1. ADVERSE
DRUGREACTIONS
WHEN LEGAL DRUGS KILL!
Hospital Internship Lab
Group Numero Uno:
1.Dumalagan, Dale Faith
2.Lim, Jai
3.Manzo, Angelie
4.Rabasto, Dominique
5.Racaza, Jacynth
6.Siegue, Ricca
7.Francisco, Sarah Luisa

2. OBJECTIVES
Definition of terms associated with Adverse Drug
Reactions (ADRs)
Classification of ADRs
Discussion on each type of ADR with examples

3. DEFINITIONS
Adverse Event (AE): Any untoward medical occurrence
that may present during treatment with a
pharmaceutical product but which does not necessarily
have a causal relationship with this treatment.
Adverse Drug Reaction (ADR): Any noxious change
which is suspected to be due to a drug, occurs at doses
normally used in man, requires treatment or decrease
in dose or indicates caution in future use of the same
drug.
Therefore, an adverse drug reaction is an adverse event
with a causal link to a drug.

5. Drug administered
Pt. develops a new condition/symptom
ADE
Drug suspected?
Yes
Check literature
Documented ?
(for the product
Or
similar class of products)
Yes
Highly suggestive of ADR

6. Not documented in literature
Drug continued Drug discontinued
Worsening of symptoms Symptoms improve
Drug restarted
Symptoms recur
Any other possible causes?
• Concomitant therapy
• Underlying conditions

8. SIMPLY….
Adverse: Untoward, unintended, possibly causing harm
(noxious)
AE: Adverse Event, Effect or Experience
ADE (Adverse Drug Event): An AE which happens in a
patient taking a drug
ADR (Adverse Drug Reaction): An ADE in which a
causal association is suspected between the drug and
the event

10. CLASSIFICATIONOFADRS
Depending on….
• Onset of event
• Type of reaction
• Severity
• Others

11. CLASSIFICATION OF ADRS ACCORDING TO
TYPE OF REACTION
Type A (Augmented)
Type B (Bizarre)
Type C (Chemical)
Type D (Delayed)
Type E (Exit/End of treatment)
Type F (Familial)
Type G (Genotoxicity)
Type H (Hypersensitivity)
Type U (Un classified)

12. • Reactions which can be predicted from the known
pharmacology of the drug
• Dose dependent,
• Can be alleviated by a dose reduction
E.g.
• Anticoagulants  Bleeding,
• Beta blockers  Bradycardia,
• Nitrates  Headache,
• Prazosin  Postural hypotension.
Type A (Augmented) reactions

13. TYPEB(BIZARRE)REACTIONS
• Cannot be predicted from the pharmacology of the drug
• Not dose dependent,
• Host dependent factors important in predisposition
E.g.
• Penicillin  Anaphylaxis,
• Anticonvulsant  Hypersensitivity

14. TYPEC(CHEMICAL)REACTIONS
• Biological characteristics can be predicted from the
chemical structure of the drug/metabolite
E.g.
• Paracetamol  Hepatotoxicity

15. TYPED(DELAYED)REACTIONS
• Occur after many years of treatment.
• Can be due to accumulation.
E.g.
• Chemotherapy  Secondary tumours
• Phenytoin during pregnancy  Teratogenic effects
• Antipsychotics  Tardive dyskinesia
• Analgesics  Nephropathy

16. TYPEE(ENDOFTREATMENT)REACTIONS
• Occur on withdrawal especially when drug is stopped
abruptly
E.g.
• Phenytoin withdrawal  Seizures,
• Steroid withdrawal  Adrenocortical insufficiency.

17. CLASSIFICATIONOFADRS….
DEPENDINGONSEVERITY
• Minor ADRs: No therapy, antidote or prolongation of
hospitalization is required.
• Moderate ADRs: Requires change in drug therapy, specific
treatment or prolongs hospital stay by atleast 1 day.
• Severe ADRs: Potentially life threatening, causes permanent
damage or requires intensive medical treatment.
• Lethal: Directly or indirectly contributes to death of the
patient.

18. SIDEEFFECTS
Unwanted but often unavoidable, pharmacodynamic effects
that occur at therapeutic doses
Predicted from the pharmacological profile of a drug
Known to occur in a given percentage of drug recipients
E.g.
Side effect based on therapeutic effect:
Atropine (preanaesthetic) dryness of mouth
Acetazolamide (diuretic-bicarbonate excretion) Acidosis
Side effect based on a different action:
Promethazine (anti-allergic) sedation
Estrogen (Anti ovulatory)  Nausea
Depending on the context:
Codeine (anti-tussive)  constipation Used in Traveller’s
diarrhea

19. SIDEEFFECTS….
Drug discovery
Occasionally, “adverse” effects may be exploited to develop an
entirely new indication for a drug.
E.g:
• Unwanted hair growth during Minoxidil treatment of severely
hypertensive patients  development of the drug for hair growth.
• Sildenafil was initially developed as an antianginal, but its effects to
alleviate erectile dysfunction  a new drug indication in erectile
tissue.
• Sulfonamides used as antibacterials were found to produce
hypoglycemia and acidosis as side effects  development of
Hypoglycemic Sulfonylureas and Carbonic anhydrase inhibitor
Acetazolamide.

20. SECONDARYEFFECTS
Indirect consequences of a primary action of the drug
E.g.
Tetracyclines Suppression of bacterial flora
Superinfections
Corticosteroids Weaken host defence Activation of
latent tuberculosis

21. TOXICEFFECTS
Result of excessive pharmacological action of the drug due
to over dosage or prolonged use.
Over dosage may be
1. Absolute (Accidental, homicidal, suicidal)
2. Relative (Gentamycin in Renal failure)
Result from
1. Extension of therapeutic effect:
E.g. Barbiturates  Coma,
Digoxin  Complete A-V block,
Heparin  Bleeding
2. Functional alteration:
E.g. Atropine  Delirium
3. Drug induced tissue damage:
E.g. Paracetamol  Hepatic necrosis

22. INTOLERANCE
Appearance of characteristic toxic effects of a drug in an
individual at therapeutic doses
Converse of tolerance,
Indicates a low threshold of the individual
E.g.
Triflupromazine (single dose)  Muscular dystonias in some
individuals
Carbamazepine (few doses) Ataxia in some individuals
Chloroquine (single tablet)  Vomiting and abdominal pain in
some individuals

23. IDIOSYNCRASY
Genetically determined abnormal reactivity to a
chemical
Certain Bizarre drug effects due to peculiarities of an
individual for which no definite genotype has been
described, are also included.
Drug interacts with some unique feature of the
individual, not found in majority subjects, and produces
the uncharacteristic reaction.
E.g.
Barbiturates Excitement and mental confusion in some
individuals
Quinine  Cramps, diarrhea, asthma, vascular collapse in some
individuals
Chloramphenicol  Aplastic anemia in rare individuals

24. DRUGALLERGY
Immunologically mediated reaction producing stereotype
symptoms, unrelated to the pharmacodynamic profile of the drug
Generally occur even with much smaller doses
Also called Drug hypersensitivity
Types:
• Type I: Immediate, anaphylactic (IgE)
• E.g: Penicillins  Anaphylaxis
• Type II: Cytotoxic antibody (IgG, IgM)
• E.g: Methyldopa  hemolytic anemia
• Type III: Serum sickness (IgG, IgM)
• Antigen-antibody complex
• E.g: Procainamide-induced lupus
• Type IV: Delayed hypersensitivity (T cell)
• E.g: Contact dermatitis
Humoral
immunity
Cell mediated
immunity

25. PHOTOSENSITIVITY`
Cutaneous reaction resulting from drug induced sensitization of the
skin to UV radiation. The reactions are of two types
Phototoxic: Drug or its metabolite accumulates in the skin, absorbs
light and undergoes a photochemical reaction resulting in local tissue
damage (sunburn-like, i.e., erythema, edema, blistering, hyper
pigmentation)
E.g. Tetracyclines (esp. Demeclocycline), and Tar products,
Nalidixic acid, Fluoroquinolones, Sulfones etc
Photo allergic: Drug or its metabolite induces a cell mediated immune
response which on exposure to light (longer wave length) produces a
papular or eczematous contact dermatitis like picture.
E.g. Sulfonamides, Sulfonylureas, Griseofulvin, Chloroquine,
Chlorpromazine

26. DRUGDEPENDENCE
Drugs capable of altering mood and feelings are liable to repetitive use
to derive euphoria, withdrawal from reality, social adjustment, etc.
Psychological dependence: Individual believes that optimal state of well
being is achieved only through the actions of the drug.
E.g. Opioids, Cocaine.
Physical dependence: Altered physiological state produced by repeated
administration of a drug which necessitates the continued presence of
the drug to maintain physiological equilibrium. Discontinuation of the
drug results in a characteristic withdrawal (abstinence) syndrome.
E.g. Opioids, Barbiturates, Alcohol, Benzodiazepines

27. DRUG DEPENDENCE….
Drug abuse: Use of a drug by self medication in a manner and
amount, that deviates from the approved medical and social
patterns in a given culture at a given time.
Drug abuse refers to any use of an illicit drug.
Drug addiction: Compulsive drug use characterized by
overwhelming involvement with the use of a drug.
Drug habituation: Less intensive involvement with the drug,
withdrawal produces only mild discomfort.
Habituation and addiction imply different degrees of
psychological dependence.

28. DRUG WITHDRAWAL
REACTIONS
Sudden interruption of therapy with certain drugs result
in adverse consequences, mostly in the form of
worsening of the clinical condition for which the drug
was being used.
E.g:
Corticosteroid Adrenal insufficiency
β-blockers  worsening of angina, precipitation of MI
Clonidine  severe HTN, restlessness, sympathetic
over activity

29. TERATOGENICITY
Capacity of a drug to cause foetal abnormalities when
administered to the pregnant mother.
Drugs can affect the foetus at 3 stages:
1. Fertilization and implantation (Conception to 17 days):
failure of pregnancy which often goes unnoticed.
2. Organogenesis(18 days to 55 days): most vulnerable period,
deformities are produced.
3. Growth and development (> 56 days): developmental and
functional abnormalities can occur.
• E.g:
• Thalidomide Phocomelia, multiple defects
• Anticancer drugs  Cleft palate, hydrocephalus, multiple defects
• ACE inhibitors  Hypoplasia of organs (lungs, kidney)

30. MUTAGENECITY AND
CARCINOGENICITY
Capacity of a drug to cause genetic defects and cancer
respectively.
Chemical carcinogenesis generally takes several (10-
40) years to develop.
E.g.
Anticancer drugs,
Radio-isotypes,
Estrogens,
Tobacco.

31. DRUG INDUCED DISEASE
Also called Iatrogenic(Physician induced) diseases.
Functional disturbances caused by drugs which
persist even after the offending drug has been
withdrawn and largely eliminated
E.g.
Salicylates, Corticosteroids  Peptic ulcer
Phenothiazines, other antipsychotics  Parkinsonism
Isoniazid  Hepatitis
Hydralazine  DLE

33. SUMMARY
Adverse Drug Reactions (ADRs) are adverse events with a
causal link to a drug.
Types of Classification of ADRs:
• Onset of event: Acute (<60 minutes), Sub-acute (1-24 hrs)
and Latent (>2 days)
• Type of reaction: Type A (Augmented), B (Bizarre), C
(Chemical),D (Delayed), E (Exit), F (Familial), G
(Genotoxicity), H (Hypersensitivity), U (Un classified)
• Severity: Minor, Moderate, Severe, Lethal ADRs
• Others: Side effects, Secondary effects, Toxic effects,
Intolerance, Idiosyncrasy, Drug allergy, Photosensitivity,
Drug Dependence, Drug Withdrawal Reactions,
Teratogenicity, Mutagenicity, Carcinogenicity, Drug
induced disease (Iatrogenic)

34. GOVERNMENT
POLICIES
SARAH LUISA A. FRANCISCO

35. GOVERNMENT
POLICIES
June 22, 1963 as
amended on May 22,
1987
April 20, 1994 June 30, 1994
RA 3720
“Food, Drugs, and
Cosmetics Act”
BFAD Memorandum
Circular no. 5 s.1994
DO 345 – 1 s. 1994
Creation of National
ADR Advisory
Committee (NADRAC)

36. HOW TO REPORT ADR
1) Fill out the RED ALERT CARDS
2) Complete the ADR REPORT FORM
3) Submit red alert card and the ADR report form to the
Central Block Pharmacy for proper referral
4) Pharmacy will then compile the reports for review of the
ADR Subcommittee and submission of the BFAD

37. CONTENTS OF ADR
REPORT FORM
• Generic and brand rand name of the suspect drug
• Manufacturer’s name and address
• Lot and batch no. of the product
SHOULD BE DONE IN DUPLICATE

38. ADR OF
CARDIO
DRUGS
SARAH LUISA A. FRANCISCO

39. CARDIO DRUGS
DRUG
CATEGORY
BRAND AND
GENERIC
NAME
THERAPEUTIC
USE
ADR
ACEi • Captopril
(Capomed)
• Enalapril
(Enalaprat)
• Decrease BP
• Increase
cardiac output
• Persistent dry
cough
• Hyperkalemia
• Skin rash
• Hypotension
• Fever
Angiotensin
receptor
blockers
• Losartan
(Hyzaar)
• Decrease BP • Angiooedema
• Hyperkalemia

40. DRUG
CATEGORY
BRAND AND
GENERIC NAME
THERAPEUTIC
USE
ADR
Alpha-
blocker/Alpha-
adrenergic
blocker
• Prazosin
• Tamsulosin
• Induces reflex
tachycardia
resulting from
the lowered BP
• Orthostatic
hypotension
• Tachycardia
• Vertigo
• Sexual
dysfunction
Beta-blocker/Beta
adrenergic
blockers
• Metoprolol
(Neobloc)
• Atenolol
• (Therabloc)
• Lower BP in
HTN
• Bronchoconstri
ction
• Increased
Sodium
retention
• Decreased
cardiac output
• Arrhythmias
• Sexual
dysfunction
• Bradycardia
• Hypotension
• Fatigue
• Insomnia

41. DRUG
CATEGORY
BRAND AND
GENERIC
NAME
THERAPEUTIC
USE
ADR
Calcium-channel
blockers
• Amlodipine
besylate
(Amvasc)
• Nicardipine
(Cardipine)
• Decrease
muscle tone
• Constipation
• Vertigo
• Headache
• Fatigue
• Hypotension

42. GASTROINTESTINAL AND
ANTIEMETIC DRUGS
DRUG
CATEGORY
BRAND AND
GENERIC NAME
THERAPEUTIC
USE
ADR
H2 Receptor
antagonist
• Cimetidine Reduce gastric
acid production
• Headaches
• Dizziness
• Diarrhea
• Muscular pain
Proton Pump
Inhibitot
• Omeprazole
• Pantoprazole
• Esomeprazole
• Reduce the risk
of bleeding from
an ulcer caused
by aspirin and
other NSAIDs.
• Low in Vitamin
B12

43. DRUG
CATEGORY
BRAND AND
GENERIC NAME
THERAPEUTIC
USE
ADR
Antacids • Aluminum
Hydroxide
• Magnesium
Hydroxide
• Sodium
Bicarbonate
• Relief of peptic
ulcer disease
and GERD.
• Promote
healing of
duodenal
ulcers.
• Constipation
• Diarrhea
• Belching
• Flatulence

44. ESTROGEN AND
ANDROGEN
Estradiol- most potent estrogen produced and secreted in
the ovary.
ESTROGEN THERAPY
● Breast cancer
● Thromboembolism
● Myocardial Infarction
● Headache
● Peripheral edema
● Hypertension
●Nausea and vomiting

45. Progestin Therapy
● Headache
● Depression
● Weight Gain
● Changes in libido

46. Contraceptives- drugs available that decrease
fertility by a number of different mechanisms, such
as preventing ovulation, impairing gametogenesis
or gamete maturation, interfering with gestation.
ADR:
Breast fullness
Depression
Fluid retention
Headache
Nausea
Vomiting

47. ANDROGENS-
GROUP OF STEROIDS THAT HAVE ANABOLIC AND
OR MASCULINIZING EFFECT IN BOTH MALES AND
FEMALES.
In females
- masculinization with acne; growth of facial
hair; deepening of the voice; male pattern baldness;
excessive muscle development; menstrual
irregularities
In males
- Priapism; impotence; decrease
spermatogenesis; gynecomastia, stimulate growth of
prostate
In children
- Abnormal sexual maturation and growth
disturbance

48. General effect
- Increase serum LDL, lower serum HDL
level, premature coronary heart disease, fluid
retention, edema
Athletes
- premature closing of the eiphysis of long
bones, reduction of testicular size, hepatic
abnormalities, increased aggression, and mood
disorder

49. CNS STIMULANTS
Psychomotor Stimulants
1. Methylxanthines ( Theophylline, Theobromine, Caffeine)
AE: moderate doses: insomnia, anxiety, agitation.
High dosage: emesis, convulsion, cardiac arrhythmias
Withdrawal: Lethargy, irritability, headache.
2. Nicotine
AE: irritability, tremors, stomach cramps, diarrhea
and increased heart rate and blood pressure.
Withdrawal: irritability, anxiety, restlessness, difficulty
concentrating, headaches, insomnia

50. 3. Cocaine
AE: Euphoria, tachycardia, respiration rate 
agitation, hypertension, dyspnea  Seizure, arrhythmias,
respiratory failure RIP
4. Amphetamine
AE:Vertigo, hypertension, insomnia, confusion,
potential for addiction, nausea, diarrhea
5.Methylphenidate
AE:GI effects

51. Hallucinogens
1. Lysergic acid diethylaminde
AE: hyperreflexia, nausea, and mascular weakness
2. Tetraydrocannabinol
AE: Tachycardia, hypertension, hallucinations

52. Anaesthetic (CNS depressants)
A. General Anaesthetics
1. Inhaled & IV
AE: Cardiac effects, malignant hyperthermia,
arrhythmias, sensitivity to catecholamines,
hepatic toxicity
B. Local Anaesthetics
AE: seizures, cardiovascular collapse, cardiotoxicity,
allergic reactions.

53. OPIOIDS
ADVERSE DRUG REACTION

54. COMMON ADVERSE
EFFECTS
Constipation
Dry Mouth
Nausea/Vomiting
Sedation
Sweats

55. ADVERSE
EFFECTS
Bad Dreams/ Hallucinations
Dysphoria/Delirium
Myoclonus/Seizures
Pruritus/Urticaria
Respiratory Depression
Urinary Retention

56. ADVERSE EFFECTS SHOULD ALSO
BE DISTINGUISHED FROM OPIOID
ALLERGY:
Many people believe that opioid-
induced nausea/vomiting,
constipation, drowsiness, or even
confusion is an allergic reaction
However, these are not allergic
reaction; they are adverse effects
Anaphylactic or true allergic reactions
to opioids are rare.

57. DIURETICS
ADVERSE DRUG REACTION

58. TYPES OF
DIURETICS
Loop Diuretic
Thiazides
Carbonic Anhydrase Inhibitors
Potassium-sparing Diuretics
Osmotic Diuretics

59. ADVERSE
EFFECTS:
Hypovolemia
Hypokalemia
Hyperkalemia
Hyponatremia
Hypercalcemia
Metabolic acidosis
Metabolic alkalosis