The Case Of The Red-skinned Man Flashcards
2 types of adverse drug reactions
type A
type B
type A
type B
dose and pharmacology related reaction, predictable, low mortality
Type B adverse drug reactions
dose and pharmacology independent, unpredictable, high mortality
aka drug hypersensitivity reactions
Types of drug hypersensitive reaction
immediate
non-immediate
time frame of immediate DHR
within an hour, often faster esp if IV treatment
symptoms of immediate DHR
urticaria angioedema rhinitis laryngeal oedema bronchospasm cardiovascular collapse
2 types of immediate DHR (mediators)
IgE mediated
non IgE mediated
How are mast cells activated?
sensitised IgE binds specific allergen
cross-linking and clustering of FceR1 receptors, receptor phosphorylation, mast cell degranulation
is DHR related to atopic phenotype?
no, independent, having atopy does NOT make you more likely to have a DHR
when does immediate DHR occur related to dose?
after the 1st dose in a course, may have had previous course of same/similar drug when sensitisation occurred
non IgE mediated DHR
non-specific mast cell activation, more likely in people with spontaneous urticaria
what types of drugs cause non IgE mediated immediate DHR?
opiates
radiocontrast media
vaccines
myorelaxants
high risk drugs for immediate DHR?
antibiotics
NSAIDs
taxane chemo
myorelaxants
serum mast cell tryptase
investigation used to confirm acute anaphylaxis
how to do mast cell tryptase test?
take blood sample 1-2hrs after symptom onset, again after 24hrs - should see rise followed by normalisation
non-immediate DHR time-frame
typically 3-5 days into drug course, 5-8 if never had it before, continue after drug stopped
which drugs cause the most non-immediate DHRs?
anti-microbial
Stevens-Johnson Syndrome
dangerous DHR on a spectrum with toxic epidermal necrolysis
symptoms of SJS
fever cough conjuctivitis mucositis erythema multiforme epidermal necrolysis
symptoms of SJS
drug induced skin reaction involving at least 30% of skin
epidemiology of SJS
affects men more, 3-8 days after dose
most common drugs causing SJS
antibiotics
anticonvulsants
allopurinol
(can also be infection induced)
type 4 hypersensitivity to drugs
occurs 3-8 days into course, get macula-papular rash, no systemic upset
true prevalence of beta lactam allergy
1-2% population although 1-% report it
why is true prevalence of beta lactam allergy lower?
sensitisation lost at a rate of 10% a year
original symptoms caused by something else
can you test for drug allergy?
only reliable antigen test is for beta-lactam allergy
challenge test
gradually increase dose under observation until therapeutic dose reached, watch for side effects
management of a probable type 1 DHR
avoid entire class
management of a probable type 4 DHR
avoid index drug, may be able to use others in class
red man syndrome
erythematous pruritic rash that involves the face, neck, and upper torso, caused by vancomycin
types of ANCA-associated vasculitis
granulomatosis with polyangiitis
microscopic polyangiitis
Churg-Strauss syndrome
Vasculitis symptoms
fever myalgia weight loss haematuria proteinuria haemoptysis dyspnoea vasculitic rash
Goodpasture syndrome
small vessel vasculitis with anti-GBM antibodies which attack type 4 collagen
Symptoms of Goodpasture’s Syndrome
cough SOB hamoptysis proteinuria haematuria *pulmonary haemorrhage major complication*
Treating Goodpasture’s syndrome?
immunosuppression and plasma exchange
symptoms of SLE
fever, fatigue, weight loss, Reynaud’s, malaria rash, discoid rash, polyarthritis, pericarditis, glomerulonephritis
treating lupus nephritis
ACEi
prednisolone with mycophenolate
antibodies found in SLE
anti-dsDNA
ANA
which SLE antibodies are more specific?
anti-dsDNA
treating SLE generally
suncream
hydroxychloroquine
Causes of drug-induced SLE (4)
procainamide
hydralazine
isoniazid
phenytoin
5 types of cardiorenal syndrome
1 - acute cardiac cause with AKI 2 - chronic cardiac cause with CKD 3 - AKI causes acute cardiac disorder 4 - CKD causes chronic HF 5 - systemic condition causes cardiac and renal dysfunction
how does cardiac disease lead to renal disease?
impaired cardiac output leads to reduced renal perfusion, reduced GFR so impaired renal function, RAAS activated, volume expansion which further injures cardiac tissue
Hepatorenal syndrome (HRS)
Acute renal failure occurs because of a decrease in renal blood flow secondary to liver disease
pathophysiology of hepatorenal syndrome
Portal hypertension –> vasodilator and angiogenic factor production –> splanchnic/systemic vasodilation –> decreased effective arterial blood volume –> increased cardiac output, neurohumoral activation –> renal vasoconstriction
Type 1 hepatorenal syndrome
rapid progression
creatinine doubles
caused by alcohol or sepsis
prognosis 2wks
Type 2 hepatorenal syndrome
develops slowly, caused by refractory ascites, prognosis 4-6 months
diagnostic criteria for hepatorenal syndrome
cirrhosis with ascites creatinine > 133 no shock no hypovolaemia no renal disease no nephrotoxic drugs
why is there low urine sodium in hepatorenal syndrome?
excess aldosterone from RAAS causes extreme sodium retention, very low urine sodium indicates severe disease
Treating HRS
sodium and water restriction
treat reversible causes
liver transplant
which infections are linked to glomerular disease? (4)
Hepatitis C
malaria
HIV
bacterial infections
which cancers are associated with glomerular disease? (3)
lymphoma
leukaemia
myeloma
what is the most common glomerular disease?
IgA nephropathy (Berger disease)
typical presentation of IgA nephropathy
frank haematuria following an URTI
pathophysiology of IgA nephropathy
autoimmune condition where IgA immune complexes are deposited in the kidney
treating IgA nephropathy
ACEi
steroids
maybe immunosuppression
outcomes very variable
IgA vasculitis (Henoch-Schonlein purpura)
excess IgA production and deposition w/in blood vessel
Symptoms of IgA Vasculitis
palpable purpuric rash over buttocks and limbs
abdominal pain
arthralgia
haematuria
treating IgA vasculitis
steroids
analgesia
mostly self-limiting, better prognosis than IgA nephropathy
most common cause of nephrotic syndrome in children
minimal change disease
histological hallmark of minimal change disease
normal on light microscopy
effacement and fusion of podocytes on electron microscopy
treating suspected minimal change disease in a child
empirical steroids, can give before the biopsy result
nephrotic syndrome
Proteinuria, hypoalbuminemia, oedema
hypercholesterolaemia
complications of nephrotic syndrome
Hypercoagulability, increased infection
treating nephrotic syndrome
salt and fluid restriction
diuretics
ACEi
membranous nephropathy biopsy result
spike and dome appearance of basement membrane
how does membranous nephropathy present?
nephrotic syndrome
most common in males in 40s and 50s
commonest glomerulonephritis in adults
treating membranous nephropathy
ACEi
immunosuppression
consider anticoagulation
