pharmacology/toxicology Flashcards
diagnosing hereditary angioedema
C4
> if low, C1-INH
skin biopsy to confirm
angioedema presentation depends on..
whether bradykinin or histamine/mast cell mediated
histamine mediated causes more urticaria and superficial swelling
angioedema treatment according to type
antihistamines- good response from allergic but not HAE or ACei induced
glucocorticoids- good response from allergic but not so much HAE or ACEi induced
hereditary angioedema treatment
C1-INH concentrates acute and prophylaxis
bradykinin inhibitors, icatibant
attenuated androgens
TXA to spare C1-INH
immunotherapy w/ biologics
penicillins adverse effects
interstitial nephritis
encephalopathy
cholestatic jaundice (coamox)
c diff colitis
cephalosporin adverse effects
anaphylaxis
c diff colitis
carbapenem adverse effects
seizures (imipenem)
macrolide mechanism
e.g. erythromycin, clarithromycin, azithromycin
inhibits 50S ribosomal subunit
macrolides adverse effects
P450 inhib (stop statin)
QTc prolongation
thrombophlebitis
cholestatic jaundice
tetracycline mechanism
30S ribosome subunit inhibition
tetracycline adverse effects
photosensitivity
renal impairment
tooth staining (avoid in pregnancy and children < 8y)
glycopeptide mechanism
e.g. vanc, teic
inhibits peptidoglycan synthesis
glycopeptide adverse effects
(teic, vanc)
ototoxic
nephrotoxic
red man syndrome
aminoglycosides are c/i in..
myaesthenia gravis
oxazolidiones mechanism
e.g. linezolid, cycloserine
50S inhibition
oxazolidione adverse effects
(linezolid, cycloserine)
agranulocytosis
pancreatitis
sulfonamide mechanism
inhibits folate and DNA synthesis
sulfonamide adverse effects
teratogenic
agranulocytosis
SJS
quinolone mechanism
e.g. ciproflox, levoflox
DNA gyrase inhib
quinolone adverse effects
(ciproflox, levoflox)
tendonitis, achilles rupture
diagnosing LMWH or DOC OD
elevated anti Xa levels
prolonged APTT
TCA OD management
activated charcoal/lavage if within 1h
sodium bicarb if ECG changes/hypotension
or vasopressors or IV glucagon
benzos for seizures
venlafaxine OD management
charcoal/lavage if within 1h
benzos for seizures
sodium bicarb for ECG changes
avoid co-prescribing TCA with…
SNRI, SSRI
antifungals
buproprion
cimetidine
diltiazem, verapamil
HIV protease inhibitors
antiemetics according to cause
intracranial- cyclizine (add dex if raised ICP)
anxiety- benzo
drug induced- haloperidol
metabolic- haloperidol
pregnancy- promethazine
postop- droperidol, dex, ondansetron
drugs for bowel obstruction during EoL
hyoscine butylbromide
ocreotide second line
managing benzo OD
flumazenil (competitive GABA A action) if requiring ventilation
c/i if pt has taken other meds that may cause seizures or head injury
beta blockers with membrane stabilising effects
propranolol and labetalol
inhibit cardiac myocyte Na channels
prolong QRS and impair cardiac conduction
beta blocker OD
prolonged QT, QRS
> VT
CNS depression, hypoglycaemia, resp depression and bronchospasm
atenolol and bisoprolol are less likely to cross BBB and cause neuro symptoms (hydrophilic)
tx:
IV glucagon for hypotension, shock
IV bicarb for wide QRS or hypotension not improving
atropine
insulin w/ dextrose
in the case of arrest, CPR should be continued for 1h
CCB OD
hyperglycaemia
CTX- alkylating agent mechanism and adverse effects
classic e.g. cyclophosphamide
form bonds with proteins
> inactivate enzymes involved in DNA production and protein synthesis
non classic e.g. cisplatin
cross link DNA strands
> interrupt normal DNA
alkylating agents adverse effects
classic e.g. cyclophosphamide
> haemorrhagic cystitis
pulm interstitial fibrosis
non classic e.g. cisplatin
> kidney failure, ototoxic, peripheral neuropathy
antimetabolite CTx mechanism and side effects
interfere with purine/pyramidine synthesis
MTX> hepatic failure, pulm fibrosis
5FU- palmar plantar, cardiotox
antibiotics for CTx
intercalate into DNA > free radicals
s/e:
anthracycline (doxorubicin) CCF
bleomycin pneumonitis, fibrosis
mitomycin kidney failure, stomatitis, alopecia
vincristine mechanism and side effects
M phase specific
prevents spindle formation
> inhibits mitosis
blistering, neuropathy, bronchospasm
paclitaxel mechanism and side effects
stabilises microtubules
> inhibits mitosis
sudden total alopecia
myalgia, peripheral neuropathy
topoisomerase inhibitors side effects
cholinergic syndrome
profuse diarrhoea
cyanide poisoning
sources: cig smoking, plastic combustion, paint and nylon, printing, dying
inhibits oxidative phosphorylation during aerobic metabolism
> hypoxia, lactic acidosis
switch from aerobic to anaerobic metabolism
chronic> predominantly neuro/neuropsychiatric e.g. parkinsonism
tx:
IV sodium thiosulfate if mild
IV hydroxycobalamin if mod
both if severe
cyanide vs CO
CO- improve rapidly after leaving environment
cyanide- seizures may occur, fixed dilated pupils
digoxin mechanism and therapeutic window
inhibits Na/K ATPase
increases intracellular Na, reduces K
0.5-0.9
digoxin toxicity
risk is increased by reduced renal clearance, hypoK, hypoMg, hyperCa, verapamil, diltiazem, amiodarone, ketoconazole, erythromycin
correct electrolyte abnormalities
more hyperkalaemia correlates with mortality
BUT calcium gluconate can cause stone heart
Fab for life threatening/unstable arrhythmia or hyperkalaemia or end organ dysfunction
drugs that can cause urticaria and anaphylaxis
penicillin
salicylates
quinidine
ACEi
opiates
cephalosporins
hydralazine
drugs that can cause exanthematous rashes
penicillins, cephalosporins
sulfonamides
allopurinol
NSAIDs
drugs that can cause fixed eruption
tetracyclines
barbiturates
dapsone
chlordiazepoxide
sulfonamides
benzos
NSAIDs
quinine
paracetamol
drugs that can cause DRESS
allopurinol
carbamazepine
lamotrigine
NSAIDs
phenytoin
sulfonamides
drugs that can cause TEN/SJS
allopurinol
sulfonamides
penicillin
carbamazepine
phenytoin
NSAIDs
gold
salicylates
barbiturates
mechanism of drug rashes
immediate- IgE
delayed (days to weeks)- IgG
occurs quicker on repeated exposure
drug rashes blood tests
DRESS or hypersensitivity- liver dysfunction and eosinophilia
AGEP- neutrophilia
causes of erythema nodosum
OCP, pregnancy
penicillin, tetracyclines
TB, strep
sarcoid, IBD
ethylene glycol poisoning
metabolite oxalic acid is nephrotoxic- calcium oxalate crystals deposit in tubules and cause necrosis
may also > hypoCa, hypoMg, hyperK
metab acidosis, raised anion and osmolar gap
antedote fomepizole or ethanol
only give calcium gluconate for hypocalcaemia if prolonged QT or persistent convulsions
haemodialysis if severe acidosis or electrolyte imbalance or renal failure
causes of gynaecomastia
chronic renal/liver disease
HCG or oestrogen producing tumours
tumours compressing pituitary stalk
male breast ca
gonadal dailure
hyperPTH, hypothyroid
digoxin, opiates
spiro, cimetidine, cyproterone, antipsychotics
metro, domperidone, antiretrovirals, PPIs
heroin, anabolic steroids, aromatherapy
gynaecomastia management
danazol (inhibits gonadotrophins)
tamoxifen
testosterone
calcineurin inhibitors
e.g. ciclosporin, tacrolimus
reduce IL2 production and T cell proliferation
antiproliferative immunosuppressants
e.g. MMF, azathioprine
reduce cytokine induced T cell proliferation
mTOR inhibitors
e.g. sirolimus, everolimus
inhibit antibody production
bind to FKBP-12
> supress T cell proliferation
steroids immunosuppression
sequestration of CD4 T lymphocytes in reticuloendothelial system
inhibit cytokines transcription
iron poisoning
impaired oxidative phosphorylation
> mitochondrial dysfunction
> anaerobic resp and cell death
> liver toxicity and myocardial siderosis, metabolic lactic acidosis, gastric outlet obstruction
tx:
observe if < 500 micrograms/dl and mild symptoms
IV desferoxamine
treating lead poisoning
dimercaprol, succimer or sodium calcium edetate chelation (CVS and neuro tox often not reversed by chelation)
ICU if encephalopathic
long term follow up due to storage in bones
lithium therapeutic window and toxicity
0.4-1
test 12h post dose
hyponatraemia, diuretics and dehydration can reduce renal clearance of lithium because it is processed similarly to Na in kidneys
tx: stop diuretics, increase fluids, dialysis
P450 inducers
cigarettes, alcohol
rifampicin
carbamazepine
st johns wort
phenytoin, phenobarbitone
> reduced therapeutic effect
increased metabolites > toxicity
liver enzyme inhibitors
chloramphenicol
erythromycin
sulfonamides
ketoconazole
isoniazid
cimetidine
ciproflox
acute ethanol
omeprazole
disulfiram
valproate
drugs causing prolonged QT
amiodarone, sotalol, procainamide
erythromycin, trimethoprim
terfenadine
ketoconazole, fluconazole
haloperidol, citalopram
causes of methaemaglobinaemia
cytochrome B5 reductase or pyruvate kinase def
haemaglobinopathy M
local anaesthetics
aniline dyes
benzene deriv
chloroquine
nitrites
metoclopramide
sulfonamide
smoke
diagnosing methb
brown blood, doesn’t oxidise
normal pao2 reduced sao2
methb gold standard
potassium cyanide distinguishes from sulfhaemaglobin
methb treatment
indicated if > 30% or symptomatic
IV dextrose
methylene blue IV
ascorbic acid if MB c/i e.g. G6PD def
exchange transfusion
methanol poisoning
metabolised to formaldehyde then formic acid
may have normal pH at presentation
tx: fomepizole, ethanol, sodium bicarb, dialysis
dialysis indications:
> 500 mg/l
visual/CNS
severe metab acidosis or electrolyte imbalance
renal failure
refractory deterioration
managing NMS
lorazepam for agitation and catatonia
dantrolene for hyperthermia and rigidity
bromocriptine/amantadine
managing opiate toxicity
aim for RR > 12 and spo2 > 90%
managing organophosphate poisoning
atropine + pralidoxime chloride
monitor tidal vol and strength of neck flexors
there may be delayed effects 1-4 days after exposure
organophosphate ECG changes
AV block
long QT
brady
peaked T
ventric arrhythmias
indications for liver transplant in paracetamol OD
pH < 7.3
or
encephalopathy III/IV
and PT > 100
and Cr > 3.4
drugs causing parkinsonism
antipsychotics
metoclopramide
prochlorperazine
tetrabenazine
valproate
lithium
drugs causing photosensitivity
thiazides
tetracyclines
NSAIDs
quinine
fluoroquinolones
voriconazole
chlorperazine
furosemide
sulfonamides
amiodarone
metformin
treating polymorphic light eruption
hydroxychloroquine
oral steroids short course
azathioprine
phototoxic vs photoallergic
toxic:
mins-hours
sun exposed skin only affected
pigment changes
epidermal degeneration, dermal oedema
allergics:
24h or more
can spread to other parts of skin
no pigment changes
epidermal spongiosis
drugs c/i in pregnancy
ACEi
topiramate
fluoxetine, lithium
sulfonamides
warfarin
androgens
drugs that are safer to prescribe in breastfeeding
highly protein bound
low plasma: milk ratio
shorter half life
drugs safe in pregnancy
topical/inhaled
poor bioavailability
heparin, insulin, gent, cephalosporins, omeprazole, lansoprazole
ibuprofen
warfarin
Levonelle emergency contraception
drugs c/i in breastfeeding
amiodarone
chloramphenicol
ergotamine
iodides
MTX
lithium
tetracyclines
cabergoline
pseudoephedrine
premature ejaculation drug treatment
dapoxetine SSRI
salicylate OD
in aspirin and wintergreen oil
metab acidosis + resp alkalosis (RA usually occurs before MA)
take levels 4 hours after asymptomatic OD, 2 hours after symptomatic
tx:
IV fluids and dextrose
IV bicarb
treat hyperkalaemia aggressively
dialyse if coma or > 900 or > 700 with acidosis
serotonin syndrome features
spontaneous clonus
inducible clonus + agitation or sweating
ocular clonus + agitation or sweating
hypertonia + temp > 38 + ocular or inducible clonus
often misdiagnosed as NMS
but presents over hours rather than days/weeks
treating serotonin syndrome
cyproheptadine
propranolol
may need ICU for hyperthermia, rhabdo, AKI, DIC
drug induced lupus
CNS and renal involvement rare
ANA positive, dsDNA neg
procainamide
isoniazid
hydralazine
cancers causing SIADH
SCLC
pancreatic
prostate
lymphoma
SIADH osmolalities
urine > 100
serum < 275
SIADH treatment
demeclocycline blocks ADH
tolvaptan vasopressin receptor antag
theophylline mechanism
adenosine antag
phosphodiesterase inhib
