Classification ADRs may be classified by e.g. cause and severity.
CauseEdit
Type A: Augmented pharmacologic effects - dose dependent and predictable
Type A reactions, which constitute approximately 80% of adverse drug reactions, are usually a consequence of the drug’s primary pharmacological effect (e.g. bleeding when using the anticoagulant warfarin) or a low therapeutic index of the drug (e.g. nausea from digoxin), and they are therefore predictable. They are dose-related and usually mild, although they may be serious or even fatal (e.g. intracranial bleeding from warfarin). Such reactions are usually due to inappropriate dosage, especially when drug elimination is impaired. The term ‘side effects’ is often applied to minor type A reactions.[4]
Type B: Idiosyncratic
Types A and B were proposed in the 1970s,[5] and the other types were proposed subsequently when the first two proved insufficient to classify ADRs.[6]
SeverityEdit
The U.S Food and Drug Administration defines a serious adverse event as one when the patient outcome is one of the following:[7]
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 abnormality
Requires intervention to prevent permanent impairment or damage
Severity 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.
Mechanisms

Adverse drug reaction leading to hepatitis (drug-induced hepatitis) with granulomata. Other causes were excluded with extensive investigations. Liver biopsy. H&E stain.
As research better explains the biochemistry of drug use, fewer ADRs are Type B and more are Type A. Common mechanisms are:
Abnormal pharmacokinetics due to
genetic factors
comorbid disease states
Synergistic effects between either
a drug and a disease
two drugs
Abnormal pharmacokinetics
Comorbid disease state
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.
The Medication Appropriateness Tool for Comorbid Health Conditions in Dementia](MATCH-D) criteria warns that people with dementia are more likely to experience adverse effects, and that they are less likely to be able to reliably report symptoms.
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.
Phase I reactions
Inheriting abnormal alleles of cytochrome P450 can 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
Phase II reactions
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.
Protein binding
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 principal plasma proteins for drug binding are:
albumin
α1-acid glycoprotein
lipoproteins
Some 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 interact
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