Adverse Drug Reactions, Rational Drug Use (trans 8) Flashcards
THE PROCESS OF RATIONAL THERAPY
- Define the patient’s problem
- State the therapeutic goals/objectives
- Determine non-drug therapy
- Make an inventory of effective groups of drugs
- Choose an effective group according to the ESSA/SANE criteria
- Choose a p-(personal) drug
- Start therapy
- Give information, instructions, and warning to the patient
- Monitor (and/or stop) therapy
THE PROCESS OF RATIONAL THERAPY:
State the therapeutic goals/objectives
**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
THE PROCESS OF RATIONAL THERAPY: Make an inventory of effective groups of drugs
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
THE PROCESS OF RATIONAL THERAPY:
Choosing an effective group according to the ESSA/SANE criteria
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
REMEMBER
In a life and death emergency:
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.
THE PROCESS OF RATIONAL THERAPY:
Choosing an effective group according to the ESSA/SANE criteria
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
THE PROCESS OF RATIONAL THERAPY:
Choosing an effective group according to the ESSA/SANE criteria
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
THE PROCESS OF RATIONAL THERAPY:
Choosing an effective group according to the ESSA/SANE criteria
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
THE PROCESS OF RATIONAL THERAPY:
Choosing an effective group according to the ESSA/SANE criteria
Patient refuses any oral drug and vomits it.
For Need/Suitability- parenteral route is primarily considered
Affordability may have to be sacrificed for Suitability
THE PROCESS OF RATIONAL THERAPY:
Choosing an effective group according to the ESSA/SANE criteria
Pregnant celebrity
While efficacy is always considered, safety becomes an important consideration
Affordability not a problem
Availability not likely a problem
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
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)
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
Pregnant Patients
The average number of drugs taken during the 10 lunar months of conception: more than 5 drugs (Excludes multivitamins)
The science and activities relating to the detection, evaluation, understanding and prevent of adverse drug reactions or any other drug related problems.
Pharmacovigilance
SERIOUS ADVERSE DRUG REACTIONS
Defined as: An adverse reaction which is fatal Is life-threatening Results in or prolongs hospitalization Causes persistent incapacity or disability Causes birth defects
ADRs: “Undesirable”
Niacin (Vit. B3)
o Has been known to cause “flushing”
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
ADRs: “Undesirable”
Thalidomide
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
ADRs: “Undesirable”
Orlistat (Xenical)
o Resulted in water stools (Undesirable)
Misoprostol (Cytotec)
o An anti-ulcer drug; powerful oxytoxic properties
o Resulted into the abortion of pregnant users (Undesirable)
ADRs: “Undesirable”
Heparin
o Used to prevent thromboembolic disorders
o Resulted in bleeding (Undesirable)
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)
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
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
ADRs: “Unintentional”
Proton Pump Inhibitor
o Periorbital swelling is a possible ADR (Unintentional and undesirable)
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
ADRs: “Suspected (But has not always been proven)”
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
Teratogenic Drugs
drug:effect
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
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
- Aplastic anemia
Due to hypersensitivity to the drug
Due to overdosing
Will result in the absence of red and/or white blood cells - 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
ADRs: “May develop as a consequence of therapy or other procedures”
Antihypertensive drugs
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
RAWLINS AND THOMPSON’S CLASSIFICATION OF ADVERSE DRUG REACTIONS
**U.S. classification
- Type A Adverse Reaction
2. Type B Adverse Reactions
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
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
RAWLINS AND THOMPSON’S CLASSIFICATION OF ADVERSE DRUG REACTIONS (U.S. classification)
Type A Adverse Reaction
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)
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
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)
PHILIPPINE CLASSIFICATION OF ADR Type A (AUGMENTED)
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
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
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
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.
Examples Prolonged steroid use o Hirsutism o Buffalo hump Ethambutol (anti-TB) o Optic neuropathy
PHILIPPINE CLASSIFICATION OF ADR
Type D (DELAYED)
Observed after several months or years of observation period
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
PHILIPPINE CLASSIFICATION OF ADR
Type E (Ending of Use)
Effects are observed after discontinuation of drug use
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
PHILIPPINE CLASSIFICATION OF ADR Type F (Failed Efficacy)
Due to lack of drug efficacy Inappropriate medicine Drug interaction/drug incompatibility Tolerance to drug use Poor compliance Expired medications Under-dosing
VULNERABLE POPULATIONS
High risk profile: Pregnancy Lactation Child Elderly Renal failure Hepatic failure History of reactions Other diseases Other medications
Predisposition of Elderly to ADRs:
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
Drugs and Pregnancy
Mechanisms of Drug Teratogenicity
direct action on fetus, causing damage, abnormal development (leading to birth defects), or death
alter the function of the placenta
cause uterine muscles contraction
Smoking and Pregnancy
Only 20% of women quit during pregnancy
Most consistent effect: low birth weight
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
TEN COMMANDMENTS FOR REDUCING ADRS:
1
Use as few drugs as possible
TEN COMMANDMENTS FOR REDUCING ADRS:
2
Know well the drugs you use.
TEN COMMANDMENTS FOR REDUCING ADRS:
3
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
TEN COMMANDMENTS FOR REDUCING ADRS:
4
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
TEN COMMANDMENTS FOR REDUCING ADRS:
5
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.
TEN COMMANDMENTS FOR REDUCING ADRS:
6
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.
TEN COMMANDMENTS FOR REDUCING ADRS:
7
Be aware of interactions of drugs with certain foods, alcohol, and even household chemicals
TEN COMMANDMENTS FOR REDUCING ADRS:
8
Review with your patient regularly, all the drugs he/she is taking and especially those bought without prescription
TEN COMMANDMENTS FOR REDUCING ADRS:
9
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.
TEN COMMANDMENTS FOR REDUCING ADRS:
10
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
KEY ELEMENTS IN REPORTING ADRS For Suspected ADRs Stop the drug immediately Reduce dose immediately Notify the hospital ADR committee of the NADRMC
Four Key Elements Patient Details Medication Details Reaction Details and Outcome Reporter Details – reported ADR is helpful and useful for patients
KEY ELEMENTS IN REPORTING ADRS
Important Information in ADR Reporting
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
