Adverse drug reactions( ADRs):

If you want to know what is ADRs click here

ADRs are 4^th leading cause of mortality in US and 6^th leading cause in world wide.

Classification of adverse drug reactions (ADRs):

Two most common classification of ADRs

1)Extended Rawlins And Thompson classification ( ERTC)

2)Dots classification

Extended Rawlins and Thompson classification:

In ERTC ADRs are classified into 6 classes

1)Type A adverse drug reactions

2)Type B adverse drug reactions

3)Type C adverse drug reactions

4)Type D adverse drug reactions

5)Type E adverse drug reactions

6)Type F adverse drug reactions

1) Type A adverse drug reactions:

Mnemonic of Type A ADRs:

Augmented ( exaggerated pharmacological action)

Features of Type A ADRs:

•Most common

•Predictable

•Related to pharmacological actions

•Low mortality

•Low morbidity

•Usually dose related/dependent

•Occurs at normal dose or toxic dose

•They include side effects, adverse effects and toxic effects.

Examples Of Type A ADRs:

•aspirin can cause peptic ulcer

•ACEI can cause hyperkalaemia

•antidiabetic cause hypoglycemia

•BB cause hypotension

•ACEI can cause angioedema , dry cough

•antihistamines cause sedation.

These all are predictable actions of drug.

Management of Type A ADRs:

•Either reduce the dose , frequency or duration of drug.

•withdraw the drug product.

2) Type B Adverse drug reactions:

Mnemonic of type B ADRs:

Bizzare ( unusual,  unpredictable )

Features of type B ADRs:

•uncommon

•not related to pharmacology of drug

•Unpredictable

•Not dose dependent

•Occurs even at subtherapeutic doses

•High mortality

•High morbidity

Example of type B ADRs:

•Idiosyncrasy reaction: quantitatively abnormal allergic reaction usually cause by a drug due to single gene inheritance. ( not predictable by pharmacology of drug)

•antimalarial cause haemolytic anaemia

How antimalarial cause haemolytic anaemia?

Antimalarial such as primaquine and sulphonamide cause haemolytic anaemia by causing the deficiency of glucose-6-phosphate dehydrogenase .

• Malignant hyperthermia

How halogenated anaesthetics ( halothane) cause malignant hyperthermia?

How muscle relaxant ( succinyl choline ) cause malignant hyperthermia?

Usually occur durning surgery due to single gene inheritance.

In sarcoplasma ca+ receptors are present which is called Ryanodine receptor. They are responsible for releasing ca+ which in turn responsible for contraction. Ryanodine receptors are coded by PYRI.

When mutation occur receptors become highly active and excessive ca+ is released and causing the severe muscular contraction and thus causing malignant hyperthermia which is life threatening condition.* adverse drug reactions 

Management of malignant hyperthermia:

Antidot: Danotroline with 100% oxygen.

Management of type B ADRs:

•withdraw the drug product

•avoid exposure to that drug product again to patient

•prescribe consummated therapy

3) Type C adverse drug reactions:

Mnemonic of type C ADRs:

Chronic ( occurs in chronic use of drugs )

Features of type C ADRs:

•Time and dose related

•Uncommon

•Related to cumulative dose of the drug ( total number of doses )

Examples of type C ADRs:

•aspirin and NSAIDs are analgesic and their chronic use can cause analgesic nephropathy.

How aspirin / NSAIDs cause analgesic nephropathy?

They block COX-1 which releases prostaglandins which is responsible for the normal blood flow to the kidney. Chronic use of aspirin and NSAIDs inhibits COX-1 therefore prostaglandins is decreased and blood flow to the kidneys is also decreased oxygen demand increases cause hypoxia , necrosis damage to medulla of kidney called analgesic nephropathy.* adverse drug reactions 

•Chronic use of PPIs cause hip or bone fracture ( especially in females)

How PPIs cause hip / bone fracture?

PPIs decreases HCL production which decreases ca+ absorption so calcium level in the blood is decreased in other words hypocalacemia occus.

Calcium is also necessary for the normal contraction of muscles so for this purpose body has to maintain calcium level in serum. So increases the para thyroid hormone secretion and it will act on bones and bones demineralization occur , bone density decreased and cause fractures.* adverse drug reactions 

•chronic use of PPIs causes gastric ulcer

How PPIs cause gastric ulcer?

PPIs inhibits HCL PH is increasing and G cell is stimulated gastrin is released which stimulate ECL . HCL is continually continuously inhibited and ECL is stimulated.  ECL thinks that he is not producing proper HCL so body make more ECL and ECL multiplied uncontrolled cause cancer.* adverse drug reactions 

Management of type C ADRs:

•Reduce the dose

•Withdraw the drug maybe for prolonged time

4) Type D adverse drug reactions:

Mnemonic of type D ADRs:

Delayed

Features of type D ADRs:

•Uncommon

•Dose dependent

•Occur after long time of exposure of drug

•Unpredictable

ADRs occur after few years of taking drug called delayed ADRs.

Examples of type D ADRs:

DES daughters ( diethyl stilbesterol daughters) used for the prevention of repeated miscarriages and post menopause symptoms.

If pregnant women having a gender inside girl take this drug then due to this drug baby girl after delivery in the future it may cause vaginal adenocarcinoma because exposed in fetal life and after 15-16 years such condition occur.* adverse drug reactions 

Management of type D ADRs:

Unmanageable,  once damaged its damaged.

5) Type E adverse drug reactions:

Mnemonic of type E ADRs:

End of therapy ( occur after abrupt withdraw of drugs.

Features of type E ADRs:

•Uncommon

•Appears after stopping the drug

Examples of type E ADRs:

•if someone addicted to opium and if you stop the drug that person is going to develop opiate withdrawal syndrome.

How BB cause myocardial ischaemia?

•if someone taking BB( particularly propranolol ), B2 receptors are inhibited and body synthesized more and more B2 receptors when abruptly withdraw the drug then adrenaline act on all the B2 receptors due to which cardiac force of contraction increases and increase heart rate then patient has chance of myocardial ischemia due to upregulation of receptors.* adverse drug reactions 

Management of type E ADRs:

Reintroduce the drug and withdraw gradually.

6) Type F adverse drug reactions:

Mnemonic of type F ADRs:

Failure of therapy ( unexpected failure of therapy )

Features of type F ADRs:

•Common

•Dose dependent

•Usually occur due to drug-drug interactions

Examples of type F ADRs:

•drug-drug interaction of oral contraceptive and rifampicin

Rifampicin induce enzyme which metabolize the oral contraceptive and convert into inactive metabolites.

•drug-drug interaction of iron preparation and PPIs

HCL is necessary for iron absorption PPIs decreases HCL then iron not absorbed cause failure of therapy.

•drug-drug interaction of warfarin and vitamin K

Taking warfarin with green tea or vegetables containing vitamin K . Vitamin K is antagonist of warfarin,  warfarin will not show therapeutic effect cause thrombosis.

•drug-drug interaction of clopidogrel and omeprazole

Clopidogrel is prodrug and activated by CYP3A4 omeprazole inhibit this enzyme then clopidogrel will not converted cause failure of therapy.

•drug-drug interaction of fluroqunilones and calcium magnesium containing antacids

Fluroqunilones have lone pair of electrons make covalent bond with ions make complex formation due to this absorption decreases cause failure of therapy.* adverse drug reactions 

Management of type F ADRs:

•increase the dose of one drug

•stop giving together

•use alternative therapy

Dots classification of adverse drug reactions:

For details of Dots classification click here

Learn more 

Topic include 

Classification of ADRs 

Types of ADRs 

Two most important classifications of ADRs 

Extended Rawlins and Thompson classification of adverse drug reactions 

What are Type A ADRs ?

What are Type B ADRs ?

What are Type C ADRs ?

What are Type D ADRs ?

What are Type E ADRs ?

What are Type F ADRs ?

What are the types of adverse drug reaction with examples?

How many types of ADRs are there?

What is the most common adverse drug reaction?

What are the 4 types of adverse drug reaction?

Mnemonic of ADRs 

Examples of ADRs 

Features of ADRs