Clinical Toxicology & Antidotes Flashcards
(104 cards)
1
Q
LO
- An “introduction to toxicology”
* Demonstrate an understanding of toxicology, poisons, drugs in
overdose and associated therapeutic interventions.
- Principles of toxicology
- Actions of poisons/drugs in overdose
- Common antidotes
* Understanding of fund
A
2
Q
what resources can be used for toxicology information? 2
A
TOXBASE and national poisons information services (NPIS)
3
Q
What are the different categories of poison causes? 4
A
- acute
- chronic
- accidental
- intentional
4
Q
intentional poisoning is generally….
A
acute. OD of paracetamol/ other prescribed med
5
Q
what is the main cause of overdosing?
A
paracetamol
ibuprofen
sertraline
diazepam
durgs of misuse
even caffeine
6
Q
term given to cluster of clinical features of a poisoned patient?
A
toxidromes
7
Q
What are examples of toxidromes? 5
A
- opioid
- serotonergic
- anticholinergic
- cholinergic
- sympathomimetic
8
Q
What are the symptoms of opioid toxidrome?
A
- pinpoint pupils
- reduced GCS
- reduced RR
9
Q
What are the symptoms of serotonergic toxidrome?
A
- agitation
- delirium
- tremor
- tachycardia
- labile BP
- sweating
- hypertonia
- brisk reflexes
- clonus
- fever
- serotonin
10
Q
What is meant by labile BP?
A
blood pressure that easily fluctuates
11
Q
drug that may -> serotonergic toxidrome?
A
sertraline
12
Q
What are the symptoms of anticholinergic toxidrome?
A
- dilated pupils
- warm, dry pupils
- confusion, restlessness, hallucinations
- brisk reflexes, myoclonic jerks
- tachycardia
- urine retention
13
Q
drug that may -> anticholinergic toxidrome?
A
amitriptyline
14
Q
What are the symptoms of cholinergic toxidrome?
A
- miosis
- bradycardia
- sweating
- excessive secretions
15
Q
give 4 sympathomimetic toxidromes that would be seen with ephidrine, amphetamine, ectasy etc overdoses?
A
hypertension, sweating, tachycardia, agitation
16
Q
Give examples of excessive secretions that occur in cholinergic toxidrome.
A
- hypersalivation
- lacrimation
- rhinorrhoea
- bronchorrhoea
- diarrhoea
17
Q
What laboratory investigations are carried out for poisoned patients?
A
- routine blood tests
- ABG: COHb, MetHb
- anion gap + osmolality gap
- analytical toxicology: emergency measurements and screening
18
Q
What are examples emergency measurements taken as laboratory investigations for poisoned patients?
A
- salicylate
- iron
- theophylline
- methanol
- ethylene glycol
- lithium
- phenytoin
- carbamazepine
19
Q
What are drugs screened for as part of laboratory investigations for poisoned patients?
A
- paracetamol
- drugs of abuse
(as may have been taken alongside other drugs)
20
Q
importance of toxidromes?
A
to make decisions quick, as sometimes dont get urine/ blood results back quick from screens etc
21
Q
What is meant by an anion gap?
A
measures the difference—or gap—between the negatively charged and positively charged electrolytes in your blood.
22
Q
What is the normal range of values for the anion gap?
A
12-16
23
Q
How does a raised anion gap affect the blood pH?
A
decreases it (added acid)
24
Q
What are causes of a raised anion gap?
A
- ketoacidosis
- lactic acidosis
- salicylate overdose
- alcohols: ethanol, methanol, ethylene glycol
- renal failure
- rhabdomyolysis
25
What is the osmolal gap?
measured osmolality - calculated osmolality
calculated osmolality = 2[Na+] + [K+] + urea + glucose
26
What is the normal reference range for the osmolal gap?
<10mOsm/kg
27
What can cause an increased osmolal gap?
alcohols: ethanol, methanol, ethylene glycol, acetone, isopropanol
eg ppl drinking poor quality spirits: may have methanol -> toxic syndorme
28
What is the general management for poisoned patients? 4
- supportive care
- prevention of absorption
- enhancement of elimination
- specific antidotes
29
prevention of further absorption of drug form bowel etc is difficult after...
about an hour
30
What techniques are used to prevent absorption?
- whole bowel irrigation
- activated charcoal
- gastric lavage (rarely used)
- emetics (not recommended)
31
What forms of poison is whole bowel irrigation used for?
- modified release medication
- body packers
32
why are emetics not recommended to prevents abs?
often too late and other risks involved (for v drowsy px.. resp danger of aspiration
33
name one compound that may be used to prevent abs of a toxic/ poisonous compound? rare
activated charcoal
34
What techniques are used to enhance elimination? 3
- multiple dose activated charcoal
- urine alkalinisation
- extracorporeal: haemofiltration, haemodialysis
35
What drugs can multiple dose activated charcoal be used to enhance elimination of?
- carbamazepine
- colchicine
- quinine
- theophylline
- phenobarbital
36
What drug can urine alkalinisation be used to enhance the elimination of?
aspirin
37
What drugs can extracorporeal techniques be used to enhance the elimination of?
haemodialysis
- lithium
- salicylates
- ethylene glycol
- methanol
38
What is an antidote?
A therapeutic substance administered to counteract the adverse effects of a xenobiotic
39
What are the limitations to antidotes?
may be rarely used, can be expensive and limited shelf life
- May need to be sourced from another hospital
40
Where can guidance on the availability of antidotes be found?
the joint RCEM/NPIS guideline
41
name some drugs that should be available immediately in A&E
acetylcysteine (as paracetamol OD common)
glucagon
naloxone
42
What are the possible mechanisms of antidotes? 7
- forms inert complex w poison
- accelerates detoxification of metabolite/poison
- reduces rate of conversion to toxic compound
- competes w toxic substances for essential receptor sites
- blocks essential receptors through which toxic effects are mediated
- bypasses effect of poison
- intralipid
43
What is the antidote to iron? (forms inert complex w poison)
desferrioxamine
44
What is the antidote to cyanide? (forms inert complex w poison - chellates)
dicobalt edeate
45
What is the antidote to digoxin? (forms inert complex w poison - chellates)
digoxin-specific antibody fragments
46
What is the antidote to heparin? (forms inert complex w poison - chellates)
protamine
47
What is the antidote to paracetamol?
acetylcysteine
48
How does acetylcysteine work?
accelerates the detoxification of paracetamol
49
What is methaemoglobinaemia? How does this compare to normal O2 transport?
- Hb w oxidised haem iron (Fe3+)
- O2 transport however depends on reduced haem iron (Fe2+)
- haem iron maintained as reduced by NADH-dependent MetHb reductase
- in this condition, excess metHb in place of normal Hb
50
How does methylene blue work?
accelerates detoxification of MetHb by acting as electron donor in reduction of metHb
to reverse effects
51
What is the antidote to methaemoglobinaemia?
methylene blue
52
How do the symptoms of methaemoglobinaemia worsen with increasing concentrations?
slide 29 table
53
What is the antidote to ethylene glycol and methanol poisoning?
stops production of toxic metabolites
fomepizole (4-methylpyrazole)
54
What is the antidote to benzodiazepines (anaesthetic use)? +midazolam
flumazenil
55
What is the antidote to opioids?
naloxone
56
What is the antidote to warfarin?
vitamin k (Phytomenadione)
57
How does flumazenil work?
competes w benzodiazepines by binding to receptor site
58
How does naloxone work?
competes w opioids for the opioid receptors
59
How does vitamin K work?
competes w warfarin for same receptor site
60
How does atropine work?
blocks receptors through which toxic effects are mediated
61
What is atropine the antidote to? 4
- nerve agents
- organophosphate insecticides
- drugs for myasthenia gravis e.g. pyridostigmine
- clitocybe mushrooms (muscarine)
62
What is the antidote to beta blockers?
glucagon
63
How does glucagon work against beta blockers?
bypasses the beta-receptor site
BB block cAMP -> dec HR
slide 34!!
64
why is it hard ot give glucagon high doses by syringe?
as it crystallises
65
why is intralipid an important antidote for many drugs? - How does intralipid work?
forms a lipid sink for lipophilic drugs to drop into and be removed
66
name one issue with naloxone?
short half life so it may seem like patient has been treated but might not be
67
name 3 antidotes that work by competing with toxic substances for essential receptor sites?
flumenazil, naloxone and vitamin K
68
ethylene glycol is used in anti freeze and screenwash, what is it metabolised in the liver by to form toxic metabolites?
alcohol dehydrogenase
69
what does tox from ethylene glycol result from?
metabolic acidosis and inhibition of oxidative phosphorylation and protein synthesis
70
what does oxalic acid precipiate with to cause end organ damage in patients that have been poisoned with ethylene glycol?
calcium
71
Schematic of ethylene glycol metabolism
slide 38
72
How do osmolar and anion gaps change over time post-toxic alcohol ingestion?
sldie 39
osmolar gap cna be normal w late presentation
but anion gap grows over time
useful to see where u are and Hx of when poisoning occurred
73
What are the 3 treatment options for ethylene glycol poisoning?
- ethanol
- fomepizole (4-methylpyrazole)
- haemodialysis
74
what is the rationale behind treating those with ethylene glycol tox with ethanol?
both metabolised by ADH
ADH has greater affinity for ethanol, decreased formation of toxic metabolites
75
lethal dose of ethylene glycol
aorund 100ml
76
treating those with ethylene glycol tox with ethanol, what serum conc should be acheived?
>100mg/dl
need doses that cause drowsiness
77
what is the rationale behind treating ethylene glycol poisoning with fomepizole?
potent inhibitor of ADH
78
cons of fomepizole?
expensive and not readily available
79
pros of fomepizole?
easier to administer, predictable PK
80
why is haemodialysis a good treatment for ethylene glycol poisoning?
removes parent compound and its metabolite
81
When is haemodialysis indicated for ethylene glycol poisoning?
when there's:
- renal failure
- severe metabolic acidosis refractory to bicarbonate
- ethylene glycol conc. >50mg/dl
82
slide 41
83
What are some sources of cyanide poisoning?
fired smoke from burning of:
- natural substances: wool, silk, cotton
- synthetic: plastics, nylon, polyurethane foam
84
How is cyanide toxic?
poisons the mitochondrial electron transport chain within cells so no ATP can be produced
kills resp in cells, rapid
85
What are the antidotes to cyanide? 4
- O2
- methaemoglobin inducers (sodium nitrite)
- dicobalt edetate
- hydroxocobalamin (cyanokit)
86
sodium nitrate (methaemoglobin inducers) used as cyanide antodotes to get what instead of what?
Fe3+ instead of Fe2+
3: less efficient at transporting, cant be affected by cyanide -> net benefit
87
What is Kelocyanor?
commercially available prep of dicobalt ededate containing dicobalt edetate 300mg + free cobalt
88
How effective is dicobalt edetate?
- rapidly after IV injection
- superior to combined sodium thiosulphate + sodium nitrate
89
dicobalt is effective after iv injection and superior to other treatments and is cheap. In the absence of cyanide it may lead to cobalt tox. list SEs
- facial + laryngeal oedema
- Vomiting
– Urticaria, anaphylactic shock
– Hypotension, cardiac arrhythmias
– Convulsions
90
What is the disadvantage of hydroxocobalamin?
- large doses (5-10g) required
- expensive
91
hydroxycobalamin used for?
cyanide poisoning
92
What are the 2 categories of sources of lead poisoning in the UK?
- occupational
- non-occupational
93
What are occupational sources of lead poisoning?
- Inhalation of lead dust/ fumes in lead-using industries (lead acid battery manufacturing and recycling; mining, smelting and refining of lead and other ores)
- During demolition/renovation of old properties
94
What are non-occupational sources of lead poisoning?
House renovation, lead paint, imported toys or cookware, pica,
old lead pipes, contaminated traditional remedies or cosmetics
95
What are possible lead poisoning symptoms?
- asymptomatic
- non-specific: abdominal pains, raised BP, etc.
96
lead poisoning may be asymptomatic . what are some of the non specific symptoms?
abdominal pains, headache, raised BP, poor concentration, anaemia, constipation
97
What can occur in severe lead poisoning? In what age group is it most common?
- encephalopathy
- children
98
What are the renal effects of lead poisoning?
- proximal tubular dysfunction
- irreversible interstitial fibrosis
- progressive renal insufficiency
99
What therapy is used for lead poisoning?
chelation therapy
100
At what blood lead concentrations should chelation therapy be considered?
>50mcg/dl
101
What are the 2 main chelation therapy options?
- oral DMSA (succimer)
- IV sodium calcium edetate
102
What is the issue w chelation therapy?
- it only removes lead from blood
- therefore repeated courses are usually required with adequate intervals of at least 1 week to allow the lead to re-distribute from the bones
103
true or false: chelation therapy only removes lead from the blood?
true
104
repeated courses of chelation therapy for lead tox are usually required with adequate intervals of at least 1 week between, why is this?
allow lead to redistribute from the bones
