Adrenergic antagonist drug

While efficacy and safety must be demonstrated for regulatory authors to permit marketing, it is not possible to discover the complete safety profile of a new drug prior to its marketing.This is because of limited number of patients (an average of 2500 patients overall) usually enrolled in those studies with just few hundreds using the drug of longer than a year, so premarketing studies don’t have the power to detect reactions that occur at rates of 1:10000 or fewer drug exposures, cannot detect Adverse drug reactions (ADRs) that are separate in the time from drug exposure and patients in those trials may not represent the whole population who may use the drug post-marketing.

Only predictable ADRs with short onset can be detected, while rare and more severe ones may not be detected.

So the inherent weakness of premarketing studies mean that post marketing assessment of ADRs is essential.The science of this process is called “Pharmacovigilance” and it has been defined as the study of the safety of marketed drugs under the practical conditions of use in large communities.

“Pharmacovigilance” is concerned with the detection, assessment and prevention of ADRs.

Methods of pharmacovigilance

1. Spontaneous reporting systems.
2. Published case reports.
3. Cohort studies.
4. Case-control studies.

Spontaneous reporting system

• Collect data about suspected ADRs in a central database.
• Cases of suspected ADRs accumulate reports submitted spontaneously by people who make a connection between a drug and a suspected event.

• Examples: yellow card scheme in the UK.

Advantages of spontaneous reporting system

• Cheap method.
• Follows the product throughout its life.
• Can provide information about OTC drugs and herbal medicines as well.
• Important form of evidence leading to drug withdrawal.

Disadvantages of spontaneous reporting system

• Passive system relay on the ability of the heath care professional to recognize possible ADRs.
• Inability to quantify the risk (incidence of reactions).

Published case reports

The first suspicion of unpredictable or less common ADR usually comes from case reports such as the case with thalidomide.However some limitations associated with this method especially the high standards of investigations needed by some journals and the time it takes to be published.

Cohort studies

• Cohort studies are prospective studies that monitor a large group of patients taking a particular drug over a period of time.
• Usually they compare the incidence of a particular ADE in two groups of patients: those taking the drug of interest and a matched group not using the drug.

case-control studies

Compare the extent of drug usage in 2 groups of patients: a group who have experienced the adverse the adverse event and a group who have not experienced the adverse event.

Examples of associations which have been established by these studies are:

1. Aspirin and Rye’s syndrome.
2. Maternal diethylstilboesterol and vaginal adenocarcinoma in the female offspring.

Advantages of case-control studies

Effective in confirming suspicion about an ADEs.

Disadvantages of case-control studies

• Rely on good record keeping about drug use.
• Not able to detect previously unsuspected ADRs.

Roles of health care professionals

Identifying and assessing ADRs in clinical practice taking into consideration the following factors that can either raise or suppress suspicion of a drug induced event:

1. The temporal relationship between the drug and the event.
2. The clinical and pathological characteristics of the event as well as the underlying or concomitant illness and drugs.
3. The pharmacological plausibility.
4. Existing information in published drug information resources.
5. De-challenges (disappearance of symptoms after dose reduction of cessation of therapy).
6. Re-challenge (reappearance of symptoms after dose increase or recommencement of therapy).