Lab 9 Flashcards
The effect that a drug has on a person may be different than expected.
Give 3 reasons why this is the case
the drug may interact with:
-another drug
-food/beverage/supplement
-disease states
name the 3 types of drug interactions
drug-drug
drug-food
drig-disease
true or false
the effects of drug interactions are usually unwanted and sometimes harmful
true
give an example of how the effects of drug interactions are usually unwanted
they may increase or decrease the actions of one or more drugs which results in side effects or failed treatment
individually, drugs can produce effects that are dependent on the _______
dose
the dose of the drug influences the ___ as well as the ____ of the response
nature as well as the magnitude of the response
how can the dose-response relationship be plotted
log dose (x axis) vs response (y axis)
how can the potency of a drug be described
by calculating ED 50 – dose required to produce an effect in 50% of the population
interactions between medications are generally categorized into ____ main categories:
2:
pharmacokinetic interactions
pharmacodynamic interactions
explain the difference between pharmacokinetic and pharmacodynamic drug-drug interactions
pharmacokinetic interactions – one of the drugs influences the ADME of the other or each other. this affects the concentrations at the receptor site/site of action
pharmacodynamic interactions –
drugs influence each other’s effects directly at the receptor level or the site of action
what is polytherapy
the administration of several drugs to a patient
what increases the risk of clinically important drug interactions?
polytherapy, - it increases the complexity of therapeutic management due to increased risk of interactions
true or false
all drug interactions are harmful
false - some are beneficial.
like the drug-food interaction:
a high fat diet taken with ketoconazole improves absorption
drug-drug interaction of probenecid and ampicillin increases ampicillin concentration in the plasma and thus INCREASES ampicillin effectiveness
many interactions have negative effects such as….
-ADR (adverse drug reactions)
-reduce the clinical efficacy
-increase the toxicity
______ interactions are generally evaluated during drug discovery
pharmacodynamic
clinically significant drug interactions are related to the _______- of the drugs
pharmacokinetics
pharmacokinetics describes what
the time course of the drug concentration in the body (normally in blood/plasma)
______ describes the time course of the drug concentration in the body (normally in the blood or plasma)
pharmacokinetics
how can the concurrent use of 2 drugs alter absorption
can influence:
-solubility
-complexation
-intestinal flora
-GI motility
drugs need to be ______ before they can pass through the cell membrane
solubilized
is ketoconazole a weak acid or weak base?
what kind of environment is needed for its dissolution?
weal base
needs an acidic environment for dissolution
what happens when ketoconazole is administered with H2 blockers like cimetidine?
this can increase the pH and thus decrease the solubility through non ionization and decreased absorption
what can improve absorption of ketoconazole?
what can reduce absorption?
high fat content in food bc ketoconazole is a hydrophobic drug
reduce - concurrent use of H2 blockers
what can reduce the absorption of tetracyclines?
cationic antacids form a complex with tetracycline and reduce its absorption
how can warfarin’s activity be increased?
antibiotics decrease bacteria flora in the large intestines. this leads to a reduction in vitamin K — increasing warfarin’s activity
what drug can reduce the absorption of acetaminophen and how?
metoclopramide increases the upper GI motility which thus reduces the absorption of acetaminophen
how can distribution be affected?
by the concurrent use of other agents that compete for protein binding
-many drugs are transported with some of their molecules in free form and the rest bound to plasma proteins – reversibly.
only the unbound molecules are free and pharmacologically active
1 drug may compete with the other and displace it from the sites it already is occupying (depending on the relative concentrations and affinities for the binding site)
give a specific example of 2 drugs that compete with the same binding sites and thus distribution is affected
warfarin and phenylbutazone
drug are often eliminated by…..
metabolism and/or excretion into the urine or bile
the liver is the major site of metabolism.
metabolism mostly occurs through either…..
enzyme induction or inhibition
what is enzyme induction?
what is enzyme inhibition?
enzyme induction is when the rate of metabolism INCREASES so the drug gets eliminated faster. thus, you will need a larger dose to get the same effect
enzyme inhibition is when the normal rate of metabolism is slowed – so the drug begins to accumulate in the body.
phenobarbital + warfarin is an example of enzyme induction or inhibition?
induction
give an example of 2 drugs that accumulate in the body due to enzyme inhibition
cimetidine + theophylline
in excretion, the drug becomes…..
either ineffective or toxic and is excreted out of the body
how can some drug interactions alter blood flow?
by increasing renal blood flow
by inhibiting active tubular secretion
altering tubular reabsorption
give an example of a drug that alters excretion by increasing renal blood flow
hydralazine increases the rate of blood flow and thus increases the excretion of DIGOXIN
give an example of a drug that alters excretion by inhibiting active tubular secretion
probenecid reduces the tubular secretion of pencillin and thus increases peniciilin serum levels
give an example of a drug that alters excretion by altering tubular reabsorption
alkanalizing agents can increase the pH which DECREASES the ionization of amphetamines and REDUCES their excretion
pharmacodynamics describes….
the time course of the drug effects (whether desired or undesired)
most drug effects are mediated by what?
interaction with a specific receptor. follows the laws of drug-receptor interactions
the amount of drug that is bound to the available receptors and the effect produced is dependent on what?
the concentration of the drug available at the site of the receptor
what is required to accurately assess pharmacodynamic interactions?
a complex analysis of the various effects and genetic impact
the mechanisms of pharmacodynamic interactions are divided into ___ groups:
3 groups:
-direct effect at receptor function
-interference with a biological or physiological control process
-increased or decreased pharamcological effect
name the 5 methods to classify pharmacodynamic interactions based on their MECHANISM and MAGNITUDE of the effect change
-additive
-summation
-antagonism
-synergism
-potentiation
explain what additive is
the combined effect of 2 drugs equal to the sum of the individual drugs
both drug responses occur via the SAME MECHANISM
2+2=4
give an example of 2 drugs that exhibit the pharmacodynamic property of additive
aspirin and acetaminophen
define summation
the combined effect of 2 drugs is equal to the sum of the originl drugs, BUT the drug responses occur via DIFFERENT mechanisms
2+2=4
give an example of drugs that exhibit summation
beta blockers + calcium channel antagonists
define the pharmacodynamic property of antagonism
the combined effect of 2 drugs is NULLIFIED by the other
occurs at the SAME RECEPTOR
1+1=0
give an example of 2 drugs that exhibit antagonism
pilocarpine + atropine
define synergism
when 2 drugs produce a larger response than the sum of their individual effects
2+2=10
give an example of drugs that exhibit synergism
sulfonamides and trimethorpim are dihydrofolic acid reductase inhibitors
define the pharmacodynamic property of potentiation
when a drug effect is increased by another drug that has no such effect
0+1 = 2
OR
0+10 = 25
give an example of drugs that exhibit potentiation
diphenhydramine + opioids
diphenhydramine potentiates narcotic effects not is NOT an endogenous opioid analgesia
drugs are generally classified based on….
their mechanism of action and/or their similarity in pharmacological effects
what 2 drugs function on the GABA receptor?
explain the significance
ethanol and pentobarbital – GABA is a neurotransmitter that binds to GABA receptors to cause an inhibitory response (sedation)
concurrent use of barbiturates and ethanol may result in excessive CNS depression, which has moderate clinical significance
name 3 barbiturates
pentobarbital
phenobarbital
thiopental
explain the mechanism of ethanol
enhances inhibitory excitability neurotransmission via NMDA and GABAA receptor operated channels
binds to the allosteric site on the GABA A receptor and thus increases the frequency of GABA chloride channel openings.
what primarily metabolizes ethanol?
what is the secondary?
primary = alcohol dehydrogenase
secondary = CYP2E1 to form acetaldehyde
explain the mechanism of barbiturates at high concentrations and in low concentrations
in general - activate inhibitory GABA A receptors and inhibit AMPA/kainate receptors
at low conc - act as positive allosteric modulators of GABA A
at high conc - activate GABA A receptors to increase the average open duration of the channel without altering the ion conductance or opening frequency
true or false
barbiturates decrease hepatic CYP450 metabolism of drugs
FALSE – increase
true or false
barbiturates competitively inhibot the metabolism of some drugs
true
