Adverse Drug Reactions Flashcards
What are adverse drug events
Preventable or unpredictable medication events with harm to the patient - due to medication errors and adverse drug reactions
What are ADRs classifications based on?
Onset, Severity and Type
What is a severe severity ADR
Disabling, life threatening, prolongs hospitalisation, causes congenital abnormalities, requires intervention to prevent further injurty
What is a moderate severity ADR
Change in therapy required, additional treatment and hospitalisation
What are different stages of onset ADR classification
onset: acute <1hr, subacute 1-24hr, latent >2 days
severity: mild, moderate, severe
What is a type A ADR
Augument/extend the pharmacological effect: usually predictable and dose dependent and represents 2/3 of ARDs. Paracetamol has a threshold below which it has minimal side effects and then exceeding this the side effects rapidly increase and digoxin has dose dependant line for example
What is a type B ADR
Bizarre - idiosyncratic or immunological reaction that is unpredictable, rare and includes allergy and ‘pseudo-allergy’ eg chloramphenicol, aplastic anaemia, ACE inhibitors, angiodema
What is a type C ADR
Chronic - long term use side effects involving dose accumulation eg methotrexate and liver fibrosis
What is a type D ADR
Delayed - delayed effects eg carcinogenicity (immunosuppressants) or teratogenicity (thalidomide)
What is a type E ADR
End of treatment side effects eg withdrawal reactions, rebound reactions, adaptive reactions
What is a withdrawal reaction? Give examples of drugs that cause this
Patient cannot make endogenous supply - opiates, corticosteroids and benzodiazepines are drugs that can cause this
What is a rebound reaction? Give examples of drugs that cause this
Disease gets worse when drugs are stopped eg clonidine, beta blockers, corticosteroids.
What are adaptive reactions? Drugs examples?
Adapted body reactions to drugs eg neuroleptics (tranquilisers)
What are the different types of allergic reactions?
Type 1 – immediate, anaphylactic. IgE E.G. anaphylaxes with penicillin.
Type 2 – cytotoxic antibody. IgG, IgM E.G. methyldopa and HA.
Type 3 – serum sickness (antibody-antigen complex). IgG, IgM E.G. procainamide-induced lupus.
Type 4 – delayed-type hypersensitivity T-Cell E.G. contact dermatitis.
What are examples of immunological ‘pseudo allergies’ - type B ADRs
Aspirin/NSAIDs cause bronchospasm: aspirin/nsaid inhibit COX so less prostaglandin synthesis and more leukotrienes made
ACE inhibitors -> cough/angiodema: ACEi inhibit production of AngII and stops the breakdown of inflammatory mediators such as bradykinin which stimulate the cough receptors of the lungs
What are common causes of ADRs
- antineoplastics - cytotoxic drugs
- cardiovascular drigs
- NSAIDs/analgesics
- CNS drugs
^main 4 - Antibiotics
- Anticoagulants
- Hypoglycaemic
- Antihypertensives
How does drug use affect ADR frequency
Increased individual drug use increases ADR frequency
How are subjective reports of ADRs detected
The patient complaints are put on a yellow card system
How are objective reports of ADRs detected
Direct observations of events and abnormal findings eg physical examination, lab tests and diagnostic features however rare events probs not found until after drug is marketed
What is the yellow card scheme
A scheme introduced after thalidomide where it can be used voluntarily by any healthcare professional and includes bloods, vaccines and contrast media in order to report ADRs
Why is drug drug interaction incidence difficult to ascertain?
- data for drug related hospital admissions do not differentiate out drug interactions, only ADRs
- lack of available comprehensive databases
- difficulty in assessing OTC drug use
- difficulty in determining drug contributions to interaction sin complicated patients
- sometimes the principle cause of ADRs is with specific drugs eg statins
What is pharmacodynamics
Drugs effect on body eg receptor site dynamics leading to additive, synergistic, or antagonistic effects from coadministration
What is pharmacokinetics
Body’s effect on the drug eg absorption, distribution, metabolism, excretion
What are synergist actions of antibiotics
Use of two ABs will increase the effect of more than their seperate contributions OR they will antagonise each other
What are two drugs that have overlapping toxicity
Ethanol and benzodiazepines
What is chemiation
Irreversible binding in the GI tract for example, antibiotics to metal ions or calcium to form chelates that prevent absorption of the antibiotic
What is a clinically significant example of protein binding interactions affecting pharmacokinetics
Warfarin is 99% albumin bound so anything to decrease that will increase the free warfarin so there is more anti coagulative effects
What are the different ways drugs can undergo metabolism and then be excreted
They can either (1) be directly excreted, (2) undergo Ph1 metabolism and be excreted, (3) undergo Ph1 and Ph2 and then be excreted or (4) only undergo Ph2 and then be excreted
What are pharmaceutical drug interactions
Drug interactions outside the body ie IV injections
What are reactions in phase 1 metabolism
Oxidation, reduction, hydrolusis
What are the reactions in phase 2 metabolism
conjugation (glutathione, amino-acid), glucuronidation, sulphation, acetylation and methylation
Why can coadministration of a CYP450 inhibitor not affect metabolism rate?
Some isoenzymes can pick up the slack for the inhibited isoenzyme
What are inhibitors of CYP450
Cimetidine Ciprofloxacin (and other related ABs) Fluoxetine (and other SSRIs) Erythromycin (and related ABs) Ritonavir (and other HIV drugs) Ketonazole Grapefruit juice
What are inducers of CYP450
Rifampicin Phenobarbitone Carbamezepine Phenytoin St John's wort (hypericin)
What are good drug elimination reactions?
Probenecid and penecillin where probenecid reduces excretion of penecillin and penecillin used to be expensive
What is a bad drug elimination reaction
Lithium and thiazides where thiazides lead to toxic accumulation of lithium
Where do drug elimination reactions almost always occur
In renal tubes
What are examples of deliberate drug elimination reactions
- Levodopa + carbidopa can use lower doses of levodopa as carbidopa reduced peripheral metabolism.
- ACEi + thiazides treat HF.
- Penicillin’s + gentamycin treat severe staph. Infections.
- Salbutamol + ipratropium beta-agonists and anti-muscarinics used in inhalers to treat asthma.
