DRUG TOXICITY x_x

Question 0

Adverse drug reaction

Answer 0

harm directly caused by the drug at normal doses

Question 1

adverse drug event

Answer 1

harm associated with a drug or the use of a drug

Question 2

medications error

Answer 2

inappropriate use of a drug that may or may not result in harm

Question 3

Toxicity is rare (~1 in 20,000 pts) so to detect more than

Answer 3

60,000 pts must be exposed after the drug is marketed

Question 4

Most new drug exposure have only ~

Answer 4

3000 short term patient exposures

Question 5

ADRs increase exponentially with

Answer 5

four or more prescriptions

Question 6

misconception about ADRs and reporting

Answer 6

all serious ADRs are documented by the time a drug is marketed
difficult to determine if a drug or another clinical cause is responsible
ADRs should be reported only if absolutely certain

Question 7

Non deleterious effects

Answer 7

side effects

Question 8

Deleterious effects

Answer 8

toxic effects

• pharmcological
• pathological
• genotoxic

Question 9

drug interactions are

Answer 9

preventable

Question 10

Types of antagonism

Answer 10

functional
chemical
dispositional
receptor

Question 11

mechanism of chemical interactions: Pharmacokinetics

Answer 11

biotransformation
distribution
absorption
excretion

Question 12

Mechanism of Pharmacodynamics

Answer 12

Receptor

non receptor

Question 13

Clinical trials Phase I

Answer 13

first in human, after animal studies 
10-100 subjects 
usually healthy volunteers, sometimes pts with advanced rare disease
Open label 
looking at safety and tolerability 
Months to 1 yr 
US 10 million 
success rate: 50%

Question 14

Clinical trials: Phase II

Answer 14

first in patient 
50-500 subjects 
patient-subjects receiving experimental drug 
randomized and controlled (can be placebo controlled) 
may be blinded 
Looking at Efficacy and dose ranging 
1-2 years 
US 20 million 
Success rate: 30%

Question 15

Clinical trials: Phase III

Answer 15

Multi site trial
few hundred to few thousand participants
patient-subjects receiving experimental drug
randomized and controlled (can be placebo controlled) or uncontrolled
may be blinded
Confirm efficacy in larger population
3-5 years
US 50-100 million
success rate: 25-50%

Question 16

Clinical Trials: Phase IV

Answer 16

Post marketing surveillance
many thousands of participants
patients in treatment with approved drug
Open label
Adverse events, compliance, drug-drug interaction

Question 17

ADR risk factors

Answer 17

age
multiple medications 
multiple co-morbid conditions
inappropriate medication prescribing, use, or monitoring 
end-organ dysfunction 
altered physiology 
Prior history of ADRs 
extent (dose) and duration of exposure 
genetic predisposition

Question 18

Limitations of ADR detection in Clinical trials

Answer 18

exposure limited to few individuals so rare and unusual ADRs not detected (1 in 10000)
3000 pts at risk are needed to detect ADR with incidence of 1/1000 with 95% certainty
exposure is often short term
external validity - excludes kids, elderly, women of child bearing age,

Question 19

Examples of medications where ADR is seen much much later

Answer 19

DES - (1940-50s) given to pregnant moms to maintain pregnancy, later on female offspring would develop rare cervical cancer
Vioxx and heart attacks

Question 20

Some drugs that manifest symptoms more than 4-6 hrs after oral overdose

Answer 20

Acetaminophen 
aspirin 
Illicit drugs in rubber or plastic packages 
Monoamine oxidase inhibitors 
Thyroid hormones 
Valproic acid 
Warfarin like anticoagulants 
Sulfonylureas 
sustained release formulation drugs

Question 21

What age group shows the highest opioid analgesic poisoning death rates?

Answer 21

45-54 yrs (most) 
35-44 yrs
25-34
55-64
15-24 
65 and over

Question 22

Some scenarios for therapeutic errors

Answer 22

inadvertently took/given medication twice 
wrong medication taken/given 
incorrect dose 
confused units of measure 
iatrogenic error 
drug interaction 
more than 1 product containing the same ingredient 
10 fold dosing error 
exposure through breast milk

Question 23

Types of allergic reactions

Answer 23

Type I - immediate, anaphylatic (IgE) - penicillins
Type II - cytotoxic antibody (IgG, IgM) - methyldopa or hemolytic anemia
Type III - serum sickness (IgG, IgM) - procainamide induced lupus
Type IV - delayed hypersensitivity (T cell) - contact dermatitis (could take weeks to show up)

Question 24

Reactions to medications could be due to

Answer 24

hypersensitivity 
life-threatening 
Casue disability
Idiosyncratic 
secondary to drug interactions 
Unexpected detrimental effect - decrease growth 
drug intolerance

Question 25

what could contribute to risk of addiction?

Answer 25

drugs that block transporters of biogenic amines (cocaine and amphetamine)
drugs that bind ionotropic receptors - Nicotine or benzos
drugs that activate G protein coupled receptors - Opioids or cannabinoids

Question 26

Healthcare professionals should advise patients not to exceed what dose of acetaminophen?

Answer 26

max total daily 4 grams/day and NOT to drink alcohol while taking

Question 27

Management options

Answer 27

discontinue offending agent - can be safely stopped, life threatening or intolerable, reasonable alternative or continuing medication will further exacerbate pt condition
continue the mediation - medically necessary, no reasonable alternative, problem is mild and will resolve with time

Question 28

More management options

Answer 28

discontinue non essential meds
Administer appropriate treatment
provide supportive or palliative care
consider desensitization

Question 29

what are some short term best practice recommendations to reduce medication administration errors?

Answer 29

maintain unit dose distribution system for non emergency medications
pharmacies prepare intravenous solutions
removed inherently dangerous meds
develop special procedures for high risk drugs
improve info resources
eudcate pts

Question 30

long term best practice recs to reduce med administration errors

Answer 30

implement technology based safe guards