Posisoning - specific drugs Flashcards
(119 cards)
1
Q
Epidemiology of paracetamol poisonning
A
50% overdoses include paracetamol
Leading cause of mortality from overdose
1<% mortality
2
Q
What are the metabolites of paracetemol
A
Para-glucorinide
Para-sulphate
N-acetyl-p-benzoquinone-imine
3
Q
How is paracetemol turned into NAPQI
A
Oxidation via CYP450 eg CYP2E1/3A4
4
Q
How is NAPQI detoxified in the liver
A
Glutathione
5
Q
How does NAPQI cause hepatocellular injury
A
glutathione absent or depleted
6
Q
Early clinical symptoms from paracetemol poisoning
A
May be none
V non specific symptoms
N+V+ abdominal pain
7
Q
delayed clinical features of paracetemol overdose
A
Hepatic necrosis
2-3 days: LIVER FAILUREN
Jaundice
Liver pain
Encephalopathy
Coagulopathy
Fulminant hepatic failure
Death - 3-6 days post overdose
8
Q
Rare delayed features of paracetemol overdose
A
Renal failure (acute tubular necrosis)
Hypoglycaemia
Metabolic acidosis
9
Q
Renal failure in paracetamol overdose
A
acute tubular necorsis
2-7 days after poisoning
Oliguria
Loin pain
10
Q
investigations for paracetemol overdose
A
Paracetamol level
Clotting - PT, INR (baseline then monitor)
U+Es, creatinine at baseline then monitor
Blood gases
LFTs
11
Q
What does paracetamol level tell you in overdose
A
- best early predictor of prognosis
Need for antidotes
12
Q
Why may urea remain low in paracetamol overdose
A
Even if decreased from kidneys - Hepatic urea production
13
Q
When is paracetamol treatment a gray area
A
0-4 hours - best to wait til after when can be interpreted
14
Q
What paracetemol level treat at 4 hours
A
100mg
15
Q
What see in heaptic injury in bloods in paracetamol overdose
A
Prolonged PT/INR
Elevated transaminases (bad prognostic)
Elevated bilirubin (hepatic necrosis)
16
Q
Poor prognostic features in paracetamol overdose
A
PT/INR rising after day 3 or
PT>100s at any time - liver transplant
Bilirubin >70micromol/l
Metabolic acidosis
Encephalopathy - III or IV
AKI:
Raised lactate
Creatinine >300 micromol/l
17
Q
What are the options for paracetamol overdose treatment
A
Prevent absorption - activated charcoal large dose within 1 hour
IV acetylcysteine
18
Q
What is important with paracetamol overdose treatment
A
Timing is vital - effectiveness declines over time of antidote
19
Q
How is acetylcysteine delivered
A
IV over 21 hours
20
Q
How long is acetyl cysteine effective for
A
8 hours
decreases gradually afterwards
Still treat after 24 hours as still beneficial even in fulminant hepatic failure
21
Q
When else is acetylcysteine used except acutely
A
For people with fulminant hepatic failure from paracetamol awaiting transplantation
22
Q
Is there a time limit to when you use acetyl cysteine
A
No - use any time after severe poisoning even if less effective
23
Q
Complications of acetylcysteine
A
Anaphylactoid reaction - urticaria, wheeze, hypotension
Dose related histamine release
24
Q
Treating anaphylactoid reaction to acetylcysteine
A
Reduce infusion rate
Give antihistamiens
No steroids - not true anaphylaxis
25
Supportive therapy for paracetamol overdose and hepatic dysfunction
Vit K
FFP if active bleeding
Hepatic intensive care - fluid balance, BP support, IC pressure monitoring if HE
Dialysis for renal failure
Liver transplantation orthotopic
26
Clinical features of aspirin overdose
Dizzy
Sweat
Tinnitus
vommiting
Vasodilation, hyperventilation, agitation, delirium, coma (esp children)
27
Metabolic abnormalities in aspirin poisoning
Initially Respiratory alkalosis - direct CNS resp centre stim
Over time -> Metabolic acidosis (salicyclic acid - inhibits aerobic metabolism)
28
Electrolye abnormalities in aspirin poisoning
Hypoglycaemia
Hypokalaemia
29
Investigations in aspirin overdose
Plasma salicyclate concentration
Urea, electrolytes, bicarbonate
Blood glucose
ABG
30
Treatment options aspirin
Gastric deconotamination
Sodium bicarbonate
Enhance elimination - MDAC
Haemodialysis
31
What does sodium bicarbonate do in aspirin overdose
Prevents CNS penetration
Enhances renal eliminateion - urinary alkalinisation
32
Treatment of severe aspirin poisoning
Haemodialysis - removes salicyclate v effectively and corrects metabolic abnormalities
33
What criteria for haemodialysis in aspirin overdose
pH<7.3
Salicyclate level >700mg/l (600 inc hildren)
Renal failure
34
Supportive treatment in aspirin poisoning
AW
IV fluids
Ventilation
GLucose for hypoglycaemia
KCl for hypokalaemia
35
Opiate vs opioid
Opiate - natural derivative on opioid receptor
Opioid - synthetic does same - methadone, methidine, tramadol
36
Presenting features of opiate overdose
CNS and resp depression
Pin point pupils
Hypotension, tachycardia
Hallucinations
Rhabdomyolysis
Non cardiac pulmonary oedema
37
Managemnet opioid overdose
A=E
AW support
Naloxone and ventilation
C
D- reduced GCS - naloxone if not already
Hep B, C and HIC precautions
38
When is naloxone used
Suspected opiate intoxication
RR <10/min
Reduced GCS <10/15
39
Doses of naloxone used
Adult - 400microgram up to 2mg or more
Children - titrate up from 0.1mg/kg
40
How tackle nalaoxone short half life
Repeat as necessary
Give as IV infusion if large overdose or opiate of long half life
2/3 initial dose required to rouse patient IV per hour
41
Symptoms of acute withdrawal from naloxone
Muscle aches, diarrhoea, palpitations, rhinorrhea, yawning, irritability, nausea, fever, tremor, cramps
42
Risks with naloxone treatmnet
Acute withdrawal
Short halflife - wear off
Self discharge during alert phase -> coma/death after
Unmasking of pain
HPTN
behavioural disturbances - high doses
Rare - fits, arrhythmias, pulmonary oedema
43
Why dont make patient fully wake up with nalaxone dose (lower dose to keep sleep)
Behavioural issues
If self discharge die in community
44
Pharmacological effects of benzodiazapines
Sedation
Hypnotic
Muscle relaxant
CNS depressant
Anaesthetic
Amnesia
Anxiolytic - anti-anxiety
45
Mechanism of benzodiazapines
Enhance GABA - inhibits CNS
46
Benzodiazapine features of overdose
Drowsiness
Ataxia
Dysarthria
Hypotension
Bradycardia
Resp depression
Coma
NO CHANGE TO PUPILS
47
Benzodiazapine overdose management
Supportive mostly - ABC support
Oral activated charcoal (1 hr)
Obs monitoring
ECG
FLUMAZENIL
Deaths are rare - supportive alone mostly
48
Flumexanil affect on the patient and administration
Reverse sedative effect of benzos in minutes
IV bolus over 15s
Repeat as shorter acting than benzos
49
What is flumazenil contraindicated in
Patients on TCAs (precipitates seizures)
If on benzos for seizure control or elevated IC
50
When is flumezanil most useful
Iatrogenic overdose with chronic resp disease - prevent intubation and ventilation
51
TCA poisoning epidemiology
6% of overdoses
High fatality
100-200 deaths a year
52
Anticholinergic effects from TCAs
Hot dry skin
Dilated pupils
Tachy
Urinary retention
Agitation
Delirum
Fits
Coma
Hypertonia, hyperreflexia
53
Sodium channel effects and alpha adrenoreceptor effects of TCAs
Na channel blocker -> cardiac arrhtyhmias, conduction block, prolonged QRS and QT intervals
Hypotension - aa antagonism
54
Investigations for TCAs
U+Es
Blood glucose
ABG
ECG
Constant cardiovascular monitoring
55
What QRS duration on ECG in TCA overdose thresholds for risk
>160ms (4 small squares) = v high risk arrhtyhmias
>120ms (3 small squares) = specific urgent action
V BROAD
56
Action when large TCA overdose or initial abnormal ECG
CCU or ITU
57
Treatment options TCA overdose
Gastric decontamination
Enhance elimination - MDAC
Activated charcoal in both
58
Why can activated charcoal still be effective at gastric decontamination over one hour after TC voerdose
TCAs delay gastric emptying due to anticholingergic effects - charcoal can still be effective
59
What tricyclics can MDAC be beneifical in
amitryptilline, nortryptilline
60
When give sodium bicarbonate in TCA overdose
Acidosis
Wide QRS complex - 120ms
Arrhtyhmias
61
WHy is sodium bicarb given in TCA overdose
Correct metabolic acidosis - arrhythmias more likely if pH<7.4
62
How treat arrhythmias from TCA overdose
Na bicarb
Correct K+
If NaBicarb fails -> DC cardioversion or overdrive pacing IF patient unstable
63
What medications must not use in TCA overdose
Anti-arrhythmic drugs - may worsen arrhythmias
64
What use to treat seizures from TCA overdose
Diazepam or lorazepam
If fail - paralysis, mechanical ventialtion
65
Examples of antidepressants more safe in overdose than TCAs
SSRIs - citalopram, escitalopram, fluoxetine, paroxetine, sertraline
SNRI - venlafaxine
NaSSa (noradrenergic and serotonergic) - mirtazipine
NaRI - noradrenaline reuptake inhbite - reboxetine
RIMA - MAOi - mocolbemide
66
Serotonin syndrome features
Cognitive behavioural changes (agitation, confusion, hallucinations, coma)
Neuromuscular dysfunction (tremor, teeht, grinding, myoclonus, hyperreflexia)
Autonomic dysfunction (tachycardia, fever, hyper/hypotnesion rapid changes between, flushing, diarrhoea)
Others - comitting, seizures, hyperpyrexia, rhabdomyolysis, renal faikure, coagulopathies
67
Triad of SS syndrome
Congitive behavioural changes
NM dysfunction
Autonomic dysfunction
Often only few symptoms present so high level of clinical suspicion
68
Early signs of iron overdose
0-6 hrs
N+V
Abdo pain
Diarrhoea bloody
Massive GI fluid loss
69
Delayed efffects of iron poisoning
Black offensive stools
Drowsines/coma
Fits
Cirulatory collapse
70
Late - 2-4 days after iron overdose presentation
Acute liver necrosis due to build uo
Renal failure
71
What forms weeks after iron overdose
Gastric strictures
72
Investigations iron overdose
History - amount of elemental iron taken
Iron concentration (4 hrs after+ monitor)
FBC
U+Es
Bicarbonate - daily monitor
Glucose
Clotting - daily monitor
LFTs (hepatotoxicity)
73
What amount is a serious iron overdose
>10mg/kg
74
Iron concentration when measured
After at least 4 hours
Repeat after 2-3 hours
75
What see in FBC in iron
Leucocytosis - raised WCC
76
What see effect onglucose in iron overdose
Hyperglycaemia
77
What gastric decontamination can give in iron poisoning
ONLY gastric lavage - activated charcoal ineffective
If large overdose
78
Which poisoning is activated charcoal ineffective in
Iron overdose
79
How does desferroxamine work
Binds to iron and chelates -> ferrioxamine - water soluble and excreted in urine (red discolouration)
80
Adverse effects of desferrioxamine
Hypotension and pulm oedema
81
What is desferrioxamine CI in
Renal failure - cleared by kidney turns wee red
82
When is desferroxamine used in iron poisoning (criteria)
V severe iron toxicity
Fits, coma, circulatory collapse
GI symptoms - leucocytosis, hyperglycaemia, high iron concentration >3mg/l
83
Supportive care for iron poisoning
IV fluids if hypo
Antiemetics if vomitting
Fits - diazepam/lorazepam
Correct acidosis w bicarb
Dialysis if renal failure
84
Where are organophosphate compounds most commonly poisoned
Major cause worldwide esp in south east asia
85
Mechanism of organophosphate compounds
Block cholinesterase enzymes esp acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) -> ACCUMULATION of acetylcholine at muscarinic receptors and nicotinic receptors and CNS -> increased activity
86
Cholinergic crisis features (organophosphate overdose) muscarinic effects
Too much acetylcholine
DUMBBBELS
Muscarinic effects
Diarrhoea
Urination
Miosis
Bradycardia
Bronchorrhoea, Bronchospasm
Emesis
Lacrimation
Salivation
87
Sympathetic NS
Mydriasis, HPTN, tachycardia
Re-entrant dysrhtyhmias
Cardiorespiratory arrest
88
Cholinergic crisis nicotinic effects
Respiratory difficulty - resp arrest, diaphragmatic weakness
Muscle weakness -fasciculations, clonus, tremor
Stimulation -of sympathetic NS
89
What stimulation of sympathetic nervous system causes in cholinergic crisis
Mydriases, HPTN, tachycardia, re-entrant dysrhythmias
Cardio-respiratory arrest
90
CNS effects with organophosphate poisoning
Malaise
Memory loss
Confusion
Disorientation
Delirium
Seizures
Resp centre depression or dysfunction
Coma
91
Initial management of organophosphate poisoning
ABC -
AW L lateral postion
Give oxygen
IV access x2
92
What are the antidotes for organophosphates
Atropine
Pralidozime/obidozime
93
What effects do atropine reduce from organophosphate poisoning
Bronchorrhoea, bronchospasm, salivation, abdominal colic
94
When should stop giving atropine
Every 10 minutes until signs of atropinisation develop - flushed red skin, tachycardia, dilated pupils, dry mouth
95
Triggers for giving atropine
Pinpoint pupils
Sweating
Difficulty breathing
96
What may be required in first 24 hours of orgaophosphate poisoning with atroping
Infusion or v large doses
97
Examples of cholinesterase reactivators
Pralidoxime, obidoxime
98
When does pralidoxime work
Within a short time period depending on type of organophosphate - otherwise complex of ACH and OP 'aged' and it cannot be reversed
99
Supportive care in organophosphate poisonning
Clearning the AW
Esure adequate ventilation
High flow O2
Manage ICU
Atropine - excesive secretions
Diazepam - seizures
100
Investigations organophosphate poisoning
ECG
U+Es
Glucose
Red cell cholinesterase activity
101
What test measures severity of organophosphate poisoning
Red cell cholinesterase activity
102
What is most helpful in determining severity of poisoning with organophosphates
Severity of clinical symptoms is more important than red cell cholinesterase activity - wide inter-individual range cholinesterase activity
103
ECG of benzodiazapine overdose
transient first and second degree block and QT prolongation
104
What effect does metoclopramide have on gastric emptying and why is it helpful?
Increases - speeds up absorption of other drugs
105
What drugs delay gastric emptying
CAs
Opiates
Antimuscarinics
106
Why dont give clarithromycin IV
Reaction at site
V good bioavailability orally - no need ot give IV
107
How do you know to step down from oral to IV abtibiotics
Decreasing white cell count
Stable CRP (not rising - CRP lag)
Apyrexial
108
What drugs do antacids make less orally bioavailable
Quinolones
Tetracyclines
Up to 70%
109
Why do thiazide like diuretics cause lithium accumulation
Thiazides cause diuresis and initial sodium loss
Compensatory sodium retention in proximal tubules
Proximal tubules do not distinguish sodium from lithium
Lithium also retained and accumulates
110
How do ciprafloxacin/clarithromycin interact with theophylline
INhibitors of CYP450
Dose of theophylline reduced and levels monitored
111
What macrolide doesnt interfere with wafarin
Azithromycin
112
Why can ACE inhibitors cause angio-oedema
Release of bradykinin
113
What mental health medication can cause galactorrhea
Antipsychotics eg risperidne - raise prolactin -> galactorrhea
114
Which antibioticscan cause childhood teeth staining if taken during pregnancy
Tetracyclines
115
When measure paracetamil overdose vs treat immediately
Explanation:
All patients taking an acute overdose more than 75 mg/kg should have their paracetamol concentration measured to determine whether acetylcysteine is indicated.
If presenting late i.e more than 8 hours, acetylcysteine should then be started before the results are available.
116
Stimulant vs TCA presentation after overdose
Both - dilated pupils, HR increase, low BP
TCA - dru skin, absent bowel sounds
Stimulant - increased bowel sounds, sweating
117
Is sodium valproate a CYP450 inhibitor
Yes
118
Is pancreatitis a side effect of sodium valproate
Yes
119
Phenytoin info around drug
Narrow therapeutic index
Inducer of CYP450
Highly protein bound
Hypotension and arrhythmias if given IV
