Medicine safety

Adverse drug reactions and drug interactions

Peter Nuwagira
 Objectives
• Define adverse drug reactions
• Describe common adverse drug reactions encountered at a
community pharmacy
• Define and discuss potential drug interactions encountered at
community pharmacies
• Outline strategies to overcome/minimize these adverse drug
reactions and drug interactions
• Describe drugs used in different trimesters in pregnancy
• Describe the available strategies of incident reporting by
National Pharmacovigilance center of NDA
• Outline the role of auxiliary staff in national pharmacovigilance
plan
 Background
• ADRs are the 4-6th largest cause of mortality in
some countries
• Percentage of hospital admissions due ADRs is
10-20%
• Concomitant high economic impact on health
care services.
• An average of 15-20% of health care budget
spent on drug related problems
 Definitions
• Side effect. Unintended effect of a pharmaceutical
product that occurs at doses normally used in
man, is related to the pharmacology of the drug
(WHO)
• Adverse drug reaction. Any response to a drug
which is noxious and unintended and which occurs
at doses normally used in man for prophylaxis,
diagnosis or therapy (WHO)
• Drug hypersensitivity. An immune-mediated
response to a drug agent in a sensitized patient.
• Drug allergy is restricted specifically to a reaction
mediated by IgE
 Definitions
• Drug interactions
 A drug interaction occurs when the effects of
one drug are altered by the presence of
another drug, food, drink or an environmental
chemical. The net effect may be synergistic (or
additive), antagonistic or alteration of effect
 Common side effects/ADRs
• Drug allergic reactions characterized by itching, skin
rash/eruption, swelling around the mouth. Occurs in
some individuals. Commonly due to penicillins and
sulphonamides
• Abdominal discomfort e.g. abdominal pain, feeling of
full stomach, diarrhoea, nausea, vomiting
(diclofenac, aspirin)
• Drowsiness (feeling sleepy and unable to remain
alert) e.g. chlorpheniramine
• Others. Headache, photosensitivity
 Mechanisms of ADRs
• Idiosyncrasy
• Hypersensitivity
• Intolerance
• Drug interaction
• pharmacologic
 Drug interactions
• Can occur in the GIT, blood, liver, the kidneys or site
of action
• GIT e.g food decreases absorption of penicillins,
antiacids reduce absorption of Ketoconazole
• Blood e.g valproate displaces phenytoin from binding
sites
• Liver e.g. rifampicin stimulates liver enzymes that
break down oral contraceptives, cimetidine inhibits
enzymes that break down diazepam
• Kidney e.g penicillins and probenecid
• Site of action e.g alcohol and antidepressants
What are predisposing factors to ADRs
• Many drugs
• Age- elderly and young are at risk
• Gender- women more likely
• Chronic diseases e.g kidney and renal diseases
• Genetic e.g absence of certain enzymes
• Drug allergies
 How do you prevent ADRs
• Use drugs only for the right indication;
• Avoid drugs in pregnancy unless it is unavoidable;
• Recognise allergy
• Always ask patients about self medication to check for
interactions;
• Avoid polypharmacy; if the patient is taking too many
drugs, alert the prescriber.
• Ensure patients understand instructions on dosage and
storage;
• Warn patient of potential ADRs;
• Look out for the elderly or patents with renal disease,
hepatic disease
 Preventing ADRS
• Report ADRs/document ADRs
• Education and training
• Intraprofessional communication
Always observe the 5 rights
• Right patient
• Right drug
• Right dose
• Right time
• Right route
 ADR reporting
• NDA National pharmacovigilance centre –
receives reports of ADRs
• Pharmacovigilance is concerned with
detection, assessment and prevention of ADR
• ADR reporting systems generally require that a
form be completed that describes the ADR,
how it was treated and its outcome
 Why pharmacovigilance?
• Animal tests insufficiently predictive of human
safety
• Limited patients, duration of trials and
different conditions from those of clinical
practice during clinical trials
• Info about rare and serious adverse reactions,
chronic toxicity, use in special conditions or
drug interactions is often incomplete or not
available
 Aims of pharmacovigilance
• Early detection of hitherto unknown adverse
reactions and interactions
• Detection of increases in frequency of (known)
adverse reactions
• Identification of risk factors and possible
mechanisms underlying adverse reactions
• Estimation of quantitative aspects of benefit/risk
analysis and dissemination of information needed
to improve drug prescribing and regulation.
 Goals of Pharmacovigilance
• the rational and safe use of medical drugs
• the assessment and communication of the
risks and benefits of drugs on the market
• educating and informing of patients.
 Reporting system
• Spontaneous reporting is regional or country
wide system of reporting suspected ADRs.
Primary method in pharmacovigilance
• Major source of information for the National
pharmacovigilance centre
 What to report?
• All suspected adverse reactions- known or
not, serious or not
• Lack of efficacy and suspected pharmaceutical
defects
 Report form-info
• The patient: age, sex and brief medical history
(when relevant).
• Adverse event: description (nature, localisation,
severity, x-tics, results of investigations and
tests, start date, course and outcome.
• Suspected drug(s): name (brand or ingredient
name + manufacturer), dose, route, start/stop
dates, indication for use (with particular drugs,
e.g. vaccines, a batch number is important).
 Report form- info
• All other drugs used (including self-medication):
names, doses, routes, start/stop dates.
• Risk factors (e.g. impaired renal function,
previous exposure to suspected drug, previous
allergies, and social drug use).
• Name and address of reporter (to be considered
confidential and to be used only for data
verification, completion and case follow-up)
 Use of drugs during pregnancy
• Medicines taken by the pregnant woman may
enter through the placenta to the blood stream
of the baby
• Benefits and risks of their use must weighed
• Effects on the unborn baby depends on the
trimester and the medicines taken
• Some medicines are harmful through out
pregnancy while others at specific
trimesters/stages
 First trimester
• Stage of organ formation
• Drug use can lead to malformations of parts of
fetus such as the heart, the limbs and facial
gestures
• Unless otherwise, drugs should be avoided at
this stage
 Second trimester
• Stage of prenatal growth
• Rapid growth of fetus in size and weight
• Medicine use can damage the organs that are still
developing such as the eyes and the nervous system
• Continued medicine use increases the risk of
miscarriage and premature delivery
• Intra-uterine growth retardation is likely to result in
low birth babies-baby born too early, too small or
both
 Third trimester
• Stage of birth
• Medicines may complicate delivery making it
difficult or create health problems for the new
born baby
 Examples of some medications and their
effects during pregnancy
• Alcohol- fetal alcohol syndrome- cluster of defects
such as microcephaly, facial and heart malformations
• Anticonvulsants, such as phenytoin (Dilantin) and
carbamezapine (Tegretol), used to prevent epileptic
seizures are associated with defects of the heart and
face, as well as mental retardation
• Isotretinoin (Accutane) and etretinate (Tegison) used
to treat chronic acne and psoriasis may cause chronic
malformations during the stage of organ development
 Examples con’t
• Antimigraine drugs, such as ergotamine and methysergide used to
head off migraine attacks raise the risk of premature labor
Aspirin, ibuprofen, and other non-steroidal anti-inflammatory
drugs (NSAIDs) interfere with blood clotting and increase the risk
of uncontrolled bleeding for both mother and baby. Toward the
end of pregnancy, they hinder production of the hormones that
stimulate labor, so that labor may be dangerously delayed or
extended.
• Anticoagulant drugs such as warfarin used in the treatment of
heart disease and stroke, to slow blood clotting are associated
with facial malformations during early pregnancy and mental
retardation. Later on they raise the risk of uncontrolled bleeding.
 Some of the least harmful drugs during
pregnancy
• Category A: These drugs have been tested and found to
be safe during pregnancy e.gs folic acid, vitamin B6, and
some thyroid medicines in prescribed doses.
• Category B: These drugs are frequently used during
pregnancy and do not appear to cause major birth
defects or other problems e.gs some antibiotics,
acetaminophen (Tylenol), aspartame (artificial
sweetener), famotidine (Pepcid), prednisone (cortisone),
insulin (for diabetes), and ibuprofin (Advil, Motrin) before
the third trimester. Pregnant women should not take
ibuprofen during the last three months of pregnancy.
 Conclusion
• It’s wise to avoid use of medicines during
pregnancy, but some times medicine therapy
is warranted.
• Always make sure the medicine given to the
patient is safe or the benefits of the
medication out weighs the risks