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Chapter 6 - Lehne
Terms in this set (59)
Three possible outcomes of drug interactions
One drug may intensify the effects of the other
One drug may reduce the effects of the other
The combination may produce a new response not seen with either drug alone
When one drug intensifies another drug.
Potentiative effects can be
Benefical, or detrimental
Beneficial potentiative example
Sulbactam and ampicillin.
Alone, ampicillin undergoes rapid inactivation by bacterial enzymes.
Sulbactam inhibites those enzymes, thereby proloning and intensifying ampicillins therapeutic effects.
Adverse potentiative example
Aspirin and warfarin.
Warfarin is an anticoagulant used to suppress formation of blood clots.
Aspirin also suppresses clotting.
Together, the patient has a significant risk of bleeding.
Interactions that result in reduced drug effects
Inhibitory drug interaction can be
beneficial or detrimental
Detrimental inhibitory drug interaction example
Propranolol and albuterol
albuterol is taken for asthma to dilate bronchi.
propranolol can act in the lung to block effects of albuterol
Beneficial inhibitory drug interaction example
Naloxone and morphine
Morphine can produce coma and profound respiratory depression in excess doses.
Naloxone can block morphines actions, thereby reversing all symptoms of toxicity. (overdose)
Creation of a unique response example
Alcohol and disulfiram (used to treat alcoholism)
Together they create a host of unpleasant and dangerous responses not seen by either alone
Four mechanisms drugs can interact by
Direct chemical or physical interaction
Combining two or more drugs in the same container
Never do it, unless it has been established that a direct interaction will not occur.
When do direct interactions occur most commonly
When drugs are combined in IV solution, and it sometimes creates a precipitate.
If a precipitate appears in an IV when drugs are mixed
Discard the solution
When two drugs are taken together, one may alter the others absorption, distribution, metabolism or excretion of the other.
Antacid alters absorption by
Elevates gastric pH, thereby decreasing ionization of basic drugs (can be absorbed easier).
Opposite effect on acidic drugs
Laxatives alter absorption by
Reduces absorption of other oral drugs by accelerating their passage through the intestine.
Drugs that depress peristalsis alter absorption by
Such as morphine and atropine, prolong drug transit time in the intesinte which increases time for absorption.
Vomiting inducing drugs alter absorption by
decrease absorption of oral drugs
Absorbent drugs (cholestyramine) alter absorption by
Absorbing other drugs onto themselves, thereby preventing absoprtion of the other drugs into the blood
Example of a drug that alters absorption by reducing regional blood flow
Epinephrine is injected with a local anesthetic, epinephrine causes local vasoconstriction, thereby reducing regional blood flow and delaying absoprtion of the anesthetic
Two principal mechanisms by which one drug can alter the distribution of another
Competition for protein binding
Alteration of extracellular pH
Competition for protein binding impact altering distribution
Two drugs bind to same site on plasma albumin, this produces competition for binding.
Binding of one or both is reduced, causing plasma levels of free drug use to rise, which causes rapid elimination of the free molecule.
Alteration of extracellular pH on distribution
If a drug increases extracelluar pH, that drug would increase the ionization of acidic drugs in extracellular fluids (plasma and interstitial fluid). as a result, acidic drugs would be drawn from within cells (where the pH was below that of the extracellular fluid) into the extracellular space. Hence, the alteration in pH would change drug distribution
Drugs that increase metabolism of other drugs do so by
Inducing synthesis of hepatic drug-metabolizing enzymes.
Drugs that decrease metabolism of other drugs do so by
Inhibiting synthesis of hepatic drug-metabolizing enzymes
Five isoenzymes responsible for the metabolism of most drugs
drugs that stimulate the synthesis of CYP isoenzymes
Inducing agent example
Phenobarbital - stimulates its own metabolism as well as that of other drugs
Inhibitors mostly result in
toxic effects, by inhibiting metabolism of certain drugs, which results increased plasma levels of that drug
Drugs that induce P-glycoprotein can have the following impact on other drugs
Reduced fetal drug exposure
Reduced brain drug exposure
Increased drug elimination
When a patient discontinues an inducing agent
dosages of other drugs may need to be lowered.
If drug a inhibits the metabolism of drug b
level of drug B will rice.
Interactions that occur at the same receptor are almost always
Two basic types of pharmacodynamic interactions
interactions in which the interacting drugs act at the same site
Interactions in which the ineracting drugs act at seperate sites.
If both drugs influence the same physiologic process
one drug can alter response produced by other
If drug a and drug b are both toxic to the same organ
then taking them together will cause more injury than if they were not combined
Most obvious way to minimize adverse interactions of drugs
minimize number of drugs a patient receives
Second most obvious way to minimize adverse interactions in drugs
Take a thorough drug history
Two ways food impacts drug absoprtion
Decreased the rate of drug absorption, as well as the extent of absorption
Reducing the rate of absorption
delays the onset of effects, peak effects are not lowered.
Reducing the extend of absorption
reduces the intensity of peak responses.
Tetracyclines and calcium containing foods
absorption is reduced and antibacterial (tetracycline) effects may be lost.
High fiber foods can
reduce absorption of some drugs, such as digoxin, resulting in therapeutic failure
High calorie meal and saquinavir
doubles the absorption of saquinavir, and without food, absoprtion may be insufficient for antiviral activity.
Can inhibit the metabolism of certain drugs, thereby raising their blood levels
Grapefruit juice inhibits
Grapefruit juice inhibition is greater in
intestinal isoenzyme than in liver isoenzyme
Grapefruit juice and IVS
little to no effect on drugs administered IV
More grapefruit juice drank
Results in greater inhibition of CYP3A4 (dose dependant)
Grapefruit juice compounds
6'7' dihyroxybergamottin both are furanocoumarins
Both are flavenoids
Inhibition of grapefruit juice lasts
up to 3 days after the last glass.
MAO inhibitors and foods rich in tyramine (cheese, yeast, chianti wine)
Combination can result in life-threatening blood pressure levels
Theophylline and caffeine
Can result in excessive CNS excitation, thus, should be avoided.
Potassium-sparing diuretics and salt substitutes
Can result in dangerously high potassium levels, and therefore, should be avoided.
Aluminum containing antacids and citrus beverages
Can result in excessive absorption of aluminum, thus, should be avoided.
foods rich in vitamin k (broccoli, brussel sprouts, cabbage)
Can reduce the effects of warfarin, because warfarrin inhibits vitamin k-dependent clotting factors.
Best solution if a drug is reduced by food but causes stomach problems
select an alternative drug that doesnt upset the stomach
Administering a drug on an empty stomach means
administer at least 1 hour before a meal or 2 hours after.
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