Pharmacokinetics 4 Flashcards
Co-administration of which drug reduces the observed potency of codeine?
a. diltiazem
b. fluoxetine
c. phenytoin
d. rifampin
B. fluoxetine
The ________ is the most important mechanism of drug biotransformation in the body.
P450 system
_________ can influence the enzymatic activity of the P450 system.
Exogenous chemicals
_________ stimulate the synthesis of additional enzymes
Enzyme inducers
Enzyme inducers _______ drug clearance
increase
Common enzyme inducers include
ethanol
tobacco
phenytoin
barbiturates
rifampin
carbamazepine
_____ compete for binding sites on the enzymes
Enzyme inhibitors
Enzyme inhibitors ______ drug clearance.
reduce
Common enzyme inhibitors include
SSRIs, omeprazole, and grapefruit juice
isoniazid, ketoconazole, erythromycin, cimetidine
The most important cytochrome P450 enzyme is
CYP 3A4 (metabolizes nearly 50% of the drugs we administer)
The P450 system carries out most of the body’s ______ biotransformations.
phase 1
The P450 enzymes are located in the
smooth endoplasmic reticulum of the hepatocyte
also located in extrahepatic tissue such as the lung, kidneys, skin, adrenal gland, and GI tract
________ contribute to variations in enzyme efficiency, and this can affect the observed drug potency from patient to patient.
Genetic polymorphisms
Which statement regarding renal clearance is true?
a. acidic urine promotes thiopental excretion
b. basic urine enhances morphine reabsorption
c. protein-bond drugs are filtered at the glomerulus
d. organic anion transporters secrete drug into the distal convoluted tubule
b. basic urine enhances morphine reabsorption
morphine is a weak base; as a weak base, the non-ionized fraction increases in an alkalotic environment; therefore, basic urine enhances morphine reabsorption
What two processes deliver a drug to the renal tubule?
glomerular filtration
organic ion transporters
__________ are resistant to glomerular filtration.
Highly protein-bound drugs
_________ in the ultrafiltrate tend to be eliminated in the urine.
Hydrophilic drugs
___________ in the ultrafiltrate tend to get reabsorbed into the peritubular fluid.
Liphophilic
Renal clearance is determined by the drug’s
polarity and the pH of the ultrafiltrate
Clearance of drugs such as furosemide, morphine, and dopamine rely on
organic ion transporters located in the proximal renal tubules
__________ influences whether drugs are excreted in the urine or reabsorbed into the peritubular capillaries.
Urine pH
In terms of urine pH and elimination, remember that
like dissolves like!
Acidic urine favors ________ of acid drugs and _______ of basic drugs
reabsorption; excretion
Basic urine favors _______ of basic drugs and ______ of acidic drugs
reabsorption; excretion
Liphophilic drugs must _________ before they can be excreted by the kidneys.
undergo biotransformation reactions to increase their water solubility
Drugs that are not bound to plasma proteins will be __________ by the glomerulus.
freely filtered
Organic anion transporters (OAT) includes
furosemide, thiazide diuretics, and penicillin
Organic cation transporters (OCT) include
morphine, meperidine, and dopamine
What two things will acidify the urine?
ammonium chloride or cranberry juice
Acidifying the urine will help to
eliminate basic drugs
What two things will alkalize the urine?
sodium bicarbonate or acetazolamide
Identify the drugs that are metabolized by nonspecific plasma esterases. (select 3)
a. esmolol
b. atracurium
c. cocaine
d. remifentanil
e. succinylcholine
f. fospropofol
a. esmolol
b. atracurium
d. remifentanil
Enzymatic drug metabolism in the plasma tends to occur via one of three pathways which include
pseudocholinesterase
nonspecific esterases
alkaline phsophatase
Unlike hepatic enzymes, plasma enzymes do not
undergo enzyme induction
Examples of drugs that undergo pseudocholinesterase metabolism include
ester-type local anesthetics, mivacurium, and succinylcholine
Examples of drugs that undergo alkaline phosphatase metabolism include
fospropofol
Examples of drugs that undergo nonspecific esterases metabolism include
remifentanil, esmolol, clevidipine, and atracurium
remimazolam, & etomidate (+ hepatic)
Drugs that undergo Hoffman elimination include
cisatracurium and atracurium (to some degree)
___________ extends the duration of action of succinylcholine, mivacurium, cocaine, and ester local anesthetics.
Pseudocholinesterase deficiency
