3.2 Adverse Drug Reactions & Interactions Flashcards
What are the types of adverse drug interactions
Augmented (dose related), Bizarre (non dose related), Chronic (dose related and time related), Delayed (time related), End of use (withdrawal), Failure (unexpected failure of therapy)
Most ADRs (70-80%) are classified as type A, due to the known pharmacologic properties of the drugs
Common examples are:
- hypoglycaemia due to oral hypogylcaemics
- hypokalaemia due to _____________
- over-warfarinisation
- hyperkalaemia due to ________________
- Cushing’s syndrome due to _____________
- It follows that many ADRs are predictable and preventable (30-60%)
- Prudent prescribing, attention to vulnerable patients and regular monitoring are ways to minimise these reactions
diuretics;
ACE inhibitors;
corticosteroids
Type B adverse drug reactions
- They are uncommon, occurring in fewer than 5%
- These encompass reactions outside of the known pharmacologic actions of the drugs e.g _____________
- Though they are uncommon and occur unpredictably, doctors need to be aware of them and to warn patients to watch for the more serious ones
- ______________ is able to provide an estimate of the risk for some drugs
Drug allergy; Pseudoallergy; Idiosyncratic reactions;
Pharmacogenetics
[Drug Allergy]
- An allergy is an adverse reaction, mediated by the immune system, that results from previous sensitisation to a particular chemical or to _________________
- For allergy to take place, the cognate immune system must have encountered the agent previously
- Usually this event does not lead to recognition by the immune system
- When it does, ______________ is said to have happened
- When the person next encounters the agent after sensitisation, the immune system may be activated, manifesting as one of the four hypersensitivity (or allergy) reactions classified by Gell and Coombs
one that is structurally similar;
sensitisation
Type I hypersensitivity reactions:
- include urticaria, angioedema and anaphylaxis that occurred very soon after drug exposure
- usually _______________
Type II hypersensitivity reactions:
- Are uncommon
- One example is haemolysis due to _____________
Type III hypersensitivity reactions:
- Are also uncommon
- Also known as _________________
- Penicillins can rarely cause this reaction
- The use of ___________________ as therapeutic agents has also led to the observation of this reaction
Type IV hypersensitivity reactions:
- _____________________, the commonest manifestation of drug allergy, is a type IV reaction
- The severe cutaneous allergy reaction, Stevens-Johnson syndrome and toxic epidermal necrolysis are also type IV reactions
15 - 60 minutes;
penicillin;
serum sickness;
monoclonal antibodies;
Maculopapular rash
Psuedo allergy
- Pseudo-allergic reactions are those that resemble drug allergy but do not involve the ______________
- Though some authors accept only mimics of type I hypersensitivity as pseudoallergy, others take all types
- One definition of pseudoallergy is a reaction that occurs when an agent directly activates ________________, without the involvement of immunoglobulins or lymphocytes
- Examples are type-I-like due to opioids, muscle relaxants and ciprofloxacin
- Unlike allergy, there is no need for sensitisation, and pseudoallergic reactions can occur on first use
- Mutation in the gene encoding human ____________________ on mast cells is associated with pseudoallergy that mimics type I hypersensitivity.
immune system;
effector cells;
G-protein-coupled receptor MRGPRX2
Idiosyncratic reactions
- This is a mixed collection of ADRs
- Examples of reactions classified in this group: _____________ due to ACE inhibitors; ___________ due to ACE inhibitors; Angioedema due to NSAIDs; Agranulocytosis due to
Angioedema;
Dry cough;
Antithyroid medication
Drug interactions
- One drug may modify the action of another sometimes in a beneficial but more frequently in an adverse way
Pharmacokinetic
- One drug may affect the _________________ of another
Pharmacodynamic
- Pharmacodynamics (PD) defines what a drug does to the body that leads to a physiological response
- Such drug-drug interactions can have ________________ effects on PD responses
absorption, distribution, metabolism and excretion (ADME);
additive, synergistic or antagonistic
Pharmacokinetic drug interaction
- This is the main way in which drugs are metabolised in the liver
- Substrates are the drugs that are the targets of the cytochrome:
- Inducers are drugs that increase the activity of the cytochrome
- Inhibitors are drugs that depress the activity of the cytochrome
- The ____________ metabolizes the largest number of drugs
- Some drugs inhibit cytochrome function: E.g. _______________
- Inhibition can occur rapidly
- Some drugs induce or potentiate cytochrome function: E.g.__________________
- Induction takes hours or days
CYP3A family;
cimetidine, fluconazole, fluoxetine, clarithromycin;
rifampicin, carbamazepine, (chargrilled meat)
- AStrong inhibitoris one that causes a _______________ in the plasma AUC values or more than 80% decrease in clearance
- AModerate inhibitoris one that causes a ______________ in the plasma AUC values or 50-80% decrease in clearance
- AWeak inhibitoris one that causes a _______________ increase in the plasma AUC values or 20-50% decrease in clearance
> 5-fold increase;
> 2-fold increase;
> 1.25-fold but < 2-fold
Drug-drug interaction in the cytochrome system
- Rifampicin induces ____________:
- Warfarin is a substrate of ______________ . When rifampicin and warfarin are taken together, the warfarin dose has to be _________
- Great care must be taken to reduce the dose of warfarin when rifampicin is discontinued
CYP2C9;
CYP2C9;
raised
- Rifampicin and ______________ induce CYP3A4
- _______________is a substrate of CYP3A4
- When taken together, the oral contraceptive is metabolised more rapidly and there may be failure of contraception
carbamazepine;
Estradiol-containing oral contraceptive
- _____________________ inhibit CYP2C19
- Clopidogrel is a pro-drug and has to be metabolised by CYP2C19 to become active
- There was concern that concomitant prescription of these drugs could result in reduced effect of clopidogrel and hence loss of protection from cardiovascular events
- It is still controversial if this interaction results in differences in clinical outcome
Omeprazole and other proton-pump inhibitors
Additive interaction occurs when the action of two drugs is simply the summing up of the individual action of each drug, for examples:
- the concurrent use of aspirin and warfarin increases the risk of _______________ (adverse effect)
- the use of ______________ plus insulin raises the possibility of hypoglycaemia (beneficial if used carefully, dangerous if not)
- the combination of an ACE inhibitor and a thiazide can produce __________ (beneficial if used carefully, harmful if not)
gastrointestinal bleeding;
tolbutamide;
hypotension
Synergistic interaction occurs when the combined action is more than the sum of the effects of two drugs, for examples:
- the combination of ______________ and ethanol markedly affects mental function (adverse effect)
- the use of paracetamol and ___________ produces a strong analgesic effect (beneficial)
- concurrent inhaled long-acting beta-agonists and ______________ use promotes bronchial dilatation in asthma (beneficial)
diphenhydramine;
tramadol;
corticosteroid
