Adverse Effects of Drugs Flashcards
Which of the following two organ systems are the most frequent sites of adverse drug effects?
A) CNS & Gastrointestinal B) Endocrine & Respiratory C) Gastrointestinal & Renal D) CNS & Cardiovascular E) Reproductive & Respiratory F) Endocrine & Renal
Answer: A
Adverse drug effects mainly involve the nervous system (both central and autonomic) and the gastrointestinal system. Other tissues frequently affected are the skin and the blood. B, C, D, E, F) Adverse drug effects can appear in every body system but they are less frequent than in the nervous and gastrointestinal systems.
Which of the following drug properties can account for most of the adverse effects of a drug?
A) Cytotoxic activity B) Allergenic potential C) Pharmacological actions D) Addiction liability E) Autoimmune potential
Answer: C
The most common mechanism of adverse drug effect is pharmacological, that is related to drug-receptor interaction. This account for about 70-80% of cases.
A, B, E) Only in 5-15% of cases the adverse effect is related to the cytotoxic activity or to the allergenic potential of the drug.
D) Drugs that have adverse effects because of their addiction liability are very few in number compared to the whole number of drugs used in therapy.
Which of the following features is shared by both overdose toxicity and allergic reactions to drugs?
A) Dose-dependency
B) Caused by drug-receptor interaction
C) Genetically determined
D) Risk of mild or even fatal drug reactions
E) High incidence (20-40% of patients taking the drug)
Answer: D
Overdose toxicity can be mild (e.g. microscopic hematuria due to an anticoagulant drug) or fatal (e.g. severe poisoning by any drug).
Allergic reactions to drugs can be mild (e.g. urticaria, cutaneous rash) or fatal (e.g. anaphylaxis)
A) Overdose toxicity is dose-dependent, allergic reactions are not.
B) Overdose toxicity can be due to drug-receptor interaction (e.g. poisoning by antimuscarinic drugs), but allergic reactions are due to antigen-antibody interaction.
C) Drug idiosyncrasy is the only adverse effect of drug that is, by definition, genetically determined
E) These percentages are absurd. The overall occurrence of adverse effects of drugs is estimated to be 10 per 100 admissions in tertiary care hospitals.
Which of the following is the most important determinant of an allergic drug reaction?
A) The dose of the drug B) The chemical structure of the drug C) The oral bioavailability of the drug D) The genetic pedigree of the patient E) The liver and kidney functions of the patient
Answer: B
Some drugs cause allergic reactions very rarely while other compounds (obviously not used as drugs) can cause sensitization in all exposed subjects. Therefore the drug structure is the major determinant of the frequency of an allergic reaction to a drug.
A) Even if in some rare occurrence the dose can be a factor predisposing to allergy (i.e penicillin-induced hemolytic anemia requires high and sustained drug concentrations) the occurrence and the seriousness of an allergic reaction is not dose-dependent, in most cases.
C) The bioavailability refer to the fraction of the drug reaching the general circulation. Since allergy is not related to dose, bioavailability is not an important factor for an allergic drug reaction. Moreover the oral route carried the lowest risk of allergic reaction.
D) The genetic pedigree is important for idiosyncratic drug reactions.
E) The patient’s liver and kidney functions are important factors for drug overdose toxicity.
Drugs with low-molecular-weight can nevertheless cause an allergic reaction because they can
A) Alter the genetic makeup of the cells B) Accumulate over time into specific tissues C) Act as haptens D) Act as antibodies E) Block specific immunologic receptors
Answer: C
Haptens are usually small molecules that are not immunogenic by themselves. However they can be bound covalently to a carrier protein and the hapten-carrier conjugate can induce antibody against the hapten.
A) An allergic reaction is not genetically determined.
B) Storage of a drug into specific reservoirs has nothing to do with an allergic reaction. D) The hapten-carrier conjugate acts as antigen.
E) Blockade of specific immunogenic receptors would hinder, not cause, the allergic reaction.
Drug-induced fetal malformations are more likely if the drug is given in which of the following weeks of pregnancy? A) Before the 3rd B) Between the 3rd and the 11th C) Between the 11th and the 28th D) Between the 28th and 34th E) After the 34th
Answer: B
Drug-induced fetal malformations are more likely during the period of organogenesis, that is between the 3 and the 11th week.
A) During the first two weeks the embryo is very resistant to drug-induced malformations. C, D, E) After the 11th week, the risk of malformations is decreased because most organs are already formed.
Which of the following is a major determinant of the teratogenic potential of a drug?
A) The bioavailability of the drug
B) The fetal distribution of the drug
C) The total dose administered to the mother
D) The genome of the fetus
E) The molecular weight of the drug
Answer: C
The total dose administered to the mother is a major determinant of the teratogenic potential of a drug. Most drugs may become teratogenic if given in very high doses and the dosage can influence both the frequency and the type of malformations.
A, B, D) Other factors like molecular, bioavailability and fetal distribution may be contributing factors in some cases, but are much less important.
Benzodiazepines are drugs with a wide therapeutic index. Therefore it may be concluded that benzodiazepines have a low risk of which of the following adverse drug reactions?
A) Idiosyncratic reactions B) Allergic reactions C) Physical dependence D) Overdose toxicity E) Teratogenic effects
Answer: D
The therapeutic index is the ratio between a toxic dose and an effective dose of the drug. A wide therapeutic index means that there is a large interval between the dose that causes a given therapeutic effect and the dose that causes a toxic effect. Therefore overdose toxicity is less likely.
A, C, D, E) These adverse drug reactions do not contribute to the definition of the therapeutic index of a drug and therefore their risk cannot be predicted from the knowledge of the therapeutic index.
Which of the following is the most frequent time of appearance of adverse drug effects?
A) After 20 days of therapy B) During the first 10 days of therapy C) Between the 2nd and the 3rd month of therapy D) After 3 months of therapy E) After six months of therapy
Answer: B
Even if some unwanted effects can appear only after many months of therapy, most of them arise during the first 10 days of treatment.
A, C, D, E) (see explanation above)
Drug A and B are analgesic drugs acting on the same receptor. In laboratory animals, drug A has an ED50 of 2 mg/Kg and a therapeutic index of 10. Drug B has an ED50 of 5 mg/Kg and a therapeutic index of 20. Which of the following statements correctly defines the TD50 of drug A and drug B, in mg/Kg?
A) Drug A 30; drug B 50 B) Drug A 20; drug B 100 C) Drug A 10; drug B 20 D) Drug A 20; drug B 50 E) Drug A 30; drug B 100
Answer: B
By definition the therapeutic index is TD50 / ED50. Therefore: Drug A: 2 x10 = 20
Drug B: 5 x20 = 100
A, C, D, E) (see explanation above)
Five new antihypertensive drugs have been tested on hypertensive patients. Each drug has a unique overdose toxicity. The results are reported below.
Which of these drugs has the highest risk of overdose toxicity?
A) Drug A B) Drug B C) Drug C D) Drug D E) Drug E
Answer: C
The ratio between an harmful dose (TD1 in this case) and an effective dose (ED99 in this case) of a drug is called therapeutic index. The lowest the therapeutic index the highest the risk of overdose toxicity. Note that the median effective dose alone can tell nothing about the risk of overdose toxicity.
A, B, D, E) (see explanation above)
Which of the following is most likely the major mechanism of the teratogenic action of a drug?
A) Activation of fetal receptors involved in the pharmacological effects of the drug
B) Transfer to the fetus of maternal antibodies against specific cell lines
C) Covalent binding of the drug, or drug metabolites, to fetal DNA
D) Drug-induced decrease of blood flow through the placenta
E) Drug-induced deficiency of a critical substance
Answer: C
Even if the mechanisms of drug teratogenetic action are still poorly understood, and likely multifactorial, alteration in fetal DNA seems the most common event associated with drug- induced teratogenesis.
A) This can be a mechanism of teratogenetic action of drugs but does not seem the most common one. It appears to be related more to fetal toxicity than to teratogenesis.
B) This mechanism can explain the development of some fetal disease (i.e. erythroblastosis fetalis) but is not a mechanism of drug-induced teratogenesis.
D, E) Both mechanism may cause malformations in some cases but are not common causes of drug-induced teratogenesis.
A 75-year-old man had been receiving gentamicin (an aminoglycoside antibiotic) to treat a urinary tract infection. After three months of therapy patient’s serum creatinine levels were 10 mg/dL (normal 0.5-1.2) and serum gentamicin concentrations obtained just before the last dose were 9 mg/dL (normal < 2). Which of the following is the most likely adverse drug reaction the patient was suffering from?
A) Type II allergic reaction B) Type III allergic reaction C) Idiosyncratic reaction D) Pseudoallergic reaction E) Overdose toxicity
Answer: E
The very high serum creatinine level indicates renal failure. Aminoglycoside antibiotics can cause nephrotoxicity if given at high doses and gentamicin concentrations point out that the drug has reached a too high steady state concentration. The mechanism of aminoglycoside- induced renal failure is complex but seems mainly related to a destruction of brush-border cells of the renal tubule.
A, B) Certain renal diseases (i.e. tubulointerstitial nephritis) may be caused by drug hypersensitivity, but aminoglycoside antibiotics rarely cause sensitization and the high gentamicin concentrations indicate that overdose toxicity is the most likely drug reaction.
C, D) These listed options are quite unlikely.
A 33-year-old heroin addict was brought to the emergency department by the police who found him unconscious in the street. Physical examination showed a patient in deep coma with very slow and shallow respiration and pinpoint pupils. Opioid overdose was suspected. Which of the following would be the best therapy for this patient?
A) Gastric lavage and administration of cathartics
B) IV administration of a functional antagonist
C) IV administration of a pharmacological antagonist
D) Hemodialysis
E) Forced diuresis and urine acidification
Answer: C
Administration of a pharmacological antagonist, when available, is the best therapy in case of overdose toxicity. The opioid pharmacological antagonist naloxone can reverse the opioid induced coma in a matter of minutes and is currently used to treat opioid overdose.
A, B, D, E) (see explanation above)
A 43-year-old man had to undergo surgery to remove a biliary calculus. The anesthesiologist chose to supplement the anesthesia with succinylcholine, a paralyzing agent that has a rapid onset and a short duration of action. In this patient however, the drug-induced paralysis lasted several hours, so necessitating the anesthesiologist to continue the anesthesia and the artificial respiration. This abnormal drug effect is likely due to which of the following adverse drug reactions?
A) Type II allergic reaction B) Immediate allergic reaction C) Idiosyncratic reaction D) Pseudoallergic reaction E) Overdose toxicity
Answer: C
Succinylcholine is a neuromuscular blocking drugs mainly metabolized by plasma cholinesterase (butyrylcholinesterase). Because of this extensive and rapid metabolism, the action of this drug is quite brief. However the neuromuscular blockade of this drug may be exceedingly prolonged in patient with a genetically-induced abnormal variant of cholinesterase. Since this variant is much less efficient than the normal enzyme, it can take 2-3 hours for the paralysis to disappear. In this case the anesthesiologist must continue the general anesthesia and the artificial respiration till the cessation of the drug effect.
A, B, D, E) All the other listed options are quite unlikely.
