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HHD 2 > Adverse Reactions to drugs > Flashcards

Adverse Reactions to drugs Flashcards

1
Q

There is no universally accepted taxonomy for classifying adverse drug reactions. Give some examples of how they can be classified

A

onset: acute, subacute, delayed
degree: mild, moderate, severe
predicability: predictable and dose related, unpredictable and not necessarily dose related e.g. anaphylaxis
most classify adverse drug reactions based on the mechanism of toxicity:
-recognition
-management
-prevention

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2
Q

auWhat are type A adverse drug reactions?

A

augmented
exaggeration of a drugs normal phamacological actions when given at a usual therapeutic dose and normally dose dependent

augmented- more than jus the target tissue/organs affected

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3
Q

What are type B adverse drug reactions?

A

bizzare
novel response not expected from known pharmacological actions of the drug
less common
idiosyncratic reactions and anaphylaxis

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4
Q

What are type C adverse drug reactions?

A

continuing reactions
persist for a very long time
e.g. osteoradionecrosis of the jaw with bisphoshonates

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5
Q

What are type D adverse drug reactions?

A

delayed
become more apparent with time after the use of a medicine
timing makes it difficult to detect
e.g. leucopenia which can occur up to 6 weels after a dose of lomustine

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6
Q

What are type E adverse drug reactions?

A

End of use reactions
associated with withdrawals of a medicine
e.g. insomnia, anxiety and perpetual disturbances following withdrawal of benzodiazepines

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7
Q

Q
Adverse drug reactions can be classified according to the DoTS pneumonic. What does it stand for?

A

dose related
time related
susceptibility factors

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8
Q

Type A adverse drug reactions have __________ effects. Give an example of this

A

extension effects
giving too much warfarin to reduce the risk of a peripheral vascular thrombosis may result in spontaneous bleeding

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9
Q

What the normal effect of a therapeutic dose of warfarin?

A

aims to increase prothrombin time so that INR is between 2-3

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10
Q

Frusemide is often prescribed in heart failure where oedema is a concern. Name the therapeutic effect and the toxic extension of this drug

A

therapeutic effect: diuresis- reduction of fluid
toxic extension- hypovolemia- reduced blood volume; hypotension, can cause the heart (in failure) to attempt to work harder; more damage to the heart

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11
Q

Heparin is an IM/IV anticoagulant, indicated for thromboemobolic dissolution. State the therapeutic effect and toxic extension of this drug

A

inhibit coagulation
spontaneous bleeding

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12
Q

Insulin is prescribed for some patients with diabetes mellitus. State the therapeutic effect and toxic extension of this medication

A

reduce blood glucose
hypoglycaemia

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13
Q

Vecuronium is often prescribed with GA for abdominal surgery. State the therapeutic effect and the toxic extension of this medication

A

skeletal muscle relaxation
prolonged respiratory paralysis

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14
Q

How do type A adverse drug reactions come about?

A
  • side effects may be produced by the same drug-receptor interaction as the therapeutic effect but at a different tissue or end organ
    *whether the side effect is toxic or therapeutic is dependent on the purpose of the treatment
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15
Q

Give an example of a type A adverse reaction that can be used therapeutically

A
  • atropine (anticholinergic) given for GI hypermobility can cause xerostomia
  • however, it can be used therapeutically in cases of hypersalivation
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16
Q

What oral side effect does diphenydramine (bendryl) have?

A

xerostomia

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17
Q

What oral side effect does griseofulvin have?

A

black hair tongue
there is an overgrowth of pigmented papillae stimulated by bacterial products

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18
Q

What oral side effect does phenytoin have?

A

gingival hyperplasia

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19
Q

What oral side effect does tetracycline (doxycycline) have?

A

pigmentation and hyperplasia of teeth

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20
Q

What side effect does amoxycillin have?

A

dermatitis
persistent scratching, localised reaction
(allergy)

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21
Q

What side effect does cyclophosphamide have?

used for autoimmune control- used to treat many cancers

A

alopecia

this chemotherapeutic agent causes alopecia

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22
Q

What is the side effect of methandrostenolone?

A

acne

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23
Q

What is the side effect of minoxidil?

A

hypertrichosis
excessive hair growth anywhere on the body- men or women

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24
Q

What is the side effect of ciprofloxacin?

A

arthralagia

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25
Q

What is the side effect of hydralazine?

A

arthralagia

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26
Q

What is the side effect of phenobarbitol?

A

osteomalacia
softened and weakened bone

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27
Q

What is the side effect of prednisolone?

A

osteoporosis
prevents the maturation of collagen
remember steroids prevent bone growth

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28
Q

What is the side effect of baclofen?

Baclofen is an antispasmodic drug, used to treat facial pain

A

blurred vision

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29
Q

What is the side effect of digoxin?

anti-arrhytmic drug

A

yellow vision

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30
Q

What is the side effect of gentamicin?

antibiotic

A

ototoxicity
hearing and balance problems
this is a very well known side effect

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31
Q

What is the side effect of thioridizine?

A

pigmentary retinopathy

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32
Q

What is the side effect of cytosine arabinoside?

A

pancytopenia
deficiency in all cellular blood components (RBC, WBC, platelets)

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33
Q

What is the side effect of prilocaine?

amide local anaesthetic

A

methaemoglobinaemia
methaemoglobin has a preference for CO2

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34
Q

What is the side effect of sodium valproate?

A

thrombocytopenia
deficiency of platelets

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35
Q

What is the side effect of zidovudine?

antiviral drug

A

granulocytopenia
(particularly of neutrophils)
eosinophils, basophils

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36
Q

What are the metabolic side effects of aspirin?

A

metabolic acidosis

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37
Q

What is the metabolic side effect of frusemide?

used in heart failure

A

hyperglycaemia

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38
Q

What is the metabolic side effect of Nadolol?

A

hypoglycaemia

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39
Q

What is the metabolic side effect of rifampicin?

anti-tuberculosis drug

A

jaundice

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40
Q

What are the side effects of atorvastatin?

A

myalgia (muscle pain)
burning mouth

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41
Q

What is the side effect of chlorpromazine on the NM system?

neuromuscular system

A

tardive dyskinesia
parkinsonism

parkinsonism- no deficiency in the substantia nigra

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42
Q

What is the side effect of lidocaine on the NM system?

aminde LA

A

convulsions

43
Q

What is the side effect of theophylline on the NM system?

oral anti-epileptic

44
Q

What is the side effect of clonidine on the CNS?

clonidine- migraine, facial pain

A

drowsiness and lethargy

45
Q

What is the side effect of dexamethasone on the CNS?

A

mental depression
note: dexamethasone 5-6x more efficacious than prednisolone

46
Q

What is the side effect of diazepam on the CNS?

BZD

A

confusion
should not be taken when driving

47
Q

What is the side effect of levodopa on the CNS?

dopamine replacement- oral

A

Mania
Levodopa with carbidopa does not get broken down before it reaches the brain; converted to dopamine in the brain

Carbidopa is a decarboxylase inhibitor so prevents break down of levodopa before it reaches the brain

Carbidopa does not pass the blood brain barrier therefore its decarboxylase inhibitory effect is not observed in the brain thus levodopa is metabolised to dopamine in the brain

Levodopa is able to cross the BBB

48
Q

What is the side effect of bupivacaine on the CVS?

amide LA

A

bradycardia
remember bupivacaine causes vasodilation at clinical doses

Most LA are vasodilators hence the need for vasoconstrictor; however bupivacaine more so than others

49
Q

What is the side effect of propofol on the CVS?

IV GA, betablocker

A

hypotension

50
Q

What is the side effect of propanolol on the CVS?

beta blocker

Beta blockers give the heart a longer time to beat harder

A

cardiac failure

51
Q

What is the side effect of ACE inhibitors on the respiratory system ?

A

cough- persistent dry cough
remember ACE enzyme is also produced in the lung

52
Q

What is the side effect of isofluorane on the respiratory system ?

inhaled GA

53
Q

What is the side effect of pethidine on the respiratory system ?

opioid - pain relief medication

A

respiratory depression

54
Q

What is the side effect of propanolol on the respiratory system ?

A

broncospasm

55
Q

What is the side effect of ketamine on the respiratory system ?

IV general anaesthetic- mostly in vets

A

larngospasm

56
Q

What are the side effects of aspirin on the GI tract?

A

melaena- passage of black, tarry stools

57
Q

What are the side effects of erythromycin on the GI tract?

A

nausea and vomiting

58
Q

What are the side effects of lithiym on the GI tract?

59
Q

What are the side effects of morphine on the GI tract?

A

constipation

60
Q

Name the original and subsequent uses of amantadine

A
  • antiviral
  • parkinsonism
61
Q

Name the original and subsequent uses of amphetamine

stimulant

A
  • CNS stimulant
  • ADHS
62
Q

Name the original and subsequent uses of chlorthiazide

A
  • diuretic
  • anti-hypertensive
63
Q

Name the original and subsequent uses of diphenhydramine

A
  • anti-hostamine
  • sedative
64
Q

Name the original and subsequent uses of lidocaine

A
  • local anaesthetic
  • anti-arrhythmic
65
Q

Name the original and subsequent uses of methadone

A
  • analgesic
  • heroin substitute
66
Q

Name the original and subsequent uses of metronidazole

interacts with bacterial DNA; prevents protein synthesis

A
  • antiparasitic
  • antibacterial
67
Q

Name the original and subsequent uses of phenytoin

A
  • anticonvulsant
  • antiarrhythmic
68
Q

Name the original and subsequent uses of probenecid

A
  • inhibit penicillin excretion
  • uricosuric - increase excretion of uric acid in urine
69
Q

Name the original and subsequent uses of quinidine

A
  • antimalarial
  • antiarrhythmic
70
Q

Give an example of instances where disturbing side effects are accepted if therapeutic action is essential?

A

cancer treatments

71
Q

What are some ways around side effects in relation to dose of a drug?

A
  1. give a second therapeutic drug (which also has its own side effects) but with the same primary therapeutic effect; reduce doses of both drugs without reducing therapeutic action thus reducing the side effects
  2. give a second drug to compensate for unwanted action of the principle drug
72
Q

Give an example of an instance where a second drug is administered to compensate for the unwanted action of a principle drug?

A
  • methotrexate (cancer treatment) is a folate antagonist- inhibits DHFR enzyme
  • folate is necessary for maturation of cells (nucleic base syntheis)
  • therefore methotrexate is always given with folinic acid
73
Q

Dose related side effects often arise as drugs have effects on receptors outside of the primary organ or tissue. How can this be combatted in the future?

A
  • research into more selective drugs where unwanted side effects are removed
  • more selective to target tissues or organs
74
Q

Type B adverse reactions are also referred to as …

A

idiosyncratic reactions
bizzare reactions

75
Q

Type B adverse reactions occur as a result of ___________ response to the drug

A

genetically determined abnormal response to the drug

76
Q

What kinds of effects will a drug have in a type B adverse reaction?

A

drug effects may be:
* strong
* weak in intensity; brief
* prolonged duration

77
Q

Give examples of drugs where there may be altered drug metabolism which can lead to a type B adverse drug reaction

A

succinylcholine
isoniazid
vitamin D
phenytoin

78
Q

Give examples of drugs where there may be abnormal distribution which can lead to a type B adverse drug reaction

A

iron
thyroxine (T4)

79
Q

Give examples of drugs where there may unusual receptor affinity which can lead to a type B adverse drug reaction

80
Q

Give an example of a novel drug effect

A

haemolytic anaemia by the antimalarial primaquinine which occurs exclusively in men of certain racial and ethnicl groups

african american
sarininans
sephradic jews
iranians
filipinos

81
Q

How can idiosyncratic drug reactions be overcome?

A

personalised medicine?
personal and family history essential if a suspected genetic bias

82
Q

State the drugs affected by a NADH- methahaemoglobin reductase deficiency and the idiosyncratic response

A

Drugs:
* prilocaine
* benzocaine (ester LA)

Methaemoglobinaemia

83
Q

State the drugs affected by a G-6-P Dehydrogenase deficiency and the idiosyncratic response

A

Drugs:
* aspirin
* primaquine
* sulphonamide

Haemolytic anaemia

84
Q

State the drugs affected by abnormal haem synthesis and the idiosyncratic response

A

Drugs
* barbiturates
* sulphomamides

Porphyria- abnormal metabolism of the blood pigment, haemoglobin

85
Q

State the drugs affected by low plasma cholinesterase and the idiosyncratic response

A
  • procaine and other ester LAs

LA toxicity, extended paralysis

86
Q

State the drugs affected by altered calcium homeostasis and the idiosyncratic response

A

volatile inhalation anaesthetics
succinylcholine

Malignant hyperthermia

87
Q

State the drugs affected by prolonged QT interval and the idiosyncratic response

A

Cisapride

Ventricular tachycardia

88
Q

10% of all untoward type B adverse drug reactions are _______.

A

allergic reactions

89
Q

What are the characteristic of type B allergic reactions to drugs?

A
  • prior exposure to drug or related compound is needed
  • severity of response is dose related
  • nature of the effect is a function of the immune system and not the function of the drug
  • reaction is unpredicable
90
Q

Give examples of drugs commonly implicated type B allergic reactions in patients

A

penicillin
sulphonamides
quinidine

occassionally some preservatives and colouring agents in the preparation cause allergy

91
Q

Drugs are not usually antigenic in their free state. What is required for an immunologic type B response?

A

covalent bond with endogenous carrier molecules such as albumin

92
Q

Drugs generally required activation by metabolism or sunlight (photoallergy) before serving as ________ in the formation of an antigen

93
Q

What are the types of drug allergy

A
  • type I- anaphylaxis
  • type II- cytotoxic reactions
  • type III, immune complex reactions
  • type IV reactions
94
Q

Briefly describe the molecular mechanism of type I allergic reactions

A

*[ clinical signs within minutes/hours of drug administration ]
* attachment of antigen to IgE antibodies bound to surface mast cell/basophils
* cell degranulation and release of histamine, leukotrienes, cytokines

95
Q

What are the major signs and symptons of type I reactions?

A
  • GIT- cramps, diarrhoea
  • skin and mucous membranes- erythema, urticarial, angioneurotic oedema
  • blood vessels: vasodilation, increased permeability
  • death by airway obstruction or CV collapse within minutes
96
Q

Individuals with type I drug reactions usually have a history of …

A

hayfever (allergic rhinitis)
asthma

97
Q

Give examples of type I drug allergic reactions

A

anaphylaxis
allergic rhinitis
asthma

98
Q

Type II allergic reactions are caused by …

A

circulating antibodies- IgG and IgM
antigen attaches to circulating RBCs or platelets (then antibody attaches to antigen on the RBCs or platelets and then activates complement and cell lysis)
cytotoxic T cells and complement involved in lysis of RBCs/platelets

  • they antibody against the antigen mediated complement activation
99
Q

Give examples of type II cytotoxic allergic reactions

A

haemolytic anaemia
thrombocytopenia

100
Q

Briefly describe how type III allergic reactions occur

A
  • soluble Ag-Ab complexes are formed in intravascular or interstitial spaces
  • deposition of these complexes occur on walls of small blood vessels
  • activation of complememt and neutrophil migration occurs to the area
  • neutrophil degranulatoon in an attempt to remove complexes
  • lysosoal enzymes are released causing tissue damage and thrombosis of vessels
101
Q

Give examples of type III allergic reactions

A
  • serum sickness
  • glomerulonephritis
  • neuropathy
  • arthus reaction
102
Q

Briefly outline how type IV (cell mediated) drug reactions occur

A
  • sensitised T lymphocytes exposed to the drug hapten release lymphokines
  • additional cells are attracted- lymphocytes, macrophages, cytotoxic T cells to site
  • lysozymes and toxic lymphokines produce local tissue necrosis
  • usually delayed because of time required for effector cells to congregate in area
103
Q

Give examples of type IV allergic reactions

A

contact dermatitis
delayed hypersensitivity

HHD 2 (37 decks)

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