Adverse Drug Reactions, Rational Drug Use (trans 8)

Question 1

THE PROCESS OF RATIONAL THERAPY

Answer 1

1. Define the patient’s problem
2. State the therapeutic goals/objectives
3. Determine non-drug therapy
4. Make an inventory of effective groups of drugs
5. Choose an effective group according to the ESSA/SANE criteria
6. Choose a p-(personal) drug
7. Start therapy
8. Give information, instructions, and warning to the patient
9. Monitor (and/or stop) therapy

Question 2

THE PROCESS OF RATIONAL THERAPY:

State the therapeutic goals/objectives

Answer 2

**Done after diagnosis
**categories and examples:
o cure – usually for infections; provide comfort to patients always
o relief – most viral infections are given relief by antipyretics
o prevention – vaccines, antibiotics (prevent complications)
o modify physiologic process or underlying pathophysiology - insulin administration for DM

Question 3

THE PROCESS OF RATIONAL THERAPY: Make an inventory of effective groups of drugs

Answer 3

 The first selection criterion for any point is EFFICACY
 At this point, you are choosing an appropriate drug group for the disease
 Know the mechanism of action, dynamics, and kinetics of the drug group

Question 4

THE PROCESS OF RATIONAL THERAPY:

Choosing an effective group according to the ESSA/SANE criteria

Answer 4

Efficacy
o Dynamics and kinetics of different drug groups
o Ability of the drug to accomplish what it is intended to do
Safety
o Side effects and toxicity
o Compare frequency and severity of the effects Affordability/Cost
o Consider and compute for the total cost of treatment
Suitability/Need
o Convenience, compliance, practicality, contraindications, possible interactions

Question 5

REMEMBER

In a life and death emergency:

Answer 5

 Efficacy is of prime importance.
 Cost should not be a big consideration,
 If life-saving, the benefit of giving the drug may far outweigh the safety risks.

Question 6

THE PROCESS OF RATIONAL THERAPY:

Choosing an effective group according to the ESSA/SANE criteria

Answer 6

Patient is a scion of a rich taipan.
 Affordability will not be a problem
 Availability may not even be a problem
 Consider drug Efficacy and Safety

Question 7

THE PROCESS OF RATIONAL THERAPY:

Choosing an effective group according to the ESSA/SANE criteria

Answer 7

Patient is a baby from the Aeta village in Tarlac
 Affordability is a problem
 Availability may also be a problem
 A drug that is less affordable but is available and safe may be used rationally

Question 8

THE PROCESS OF RATIONAL THERAPY:

Choosing an effective group according to the ESSA/SANE criteria

Answer 8

Patient lives in the slums of Brgy. Imelda, QC
 Affordability is a problem
 Availability may be a lesser problem
 A drug that is less affordable and safe may be rational

Question 9

THE PROCESS OF RATIONAL THERAPY:

Choosing an effective group according to the ESSA/SANE criteria

Answer 9

Patient refuses any oral drug and vomits it.
 For Need/Suitability- parenteral route is primarily considered
 Affordability may have to be sacrificed for Suitability

Question 10

THE PROCESS OF RATIONAL THERAPY:

Choosing an effective group according to the ESSA/SANE criteria

Answer 10

Pregnant celebrity
 While efficacy is always considered, safety becomes an important consideration
 Affordability not a problem
 Availability not likely a problem

Question 11

ADVERSE DRUG REACTIONS

• *A retrospective study was done among ambulatory patients: 20% incidence of ADR was reported
• *The average intake of hospitalized patients: 10 drugs during their hospital stay

Answer 11

Chance of ADRs occurring in a hospitalized patient:
5 drugs: 5% chance
15 drugs: 40% chance
**The three most vulnerable groups are: Elderly patients, very young patients and the pregnant (refers to both the mother and the baby)

Question 12

ADVERSE DRUG REACTIONS
Elderly Patients (In the USA)
1 out of every 6 people is over 60 years old, but will consume:
o 1 out of every 3 tranquilizers
o 1 out of every 3 antidepressants
o 2 out of every 3 antihypertensives
o 2 out of every 5 gastrointestinal drugs

Answer 12

Pregnant Patients

The average number of drugs taken during the 10 lunar months of conception: more than 5 drugs (Excludes multivitamins)

Question 13

The science and activities relating to the detection, evaluation, understanding and prevent of adverse drug reactions or any other drug related problems.

Answer 13

Pharmacovigilance

Question 14

SERIOUS ADVERSE DRUG REACTIONS

Answer 14

Defined as:
 An adverse reaction which is fatal
 Is life-threatening
 Results in or prolongs hospitalization
 Causes persistent incapacity or disability
 Causes birth defects

Question 15

ADRs: “Undesirable”
Niacin (Vit. B3)
o Has been known to cause “flushing”

Answer 15

Thalidomide
o It was marketed as a safe to use drug for Hyperemesis Gravidarum (which occurs during the first 3 months of pregnancy)
o Considerably bad to take during the first 3-4 months of pregnancy
o The drug was discontinued and taken off the market in 1961
o It has affected around 10,000 babies worldwide
o Phocomelia –an undesirable reaction that resulted into babies which seal-like limbs

Question 16

ADRs: “Undesirable”

Thalidomide

Answer 16

malformations related to thalidomide use:
 Missing or malformed limbs (bilateral)
 No ears or deafness
 Partial or total loss of sight
 Improper formation of the heart, kidney, and other internal organs
 Improper formation of the anus and/or genitalia
 Cleft palate
 Flattening of the bridge of the nose

Question 17

ADRs: “Undesirable”
Orlistat (Xenical)
o Resulted in water stools (Undesirable)

Answer 17

Misoprostol (Cytotec)
o An anti-ulcer drug; powerful oxytoxic properties
o Resulted into the abortion of pregnant users (Undesirable)

Question 18

ADRs: “Undesirable”
Heparin
o Used to prevent thromboembolic disorders
o Resulted in bleeding (Undesirable)

Answer 18

Rifampicin
o Has been noted to cause the reddish discoloration of urine
o Jaundice has also been a noted adverse effect of the anti-Koch’s agents: isoniazid, rifampicin, and pyrazinamide (Anti-tuberculosis drugs)

Question 19

ADRs: “Unintentional”
Hives
o Appears as raised, itchy, map-like rashes
o Sedation – a side effect of some drugs such as antihistamines which can be favorable/unfavorable depending on the patient

Answer 19

Diazepam (Valium)
o Anxiolytic
o Sedation of family members due to diazepam during the wake – undesirable
o Given after the funeral – sedation may be wanted and therefore NOT an ADR

Question 20

ADRs: “Unintentional”
Proton Pump Inhibitor
o Periorbital swelling is a possible ADR (Unintentional and undesirable)

Answer 20

Captopril
o An ACE inhibitor that reduced levels of angiotensin II and prevents the inactivation of bradykinin (It’s a potent vasodilator)
 Indications: Hypertension, CHF and diabetic renal disease
 ADRs: Fetotoxicity – it is contraindicated in pregnancy, cough, hypotension, taste changes, rash, proteinuria, hyperkalemia, angioedema, & neutropenia

Question 21

ADRs: “Suspected (But has not always been proven)”

Answer 21

 Anaphylactic Shock (Due to Penicillin)
o It is not needed to prove by giving another dose
o The next episode may be fatal for the patient
 Accutane (Isoretinoin)
o It is not needed to prove anymore because clinical history validates this

Question 22

Teratogenic Drugs

drug:effect

Answer 22

Alcohol: Fetal alcohol syndrome
Isoretinoin: Facial, ear anomalies, congenital heart disease
Phenytoin: Hypoplastic nails, typical facies, IUGR
Diethylstilbestrol (DES): Vaginal adenocarcinoma
Tetracycline: Enamel hypoplasia, discolored teeth
Lithium: Ebstein’s anomaly
Warfarin: Facial dysmorphism and chondrodysplasia
Valproate/ Carbamezepine: Mental retardation
ACE inhibitors: Craniofacial abnormalities

Question 23

ADRs: “May develop as a consequence of therapy or other procedures”
Chloramphenicol
o It is a broad spectrum antibiotic
o Can cover for gram (+) and gram (-) bacteria & anaerobes

Answer 23

1. Aplastic anemia
    Due to hypersensitivity to the drug
    Due to overdosing
    Will result in the absence of red and/or white blood cells
2. Gray Baby Syndrome
    This is the result of enzyme deficiency causing the baby to turn gray. Due to the lack of glucoronidation reactions occurring in the baby leading to the accumulation of toxic substances: chloramphenicol & metabolites

Question 24

ADRs: “May develop as a consequence of therapy or other procedures”
Antihypertensive drugs

Answer 24

o Propranolol (Beta blocker) – Causes couching secondary to bronchoconstriction
o Nifedipine (Ca-channel blocker) – Causes the vasodilation of blood vessels in the body including those of the CNS; Can result into headaches
o Hydrochlorothiazide (Thiazide diuretic) – Causes overfrequent urination
o Hydralazine (Direct acting vasodilator) – Causes a lupus-like reaction in the face (Butterfly rash)
o Captopril (ACE inhibitor) – Causes halitosis

Question 25

RAWLINS AND THOMPSON’S CLASSIFICATION OF ADVERSE DRUG REACTIONS
**U.S. classification

Answer 25

1. Type A Adverse Reaction

2. Type B Adverse Reactions

Question 26

RAWLINS AND THOMPSON’S CLASSIFICATION OF ADVERSE DRUG REACTIONS (U.S. classification)
Type A Adverse Reaction
 It’s considered a Type A Adverse Reaction if it is expected because it is part of the usual pharmacological actions of the drug, except that the reaction is augmented or exaggerated
 Predictable: May be dose-dependent

Answer 26

Causes:
1. Pharmaceutical
o Altering of the quantity of the drug available for system absorption
o Influencing release rates
2. Pharmacokinetic
o Altering Drug Absorption
- biopharmaceutical factor; psychological factors
Examples: Digoxin, propantheline
o Altering drug Distribution
- Blood flow, capillary permeability to tissues, cardiac output, drug binding to plasma proteins, tissue lipid content, physiochemical properties of the drug, environmental pH
o Altering Drug Elimination
- Reduced rate may cause ADR
- Enhanced rate may cause therapeutic failure
Pharmacodynamics
o Increased sensitivity is related to:
- Drug receptor, disease, altered physiologic homeostatic mechanisms

Question 27

RAWLINS AND THOMPSON’S CLASSIFICATION OF ADVERSE DRUG REACTIONS (U.S. classification)
Type A Adverse Reaction

Answer 27

Types:
1. Primary (extension effect)
- The ADR is related to the drug’s known therapeutic actions
Examples:
Atropine – mouth dryness
Nitroglycerine – a powerful vasodilator that may cause headaches
Propranolol – May block beta-1 receptors and cause bronchoconstriction
Secondary
- If the ADR is different from the drug’s known therapeutic action; it can be predicted due to the MOA
Examples:
NSAIDs – May cause gastrointestinal ulcers due to its effect on PGE synthesis (PGs have protective functions, so a decrease in its synthesis results into a higher possibility of gastric irritations)

Question 28

RAWLINS AND THOMPSON’S CLASSIFICATION OF ADVERSE DRUG REACTIONS (U.S. classification)
Type B Adverse Reactions
 If the reaction is unrelated to the pharmacological actions
 It is idiosyncratic (unpredictable and not all will experience the reaction) and can be severe like in Steven Johnson Syndrome
 Incidence rate is approximately 1 in 6000 patients; hence it is undetected in clinical trials
 The ADR is unrelated to dosage (The MOA is not usually known)
 However, it becomes predictable when the mechanisms are known
 It is more likely to influence drug withdrawal from the market to avoid any more cases / ADRs

Answer 28

Causes:
1. Pharmaceutical
o The decomposition of active ingredients – tetracycline
o Toxic effects of excipients – polypropylene, glycol, tartrazine
2. Pharmacokinetic
o Usual metabolites possess toxic properties
3. Pharmacodynamic
o Genetics – slowly acetylators of INH (Peripheral neuropathy), hydralazine (Lupus-like disease)

Question 29

PHILIPPINE CLASSIFICATION OF ADR
Type A (AUGMENTED)

Answer 29

 Results from an augmented or exaggerated form of the drug’s usual pharmacological action
 Predictable, may protect patient
 May be related to dose
- May be side effect or,
- Primary toxic effect

Question 30

PHILIPPINE CLASSIFICATION OF ADR
Type B (BIZZARE)
 Unrelated to pharmacological actions
 Unpredictable, idiosyncratic, usually severe
 Happens in approximately 1 in 6,000 patients, making it undetectable in early clinical trials
 Unrelated to dosage
 May be predictable if mechanisms are known
 May be caused by either genetic, teratogenic and immunologic factors
 More likely to influence drug withdrawal from markets

Answer 30

Example: Stevens Johnson Syndrome
o Rare, serious disorder of the skin and mucous membranes caused by an adverse reaction
to medication or infection.
o Known medications that cause Stevens Johnson Syndrome are:
 sulfonamides
 penicillins
 antibiotics
 Dilantin (phenytoin)
 Bextra (valdecoxib)
o Bacterial and viral infection, such as the herpes simplex virus and mycoplasma
o Radiation therapy
o When ADR is suspected, stop the prescription of the drug immediately

Question 31

PHILIPPINE CLASSIFICATION OF ADR
Type C (CONTINUOUS)
 Long term effects usually related to dose and duration of the treatment.
 Commonly due to prolonged drug use.

Answer 31

Examples
Prolonged steroid use
o Hirsutism
o Buffalo hump
Ethambutol (anti-TB)
o Optic neuropathy

Question 32

PHILIPPINE CLASSIFICATION OF ADR
Type D (DELAYED)
 Observed after several months or years of observation period

Answer 32

Examples:
Diethylstilbestrol (DES)
o Marketed as “to prevent ABORTION, MISCARRIAGE and PREMATURE LABOR” and for “routine prophylaxis in ALL pregnancies”
o Can actually cause vaginal carcinoma
Fetal Alcohol Syndrome
o Caused by smoking/alcohol intake during pregnancy
o May lead to mental retardation
o Facial abnormalities:
o Microcephaly, short palpebral fissures, epicanthal fold, low nasal bridge, short nose, minor ear abnormality, micrognatha, thin upper lip, flat midface, indistinct philtrum

Question 33

PHILIPPINE CLASSIFICATION OF ADR
Type E (Ending of Use)
 Effects are observed after discontinuation of drug use

Answer 33

Examples:
 Clonidine (anti-hypertensive) – rebound hypertension, bleeding if stopped immediately
 Corticosteroids –acute adrenal insufficiency; this drug should be withdrawn slowly, especially if the patient has been on the drug for a long time
 Patients who have renal problems and allergies who need prolonged steroids
 Opioids – narcotic withdrawal symptoms

Question 34

PHILIPPINE CLASSIFICATION OF ADR
Type F (Failed Efficacy)

Answer 34

 Due to lack of drug efficacy
 Inappropriate medicine
 Drug interaction/drug incompatibility
 Tolerance to drug use
 Poor compliance
 Expired medications
 Under-dosing

Question 35

VULNERABLE POPULATIONS

Answer 35

High risk profile:
 Pregnancy
 Lactation
 Child
 Elderly
 Renal failure
 Hepatic failure
 History of reactions
 Other diseases
 Other medications

Question 36

Predisposition of Elderly to ADRs:

Answer 36

Increased sensitivity to drug effects
o Pharmacokinetic changes
- Changes in GI, hepatic, and renal function
- Changes in body composition
o Pharmacodynamic changes
- Changes in drug receptor dynamics
- Increased vulnerability to drug-drug and drug-disease interaction
Prevalence of predisposing conditions
o Insomnia – may result in increased use of sedatives
o Forgetfulness
o Loss of bone mass

Question 37

Drugs and Pregnancy

Mechanisms of Drug Teratogenicity

Answer 37

 direct action on fetus, causing damage, abnormal development (leading to birth defects), or death
 alter the function of the placenta
 cause uterine muscles contraction

Question 38

Smoking and Pregnancy
 Only 20% of women quit during pregnancy
 Most consistent effect: low birth weight

Answer 38

Increased incidence of:
o birth defects of heart, brain, and face
o SIDS
o uterine and placental problems
o stillbirths
o deficient physical growth and
o poor intellect

Question 39

TEN COMMANDMENTS FOR REDUCING ADRS:

1

Answer 39

Use as few drugs as possible

Question 40

TEN COMMANDMENTS FOR REDUCING ADRS:

2

Answer 40

Know well the drugs you use.

Question 41

TEN COMMANDMENTS FOR REDUCING ADRS:

3

Answer 41

Do not change too readily from one drug you know to another one you don’t know and if you decide to use a new drug, acquaint yourself with its pharmacology, interactions, metabolism, and adverse effects

Question 42

TEN COMMANDMENTS FOR REDUCING ADRS:

4

Answer 42

Do not hesitate to use textbooks and tables providing information on drug reaction and drug interactions. No physician or pharmacologist, not even specialists in clinical pharmacology, can remember all the potential drug interactions without consulting these texts

Question 43

TEN COMMANDMENTS FOR REDUCING ADRS:

5

Answer 43

Be especially careful when you prescribe drugs known to exhibit a large variety of interactions such as anticoagulants, oral hypoglycemics, anti-inflammatory drugs, and drugs affecting the central nervous system.

Question 44

TEN COMMANDMENTS FOR REDUCING ADRS:

6

Answer 44

Look at lists of drugs your patient is receiving. If you see that the list is getting too long, think carefully whether you can discontinue some of the medicine. If this is not possible, look at the list again, with drug interactions in mind.

Question 45

TEN COMMANDMENTS FOR REDUCING ADRS:

7

Answer 45

Be aware of interactions of drugs with certain foods, alcohol, and even household chemicals

Question 46

TEN COMMANDMENTS FOR REDUCING ADRS:

8

Answer 46

Review with your patient regularly, all the drugs he/she is taking and especially those bought without prescription

Question 47

TEN COMMANDMENTS FOR REDUCING ADRS:

9

Answer 47

Be particularly careful when you prescribe for children, the elderly, the seriously ill and the patient with hepatic and renal disease. Adverse drug effects are more frequent in these groups.

Question 48

TEN COMMANDMENTS FOR REDUCING ADRS:

10

Answer 48

If your patient shows symptoms or signs not clearly explained by the course of their illness, think of adverse drug reactions or drug interaction. You may well find the answer

Question 49

KEY ELEMENTS IN REPORTING ADRS
For Suspected ADRs
 Stop the drug immediately
 Reduce dose immediately
 Notify the hospital ADR committee of the NADRMC

Answer 49

Four Key Elements
 Patient Details
 Medication Details
 Reaction Details and Outcome
 Reporter Details – reported ADR is helpful and useful for patients

Question 50

KEY ELEMENTS IN REPORTING ADRS

Important Information in ADR Reporting

Answer 50

 Name of the suspected drug
- Include brand name
- For vaccine, provide batch/lot number
 Description of the reaction
 Information of the patient
 Contact number of the person who submits the report
**In ADR Monitoring, always try to determine:
- Brand name of the drug
- Where the drug comes from