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Only 10 to 20% of adverse drug reactions are considered allergic

Only 10 to 20% of adverse drug reactions are considered allergic

Adverse reaction to the drug according to ANVISA is any harmful, unintended and undesired effect of a drug, observed at the usual therapeutic doses in humans for therapeutic, prophylactic or diagnostic purposes .

Adverse drug reactions are divided into two types.

Predictable reactions

Can occur in any individual and are related to the pharmacological action of the drug, usually dose-dependent. They account for approximately 75% of adverse drug reactions. There are four varieties of this type of reaction:

1) Toxicity: effects are related to the amount of drug in the body, happen when the limit is exceeded. As an example, we have central nervous system depression with barbiturates, hepatic injury by the use of acetaminophen.

2) Secondary or indirect effect: it is an indirectly related effect to the pharmacological action of the drug. For example, administration of an antibiotic stimulates the production of a toxin that causes membranous colitis.

3) Collateral effect: undesirable effect even at commonly used doses. How to feel drowsy with antihistamines.

4) Drug Interaction: Medications administered simultaneously may interact by increasing or decreasing an expected response or by determining an unexpected response. Phenytoin may increase in serum if given along with fluoxetine or sulfonamide.

Unprovoked reactions

Occur in susceptible patients (due to their own characteristics) not related to the pharmacological action of the drug, but with individual response, deficiencies genetic or immunological response, usually independent doses. There are also four varieties of this type of reaction:

1) Drug intolerance: this is a diminished threshold for the pharmacological action of a drug in susceptible individuals. For a single dose of medication, an individual with an intolerance to this substance will respond with a more obvious undesirable effect than most individuals exposed to it, such as acetylsalicylic acid hypothermia in children.

2) Idiosyncratic reaction: abnormal reaction to the drug by inhibition of an enzymatic activity, without immunological mechanism involved. It may occur in patients who, when they ingest primaquina, develop hemolytic anemia (a genetic deficiency related to the metabolism of the drug that manifests itself when exposed to the drug).

3) Hypersensitivity reaction or allergy: a reaction to drugs resulting from response to the immunological mechanism, ie when specific circulating antibodies (IgE, IgM and IgG) or specific sensitized lymphocytes are involved. This reaction has no relation to the amount of drug administered. They correspond to 10 to 20% of adverse drug reactions. An allergic reaction usually does not happen at the first exposure of the medicine because a previous sensitization period is required. Re-exposure to the drug will result in a new reaction generally faster than the previous one. As an example, we have urticaria caused by penicillins.

4) Anaphylactoid or pseudoalergic reaction: it is a reaction that does not involve specific antibody or sensitized T lymphocytes. It occurs the release of mediators directly from mast cells or basophils and or activation of a system called complement. The clinical manifestations are similar to an allergic reaction. An example is urticaria related to acetylsalicylic acid.

Allergies

Most drugs that cause adverse reactions are not due to immunological mechanisms, ie it is not an allergic reaction. However, when they do occur, there are some specific classifications.

1) Immediate type I reaction: IgE antibody involvement, resulting in a clinical picture with rhinitis, asthma, urticaria, angioedema (edema of the deep dermis reaching the eyelids and lips) and anaphylaxis (in which the patient may present itchy skin, redness , sensation of fainting, shortness of breath, wheezing in the chest, pressure drop, shock, nausea, vomiting and diarrhea, urticaria and angioedema Progressive airway obstruction and circulatory collapse can lead to coma and death.)

2 ) Type II reaction: direct action of the IgM or IgG antibody on the tissue or organ, with activation of the complement system. It can reach skin, lung, liver, muscles, peripheral nerves and blood cells. It can cause hemolytic anemia, platelet count and interstitial nephritis. <3> 3) Type III reaction: It involves the formation of an antigen-antibody complex that causes tissue damage with activation of the complement system. The clinical picture involves fever, urticaria, presence of lymph nodes, inflammation of the joints, vasculitis and renal involvement.

4) Type IV reaction: which is mediated by T lymphocytes sensitized with lymphokine production, such as contact dermatitis.

Allergic reactions may be immediate (30 minutes to 2 hours after drug administration), accelerated (2 to 48 hours after drug administration) and late (48 hours after drug administration).

Adverse reaction is acquired. It is possible never to have been allergic to a drug and suddenly to become. Atopic patients (with asthma, rhinitis and / or atopic dermatitis) may present more severe IgE-mediated reactions. The route of parenteral administration, i.e. by serum or topical application, causes more complex reactions. The incidence of allergic reaction to the drug is greater when given intermittently. Continuous use is associated with a lower incidence of allergic sensitization.

Sometimes the drugs have similar chemical structures and for this reason we say that they cross-react, that is, they can cause the same effects. This explains why it may be necessary to suspend a group of medications. The incidence of allergic skin reactions is 35% more frequent in women. The drugs that cause the most adverse reactions are antibiotics and non-hormonal anti-inflammatories.

Diagnosis of allergy to a drug

Tests for drug allergy do not show efficacy and specificity for all drugs. Most drug reactions are not mediated IgE-dependent, so they do not respond to an allergy test. Many immune reactions are caused by metabolites and not by the main drug. The most commonly used tests are:

immediate hypersensitivity skin test

challenge test

  • contact test
  • detection of specific IgE, IgM, IgG antibodies
  • Many of these tests are not performed in the office because they require monitoring in a hospital environment. What is best characterized by the diagnosis is the meticulous clinical history. The tests are reserved for the patient who can not replace the drug.
  • Treatment

The most important measure is the withdrawal of the suspect drug. As there is often a cross reaction with other drugs, it is necessary to avoid the whole group. The specialist physician should direct the substitution with a similar drug.

There is a treatment carried out at Hospital Escola called desensitization, which consists of, through well-defined protocols, inducing drug tolerance. The specific pharmacological treatment of adverse reactions includes administration of corticosteroids, antihistamines and adrenaline, in addition to all support in case of anaphylaxis (oxygen and ICU structure).


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