Drug Interactions Flashcards
drug interactions in vitro commonly occur from
formulation or combination of drugs in IV bags in hospital settings
facotrs which impact absorption in the intestines (2)
- pH changes
- alter ration of ionized: non-ionized forms of a drug
- motility
- delayed gastric emptying and reduced gut motility delay absorption
non-ionized drugs are more lipid soluble and therefore more readily absorbed True or false
true
Factors affecting drug interactions in the intestines include
- ionic interactions
- drug drug absorption interactions
- effect of diet
- kitamin k
- enterohepatic shunt
ionic interactions in the intestine impact drug interactions and reduce effectiveness by
- forming inactive complexes with divalent or triavlent ions
- e.g. tetracycline and milk or antacids (Ca2+, Mg3+)
- interfering with absorption of aspirin, warfarin by acidic molecules
warfarin is inhibited by
pentobarbitone
high fat diets are an example of how diet can enhance solubility of lipid soluble drugs and cause
- can cause drug ineffectiveness if drug is not intended to be absorbed in GIT
- may cause systemic absorption causing more toxicity
grapefruit juice is another example of the effect of diet on drug interactions and causes
agumented oral bioavailability of CYP3A4 drugs
coumarin and indanedione anticoagulants are Vitamin K
antagonists
interactions of drugs with vitamin K antagonists cna lead to what
bleeding episodes
these drugs reduce the absorption of vitamin k
- chloramphenicol
- chlortetracycline
- neomycin
use of antibiotics with people on coumadin are challegning as they
reduce the microbial synthesis of vitamin K which causes plasma levels to drop potentiating the anticoagulant activity of warfarin
the enterohepatic shunt allows for
- the recirculation of drug secreted into the bile back into the intestine where it re-enters circulation
- this causes increased persistence of drug and increased duration of action
these drugs inhibit the enterohepatic shunt and may cause failure of contraceptives
antimicrobials
what is the hERG channel
- human ether-agogo related gene
- cardiac potassium channel
what is the major difference b/t hERG and normal potassium channels
- gating kinetics
- hERG channel target for Class III antidysrhthmic drugs
individuals with genetic abnormalities in hERG channels predispose them to
Long QT syndrome
Long QT syndrome is
- long QT interval
- ventricular dysrythmia
- torsades de Pointes (sudden ddeath)
what is acquired long QT syndrome caused by
- electrolyte imbalances (potassium and magnesium)
- hERG channel drug use
what are some examples of drugs which target hERG as their mechanism of action
- antidysrhythmic drugs
- amiodarone
- quinidine
- procainamide
- chlorpormazine
- haloperidol
- erythromycin
- clarithromycin
enzyme induction related drug interactions occur when
one drug has the ability to induce enzymes responsible for the metabolism of other drugs
chronic administration of a drug can cause tolerance by
inducing enzymes responsible for the metabolism of the drug
what are two drugs that are examples of enzyme induction and drug interaction, and what happens
- barbituates and anticoagulants
- enzyme induction by the administration of barbituates causes the metabolism of vitamin K anticoagulants reducing their effectiveness
True/False: drug interactions can occur when two structurally similar drugs compete for the same enzyme
what is an example
- True
- trycylic antidepressants and phenothiazine tranquilizers
- e.g. amytriptyline and phenotiazine
in the case of amitryptiline and phenothiazine tranquilizers, what happens when enzyme inhibition via competion occurs
- the activity of the tricyclic can be inhibited
- the drug is not metabolized
- antidepressants inhibitors of catecholamines which increase sympathetic effects
- increased hypertension, cardiac events
Monoamine oxidase inhibitors (MAOIs) can
- reduce sympathetic drive
- enhace parasympathetic drive
- interact with many foods
after treatment with an MAOI there is a build up of noradrenaline in the nerve terminal and a greater release of noradrenaline which causes
hypertensive crisis, hemorrhage and cerebral bleeding/stroke
these drugs are contraindicated with MAOIs as their affect can be enhanced
- amphetamine
- ephedrine, pseudoephedrine (cough syrups)
many drug interactions occur because of mixed function oxidase system
cytochrome P450
CP450 metabolism mainly occurs in the
liver
CP450 enzymes also exist in
intestines, lungs, orther organs
poor metabolizers of drugs are at risk because
- drug may accumulate to toxic levels due to inability to metabolize
- cannot change a prodrug into its active form
- or have less response
what are some of the different types of cytochome P450 isoforms
- CYP2D6
- CYP1A2
- CYP2E1
- CYP3A
- CYP3A4
drugs which are bound to albumin are active or inert
inert
True/False: drug interactions can commonly occur due to displacement of drugs bound to plasma proteins increasing the soluble concentraton
True
how is the effect of drug displacement from binding sites calculated
=1+ (% bound + % Displaced)/ (1500 x % unbound)
drug interaction at binding sites can occur as a result of
- competitive antatognism
- physiological antagonism
- physiological addition/augmentation
- drug synergism
- drug interaction at nerve terminal
drug interaction by competitive antagonism occurs when
- an agonist and antagonist are competing for the same receptor site
why is drug interaction by competitive antagonism unlikely to occur
- the clinician would be prescribing drugs to do opposite things
physiological antagonism is when
the action of one drug at a recoptor site opposes the actions of a drug at a different receptor site
thiazide diuretics promote loss of K+ and convert a normal dose of cardiac glycosides to a fatal toxic dose. this is an example of what type of drug interaction
physiological augmentation
effect produced by a combination of two or more drugs is greater than the effect of each on its own
drug synergism
e.g. alcohol and antihistamines
