
Most ibuprofen is in the ____ form in the stomach
Most ibuprofen is in the protonated form in the stomach
pH differences across the gastric cell membrane lead to ____
pH differences across the gastric cell membrane lead to ion trapping
Uncharged form of ibuprofen is near 100% in the ____ and 1% in the ____
Uncharged form of ibuprofen is near 100% in the stomach and 1% in the small intestine in the intestine
- Surface area of intestines is several thousand times larger than that of the stomach
- Large surface of the small intestines accounts for increased drug absorption
- Longer transit times: <1 hr in stomach and >3 hr in small intestine also contributes
Ibuprofen largely absorbed from intestine
____ is the fraction of an administered dose of unchanged drug that reaches the systemic circulation
Bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation
- Metabolism in either the intestinal wall or liver before the drug can reach the systemic circulation reduces bioavailability
First pass metabolism via CYPs occurs in the ____ and ____
First pass metabolism via CYPs occurs in the small intestine and liver
Describe drugs with high bioavailability
Drugs with high bioavailability
- Acetaminophen
- Amoxicillin
- Codeine
- Diazepam
- Metronidazole
- Trimethoprim
- Warfarin
Describe drugs with low bioavailability
Drugs with low bioavailability due to first pass metabolism
- Morphine
- Demerol
- Lidocaine
- Nitroglycerin
- Propranolol
Phase I of drug metabolism requires ____, while phase II involves ____
Phase I of drug metabolism requires CYP450 enzymes, while phase II involves conjugation pathways
Phase I metabolism most commonly involves ____, while phase II metabolism is most commonly ____
Phase I metabolism most commonly involves CYP3A4/5, while phase II metabolism is most commonly glucuronidation
Morphine-3-glucuronide is ____, while morphine-6-glucuronide is ____
Morphine-3-glucuronide is inactive, while morphine-6-glucuronide is active
Clh = ____ x ____
Clh = Qh x E
Hepatic clearance = hepatic blood flow x extraction ratio
Protein binding to drugs ____ and ____
Protein binding to drugs lowers the effective concentration and slows the distribution to extravascular sites
- Greater binding: less available free active drug, longer half-life because less metabolized and eliminated
Describe parameters of drugs by extraction
Parameters of drugs by extraction
Cirrhosis ____ drug metabolism and ____ volume of distribution for hydrophilic drugs
Cirrhosis decreases drug metabolism and increases volume of distribution for hydrophilic drugs
- Decreased drug metabolism: decreased clearance for drugs with high extraction ratios, increased bioavailability for drugs with high first-pass metabolism
____ bioavailability is higher and half-life is longer in advanced cirrhosis
Morphine bioavailability is higher and half-life is longer in advanced cirrhosis
- Lower dose and longer inter-dose interval are recommended
- Avoid combining with other sedatives
Describe biliary drug excretion
Biliary drug excretion
- Transfer of drug or metabolites from plasma to the bile through the hepatocytes
- Drugs handled by biliary excretion are eliminated in feces
- Drugs may be excreted into bile either in native form or after metabolism into more polar conjugates
- Bile is released in the gut lumen, from which the native drug can be reabsorbed (enterohepatic cycle)
- Conjugated drug can be liberated by intestinal bacteria and also reabsorbed
Drugs travel from the ____ to the ____, undergo metabolism, and then enter ____ pockets
Drugs travel from the portal vein to the hepatocytes, undergo metabolism, and then enter bile pockets
In the enterohepatic cycle, drugs ____ in the liver to form ____ are secreted into the ____
In the enterohepatic cycle, drugs conjugated in the liver to form glucuronides are secreted into the bile
- Can be cleaved by bacterial B-glucuronidases in the colon to liberate the drug molecule, which is then reabsorbed
- Create a reservoir of 20% of total drug in the body -> can prolong drug half-life
- Examples of recycled drugs: digoxin, morphine, estradiol
Antibiotic treatment can impair recycling of and reduce plasma levels of ____
Antibiotic treatment can impair recycling of and reduce plasma levels of oral contraceptives
Gilbert syndrome is a common genetic disorder of bilirubin conjugation resulting in ____ and ____
Gilbert syndrome is a common genetic disorder of bilirubin conjugation resulting in unconjugated hyperbilirubinemia and episodic jaundice
- Autosomal recessive
- Mutations in glucuronosyltransferase (UGT1A1)
- 80% reduced enzyme activity
- More severe allelic disorder: Crigler-Najjar syndrome
Irinotecan is a ____ that is activated by ____
Irinotecan is a pro-drug that is activated by carboxyesterases
- SN-38 is a cytotoxic topoisomerase I inhibitor
- SN-38 is responsible for dose-limiting toxicity
