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Posisoning - specific drugs Flashcards

1
Q

Epidemiology of paracetamol poisonning

A

50% overdoses include paracetamol
Leading cause of mortality from overdose
1<% mortality

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2
Q

What are the metabolites of paracetemol

A

Para-glucorinide
Para-sulphate
N-acetyl-p-benzoquinone-imine

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3
Q

How is paracetemol turned into NAPQI

A

Oxidation via CYP450 eg CYP2E1/3A4

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4
Q

How is NAPQI detoxified in the liver

A

Glutathione

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5
Q

How does NAPQI cause hepatocellular injury

A

glutathione absent or depleted

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6
Q

Early clinical symptoms from paracetemol poisoning

A

May be none
V non specific symptoms
N+V+ abdominal pain

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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

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8
Q

Rare delayed features of paracetemol overdose

A

Renal failure (acute tubular necrosis)
Hypoglycaemia
Metabolic acidosis

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9
Q

Renal failure in paracetamol overdose

A

acute tubular necorsis
2-7 days after poisoning
Oliguria
Loin pain

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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

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11
Q

What does paracetamol level tell you in overdose

A
  • best early predictor of prognosis
    Need for antidotes
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12
Q

Why may urea remain low in paracetamol overdose

A

Even if decreased from kidneys - Hepatic urea production

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13
Q

When is paracetamol treatment a gray area

A

0-4 hours - best to wait til after when can be interpreted

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14
Q

What paracetemol level treat at 4 hours

A

100mg

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15
Q

What see in heaptic injury in bloods in paracetamol overdose

A

Prolonged PT/INR
Elevated transaminases (bad prognostic)
Elevated bilirubin (hepatic necrosis)

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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

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17
Q

What are the options for paracetamol overdose treatment

A

Prevent absorption - activated charcoal large dose within 1 hour
IV acetylcysteine

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18
Q

What is important with paracetamol overdose treatment

A

Timing is vital - effectiveness declines over time of antidote

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19
Q

How is acetylcysteine delivered

A

IV over 21 hours

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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

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21
Q

When else is acetylcysteine used except acutely

A

For people with fulminant hepatic failure from paracetamol awaiting transplantation

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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

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23
Q

Complications of acetylcysteine

A

Anaphylactoid reaction - urticaria, wheeze, hypotension
Dose related histamine release

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24
Q

Treating anaphylactoid reaction to acetylcysteine

A

Reduce infusion rate
Give antihistamiens
No steroids - not true anaphylaxis

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25
Q

Supportive therapy for paracetamol overdose and hepatic dysfunction

A

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

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26
Q

Clinical features of aspirin overdose

A

Dizzy
Sweat
Tinnitus
vommiting
Vasodilation, hyperventilation, agitation, delirium, coma (esp children)

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27
Q

Metabolic abnormalities in aspirin poisoning

A

Initially Respiratory alkalosis - direct CNS resp centre stim
Over time -> Metabolic acidosis (salicyclic acid - inhibits aerobic metabolism)

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28
Q

Electrolye abnormalities in aspirin poisoning

A

Hypoglycaemia
Hypokalaemia

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29
Q

Investigations in aspirin overdose

A

Plasma salicyclate concentration
Urea, electrolytes, bicarbonate
Blood glucose
ABG

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30
Q

Treatment options aspirin

A

Gastric deconotamination
Sodium bicarbonate
Enhance elimination - MDAC
Haemodialysis

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31
Q

What does sodium bicarbonate do in aspirin overdose

A

Prevents CNS penetration
Enhances renal eliminateion - urinary alkalinisation

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32
Q

Treatment of severe aspirin poisoning

A

Haemodialysis - removes salicyclate v effectively and corrects metabolic abnormalities

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33
Q

What criteria for haemodialysis in aspirin overdose

A

pH<7.3
Salicyclate level >700mg/l (600 inc hildren)
Renal failure

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34
Q

Supportive treatment in aspirin poisoning

A

AW
IV fluids
Ventilation
GLucose for hypoglycaemia
KCl for hypokalaemia

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35
Q

Opiate vs opioid

A

Opiate - natural derivative on opioid receptor
Opioid - synthetic does same - methadone, methidine, tramadol

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36
Q

Presenting features of opiate overdose

A

CNS and resp depression
Pin point pupils
Hypotension, tachycardia
Hallucinations
Rhabdomyolysis
Non cardiac pulmonary oedema

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37
Q

Managemnet opioid overdose

A

A=E
AW support
Naloxone and ventilation
C
D- reduced GCS - naloxone if not already
Hep B, C and HIC precautions

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38
Q

When is naloxone used

A

Suspected opiate intoxication
RR <10/min
Reduced GCS <10/15

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39
Q

Doses of naloxone used

A

Adult - 400microgram up to 2mg or more
Children - titrate up from 0.1mg/kg

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40
Q

How tackle nalaoxone short half life

A

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

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41
Q

Symptoms of acute withdrawal from naloxone

A

Muscle aches, diarrhoea, palpitations, rhinorrhea, yawning, irritability, nausea, fever, tremor, cramps

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42
Q

Risks with naloxone treatmnet

A

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

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43
Q

Why dont make patient fully wake up with nalaxone dose (lower dose to keep sleep)

A

Behavioural issues
If self discharge die in community

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44
Q

Pharmacological effects of benzodiazapines

A

Sedation
Hypnotic
Muscle relaxant
CNS depressant
Anaesthetic
Amnesia
Anxiolytic - anti-anxiety

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45
Q

Mechanism of benzodiazapines

A

Enhance GABA - inhibits CNS

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46
Q

Benzodiazapine features of overdose

A

Drowsiness
Ataxia
Dysarthria
Hypotension
Bradycardia
Resp depression
Coma
NO CHANGE TO PUPILS

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47
Q

Benzodiazapine overdose management

A

Supportive mostly - ABC support
Oral activated charcoal (1 hr)
Obs monitoring
ECG
FLUMAZENIL
Deaths are rare - supportive alone mostly

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48
Q

Flumexanil affect on the patient and administration

A

Reverse sedative effect of benzos in minutes
IV bolus over 15s
Repeat as shorter acting than benzos

49
Q

What is flumazenil contraindicated in

A

Patients on TCAs (precipitates seizures)
If on benzos for seizure control or elevated IC

50
Q

When is flumezanil most useful

A

Iatrogenic overdose with chronic resp disease - prevent intubation and ventilation

51
Q

TCA poisoning epidemiology

A

6% of overdoses
High fatality
100-200 deaths a year

52
Q

Anticholinergic effects from TCAs

A

Hot dry skin
Dilated pupils
Tachy
Urinary retention
Agitation
Delirum
Fits
Coma
Hypertonia, hyperreflexia

53
Q

Sodium channel effects and alpha adrenoreceptor effects of TCAs

A

Na channel blocker -> cardiac arrhtyhmias, conduction block, prolonged QRS and QT intervals
Hypotension - aa antagonism

54
Q

Investigations for TCAs

A

U+Es
Blood glucose
ABG
ECG
Constant cardiovascular monitoring

55
Q

What QRS duration on ECG in TCA overdose thresholds for risk

A

> 160ms (4 small squares) = v high risk arrhtyhmias
120ms (3 small squares) = specific urgent action
V BROAD

56
Q

Action when large TCA overdose or initial abnormal ECG

A

CCU or ITU

57
Q

Treatment options TCA overdose

A

Gastric decontamination
Enhance elimination - MDAC
Activated charcoal in both

58
Q

Why can activated charcoal still be effective at gastric decontamination over one hour after TC voerdose

A

TCAs delay gastric emptying due to anticholingergic effects - charcoal can still be effective

59
Q

What tricyclics can MDAC be beneifical in

A

amitryptilline, nortryptilline

60
Q

When give sodium bicarbonate in TCA overdose

A

Acidosis
Wide QRS complex - 120ms
Arrhtyhmias

61
Q

WHy is sodium bicarb given in TCA overdose

A

Correct metabolic acidosis - arrhythmias more likely if pH<7.4

62
Q

How treat arrhythmias from TCA overdose

A

Na bicarb
Correct K+
If NaBicarb fails -> DC cardioversion or overdrive pacing IF patient unstable

63
Q

What medications must not use in TCA overdose

A

Anti-arrhythmic drugs - may worsen arrhythmias

64
Q

What use to treat seizures from TCA overdose

A

Diazepam or lorazepam
If fail - paralysis, mechanical ventialtion

65
Q

Examples of antidepressants more safe in overdose than TCAs

A

SSRIs - citalopram, escitalopram, fluoxetine, paroxetine, sertraline
SNRI - venlafaxine
NaSSa (noradrenergic and serotonergic) - mirtazipine
NaRI - noradrenaline reuptake inhbite - reboxetine
RIMA - MAOi - mocolbemide

66
Q

Serotonin syndrome features

A

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
Q

Triad of SS syndrome

A

Congitive behavioural changes
NM dysfunction
Autonomic dysfunction
Often only few symptoms present so high level of clinical suspicion

68
Q

Early signs of iron overdose

A

0-6 hrs
N+V
Abdo pain
Diarrhoea bloody
Massive GI fluid loss

69
Q

Delayed efffects of iron poisoning

A

Black offensive stools
Drowsines/coma
Fits
Cirulatory collapse

70
Q

Late - 2-4 days after iron overdose presentation

A

Acute liver necrosis due to build uo
Renal failure

71
Q

What forms weeks after iron overdose

A

Gastric strictures

72
Q

Investigations iron overdose

A

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
Q

What amount is a serious iron overdose

A

> 10mg/kg

74
Q

Iron concentration when measured

A

After at least 4 hours
Repeat after 2-3 hours

75
Q

What see in FBC in iron

A

Leucocytosis - raised WCC

76
Q

What see effect onglucose in iron overdose

A

Hyperglycaemia

77
Q

What gastric decontamination can give in iron poisoning

A

ONLY gastric lavage - activated charcoal ineffective
If large overdose

78
Q

Which poisoning is activated charcoal ineffective in

A

Iron overdose

79
Q

How does desferroxamine work

A

Binds to iron and chelates -> ferrioxamine - water soluble and excreted in urine (red discolouration)

80
Q

Adverse effects of desferrioxamine

A

Hypotension and pulm oedema

81
Q

What is desferrioxamine CI in

A

Renal failure - cleared by kidney turns wee red

82
Q

When is desferroxamine used in iron poisoning (criteria)

A

V severe iron toxicity
Fits, coma, circulatory collapse
GI symptoms - leucocytosis, hyperglycaemia, high iron concentration >3mg/l

83
Q

Supportive care for iron poisoning

A

IV fluids if hypo
Antiemetics if vomitting
Fits - diazepam/lorazepam
Correct acidosis w bicarb
Dialysis if renal failure

84
Q

Where are organophosphate compounds most commonly poisoned

A

Major cause worldwide esp in south east asia

85
Q

Mechanism of organophosphate compounds

A

Block cholinesterase enzymes esp acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) -> ACCUMULATION of acetylcholine at muscarinic receptors and nicotinic receptors and CNS -> increased activity

86
Q

Cholinergic crisis features (organophosphate overdose) muscarinic effects

A

Too much acetylcholine
DUMBBBELS
Muscarinic effects
Diarrhoea
Urination
Miosis
Bradycardia
Bronchorrhoea, Bronchospasm
Emesis
Lacrimation
Salivation

87
Q

Sympathetic NS

A

Mydriasis, HPTN, tachycardia
Re-entrant dysrhtyhmias
Cardiorespiratory arrest

88
Q

Cholinergic crisis nicotinic effects

A

Respiratory difficulty - resp arrest, diaphragmatic weakness
Muscle weakness -fasciculations, clonus, tremor
Stimulation -of sympathetic NS

89
Q

What stimulation of sympathetic nervous system causes in cholinergic crisis

A

Mydriases, HPTN, tachycardia, re-entrant dysrhythmias
Cardio-respiratory arrest

90
Q

CNS effects with organophosphate poisoning

A

Malaise
Memory loss
Confusion
Disorientation
Delirium
Seizures
Resp centre depression or dysfunction
Coma

91
Q

Initial management of organophosphate poisoning

A

ABC -
AW L lateral postion
Give oxygen
IV access x2

92
Q

What are the antidotes for organophosphates

A

Atropine
Pralidozime/obidozime

93
Q

What effects do atropine reduce from organophosphate poisoning

A

Bronchorrhoea, bronchospasm, salivation, abdominal colic

94
Q

When should stop giving atropine

A

Every 10 minutes until signs of atropinisation develop - flushed red skin, tachycardia, dilated pupils, dry mouth

95
Q

Triggers for giving atropine

A

Pinpoint pupils
Sweating
Difficulty breathing

96
Q

What may be required in first 24 hours of orgaophosphate poisoning with atroping

A

Infusion or v large doses

97
Q

Examples of cholinesterase reactivators

A

Pralidoxime, obidoxime

98
Q

When does pralidoxime work

A

Within a short time period depending on type of organophosphate - otherwise complex of ACH and OP ‘aged’ and it cannot be reversed

99
Q

Supportive care in organophosphate poisonning

A

Clearning the AW
Esure adequate ventilation
High flow O2
Manage ICU
Atropine - excesive secretions
Diazepam - seizures

100
Q

Investigations organophosphate poisoning

A

ECG
U+Es
Glucose
Red cell cholinesterase activity

101
Q

What test measures severity of organophosphate poisoning

A

Red cell cholinesterase activity

102
Q

What is most helpful in determining severity of poisoning with organophosphates

A

Severity of clinical symptoms is more important than red cell cholinesterase activity - wide inter-individual range cholinesterase activity

103
Q

ECG of benzodiazapine overdose

A

transient first and second degree block and QT prolongation

104
Q

What effect does metoclopramide have on gastric emptying and why is it helpful?

A

Increases - speeds up absorption of other drugs

105
Q

What drugs delay gastric emptying

A

CAs
Opiates
Antimuscarinics

106
Q

Why dont give clarithromycin IV

A

Reaction at site
V good bioavailability orally - no need ot give IV

107
Q

How do you know to step down from oral to IV abtibiotics

A

Decreasing white cell count
Stable CRP (not rising - CRP lag)
Apyrexial

108
Q

What drugs do antacids make less orally bioavailable

A

Quinolones
Tetracyclines
Up to 70%

109
Q

Why do thiazide like diuretics cause lithium accumulation

A

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
Q

How do ciprafloxacin/clarithromycin interact with theophylline

A

INhibitors of CYP450
Dose of theophylline reduced and levels monitored

111
Q

What macrolide doesnt interfere with wafarin

A

Azithromycin

112
Q

Why can ACE inhibitors cause angio-oedema

A

Release of bradykinin

113
Q

What mental health medication can cause galactorrhea

A

Antipsychotics eg risperidne - raise prolactin -> galactorrhea

114
Q

Which antibioticscan cause childhood teeth staining if taken during pregnancy

A

Tetracyclines

115
Q

When measure paracetamil overdose vs treat immediately

A

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
Q

Stimulant vs TCA presentation after overdose

A

Both - dilated pupils, HR increase, low BP
TCA - dru skin, absent bowel sounds
Stimulant - increased bowel sounds, sweating

117
Q

Is sodium valproate a CYP450 inhibitor

A

Yes

118
Q

Is pancreatitis a side effect of sodium valproate

A

Yes

119
Q

Phenytoin info around drug

A

Narrow therapeutic index
Inducer of CYP450
Highly protein bound
Hypotension and arrhythmias if given IV

errors and drugs (8 decks)

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