Adverse drug reaction

# Overview
An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted, negative consequences  associated with the use of given medications. An ADR is a particular type of adverse effect. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can 
be beneficial. The  study of ADRs is the concern of the field known as pharmacovigilance.
Informing a patient that ARDs may be a sign that a drug is working may increase acceptance of a medication.

# Classification
ADRs may be classified by cause and severity.

## Cause
- Type A: pharmacologically predictableddfd
- Type B: bizarre and unpredictable (or idiosyncratic)
- Type C: arising from chronic use
- Type D: delayed reaction
- Type E: end of dose reaction
- Type F: failure of therapy
Types A and B were proposed in the 11970s, and the other types were proposed subsequently when the first two proved insufficient to classify ADRs.

## Severity
The American Food and Drug Administration defines severe adverse event (SAE) as::
- Death
- Life-Threatening
- Hospitalization (initial or prolonged)
- Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life.
- Congenital Anomaly
- - or -
- Requires Intervention to Prevent Permanent Impairment or Damage

## Overall Drug Risk
While no official scale exists yet to communicate overall drug risk, the iGuard Drug Risk Rating System is a five color rating scale similar to the Homeland Security Advisory System:
- Red (High Risk)
- Orange (Elevated Risk)
- Yellow (Guarded Risk)
- Blue (General Risk)
- Green (Low Risk)

## Location
Adverse effects may be local, i.e. limited to a certain location, or systemic, where a medication has caused adverse effects throughout the systemic circulation.
For instance, some ocular antihypertensives cause systemic effects, although they are administered locally as eye drops, since a fraction escapes to the systemic circulation.

# Mechanisms
As research better explains the biochemistry of drug use, less ADRs are Type B and more are Type A. Common mechanisms are:
- Abnormal pharmacokinetics due to
genetic factors
comorbid disease states
- genetic factors
- comorbid disease states
- Synergistic effects between either
a drug and a disease
two drugs
- a drug and a disease
- two drugs

## Abnormal pharmacokinetics

### Comorbid disease states
Various diseases, especially those that cause renal or hepatic insufficiency, may alter drug metabolism. Resources are available that report changes in a drug's metabolism due to disease states.

### Genetic factors
Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II conjugation.  Pharmacogenomics is the study of the inherited basis for abnormal drug reactions.
Inheriting abnormal alleles of cytochrome P450can alter drug metabolism. Tables are available to check for drug interactions due to P450 interactions..
Inheriting abnormal butyrylcholinesterase (pseudocholinesterase) may affect metabolism of drugs such as succinylcholine
Inheriting abnormal N-acetyltransferase which conjugated some drugs to facilitate excretion may affect the metabolism of drugs such as isoniazid, hydralazine, and procainamide.
Inheriting abnormal thiopurine S-methyltransferase may affect the metabolism of the thiopurine drugs mercaptopurine and azathioprine.

### Interactions with other drugs
The risk of drug interactions is increased with polypharmacy.
These interactions are usually transient and mild until a new steady state is achieved. These are mainly for drugs without much first-pass liver metabolism. The prinicple plasma proteins for drug binding are:
- albumin
- 1-acid glycoprotein
- lipoproteins
Some drug interactions with warfarin are due to changes in protein binding.
Patients have abnormal metabolism by cytochrome P450 due to either inheriting abnormal alleles or due to drug interactions. Tables are available to check for drug interactions due to P450 interactions..

## Synergistic effects
An example of synergism is two drugs that both prolong the QT interval.

# Assessing causality
A simple scale is available at .
A more complicated scale is the Naranjo algorithm.

# Publications reporting adverse drug reactions

## Reporting standards
Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommends standard items to be included in publications.
Systematic reviews do not well search for or report adverse drug reactions. This difficulty may in part be due to problematic reporting of adverse drug reactions in trials incuding outcome reporting bias.

## Searching for publications
Various search strategies have been developed to locate publications that report adverse drug reactions.

# Monitoring bodies
Many countries have official bodies that monitor drug safety and reactions. On an international level, the WHO runs the Uppsala Monitoring Centre, and the European Union runs the European Medicines Agency (EMEA). In the United States, the Food and Drug Administration (FDA) is responsible for monitoring post-marketing studies.

# Diagnosis

## Physical Examination

### Skin
- Drug reactions. Adapted from Dermatology Atlas.
- Drug reactions. Adapted from Dermatology Atlas.
- Drug reactions. Adapted from Dermatology Atlas.
- Drug reactions. Adapted from Dermatology Atlas.
- Drug reactions. Adapted from Dermatology Atlas.
- Drug reactions. Adapted from Dermatology Atlas.
- Drug reactions. Adapted from Dermatology Atlas.