Adverse Drug Reactions (ADRs)


Script, 2018

30 Pages, Grade: A


Excerpt


List of Contents

1. Definition

2. Incidence

3. Classification of Adverse Drug Reactions

4. Drug Hypersensitivity

5. Immunologic and Non-Immunologic Drug Reactions

6. Immune Reaction, Its Mechanism, Clinical Manifestations

7. Hypersensitivity Syndromes of Specific Drug

8. Mechanisms

9. Examples of Adverse Effects Associated with Specific Drugs

14. Predisposing Factors

15. ADR Monitoring

16. Spontaneous Reporting

17. Preventing ADRs

18. Communicating

19. Educating

20. Documenting

21 References

INTRODUCTION

DEFINITION

The WHO defines an “Adverse Drug Reaction as any response to a drug which is noxious and unintended and which occurs or doses normally used in a man of prophylaxis diagnosis or therapy of disease or for the modification of physiologic function".1,2

Adverse Drug Reactions (ADRs) are types of Adverse Drug Events (ADEs). Adverse Drug Events include ADRs, prescription errors, medication errors and other drug-related problems. ADEs are the negative consequences’ of drug misadventures. Henri Manasse defined drug misadventure as the iatrogenic hazard that is an inherent risk when drug therapy is indicated.

The American Society of Health-System Pharmacists (ASHP) defines significant ADRs as an unexpected, unintended, undesired, or excessive response to a drug that includes the following. 3,4,5

- Requires discontinuing the drug
- Requires changing the drug therapy
- Requires modifying the dose
- Necessitates admission to the hospital
- Prolongs stay in a healthcare facility
- Necessitates supportive treatment
- Significantly complicates diagnosis
- Negatively affects prognosis or results in temporary or permanent harm, disability or death.

Pharmacovigilance is an integral part of drug therapy. But it is still not widely practised in the hospitals of India. In many studies, adverse drug reactions have been considered as a leading cause of morbidity and mortality. The incidence of adverse drug reactions varies with studies which show incidences ranging from as low as 0.15% to as high as 30%. Older adults and hospitalized in-patients are shown to be more susceptible to ADRs than the adult population (16.6% vs. 4.1%). Indian reports on ADR monitoring have been very few. This may be because ADR monitoring is still evolving here. After decades of hibernation, the need for an efficient pharmacovigilance programme was felt, the result of which was the institution of National Pharmacovigilance Programme in November 2004. Under this programme, the Central Drugs Standards Control Organization, New Delhi officiates as the central coordinating body under which two zonal, five regional and 24 peripheral centres have been established. The objective of this programme is to create awareness among the health professionals on ADR monitoring and to encourage a reporting culture. ( 3)

Hospital-based ADR monitoring and reporting programmes aim to identify and quantify the risks associated with the use of drugs. This is important information which is useful in identifying and minimizing the ADRs where it can be preventable and generally enhances the knowledge of the physicians to deal with ADRs more efficiently and effectively. The participation of pharmacists in national pharmacovigilance programmes is not a common feature. The pharmacist's involvement in such programmes is seen only in some countries. In India, clinical pharmacy is still evolving and hence, pharmacists involvement in such activities has been low. The aim of the present study was to undertake ADR monitoring in a government hospital where a clinical pharmacy programme is well established. The primary objectives included monitoring and documenting ADRs and evaluating them according to set criteria. The secondary objective was to analyze the cost burden involved in managing ADRs.6

INCIDENCE

The frequency of ADRs in the general population is unknown. However, the reported rates of new occurrences for ADRs are noted for selected patient7-10 populations. A meta-analysis of 39 prospective studies reported an overall incidence of serious ADRs in hospitalized patients of 6.7% and of fatal ADRs of 0.32%. The fatality rate makes ADRs the fourth to the sixth leading cause of death in the United States. Another meta-analysis of 36 studies indicated that approximately 5% of hospital admissions are due to ADRs. The costs of ADRs are estimated to be $1.56-$4 billion in direct hospital costs per year in the United States.

CLASSIFICATION OF ADVERSE DRUG REACTIONS 11

According to the Wills & Brown classification, these ADRs are classified

Type A: Augmented Reactions

Type A reactions are dose-related actions of a medicine upon the human body, which could have been predicted based upon a knowledge of the mode of action and pharmacology of a drug or excipient. These reactions can only occur while the subject is still receiving the preparation and improve partially or completely when the causative agent is withdrawn or the dose reduced.

Type B: Bugs Reactions

These are adverse reactions that rely upon promoting the growth of certain microorganisms. These type B reactions are pharmacologically predictable events, but they do not type A according to the definition used in the preceding section since the direct and principal pharmacological action is on the bodies of microorganism rather than on the human body. Examples include sugar-containing medicines promoting dental caries, antibiotics causing overgrowth of resistant bacterial species in the intestine, broad-spectrum antibiotics causing oral thrush and over the use of one agent stimulating the development of resistance among a specific species of microorganism rendering further use of the agent ineffective.

Note that an infection arising as a result of drug-induced immune-suppression would not be a type B reaction. The primary adverse event in such a case would be suppression of the human immune system, which is usually a type A reaction. Infections arising as a result of this would be a secondary event.

Type C: Chemical Reactions

A number of adverse reactions depend upon the chemical nature of a drug or excipient rather than pharmacological properties. They are all basically forms of chemical irritation, which makes it likely that, when exposed to the preparation, most people could experience a similar reaction. The severity of a type C reaction is more a function of the concentration of the offending substance than dose.

The side-effects which are typical in this category include extravasation reactions, vein inflammation, inflammation and pain at the site of an injection owing to the irritant action of a drug or excipient, acid or alkali burns, contact (irritant) dermatitis and gastrointestinal mucosa damage caused by the local irritant action. All these reactions are not so predictable pharmacologically, but knowledge may enable on the physicochemical characteristics of the causative agents to be foreseen on them.

Type D: Delivery Reactions

A variety of adverse reactions occur as a specific consequence of the method of drug delivery. These reactions do not depend upon the chemical or pharmacological properties of the constituents of the preparation but occur because of the physical nature of the formulation and/or the method of administration. These reactions will be heterogeneous. Methods of delivery vary and so the specific nature of the adverse reactions must also vary.

The unifying characteristic is that, if the method of delivery is changed, the adverse reaction will cease to occur. Examples such as inflammation or fibrosis around implants, thrombosis or occlusion of blood vessel due to injection particles, a tablet lodging in the throat, inhaling the ‘dust cap’ of an inhaler, cough after using a dry powder inhaler, infections at the site of an injection (owing to the opening of a port of entry for bacteria) and infections because of contamination of injection solution with microorganisms.

Type E: Exit Reactions

These are known as withdrawal reactions and are a manifestation of physical dependence. It is only possible for them to occur after administration of the medicine has ceased or the dose suddenly reduced. Unlike all other adverse reactions, which typically worsen if the causative agent is continued, the reintroduction of the drug will actually ameliorate symptoms. The likelihood of a reaction is linked more to the duration of administration than dose. In addition, although these reactions are pharmacologically predictable to an extent, the development of withdrawal reactions is not universal. Many patients do not experience them despite continuous high dose exposure.

Type F: Familial Reaction

Certain adverse drug reactions occur only in susceptible individuals with genetically determined, inherited metabolic disorders. Some of the more common familial disorders include phenylketonuria, glucose 6-phosphate dehydrogenase deficiency; esterase inhibitor deficiency, porphyria and sickle cell anaemia.

These reactions must not be confused with those that occur because of the normal variation inability to metabolize a drug among the population. For example, up to 10% of the population of the western world are deficient in CYP 2D6. However, this does not make them liable to suffer unique adverse effects compared with the rest of the population.

Type G: Genotoxicity Reactions

A number of drugs can produce genetic damage in humans. Notably, some are potentially carcinogenic or genotoxic. Some, but not all, teratogenic agents damage genetic material within the foetus.

Type H: Hypersensitivity Reactions

These are side-effects caused by allergy or hypersensitivity. They are probably the most common adverse reactions after Type A reactions. There are many different types, but all involve activation of an immune response. They are not pharmacologically predictable and neither are they dose-related according to the definition of ‘dose-dependent' given above (although very small doses can sometimes be used for desensitization). Accordingly, reducing the dose does not usually lead to amelioration of symptoms; the drug must be stopped. Some examples are anaphylaxis, allergic skin rashes, Stevens-Johnson syndrome, photoallergy, acute angioedema, hypersensitivity, cholestasis and hypersensitivity mediated blood dyscrasias.

Type U: Unclassified Reactions

Some ADRs have a mechanism that is not understood and these must remain unclassified until more is known about them. This may necessitate the introduction of new adverse reaction categories in the future. Examples include drug-induced taste disturbance, muscular adverse effects of Simvastatin, and nausea and vomiting after a gaseous general anaesthetic. The severity of the reaction was determined according to Hartwig et al. as given below (12)

Mild reactions which were self-limiting and able to resolve over time without treatment and did not contribute to the prolongation of the length of stay.

Moderate ADRs were defined as those that required therapeutic intervention and hospitalization prolonged by 1 day but resolved in <24 h or change in drug therapy or specific treatment to prevent a further outcome.

Severe ADRs were those that were life-threatening, producing disability and those that prolonged hospital stay or led to hospitalization required intensive medical care or led to the death of the patient.12,13

Patient outcomes were reported as:

- Fatal
- Fully recovered (Patient fully recovered during hospitalization)
- Recovering (Patient recovering, but not fully recovered during hospitalization)
- Unknown (not documented)

DRUG HYPERSENSITIVITY

The terms “drug allergy,” “drug hypersensitivity” and “drug reaction” are often used interchangeably. Drug reactions encompass all adverse events related to drug administration, regardless of aetiology. Drug hypersensitivity is defined as an immune-mediated response to a drug agent in a sensitized patient. Drug allergy is restricted specifically to a reaction mediated by IgE. Drug reactions can be classified into immunologic and nonimmunologic etiologies. The majority (75 to 80 percent) of adverse drug reactions are caused by predictable, non- immunologic effects. The remaining 20 to 25 percent of adverse drug events are caused by unpredictable effects that may or may not be immune- mediated. Immune-mediated reactions account for 5 to 10 percent of all drug reactions and constitute true drug hypersensitivity, with IgE-mediated drug allergies falling into this category.

IMMUNOLOGIC AND NONIMMUNOLOGIC DRUG REACTIONS14,15

Abbildung in dieser Leseprobe nicht enthalten

The following classification describes the predominant immune mechanisms that lead to clinical symptoms of drug hypersensitivity. This classification includes: Type I reactions (IgE-mediated); Type II reactions (cytotoxic); Type III reactions (immune complex); and Type IV reactions (delayed, cell-mediated). However, some drug hypersensitivity reactions are difficult to classify because of a lack of evidence supporting a predominant immunologic mechanism. These include certain cutaneous drug reactions (i.e., maculopapular rashes, erythroderma, exfoliative dermatitis, and fixed drug reactions) and specific drug hypersensitivity syndrome.

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Excerpt out of 30 pages

Details

Title
Adverse Drug Reactions (ADRs)
Course
Pharm. D
Grade
A
Author
Year
2018
Pages
30
Catalog Number
V425372
ISBN (eBook)
9783668702806
ISBN (Book)
9783668702813
File size
630 KB
Language
English
Keywords
Adverse, drug, reactions, classification, hypersensitivity, syndromes, ADR Monitoring, reporting, documenting, educating
Quote paper
Dr. Sagar Pamu (Author), 2018, Adverse Drug Reactions (ADRs), Munich, GRIN Verlag, https://www.grin.com/document/425372

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