The term side effects is often applied to minor type A reactions.Type B: IdiosyncraticTypes A and B were proposed in the 1970s, and the other types were proposed subsequently when the first two proved insufficient to classify ADRs. Seriousness
The U.S Food and Drug Administration defines a serious adverse event as one when the patient outcome is one of the following:
Death
Life-threatening
Hospitalization (initial or prolonged)
Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patients body function/structure, physical activities or quality of life. Congenital abnormality
Requires intervention to prevent permanent impairment or damageSeverity is a point on an arbitrary scale of intensity of the adverse event in question. The terms "severe" and "serious", when applied to adverse events, are technically very different. They are easily confused but can not be used interchangeably, requiring care in usage. A headache is severe if it causes intense pain. There are scales like "visual analog scale" that help clinicians assess the severity. On the other hand, a headache is not usually serious (but may be in case of subarachnoid haemorrhage, subdural bleed, even a migraine may temporally fit criteria), unless it also satisfies the criteria for seriousness listed above. Location
Adverse effects may be local, i.e. limited to a certain location, or systemic, where 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.
The principal plasma proteins for drug binding are:
albumin
α1-acid glycoprotein
lipoproteinsSome drug interactions with warfarin are due to changes in protein binding. Cytochrome P450
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
Causality assessment is used to determine the likelihood that a drug caused a suspected ADR. There are a number of different methods used to judge causation, including the Naranjo algorithm, the Venulet algorithm and the WHO causality term assessment criteria. Each have pros and cons associated with their use and most require some level of expert judgement to apply. An ADR should not be labeled as certain unless the ADR abates with a challenge-dechallenge-rechallenge protocol (stopping and starting the agent in question). The chronology of the onset of the suspected ADR is important, as another substance or factor may be implicated as a cause; co-prescribed medications and underlying psychiatric conditions may be factors in the ADR.Assigning causality to a specific agent often proves difficult, unless the event is found during a clinical study or large databases are used. Both methods have difficulties and can be fraught with error. Even in clinical studies some ADRs may be missed as large numbers of test individuals are required to find that adverse drug reaction. Psychiatric ADRs are often missed as they are grouped together in the questionnaires used to assess the population.