Drug Interactions Flashcards
How many Americans take at least one prescription drug?
70%
How many Americans take at least two prescription drugs?
> 50%
How many Americans take at least 5 prescription drugs?
20%
What is a drug interaction?
A situaiton in which a substance (usually another drug) affects the activity of a drug when both are administered together
This can be synergistic, or antagonistic, or a new effect can be produced that neither produces on its own
Antagonism
Biologic or clinical response to a drug is reduced by administration of a second drug
What is an example of antagonism?
Penicillin inhibits bacterial wall synthesis
Tetracycline inhibits bacterial protein synthesis
P + T produces less antimicrobial activity that can be achieved with either alone
What are the different ways antagonism can occur?
Opposing mechanisms of action Chemical Antagonism Altering drug metabolism Drugs compete at the same receptor Drugs create opposing actions through signaling at different receptors
What is an example of chemical antagonism?
Taking antacid will diminish the effectiveness of tetracycline
Potentiation
A second drug with a different activity enhances the activity of the first drug
How can potentiation happen?
Example: Drug B enhances absorption, which could alter distribution or inhibit elimination of drug A
What is an example of potentiation?
Neostigmine potentiates the activity of succinycholine
How does neostigmine potentiate the effect of succinylcholine?
Succinylcholine acts at nicotinic ACh receptors to produce neuromuscular block
Succinylcholine is hydrolyzed by pseudocholinesterase
Pseudocholinesterase is inhibited by neostigmine
Whats an example of an unexpected drug effect?
Disuldiram was develop to treat parasitic infections, but found to be an inhibitor of alcohol dehydrogenase, thus producign undesirable side effects if taken with alcohol
Summation
The combined activity of two drugs acting at the same or similar sites
What are the types of summation?
Additive
Infra-additive
Supra-additive
Additive
Drug action is interchangeable when dosed at fractions of their EC50s
Infra-additive
Yield less than additive response when dosed at fractions of their EC50s
Supra-additive
Yield more than additive response when dosed at fractions of their EC50s
Synergism
The combined activity of two drugs produces greater than the maximal effect produced by either drug alone
Pharmaceutical Interactions
Drug incompatability of a physical or chemical nature
Basically, drugs should not be mixed within the same syringe
How can drug interactions affect drug absorption?
An interaction can affect the rate or extent of effective absorption of the drug into the circulation, causing an increase or decrease in the drug’s effect
What factors can effect drug absorption?
pH of lumen fluids
Enzyme activity
Intestinal motility
How can drug interactions affect distribution?
After a drug is absorbed, an interaction may alter it’s distribution or it’s rate of transfer from one site to another
IE: Avaliability of ‘free’ drug A for distribution, metabolism, or excretion affected by the presence of drug B
What can affect blood concentrations of a drug?
Plasma proteins can bind free drugs
Distribution across plasma membrane can be affected by drugs that do what?
Alter p-glycoprotein activity or levels
Alter pH gradients
Disrupt membrane barriers
What enzyme metabolizes most drugs?
P450 in the liver
Inhibition of what is responsible for many drug interactions?
CYP enzymes
What types of drugs can effect the metabolism of other drugs?
Drugs that effect hepatic blood flow
What factors affect drug excretion?
Urinary pH
Renal transport inhibition
Weak acids are more readily excreted in what type of urine?
alkaline
Weak bases are more rapidly in what type of urine?
acidic
Probenacid competes with penicilin for transport into renal tubules, which has what effect?
Probenacid increases the duration of the action of penicillin
By administering NaHCO3, it will do what to aspirin clearance?
Increase aspirin clearance
By administering NH4Cl, it will have what affect on amphetamine clearance?
Increase amphetamine clearance
If drug A blocks transmitter reuptake, but drug B stimulates transmitter release, what will happen?
Drug B will be less effective after administration of drug A, because transmitter stores will be depleted
What are 3 examples of Pharmacodynamic interactions
1) Drug A blocks transmitter reuptake, whie drug B stimulates transmitter release
2) CNS stimulants and depressants acting at the same time
3) Competition at a receptor site
