ADR + Interactions Flashcards
What is ADR
preventable or unpredicted medication event with harm to the patient.
Classification of ADRs - 3 sections
Onset
Severity
Type
Types of onset classification
Acute - within 1 hour
Sub-acute - 1-24hrs
Latent >2days
Types of severity classification
Mild - requires no change in therapy
Moderate - requires change in therapy, additional treatment, hospitalisation
Severe - disabling/life-threatening. Can result in death, prolongs hospitalisation, causes congenital abnormalities, requires intervention
How many types of ADRs are there?
5
ABCDE
Augmented Bizarre Chronic Delayed Endoftreatment
What happens in Type A ADR
Extension of pharmacologic effect
Dose dependent
Most ADRs
Examples of Type A ADR
o Atenolol (beta blocker) will slow the heart down but if you give too much of it, it may cause complete heart block
o Chronic use of NSAIDs can cause peptic ulcers
o Anticholinergics can lead to dry mouth
What happens in Type B ADR
Idiosyncratic/immunologic reactions
Allergy
Rare + unpredictable
Examples of Type B ADR
- Chloramphenicol can cause aplastic anaemia (1 in 10,000)- it is usually irreversible than fatal
- ACE inhibitors can cause angioedema
What happens in Type C ADR
More common
Assoc w long term use of drug
Dose accumulation over long period
Examples of Type C ADR
- Methotrexate – leads to liver fibrosis/ toxicity
* Antimalarials - ocular toxicity (can damage the optic nerve and retina)
What happens in Type D ADR
Delayed effects - sometimes dose independent
Examples of Type D ADR
o Carcinogenicity - e.g. immunosuppression
o Teratogenicity - e.g. thalidomide
What happens in Type E ADR
End of dosing/treatment reactions
o Withdrawal reactions (opiates, benzodiazepines, corticosteroids)
o Rebound reactions
o Adaptive reactions
What happens when u stop taking clonidine
Withdrawl - rebound reactions
It used to be antihypertensive- is an alpha2 agonist so it reduces release of NA from S neurones.
This leads to drop in BP. Without clonidine, can lead to large rise in BP = stroke/death. Long term use = compensatory upregulation in adrenergic receptors on post-synaptic neuron. Thus when inhibition of NA release by clonidine is removed, NA starts being produced again and more receptors = cause great affect = rise in BP
How many classifications of allergy are there
4
What is Type I alergy
Immediate - anaphylactic (IgE)
Lifethreatening + rapid onset
Treated as emergency
What is Type 2 allergy
Cytotoxic Antibody (IgG + IgM)
What is Type 3 allergy
Serum Sickness (IgG + IgM) Antigen-antibody complex
What is Type 4 allergy
Delayed hypersensitivity (T cell) Common
What pseudoallergy does aspirin/NSAIDs cause
Bronchospasm
- Inhibiting production of prostanoids + prostaglandings via COX pathway which are bronchodilators
- Arachidonic acid is diverted to make leukotrienes (proinflamm + bronchoconstriction = bronchospasm + mucus secretion in airways)
Thus giving these to asthmatics = caution
What pseudoallergy does ACE inhibitor cause
Cough/Angioedema
ACE inhibitor stops production of AT2, stops breakdwon of bradykinins (inflamm peptides). Thus these accumulate = triggers coughing as it acts on sensory nerves of lungs.
Angioedema - leads to bronchospasm, swelling of mouth + lips
Another way of classifying ADRs - DoTS
Dose
Time
Susceptibility
4 common causes of fatal ADRs
Antineoplastics
CV drugs
NSAIDs/analgesics
CNS drugs
4 common causes of nonfatal ADRs
- Antibiotics
- Anticoagulants
- Hypoglycaemics
- Anti-hypertensives
What affects frequency of ADRs
polypharmacy - number of drugs pt taking
What is the Yellow Card Scheme
This is a system for reporting adverse drug reactions.
3 types of pharmacodynamic drug interactions
- Additive effects - two drugs add together
- Synergistic effects - two drugs potentiate each other’s actions to get a greater2 effect than expected
- Antagonist effects - drugs that antagonise each other’s actions
2 types of pharmacokinetic drug interactions
- Alteration in absorption
* Protein binding effects
How can there be alteration in absorption
Chelation - irreversible binding of drugs in GIT making it difficult to absorb
How can protein binding effects occur as a drug interaction
o Competition between drugs for protein or tissue binding sites- two drugs may have the same binding site on the protein circulating in the blood which means that one drug may displace the other.
Over half of drug metabolism is done by….
CYP2D6/CYP3A4
these are CYP450 isoenzymes
CYP450 Inhibitors
Erythryomycin + related abx
Ciproflaxin + related abx
Ritonavir + HIV drugs
Grapefruit juice
How long does inhibition of CYP450 take
rapid - within hours
How long does induction of CYP450 take
hours/days - need to produce new gene products/proteins
CYP450 Inducers
- Rifampicin
- Carbamazepine
- (Phenobarbitone)- anti-convulsants
- (Phenytoin)
- St. John’s Wort (hypericin is the compound that induces CYP450)
Where do drug elimination interactions occur
renal tubule
what is used to stop penicillin being excreted (thus use less + have substantial effects
Probenecid
What stops lithium being cleared thus it accumulates + is toxic
thiazides/NSAIDs
Why are Levodopa + carbidopa used together
Carbidopa prevents Levodopa from being broken down in the periphery so more can act in the brain, thus lower doses of Levodopa can be used.
Which 2 drugs enhance each others antiHTN effects so are used together
ACE inhibitors + Thiazides
Which 2 drugs used in pt w severe Staph A infection
• Penicillins + Gentamycin
why are salbutamol + ipratropium used together
beta-agonists and anti-muscarinic inhalers are used in the treatment of COPD and asthma
