M1s5 Drug Toxicity And Drug Interactions Flashcards
The Toxic effects of drugs can be divided into what categories
-adverse effects
-drug-drug and drug-food interactions
Adverse effects of drug definition
Any effect produced by a drug in a patient that is not the intended effect
Adverse effects of drugs examples
Extension of therapeutic effect
-too much of the drug in blood. Commonly happens when in drug overdose
Unrelated to the Main Drug Action
-drug can cause effects unrelated to intended pharmacological action of the drug (ex. Nauseas) may or may not be expected adverse effects
Allergic Reactions
-mediated by immune system
-an antigen-antibody combination provokes an adverse reaction in patient. Reaction may be very mild (ex skin rash) or very severe (ex anaphylaxis)
Withdrawal and Addiction
-refers to unwanted physiological and psychological effects of the drug
Teratogenesis
-drug produces defects in the developing fetus
Adverse Biotransformation Reaction
-drug converted to a chemically reactive metabolite that can bind to tissue components and cause tissue or organ damage
Predicting Adverse Drug Reactions
-drug at first that had no adverse effects can later have significant toxicities
-reason could be toxic reaction rare and only appear after prolonged use, is not detected in animals or unique to a particular time period
Rarity of occurrence:
-hard to predict rare
Ex antibiotic, chloramphenicol, used for several years before realized 1 in 50,000 patients could cause fatal bone marrow damage. Not picked up on initial testing
Length of Usage:
-toxic reaction may only appear after prolonged period
Ex. Streptomycin first invented for treatment of tuberculosis, not realized that it could cause deafness if used for extended period of time
Detectability in Animals:
-toxic effect may not be detectable in animals so it only appears once drug is being tested in humans
Ex headache, insomnia, nausea, and mental disturbances will not be readily picked up in animal testing
Time Period Specificity:
-may be unique to specific period of time
Ex. Found that thalidomide, drug marketed to treat nausea produced abnormal limb growth in the fetus, drug testing was not done in pregnant animals. Even if drug tested in pregnant animals, results not necessarily reflect what occurs in pregnant human. All new drugs have to be used with great caution in pregnant women
Assessing Drug Toxicity using measure called therapeutic index formula
Therapeutic Index (TI) = TD50/ED50
-measure safety of drug (drug generally safe if exceed value of 10)
The TI calculated answer is the number of fold differences between the beneficial dose and toxic dose which indicates that if the drug in taken correctly, it is improbable that adverse effects will occur
TI:
-tells how safe drug is
-relates to dose of drug required to produce a beneficial effect to the dose required to produce an undesirable or adverse effect
-higher TI, the safer the drug is
-when TI low, more likely that toxicities will be observed
TD50:
-dose of drug that is toxic in 50% of the population
ED50:
-dose of drug that is effective in 50% of the population
Population who respond to drug appears with normal distribution
Percent cumulative dose response who accounts everyone so by to 40 mL all individuals have responded so get tall straight like going up over bell curve
Look at percent cumulative line to find 50% as then true 50% everyone from that point and left on graph were effected
*look at good notes for image under section 3 notes
Ex. TI + 330/6 get those numerical numbers from x axis
As normal distribution, some patients show toxic effect at therapeutic doses
Only 2 fold difference between the beneficial dose and toxic dose, much more probable that adverse effects will occur within the use of this drug
12.5 probably safe
Drug to drug interactions
-one drug changes the pharmacological effects of a second drug
-many patients like elders take several drugs which results in the possibility of this interact
-can occur at many points during drug’s journey throughout body
Absorption:
-can increase intestinal movement, speeding the passage of a second drug through intestinal movement and decrease contact of second drug with intestinal wall=decreased absorption
Metabolism:
-drug can block the inactivation of a second drug in liver, increasing blood level and pharmacological effects of second drug
Excretion:
-drug can facilitate excretion of second drug by kidney, decreasing the blood level and pharmacological effect of second drug
Drug-Food Interactions
-involves the interference of food with drugs taken concurrently
Ex. Tyramine found in well-matured cheeses and other food
-can raise blood pressure and broken down in liver by enzyme, monoamine oxidase (MAO)
-one class of antidepressant drug are inhibitors of MAO
-would cause tyramine to not be broken down to inactive products and blood pressure raising effects of tyramine would be greatly intensified
Ex. Grapefruit and other citrus fruit can alter absorption of some drugs
-some drugs are biotransformed and inactivated by drug metabolizing enzymes located in cells in gastrointestinal tract
-common component of grapefruit inhibits these enzymes, resulting in greater amount of active drug being absorbed than would occur without grapefruit
-results in higher blood levels of the drug than expected, could lead to overdose
-cause of this interaction, no hospital in Ontario serves grapefruit
When do drug allergies occur
When an antigen-antibody combination provokes an adverse reaction in the patient’s immune system
