Improving drug safety

The following topics should be considered:

1-Select the suitable drug for each case.

2-Avoid high-risk drugs.

3-Avoid multiple medications

4-Discontinue unnecessary drugs.

5-Avoid treating side effects with another drug as

possible.

6-Avoid drug-drug interactions& drug–food

interactions by understanding of interactions between
drugs& biological system.

7-Adjust dosing based on age and renal and hepatic

functions

8-Take care of precautions& contraindications of

using drugs.

9-Early detection and accurate prediction of ADRs is

vital for drug development and patient safety

10-Avoid or minimize drug adverse effects by:

-Many adverse effects can not be avoided but we can prevent or
minimize some of the adverse effects as follows:

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 -We can avoid toxicity by careful adjustment of the dose and
avoidance of overdoses.
-We can avoid manifestations of abrupt withdrawal with
gradual withdrawal of certain drug..
-Some allergic reactions can be avoided if sensitivity test is
performed before using the drug.

-Management of adverse effects.

-Some mild adverse effects may need no therapy.
-Severe adverse effects may require discontinuation of the drug
and change of the drug therapy.
-Some severe adverse effects require intake of the specific
antidote, if it is available.
-Symptomatic treatment or hospitalization & intensive care in
severe or life threatening cases.

11-Post-marketing surveillance can discover the

genetic and phenotypic risk factors of ADRs.
.

12-Precautions of using drugs in special cases e.g

newborn, and elderly, during menstruation, pregnancy, labor
and lactation, in presence of certain diseases, liver, renal ,
cardiovascular, endocrinal , metabolic diseases e,g
diabetes……..etc.

13-Avoid drug toxicity which may occur by:

1-Over doses of drugs lead to acute drug toxicity.
2-Impairement of drug biotransformation
3-Additive/ synergistic responses of co-administered drugs.
4-Displacement of drugs from their plasma proteins sites.
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5-Interference with drug excretion
6-Drug accumulation

- Management of acute drug toxicity:

1-Assessment of the vital functions, (respiration, airways, pulse,
blood pressure and temperature) and general supportive measures.
2-Blood sample should be withdrawn, immediately for
determination of glucose and electrolyte levels, blood gases as
well as for testing renal and hepatic functions.

3-Prevention of further absorption:

a-If the drug is taken orally, the following steps should be
done:
-Induction of emesis (if the patient is conscious) or gastric
lavage.
-Chemical inactivation by neutralization. If the drug is acidic
and irritant and given orally e.g salicylates, dilution by using
water& milk followed by gastric lavage may be required to
minimize the irritant effect and to avoid ulceration of gastric
mucosa..
-Physical adsorption by oral charcoal if the patient is conscious..
-Induction of diarrhea by using cathartics e.g. castor oil.
b-In case of inhalation:Stop inhalation and remove the patient
from the source of exposure to a fresh air area.
c-If the drug is absorbed from skin:Remove the contaminated
clothes and wash the skin by water and soap.
4-Enhancement of excretion and clearance: by giving
diuretics to produce forced diuresis or by preventing
reabsorption via alkalinization or acidification of urine
according to whether the drug is acidic or alkaline or even
dialysis in severe cases.
5-Pharmacological antagonism by giving the specific antidote
or the pharmacological antagonist as early as possible, if it is
available.
Examples:
-Naloxone is given for acute toxicity of opioids.
-Atropine is given for acute poisoning of cholinergic drugs and
organophosphate poisoning.
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-Neostigmine is given for acute toxicity of competitive
neuromuscular blockers ( e.g. d-tubocurarine).
-Flumazenil is given for acute toxicity of benzodiazepines.

6-Physiological antagonism or symptomatic therapy if there

is no specific antidote or even in presence of the antidote if the
manifestations are severe e.g. convulsions, hyperpyrexia,….etc.

7-Management of the complications:

Examples:
-Blood transfusion in case of hemorrhage.
-Fluid intake in case of dehydration.
-i.v. concentrated glucose in case of hypoglycemic coma.
-Digitalization in case of heart failure.
-Management of shock.

Management of chronic toxicity

1-Discontinuation of the drug if possible and necessary.
2-Reducing and careful adjustment of the dose if the drug
discontinuation is not possible.
3-Symptomatic treatment.
4-Supportive measures if required.

.
14-Avoid abrupt withdrawal of certain drugs e.g beta
blockers, clonidine, corticosteroids, opioids, antidepressants,
antipsychotics, sedatives & hypnotics, antiepileptics,
antiparkinsonian drugs,…etc., should be gradual if their
discontinuation is must, to avoid serious withdrawal
manifestations which may be fatal.
-Readministration of the drug can terminate the withdrawal
manifestations abruptly.
-All patients taking these drugs should be warned and informed
about hazards of abrupt withdrawal.
-If discontinuation of the drug is must, its withdrawal should be
gradual with substitution with other suitable alternative if
required.

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15-Management of drug addiction:
1-Hospitalization (inpatients programs) or out-patients
programs.
2-Psychotherapy, social care and avoidance of the predisposing
factors e.g. social problems and good nutrition.
3-Gradual withdrawal of the addicting substance.
4-For opioids; Substitution of the highly addicting substance
with less addicting substance that possess the same actions e.g.
substitution of opioids e.g. morphine, heroin and others with
methadone, the synthetic less addicting opioid which possesses
the same actions. These less addicting substances should be also
withdrawn gradually later on.

-Management of alcoholism;
1-Substitution of alcohols with benzodiazepines (detoxication),
then benzodiazepines should be gradually withdrawn.
2-Good nutrition with restoration of potassium, phosphate and
magnesium balances and intake of thiamine.

16-Avoid Secondary effects of drugs as possible e.g

avoid antibiotic misuse:
-Antibiotic- induced moniliasis and pseudomembraneous colitis
due to inhibition of the intestinal flora and emergence of
resistant organisms.

17-Detect and Manage drug allergy:-

-Detection of allergy:-
1-Skin scratching and intradermal tests, for type-1 anaphylactoid
hypersensitivity reactions.
2-Serum immunoglobulins & specific antibodies to various
agents

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3-Total lymphocyte count & percentage of T & B cells.

Management of drug allergy:

1-Immediate discontinuation of the drug. Most mild drug
reactions e.g. skin rash subsides spontaneously after
discontinuation.
2-In mild anaphylactoid (type-I)reactions, antihistaminics are used.
3-In severe anaphylactoid (type-I)reactions e.g. anaphylactic
shock, severe bronchospasm, angioedema or edema of the
larynx, the following should immediately done:
a-Putting the patient in shock position (in case of hypotension or
shock), administration of oxygen at high flow rate with
cardiopulmonary resuscitation if required.
b-Injection of adrenaline i.m.
c-Injection of corticosteroids e.g. hydrocortisone i.v.
d-Injection of chlorpheniramine (antihistaminic) i.m.or i.v.
e-Theophylline also can be used as a bronchodilator and to
inhibit liberation of allergic mediators
4-For type-II& III humoral and the cell mediated reactions, oral
corticosteroids e.g. prednisolone are used.

18-Avoid drugs during pregnancy if possible, or use drugs of

proven safety if necessary & use the smallest doses for short periods.

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19-Drug-induced idiosyncratic reactions:
1-Succinylcholine apnea:
Causes:1-Genetic deficiency of pseudo or
butyrylcholinesterase. The enzyme which normally, it
degradates succinylcholine (the depolarizing neuromuscular
blocker used in surgery).
2-Presence of atypical slowly acting peudocholinesterase
enzyme. Genetic deficiency or presence of atypical slowly
acting enzyme, leads to accumulation of succinylcholine and
prolongation of its relaxant effect on respiratory skeletal
muscles leading to apnea which may last for several hours after
discontinuation of infusion.
Management: Artificial respiration, mechanical ventilation or
oxygen inhalation -Other supportive measures.
2-Malignant hyperthermia:
The cause: Increase in the sarcoplasmic (free intracellular)
calcium due to genetic factor leads to violent contractile effect
on the skeletal muscles leading to excessive heat production.
Clinical manifestations: Malignant hyperthermia is a disorder,
characterized by tachycardia, arrhythmia, very high fever (more
than 42), muscular rigidity and lactic acidosis.
Precipitating drugs: The condition may occur in susceptible
individuals with inhalational halogenated general anesthetics
e.g. halothane and with succinylcholine. The incidence is
increased in with their combination.
Management:
1-Dantroline (the direct skeletal muscle relaxant which act by
inhibiting release of calcium from its intracellular stores).
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2-External cooling (e.g. by cold water fomentations or cooling
blankets and removal of cloths to help evaporation of heat.
3-Carbonates for acidosis.
4-Oxygen inhalation or ventilation for respiratory distress.

3-Drug-induced haemolysis:
Causes: 1-Genetic deficiency of glucose-6 phosphate
dehydrogenase.
2-Deficiency of glutathione which is essential for preserving the
erythrocyte membrane viability.
3-Presence of abnormal hemoglobins.
-Glucose -6-phosphate dehydrogenase is required for
regeneration of glutathione from its binding.
-Deficiency of the Glucose -6- phosphate dehydrogenase
enzyme leads to depletion of glutathione resulting in loss of
viability and integrity of the cell membrane of erythrocytes
leading to hemolysis & hemolytic anemia.
-Drugs and chemicals that have been shown to cause hemolytic
anaemia in G6PD deficiency include; niridazole,
nitrofurantoin, primaquine, sulfacetamide, sulfamethoxazole
…etc.
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