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Flashcards in adverse drug reactions Deck (27)
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1
Q

Therapeutic Goods Administration (TGA)

A

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

2
Q

registered vs listed medicines

A

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

2
Q

registered vs listed medicines

A

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

3
Q

registered vs listed medicines

A

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

4
Q

Post-Marketing Surveillance/Pharmacovigilence

A

Once on the market, the TGA continues to monitor safety and efficacy (performance). Post-marking surveillance is phase IV of a clinical trial.

5
Q

what is required in an ADR report

A

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

6
Q

Characterisation of Adverse Drug Reactions

A

A
Augmented

B Bizarre

C
Chronic

D
Delayed

E
End of Use (Withdrawal)

F
Failure

7
Q

type A

A

augmented

common and predictable
dose relgaed

digoxin toxicity

8
Q

type B

A

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
9
Q

type C

A
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
10
Q

Type D

A
delayed 
•	Uncommon 
•	Usually dose related 
•	Occurs or becomes apparent some time after using drug 
•	Ex 
o	Teratogenesis
11
Q

type E

A
  • After withdrawl
  • Opiod withdrawal
  • Beta blocker withdrawal
  • Withdrawal very slowly

end of use

12
Q

Type F

A
  • Common
  • Dose related
  • Often caused by drug interaction
  • Oral contraceptive failure
  • Increase dosage
  • Consider effects of concomitant therapy
13
Q

Factors FOR ADR

A
  • 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

14
Q

type A digoxin toxicity

A

• 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

15
Q

Digoxin toxicity type A prevention and treatment

A

• 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

16
Q

type b reactions types

A
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

17
Q

Type B sulfonamide hypersensitivity

A
  • Sulfonamides are antibiotics that interfere with folate synthesis
  • Sulfamethoxazole commonly combined with trimethoprim
  • Mild: fever dyspnea rash
  • Serious: anaphylaxis Steven Johnson syndrome
18
Q

Type C chronic administration of corticosteroids

A
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

19
Q

Type D drug induced teratogenesis

A
•	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
20
Q

Withdrawal of opioids symptoms

A
  • Restlessness
  • Runny nose
  • Diarrhea
  • Vomiting
  • Shivering
  • Piloerection
  • Muscle aches
  • Hostility
  • Tachycardia
  • Increased bp
  • Unpleasant but not life threatening
21
Q

withdrawal of opioids treatment Rationale : substitution of opioids maintenance

A

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

22
Q

End of use/withdrawal of benzo symptoms

A
  • 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
23
Q

Type F oral contraceptive failure

A
  • 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
23
Q

Type F oral contraceptive failure

A
  • 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
24
Q

DOTS classification

A

• Proposed since some drugs do not fit into the above catergories
• Takes into account the time course of the reaction and susceptibility of the individual
o D = dose related
o T = time related
o S = susceptibility related

25
Q

• Understand how genetic polymorphisms may contribute to the flushing response following alcohol ingestion

A
  • Patient has ALDH22 (lysine) instead of ALDH21 (glutamine)
  • Therefore they have decreased activity of ALDH
  • Cannot metabolise acetaldehyde to acetate effectively – leads to build up of it
  • Accumulation of acetaldehyde = flushing response
  • Caucasians = ALDH2*1
  • East Asians = ALDH2*2