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32 Cards in this Set

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pharmacokinetic interaction def
occurs when one drug alters the absorption, distribution, metabolism, or elimination of another.
pharmaceutical interaction def
is a chemical or physical interaction that occurs before a drug is administered or absorbed systemically
pharmacodynamic interaction
occurs when one drug alters the sensitivity of a target receptor or tissue to the effects of a second drug. We commonly classify these interactions by their direction and intensity, that is, additive, antagonistic, or supra-additive (synergistic).
administration of bicarbonate + bupivicaine
precipitation and occlusion of IV
Catecholamine solutions + sodium bicarb
precipitation and inactivation of the catecholamine solution ( norepi, epi)
Danger of using NO w/ oxygen for pulmonary hypertension in the newborn?
formation of Nitrous dioxide, quite toxic, and concentrations >10 ppm can produce pulmonary edema and alveolar hemorrhage. The problem is circumvented by allowing oxygen and NO to mix in the breathing circuit just before administration
tetracycline is inactivated by?
by chelation if it is given together with antacids containing polyvalent cations such as Mg2+, Ca2+, or Al3+.
digoxin should not be given w/
Oral antidiarrheal drugs such as kaolin and pectin can physically adsorb digoxin and prevent it from being absorbed.
warfarin should not be given with?
The bile acid-binding resin, cholestyramine, can bind to warfarin and prevent its absorption. It can also reduce the absorption of vitamin K and other fat-soluble compounds.
drugs in which state ( ionized vs. non-ionized) cross the lipid membranes?
non-ionized
It is apparent from this relationship that a weak base (fentanyl, lidocaine) will be progressively ionized as the pH decreases, whereas a weak acid (aspirin, phenobarbital) will be more nonionized.
weak acids get trapped in
weak bases get trapped in>>.
more basic environment
more acidic environment
why is protein binding important?
because it is only the unbound fraction that is available for crossing membranes, entering tissues, and binding to receptors to produce the pharmacologic effect. Protein-bound drug is not filtered by a normal glomerulus and (for some drugs) is not acted on by drug-metabolizing enzymes. A drug that is highly bound to plasma protein effectively exists in a “depot,”
warfarin protein binding?
98% of drug is protein bound. Drugs that displace the binding alter INR
non-depolarizing drugs and succinylcholine
larger dose required
how is esmolol and remifentanyl metabolised?
hydrolyzed by so-called nonspecific esterases in blood and peripheral tissues.
what are non-specific esterases? and their role in drug-drug interactions?
The nonspecific esterases constitute a large group of isozymes with extremely high capacity and low substrate specificity. This enzyme system is not likely to be involved in drug–drug interactions because inhibition of any one isozyme usually does not affect overall drug clearance.
monamide oxidase, distribution of the enzyme,
function
is distributed throughout the body, with the largest amounts found in the liver, kidney, and brain. MAO is located on the outer surface of mitochondria in the presynaptic terminals of noradrenergic, dopaminergic, and serotonergic neurons in the CNS and periphery. It acts to regulate the presynaptic pool of norepinephrine, dopamine, epinephrine, and serotonin available for synaptic transmission
MAO - A vs MAO-B
MAO exists in two isoforms: MAO-A predominates in the gut wall, whereas MAO-B is the major isoform in the CNS.
MAOi + which drugs can cause serotoninergic syndrome?
SSRIs / meperidine
dextromethorphan,28 and the analgesics, propoxyphene, and tramadol. Other than some poorly documented case reports, the evidence suggests that morphine and fentanyl do not produce this interaction.
Serotonin syndrome?
excitation, hyperpyrexia, hypertension, profuse sweating, and rigidity.26 This may progress to seizures, coma, and death
how long does it take for MAO to regenerate?
2 weeks
lidocaine concentration incrases w/
decreased hepatic blood flow, pressor administration
hepatic clearance =
hepatic blood flow + extraction ratio for a given drug
what is extraction ratio?
extraction ratio (ER)—the fraction of drug that can be metabolized in a single pass through the liver
rate limiting fractors for elimination in drugs w/ high extraction ratio?
hepatic blood flow
rate limiting factor for elimination in drugs w/ low extraction ratio?
enzyme activity ; diazepam, lorazepam
inducers of hepatic metabolism
INDUCERS I
Phenobarbital
Phenytoin
Rifampicin
Carbamazepine
Ethanol
inhibitors of hepatic metabolism
INHIBITORS
Cimetidine
Ketoconazole
Erythromycin
Disulfiram
Ritonavir
role of cimetidine and clearance of drugs?
Cimetidine has an imidazole group that binds to the heme iron of cytochrome P450 and forms an inactive complex. Cimetidine inhibits the metabolism of many drugs, including warfarin, diazepam, phenytoin, and morphine. Several studies have demonstrated that coadministration of cimetidine and diazepam causes clinically significant elevations in the concentration of both diazepam and its active metabolite.49 As stated previously, cimetidine can decrease hepatic blood flow, so it can also decrease the clearance of high-extraction drugs
saquinavir and ritonavir role in drug metabolism?
can inhibit the metabolism of midazolam and fentanyl, respectively, by inhibiting CYP3A4.
antifungals, ketoconazole and itraconazole role in drug metabolism?
They have been shown to decrease the clearance (and increase the toxicity) of glyburide, terfenadine, digoxin, midazolam, theophylline, and warfarin.
a weak base can be excreted in urine when urine is ... ( high or low ph?)
what about the reverse?
excretion can be promoted when the urine is acidified.
weak acid such as phenobarbital is largely nonionized when the urine pH is 6.0. This means that much of the filtered drug is in a relatively lipid-soluble form and available for tubular reabsorption. If the urine pH is raised to 8 or 9 (e.g., with sodium bicarbonate), most of the phenobarbital becomes ionized, reabsorption decreases, and clearance increases