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Chapter 5, Drug Toxicity
Learning Objectives
“All substances are poison; there is none which is not poison
The right dose differentiates a poison and a remedy” –Paracelsus
1.
Diphenhydramine is a first generation H1 receptor antagonist that has the side effect of
somnolence? What do you call this effect?
 This is an “on target” adverse effect in an unintended tissue (the brain)
2.
How does haloperidol cause its adverse effects?
 D2 receptor blockade causes increase in prolactin secretion => amenorrhea, galactorrhea
3.

4.

What is a rare side effect of -statin therapy?
Rhabdomyolyisis and myositis occurs in -statin therapy due to the geranyl-geranylation of
muslce proteins
i. Muscle disorders also occur in corticosteroid therapy
What kind of compound that inhibits the hERG channel is safe for the heart?
hERG (IKr potassium channel) inhibitors that have an IC50 (half-maximal inhibitory
concentration ) more than 30 times the Cmax (maximum plasma conc. at therapeutic dose)
pose a low risk of torsades de pointes
i. Ex) fexofenadine
5. Which enantiomer of thalidomide is teratogenic?
 (S)-thalidomide
[S is closer to T, for Teratogenic]
6.
How can the effectiveness of penicillin be extended?
 probenecid can lengthen the half life of penicillin by inhibition of renal tubular transport
7.
How does the combination of sildenafil and nitroglycerin cause dangerous hypotension?
 Sildenafil inhibits PDE5,which prolongs the action of cGMP
 nitroglycerin stimulates guanylyl cyclase to increase cGMP
8.
Drug-herb interactions:
 Ginko biloba
 Echinacea
 St. John’s wort
9.
+ NSAIDS = bleeding
[Said the gecko drinking blood]
+ acetominophen = hepatotoxicity
[echidna liver]
+ SSRIs = serotonergic syndrome
[st John trippin]
What is a hapten?
 Small molecule drugs can act as haptens, which can bind to proteins in the body and trigger
an immune response
10. What are immediate and delyaed hypersensitivity reactions? Give examples of drugs causing
hypersensitivity reaction types I-IV:
 I (immediate ~30 min): IgE, wheal and flare
i. penicillin
 II: IgG and CD8+ T cells on cell surfaces (usually RBCs), hemolysis


i. Quinidine
[planes/surfaces are II dimensional]
III: IgG or IgM deposition, serum sickness, antivenins help
i. bupropion
IV (delayed 2-3 days): Th1 and CD8+ T cells, contact dermatitis, eventual cytokine storm
i. Ciprofloxacin, latex, mantoux test
11. Where does red man syndrome show on the body? What drugs can cause red man syndrome?
 Red man syndrome is caused when mast cells are stimulated, and presents as cutaneous
wheals and urticaria localized to the neck, arms, and upper trunk
 Vancomycin is the main causative agent, but ciprofloxacin, amphotericin B, rifampin,
cremophor, and teicoplanin can also cause red man syndrome
12. What drugs cause the skin rashes known as Stevens-Johnson sydrome and toxic epidermal
necrolysis?
 Phenytoin, carbamazepine, ibuprofen, celecoxib, and allopurinol cause Stevens-Johnson
syndrome (anti-epileptics, painkillers, and anti-gout)
13. What drug in the text causes a resurgence in dormant JC virus and hepatitis B, leading to
progressive multifocal leukoencephalopathy?
 Rituximab (B cell NHL) causes this syndrome because it inhibits CD20+ B cells
(immunosuppression)
i. Natalizumab can also unleash PML
14. What is the antiobiotic gentamicin’s negative effect? What is the bad effect of the antifungal
Amphotericin B?
 Gentamycin causes renal phospholipidosis, which leads to lysozomal rupture and acute
tubular necrosis
 Amphotericin-B reacts with cholesterol to form pores, which causes kidney injury
15. What kinds of compounds cause peripheral neuropathy?
 Vinca alkaloids (vincristine), paclitaxel, and platinum compounds (cisplatin) cause peripheral
neuropathy by disrupting microtubules
16. What drug is toxic to cardiac myocytes? What drug is toxic to heart valves?
 Doxorubicin binds to iron and disrupts cardiac myocytes
 Fenfluramine increases serotonin, which is a mitogen for heart valve myofibroblasts
17. What drugs in the text are contraindicated in patients with pulmonary disease?
 Bleomycin (chemotherapeutic) and amidarone (antiarrhythmic) cause chronic injury in the
form of fibrosis to the lungs
18. Which drug acts as an antagonist of estrogen receptors in the breast, but a partial agonist in the
uterus and other tissues?
 Tamoxifen can often cause endometrial cancer when it is used to treat breast cancer
i. Use raloxifene instead
19. What does Pregnancy Category B mean?

Animal studies have shown no risk, and there are no adequate studies in humans
20. Category D?
 There is positive evidence of human fetal risk, but potential benefits may warrant use
21. How do you treat benzodiazepine overdose?
 Use the GABAA receptor antagonist flumazenil to treat benzodiazepine overdose