adverse drug reactions Flashcards
Therapeutic Goods Administration (TGA)
Regulatory authority for therapeutic goods and maintains the Australian Register of Therapeutic Goods (ARTG)
TGA carries out assessment and monitoring of therapeutic goods in Australia
Evaluate and regulate therapeutics BEFORE they reach the market
Monitor therapeutics AFTER the reach the market
Regulatory decisions are made based on risk-benefit analyses
registered vs listed medicines
registered with higher risk when the benefits of taking the medicine outweight the risk
listed products with lower risk including vitamins minerals and complementary medicines
registered vs listed medicines
registered with higher risk when the benefits of taking the medicine outweight the risk
listed products with lower risk including vitamins minerals and complementary medicines
registered vs listed medicines
registered with higher risk when the benefits of taking the medicine outweight the risk
listed products with lower risk including vitamins minerals and complementary medicines
Post-Marketing Surveillance/Pharmacovigilence
Once on the market, the TGA continues to monitor safety and efficacy (performance). Post-marking surveillance is phase IV of a clinical trial.
what is required in an ADR report
Contact details for the reporter
Patient identifier (e.g., initials, DOB – NOT their full name)
Product details (now includes a tab for vaccines)
Description of the suspected ADR
Characterisation of Adverse Drug Reactions
A
Augmented
B Bizarre
C
Chronic
D
Delayed
E
End of Use (Withdrawal)
F
Failure
type A
augmented
common and predictable
dose relgaed
digoxin toxicity
type B
bizzare
uncommon
not related to pharmological action
unpredicable
• Examples o Immunological reaction o Malignant hyperthermia • Management o Withhold treatment o Avoid in future
- Allergic
- Rashes
- Serious reaction eg anaphylaxis
- Penicillin most common cause
- Allergic or hypernsensitive reacitons are immunological response
- These response cause inflammation and subsequent damage
- Hypersensitivity reaction
type C
chronic • Uncommon • Related to cumulative dose o ICS induced adrenal suppression o NSAIS and peptic ulcer o Bisphosphates ostecrosis • Reduced dose or withdrawl or a period of time
Type D
delayed • Uncommon • Usually dose related • Occurs or becomes apparent some time after using drug • Ex o Teratogenesis
type E
- After withdrawl
- Opiod withdrawal
- Beta blocker withdrawal
- Withdrawal very slowly
end of use
Type F
- Common
- Dose related
- Often caused by drug interaction
- Oral contraceptive failure
- Increase dosage
- Consider effects of concomitant therapy
Factors FOR ADR
- Age
- Sex
- Genetics
- Polypharmacy drug interactions
Not all ADRs fit into these categories
Eg metabolism of alchol
Rapidly absorbed
90% metabolized
5-10 percent expelled
type A digoxin toxicity
• Heart failure?af lecture
• Cardiac glycoside used in the treatment of HF last line and cardiac dysrhythmias
• Narrow therapeutic range
• Adverse effects are related to its plasma concentration
• Low therapeutic index
o Aka low therapeutic range
o Relationship between efficacy and safety
o Determining TI can be complex and depends on the stage of drug development
o A high therapeutic index is desirable a low index means adverse effects can occur
Type A diogixn toxcitiy
• MOA
o Afib slows HR and reduce AV nodal conduction by an increase in vagal tone and a reduction in SNS activity at higher dose can lead to AV node block
o HF: increases the force of myocardial contraction by increasing the release and availability of stored intracellular calcium
o Rate control by slowing the conduction rate of av node and increasing refractory period of av node
o Can be achieved with meds lf atenolol digoxin verapamil
• Inhibits NA/K pump
o Increase intracellular NA
o An increased intracellular concentration of NA reduces the efflux of CA from the cell which normally occurs via the NA/Ca pump
o This results
• Pharmacokinetics
o IV or oral
o Absorbed in stomach
o Majority eliminated unchanged via kidney
Substrate of p glycoprotein
Digoxin toxicity type A prevention and treatment
• Prevention
o Dose tailored to
Renal function
Clinical response
Concentration monitoring
Caution with concomitant drugs causing hypokalemia
o Concentration monitoring
Toxic effects can occur at lower concentration
Gi symptoms may precede cardiac symptoms
• Treating toxicitiy
o Antidote: Digifab
o Stops drug being binded to pump with high affinity
type b reactions types
Type 1 • Immediate o IGE forms a coat on mast cells o Body encountewrs an antigen eg pollen o Upon reexposure the pollen antigen binds to the IGe this causes the mast cells to degranulate/release inflammatory mediators
Type IV
• Delayed reaction
• Activation of adaptive immune system and T cell involvement
• Infiltration of immune cells and release of cytokines
Type B sulfonamide hypersensitivity
- Sulfonamides are antibiotics that interfere with folate synthesis
- Sulfamethoxazole commonly combined with trimethoprim
- Mild: fever dyspnea rash
- Serious: anaphylaxis Steven Johnson syndrome
Type C chronic administration of corticosteroids
Immune suppression infection or injury • Osteoporosis • Thin skin bruising • Hyperglycemia with diabetes • Muscle wasting • Inhibition of growth in children • Cushing syndrome • Adrenal suppression • Oral candidiasis thrush o Lead to local anti-inflammatory and immunosuppressive effects o Managed using a spacer Increase drug delivery to airways Reduce deposition in the mouth
Type C chronic administration of corticosteroids adrenal suppression
• Glucocorticoid release is controlled by a negative feedback mechanism involving the hypothalamus and anterior pituitary HPA axis
• Administration of glucosteriod reduces the patients ability to synthesize corticosteroids due to suppression of feedback mechanism
• May lead to atrophy of the adrenal glands
Must not be suddenly withdrawn
Can lead to adrenal insufficiency
Type D drug induced teratogenesis
• A process which congenital malformations are produced in an embryo or fetus • Caused by a agent or factor termed a terogen • Agent orange • Many drugs are teratogenic in animals • Teratogenesis o Warfarin Fetal bleeding Spontaneous abortion o Sodium valproate Neural tube defects Spinal bifida o Isotretinoin: Accutane Ear malformations cleft palate micrognathia heart defects brain malformations
Withdrawal of opioids symptoms
- Restlessness
- Runny nose
- Diarrhea
- Vomiting
- Shivering
- Piloerection
- Muscle aches
- Hostility
- Tachycardia
- Increased bp
- Unpleasant but not life threatening
withdrawal of opioids treatment Rationale : substitution of opioids maintenance
Methadone
• Opiod agonist – greater level of opioid effect
• Sedating
• More efficacy data but OD more likely
Buprenorphine
• Partial opioid agonist
• Safert OD less likely but lower rates of retention
• Weekly injections
Buprenorphine/naloxone
• +- opioid antagonist
Symptomatic treatment • Eg paracemtol • Metoclopramide • Loperamide • Benzos
• Choice dependent on the patient may be on therapy for years
End of use/withdrawal of benzo symptoms
- Anxiety
- Dysphoria
- Irritability
- Insomnia or nightmare
- Sweating
- Memory impairment
- Hallucinations or psychosis
- Tremors and seizures/convulsions
- Onset of withdrawal symptoms is due to half life of drug
- When treating give a benzo with a longer half life and then reduce dose
Type F oral contraceptive failure
- The pill prevents pregnancy
- Combined pills contains an estrogen and a progestogen compontent
- Also progestogen only pill
MOA
• Prevents ovulation
• Reduce likelihood of implantantion in endometrium
• Thickens secretion to form physical barrier
Adverse effects of oral contracetpvies • Weight gain • Nausea • Flhisng • Depression or irritability • Skin changes • Amenorrhoea upon withdrawal of the pill • Thromboemlism type A
