4. Drug Toxicity Flashcards
Poison: a chemical substance that, in relatively ____ doses, seriously impairs ____ or destroys life.
Distinction between drug and poison is often ____. No drug is so selective in its pharmacotherapeutic action that it produces no ____.
Drugs we will be prescribing were all tested in ____
small
health
arbitrary
adverse effects
Acute Toxicity
Standard measure of acute toxicity is the ____ or ____. Defined as a dose (usually a single administration) which kills 5O% of an experimental animal population within a specified time after administration (generally 24 hours).
LD5O determined experimentally by administering progressively ____ doses to groups of animals. Mortality plotted as a function of ____; LD5O found by ____.
median lethal dose LD50 larger dosage interpolation
Therapeutic Index
Ratio between ____ and ____.
Therapeutic Index = LD5O/ED5O
In general, the larger the ratio, the greater the margin of ____
Therapeutic index, as determined in laboratory ____, provides the initial estimation of relative safety of a drug which will be used in humans.
- no value in predicting occasional ____ patient.
- not useful for evaluation of therapeutic ____.
LD50 ED50 safety animals hypersensitive effectiveness
Acute Toxicity (within 24 hours) • Looking at the 50% response; extrapolate down to log dose > "10 mg/kg" > ED; push dose to lethality > looking at same response > "100 mg/kg" ○ Therapeutic index = LD50/ED50; here it's 10 ○ Wider the ranger > the more \_\_\_\_ you have as prescriber § Lithium (for manic depressive) - \_\_\_\_ only a slight increase pushes a person into adverse reactions § \_\_\_\_ - 40:1 - can increase doses without hitting a major problem § \_\_\_\_ - 10:1 • Animals require \_\_\_\_ doses than humans do ○ Amount of barb in a cat - need 10mg/kg, but if you use the same dose in a 70kg they're dead
flexibility 2/3:1 valium/benzo's alcohol higher
Chronic Toxicity
Toxic effects which develop only after ____ exposure to a drug for relatively long periods of time.
Potential long-term toxicity in humans can be estimated in animals with ____ lives, e.g., drug administration for ____ months in mice (life-span: 2.5 - 3 years) is equivalent to ____ years of drug administration in humans.
repeated
6
10-15
Other Animal Toxicity Tests Depending on anticipated clinical use of a new drug, other types of animal toxicity studies may be required, e.g., 1. \_\_\_\_; sensitization 2. neonatal toxicity 3. \_\_\_\_ 4. carcinogenicity
• Carcinogenicity is good; teratogenicity is not as \_\_\_\_ (don't get good results from animals)
irritation
teratogenicity
Drug Toxicity in Humans
Adverse Drug Reactions (ADRs)
- Mild
Considered to be ____ to life.
Annoying, possibly to point of pt wanting to D/C the drug, e.g., ____ induced by antihistamines given for relief of an allergic disorder.
However, drowsiness could be strong enough to reduce the ability to ____ operate a car. - Toxic
Undesired drug effects which are can produce severe
effects, e.g., hepatotoxicity associated with ____.
Obviously, toxic reactions are potentially fatal.• ____ - on the market for 50 years, the data indicated that it had cardiotoxicity
non-threatening
safely
valproic acid therapy
darvarn
Predictable vs. Unpredictable Toxicity
Some adverse reactions are predictable extensions of the major pharmacologic actions of drugs (e.g., electrolyte and water depletion during ____ therapy; hemorrhage during ____ therapy).
Other ADRs (e.g., headache, skin rash, pruritus) are largely unpredictable, i.e., based upon the pharmacologic actions of the drug, they were ____.
Proper ____ and ____ selections are necessary to obtain an optimum therapeutic response with minimum adverse reactions.
• Predictable - someone on an antidepressant, or a patent who has hypertension and is on an antihypertensive > problem within your chair > can feint because of postural hypotension; antihypertensive interferes with reflexes, \_\_\_\_ blocked and then they pass out ○ This is the dentist's fault • Unpredictable - who's going to get a \_\_\_\_ rash > ask the person what they're allergic to ○ Given from tetracycline - interferes with \_\_\_\_ (contraindicated for pediatric patients)
diuretic anticoagulant unexpected drug dosage alpha1 tooth structure
C. Relative Risk
All drugs are potentially dangerous but little or no risk should occur with drugs used to relieve minor disorders such as ____ or a cough.
For those drugs employed in treatment of serious or life- threatening diseases (e.g., ____), a high degree of risk is more acceptable.
The benefit to risk ratio (potential benefit vs. possible toxicity) is a judgment made by the ____ and the ____.
• Relative risk - part of every drug; at one end, the \_\_\_\_ drugs (a lot of toxicity), at the other end are \_\_\_\_ (should be zero risk, but there's not) (risk of blood clotting, particualrly if they're smoking) ○ \_\_\_\_ has no side effects, unless you bring the patient back up too quickly Patients bialing out of studies is in chemo trial
headache cancer patient physician antineoplastic oral contraceptives
Drug Allergy (Hypersensitivity)
Allergic reactions to a drug occur because the patient has been exposed ____ (knowingly or ____) and the drug has functioned as an ____.
In addition, there appears to be a ____-determined predisposition regarding the development of an allergenic (hypersensitive) reaction to a drug.
In contrast to toxic reactions, allergic reactions: 1. are unrelated to \_\_\_\_; 2. occur only in \_\_\_\_ person; 3. are the \_\_\_\_ (not related to the \_\_\_\_ classification of the drug).
____ reactions to a drug have more characteristics of allergenicity than toxicity.
previously unknowingly antigen geneticlaly dose susceptible same pharmacologic pharmacogenetic
• Drug allergy, in contrast to toxic
○ Toxic - related to dose, can do a ____ curve with a toxic reaction
○ Allergic - no ____ - first time patient gets a drug they own’t get an allergic reaction without being exposed to it
§ Penicillin > disk test > put it in milk, and put the disk on two types ofbacteria, if there was penicillin in that milk > ____ > there was penicillin in the milk
□ Couldve been exposed without the patient not knowing they were, so allergic reactions
§ Unaware of the extent
§ Reactions are all the same regardless of the trigger > ____ reactions, and from there you get edema, ____, anaphylactic shock (BV dialte bc histamine from mast cells)
§ Pharmacogenetics is more like an allergic reaction than a toxic one
□ ____ population, diff reactions to drugs > cutanoeus response to a certain drug toa certain group > they havea c ertain ____ when they get this drug they get a major skin cutanoeous reaction
dose response dose response zone of inhibition skin bronchoconstriction heterogeneous gene
Iatrogenic (Physician-induced) Disorders
Many drugs employed today are extremely powerful and possess complex mechanisms of action.
However, when any drug is prescribed, the physician must know AND understand its ____ and potential ____.
Failure of certain physicians to be so informed has caused some of their respective patients to suffer needlessly.
Examples include:
____ > degeneration of bone
____ > tardive dyskinesia
• Iatrogenic ○ When physician doesn't understand the drug > woman prescribed drug for GI > metacroplamide (DA blocking agent) [people with PD have less DA from substantia nigra] > was taking drug for 10 months, and \_\_\_\_ and its permnanent ○ Degerantion of bone > dose of corticosteroid into jaw, and was giving higehr dose and giving more frequently > dose was 0.1mg, he was using 0.2mg, and given in a more frequent imte interval > degenration of her bone • Increase with antibiotic resistance > prescribers encourgaed to not use \_\_\_\_ unless you need it
pharmacology toxicity corticosteroids metoclopramide drug-induced PD antibiotics
Drug Abuse
Despite a significant amount of time and funds spent to decrease drug abuse, the illegal and/or excessive consumption of alcohol, controlled substances (e.g., cocaine, Dilaudid), and illicit drugs (e.g., heroin) remains a serious national problem.
Health professionals (e.g., nurses, pharmacists, physicians) are also vulnerable; they can–and have–become drug addicts and/or alcoholics (on a pharmacological basis, however, ____ is a drug).
____ a person from developing into a substance abuser is the most humane and efficient way of reducing drug addiction.
In order to understand substance abuse, it is necessary to recognize the important difference between ____ and ____.
• Differecne bt addiciton and physical dependence ○ Drugs don’t cause addiction
alcohol
preventing
physical dependence
addiction
Addiction
It is now recognized that the clinical problem classified as ‘addiction’ is a ____, i.e., addiction is ____.
A person may be addicted to anything if it meets a need, e.g., gambling, shopping, dieting (anorexia nervosa), drugs. Three major criteria characterize addiction:
1. it is a ____ disorder
2. a substantial amount of the addict’s time (both day and night) is devoted to:
a. ____ about doing/using it
b. ____ it
c. obtaining the necessary ____ (by legal and/or
illegal methods) to continue doing/using it
3. there is a high rate of ____
• Drug abuse - connection to \_\_\_\_ effects; PD cannot; so drug abuse is not really a disease, but it is a disorder
Life expectancy has dropped ____ years bc of the deaths from the opioid issue
mental disorder physical dependence compulsive thinking doing/using time recidivium (relapse)
psychosocial
2
Physical Dependence
For many types of drugs, prolonged use will trigger the development of an ____ process. Tolerance develops when cells change (e.g., ____ up-regulation or down-regulation) to ensure that the body maintains normal functioning.
Physical dependence begins with the occurrence of ____.
Patients can become ____ dependent not only to psychoactive drugs such as ____ (e.g., diazepam [Valium]) but to other types of medication (e.g., ____).
adaptive
receptor
tolerance
physically
benzodiazepines
propranolol
