Dr Htet Htet
MBBS, MMedSc (Pharmacology)
Lecturer
Clinical Pharmacology
Thalidomide Tragedy
History
• Thalidomide - 1957 - in West Germany

• The German drug company “Grünenthal” developed and sold
the drug.

• Pri...
• became an over the counter drug in Germany around

1960, and
• could be bought without a prescription.

• Shortly after ...
Time to Investigate
•

statistic - “50 % of the mothers with deformed children had taken thalidomide during
the first trim...
Time to withdrawn from market
• Thalidomide was withdrawn from the market
in 1961
• IT WAS A BIG LESSON FOR THE WHOLE
WORL...
- An adverse drug reaction (ADR) is an expression that

describes harm associated with the use of given
medications at a n...
• Over 2 MILLION serious ADRs yearly

• 100,000 DEATHS yearly
• ADRs 4th leading cause of death ahead of pulmonary disease...
• Type A:
– Augmented pharmacologic effects - dose dependent and predictable

• Type B:
– Bizarre effects (or idiosyncrati...
• 80% of ADR,
• usually a consequence of the drug’s primary pharmacological effect (e.g.
bleeding from warfarin)or
• a low...
• Bizarre effects (or idiosyncratic)
• dose independent and

• Unpredictable

(not

an

extension

pharmacological action ...
• Results from Chronic or continuous use
For example
• Analgesic nephropathy

• osteoporosis during continued high-dose
gl...
• Teratogenic
Thalidomide

- amelia or micromelia or phocomelia

phenytoin

-fetal hydantoin syndrome

tetracyclines

-tee...
• Rebound adrenal insufficiency

• Withdrawal syndrome (tachycardia on abrupt

discontinuation of β-adrenoceptor blockade)...
a. Adverse effects related to the
pharmacological action of the drug

main

a. Adverse effects unrelated to the main
pharm...
• predictable,
• at least this action is well understood.
• They are sometimes referred to as type A
('augmented‘)
Examples:
• postural hypotension occurs with α1-adrenoceptor

antagonists,
• bleeding with anticoagulants,

• sedation wit...
Examples
• paracetamol hepatotoxicity
• aspirin-induced tinnitus
when susceptibility is increased
• eg. during pregnancy

...
Unpredictable idiosyncratic reactions
– drug-induced hepatic or renal necrosis,
– bone marrow suppression,

– carcinogenes...
• such reactions cannot be excluded by preapproval clinical

trials (which might typically expose only a few thousand
indi...
Erythematous maculopapular eruption due to penicillin: rashes of this kind are by far the
most common reactions to drugs.
...
Erythema multiforme due to sulphonamide treatment, showing characteristic target-like
lesions.

Vervloet D , and Durham S ...
Fixed drug eruption, so called because the lesion recurs at the same site after each
administration—in this case, due to b...
Exfoliative dermatitis—a severe complication in this case due to co-trimoxazole.

Vervloet D , and Durham S BMJ 1998;316:1...
Eiferman et al.
Ciprofloxacin
microprecipitates and
macroprecipitates in the
human corneal
epithelium.
J Cataract Refract ...
Brazier et al. Ecstasy
related periodontitis and
mucosal ulceration—a case
report. Br Dent J 2003;
194(4): 197-9
• toxicity testing in animals and humans are important for seeking

approval to market a new drug.

• Nevertheless, harmfu...
1. Listen to your patient (Patients may tell you about

symptoms they have experienced since taking a
new medicine and it ...
3. Trust your own observations and initiative
- vital in this respect, in linking a sign or
symptom to either current or p...
Other things to be alert for include:

• Abnormal clinical measurements
(e.g. temperature, pulse, blood pressure, blood

g...
• Introduced in 1964 after Thalidomide tragedy

• Spontaneous reporting system
• Early warning system
• Over 600,000 confi...
Who can report?
•
•
•
•
•
•
•
•
•

Doctors
Dentists
Pharmacists
Nurses
Midwives
Health visitors
Non medical prescribers
No...
Where to report?
• www.yellowcard.gov.uk (online completion)
• http://yellowcard.mhra.gov.uk/
• Or by calling to 0808 100 ...
When to report?
•
•
•
•
•

If you suspect ADR,
Do not assume someone else will be reported.
Only 2-4% of ADR are reported....
How to get latest informations for
yourself?
• don’t miss for updates for yourself also.
• DRUG SAFETY UPDATES!!
• Publish...
• Vigabactrin – visual field defects
• Cyproterone acetate – hepatotoxicity
• Alendronate – severe oesophageal toxicity
• ...
“All health care professionals have a responsibility to
inform colleagues about clinically important drug

reactions that ...
References
• http://en.wikipedia.org/wiki/Thalidomide
• http://www.who.int/bulletin/volumes/91/8/BLT12-111609-table-T1.html
• http://...
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
Common Adverse Drug Reactions
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Common Adverse Drug Reactions

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Adverse Drug Reactions by Drugs
history
classifications
how to report
how it is important

Published in: Health & Medicine

Transcript of "Common Adverse Drug Reactions"

  1. 1. Dr Htet Htet MBBS, MMedSc (Pharmacology) Lecturer Clinical Pharmacology
  2. 2. Thalidomide Tragedy
  3. 3. History • Thalidomide - 1957 - in West Germany • The German drug company “Grünenthal” developed and sold the drug. • Primarily prescribed as a sedative or hypnotic, to cure “anxiety, insomnia, gastritis, and tension". • Afterwards it was used against nausea and to alleviate morning sickness in pregnant women.
  4. 4. • became an over the counter drug in Germany around 1960, and • could be bought without a prescription. • Shortly after the drug was sold, in Germany, between 5,000 and 7,000 infants were born with malformation of the limbs (phocomelia). Only 40% of these children survived.
  5. 5. Time to Investigate • statistic - “50 % of the mothers with deformed children had taken thalidomide during the first trimester of pregnancy.” • Throughout Europe, Australia, Canada and some part of America - cases were reported of infants with phocomelia; only 50% of them survived. • Those subjected to thalidomide while in the womb experienced- limb deficiencies - long limbs either were not developed or presented as stumps. • Other effects - deformed eyes, hearts, alimentary, and urinary tracts, and blindness and deafness. • During that time period the use of medications during pregnancy was not strictly controlled, and drugs were not thoroughly tested for potential harm to the fetus.
  6. 6. Time to withdrawn from market • Thalidomide was withdrawn from the market in 1961 • IT WAS A BIG LESSON FOR THE WHOLE WORLD CONCERNING WITH DRUG SAFETY AND REGULATION
  7. 7. - An adverse drug reaction (ADR) is an expression that describes harm associated with the use of given medications at a normal dosage during normal use. - ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. - The meaning of this expression differs from the meaning of "side effect", as it might also imply that the effects can be beneficial.
  8. 8. • Over 2 MILLION serious ADRs yearly • 100,000 DEATHS yearly • ADRs 4th leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents and automobile deaths • Ambulatory patients ADR rate—unknown • Nursing home patients ADR rate— 350,000 yearly Data from Institute of Medicine, National Academy Press, 2000 Lazarou J et al. JAMA 1998;279(15):1200–1205 Gurwitz JH et al. Am J Med 2000;109(2):87–94
  9. 9. • Type A: – Augmented pharmacologic effects - dose dependent and predictable • Type B: – Bizarre effects (or idiosyncratic) - dose independent and unpredictable • Type C: Chronic effects (continuous) • Type D: Delayed effects • Type E: End-of-treatment effects • Types A and B were proposed in the 1970s,and the other types were proposed subsequently when the first two proved insufficient to classify ADRs.
  10. 10. • 80% of ADR, • usually a consequence of the drug’s primary pharmacological effect (e.g. bleeding from warfarin)or • a low therapeutic index (e.g. nausea from digoxin), and • predictable • dose-related, usually mild, • But may be serious or even fatal (e.g. intracranial bleeding from warfarin). • usually due to inappropriate dosage, especially when drug elimination is impaired. • The term ‘side effects’ is often applied to minor type A reactions.
  11. 11. • Bizarre effects (or idiosyncratic) • dose independent and • Unpredictable (not an extension pharmacological action of the drug) For example: • hepatotoxicity due to paracetamol • tinnitus induced by aspirin • ototoxicity with aminoglycosides of main
  12. 12. • Results from Chronic or continuous use For example • Analgesic nephropathy • osteoporosis during continued high-dose glucocorticoid therapy • tardive dyskinesia during continuous use of antipsychotic drugs
  13. 13. • Teratogenic Thalidomide - amelia or micromelia or phocomelia phenytoin -fetal hydantoin syndrome tetracyclines -teeth malformation and discoloration aspirin -early closure of ductus arteriosus carbamazepine -cleft lip and palate, microcephaly wafarin - saddle nose sodium valproate - spina bifida DES - vaginal clear cell adenocarcinoma
  14. 14. • Rebound adrenal insufficiency • Withdrawal syndrome (tachycardia on abrupt discontinuation of β-adrenoceptor blockade) • second malignancies following successful chemotherapy.
  15. 15. a. Adverse effects related to the pharmacological action of the drug main a. Adverse effects unrelated to the main pharmacological action of the drug
  16. 16. • predictable, • at least this action is well understood. • They are sometimes referred to as type A ('augmented‘)
  17. 17. Examples: • postural hypotension occurs with α1-adrenoceptor antagonists, • bleeding with anticoagulants, • sedation with anxiolytics • intracerebral bleeding caused by anticoagulants, • hypoglycaemic coma from insulin • drug dependence produced by opioid analgesics
  18. 18. Examples • paracetamol hepatotoxicity • aspirin-induced tinnitus when susceptibility is increased • eg. during pregnancy Or if the patient has some predisposing conditions, • glucose 6-phosphate dehydrogenase deficiency • mutation in the mitochondrial DNA that predisposes to aminoglycoside ototoxicity
  19. 19. Unpredictable idiosyncratic reactions – drug-induced hepatic or renal necrosis, – bone marrow suppression, – carcinogenesis and – disordered fetal development. – aplastic anaemia from chloramphenicol – anaphylaxis in response to penicillin idiosyncratic reactions are termed type B ('bizarre') in the Rawlins & Thomson (1985) classification.
  20. 20. • such reactions cannot be excluded by preapproval clinical trials (which might typically expose only a few thousand individuals to the drug), and • the association may come only after years of use, • so there is a need for continued monitoring by regulatory authorities after drugs have been licensed and marketed. • An example is the association between pulmonary hypertension and valvular heart disease with fenfluramine, an appetite suppressant that had been used for several years, and also with dexfenfluramine.
  21. 21. Erythematous maculopapular eruption due to penicillin: rashes of this kind are by far the most common reactions to drugs. Vervloet D , and Durham S BMJ 1998;316:1511-1514 ©1998 by British Medical Journal Publishing Group
  22. 22. Erythema multiforme due to sulphonamide treatment, showing characteristic target-like lesions. Vervloet D , and Durham S BMJ 1998;316:1511-1514 ©1998 by British Medical Journal Publishing Group
  23. 23. Fixed drug eruption, so called because the lesion recurs at the same site after each administration—in this case, due to barbiturates. Vervloet D , and Durham S BMJ 1998;316:1511-1514 ©1998 by British Medical Journal Publishing Group
  24. 24. Exfoliative dermatitis—a severe complication in this case due to co-trimoxazole. Vervloet D , and Durham S BMJ 1998;316:1511-1514 ©1998 by British Medical Journal Publishing Group
  25. 25. Eiferman et al. Ciprofloxacin microprecipitates and macroprecipitates in the human corneal epithelium. J Cataract Refract Surg 2001; 27(10): 1701-2
  26. 26. Brazier et al. Ecstasy related periodontitis and mucosal ulceration—a case report. Br Dent J 2003; 194(4): 197-9
  27. 27. • toxicity testing in animals and humans are important for seeking approval to market a new drug. • Nevertheless, harmful effects are often encountered during therapeutic use, often the result of misprescribing, but also due to the emergence of toxic effects not detected in animals. • These harms are usually referred to as 'adverse drug reactions' (ADRs) and are of great concern to drug regulatory authorities, • For establishing the safety as well as the efficacy of drugs.
  28. 28. 1. Listen to your patient (Patients may tell you about symptoms they have experienced since taking a new medicine and it is important to listen to the patient’s own concerns regarding their drug therapy.) 2. Alert by yourself (some adverse reactions may not be apparent to the patient, you will need to be alert to the possible occurrence of ADRs.)
  29. 29. 3. Trust your own observations and initiative - vital in this respect, in linking a sign or symptom to either current or previous therapy. (Remember these can include overthe-counter (OTC) drugs and unlicensed herbal remedies).
  30. 30. Other things to be alert for include: • Abnormal clinical measurements (e.g. temperature, pulse, blood pressure, blood glucose, body weight) while on drug therapy • Abnormal biochemical or haematological laboratory results while on drug therapy. For example, plasma drug concentrations or liver biopsy where drug-induced hepatitis is suspected
  31. 31. • Introduced in 1964 after Thalidomide tragedy • Spontaneous reporting system • Early warning system • Over 600,000 confidential reports received in UK
  32. 32. Who can report? • • • • • • • • • Doctors Dentists Pharmacists Nurses Midwives Health visitors Non medical prescribers Now Patients also ………..
  33. 33. Where to report? • www.yellowcard.gov.uk (online completion) • http://yellowcard.mhra.gov.uk/ • Or by calling to 0808 100 3352 • Yellow cards can be available in BNF books ..
  34. 34. When to report? • • • • • If you suspect ADR, Do not assume someone else will be reported. Only 2-4% of ADR are reported. Only 10% of serious ADR are reported. “No” You don’t need to be completely certain that what you have seen is ADR. ***
  35. 35. How to get latest informations for yourself? • don’t miss for updates for yourself also. • DRUG SAFETY UPDATES!! • Published monthly • Register for updates .. • http://www.mrha.gov.uk/publications/safetyg uidance/DrugSafetyUpdate/index.htm
  36. 36. • Vigabactrin – visual field defects • Cyproterone acetate – hepatotoxicity • Alendronate – severe oesophageal toxicity • sibutramine – (Meridia (sibutramine): – Market Withdrawal Due to Risk of Serious Cardiovascular Events) 2010-2011
  37. 37. “All health care professionals have a responsibility to inform colleagues about clinically important drug reactions that they detect, even if a well recognized or causal link is uncertain”. Edwards IR and Aroson JK. Adverse Drug Reactions: Definitions, Diagnosis and Management. Lancet 2000; 356:
  38. 38. References
  39. 39. • http://en.wikipedia.org/wiki/Thalidomide • http://www.who.int/bulletin/volumes/91/8/BLT12-111609-table-T1.html • http://www.fda.gov/Drugs/DevelopmentApprova lProcess/DevelopmentResources/DrugInteraction sLabeling/ucm114848.htm • http://www.mhra.gov.uk/Safetyinformation/How wemonitorthesafetyofproducts/Medicines/TheYe llowCardScheme/Informationforhealthcareprofes sionals/Adversedrugreactions/index.htm • http://www.docstoc.com/docs/57017777/TheYellow-Card-Scheme-Reporting • British National Formularly (61st Edition)

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