Clinical Toxicology Flashcards
1
Q
What science studies the harmful effects of drugs?
A
Clinical Toxicology
2
Q
What’s the main difference between toxicology + pharmacology?
A
Overdose
3
Q
Alcohol intoxication is what type of poisoning?
A
Ethanol (C2H5OH) poisoning
4
Q
What are the symptoms of salicylate (aspirin) poisoning?
A
- tinnitus
- hyperventilation
- sweating
- coma
5
Q
What are the side effects of too much aspirin?
A
- causes internal bleeding + renal failure (toxic for kidneys)
- stimulates resp centre = resp alkalosis, uncoupled oxidative phosphorylation = metabolic acidosis
6
Q
What is the management of aspirin overdose?
A
- measure plasma salicylate concentration (4-6h post ingestion), electrolytes + blood gas
- gastric lavage (up to 1h after ingestion) followed by active charcoal
- in severe poisoning (plasma concentration above 500mgL-1) requires urinary alkalisation or haemodialysis
7
Q
After an overdose of paracetamol, 48-72h later, can cause what?
A
Fatal hepatocellular necrosis
8
Q
What is coproxamol?
A
Distalgesic, contains opioids + paracetamol
9
Q
What is myosis?
A
Pin-point pupils
10
Q
What is mitrisis?
A
Dilated pupils
11
Q
Types of stimulant drugs..
A
- amphetamines
- cocaine + ecstasy
- piperazimes (contain stimulant + hallucinogenic activity)
- eugeroics e.g. modafinil prescribed for narcolepsy (abused as wakefulness agents + CNS stimulant in sport)
- methylxanthines e.g. caffeine
- nicotine
12
Q
How do stimulants work + what are the side effects?
A
increase dopamine + NA (cause cardiovascular effects)
- hyper-arousal
- pleasure
- paranoia (works same as antipsychotics by increasing dopamine)
Increased levels of serotonin due to reduced reuptake
- reduces hunger
- insomnia
Readily excreted urine with varying degrees of metabolism
Side effects;
Tachycardia, hyperpyrexia, dehydration, convulsions, coma
=similar to serotonin syndrome
13
Q
Name types of hallucinogens
A
- LSD
- magic mushrooms
- psilocybin
14
Q
What’s the toxicology of LSD?
A
- agonist + antagonist at serotonin receptors
- serotonin 2A receptors in prefrontal cortex modulate cognition, mood, perception, fear + euphoria (receptors throught to be associated with Schizophrenia)
- serotonin receptors associated with sympathomimetic stimulation
- can take 12h to metabolise
15
Q
What’s the toxicology of psilocybin?
A
-agonist at serotonin receptors
16
Q
When there is a drug tolerance, why is there an increased toxic effect seen in cardiovascular tissue?
A
The brain becomes less sensitive due to receptors becoming down regulated. Different tissues desensitise in different ways; the brain becomes densitised fast, however, cardiovascular system doesn’t desensitise at same speed as brain (means cardiovascular system remains sensitive). Therefore, drug dose is increased = causing increased toxic effect in cardiovascular tissue.
17
Q
What’s the difference between opiates + opioids?
A
Opiates - broader classification, includes naturally extracted from plants e.g. opium (morphine + codeine)
Opioids -e.g. carentanil created in lab
18
Q
What drug is used to treat alcohol addiction?
A
Acetaldehyde
19
Q
What are 4 routes of poisoning?
A
- injection e.g. insects, needle stick injury
- inhalation e.g. gases, insecticides
- ingestion e.g. alcohol
- absorbtion e.g. eyes, plants, pesticides
20
Q
What are 5 accidental circumstances leading to poisoning?
A
- medicines e.g. children, elderly
- food e.g. poor hygiene
- CO e.g. faulty boilers
- Chemicals e.g. children mistake for drink
- plants e.g. children
21
Q
What poisons have action on cardiovascular system?
A
Cardiac arrhythmias
-belladonna (atropine main component)
-stimulants
Digoxin
Blood
- CO displaces oxygen from haemoglobin
- warfarin can cause haemorrhage
22
Q
What poisons are neurotoxins?
A
depressive drugs
- opiates
- alcohol
- antidepressants
- hypnotics
Stimulants
- ecstasy
- cocaine
Hallucinogens
-LSD
23
Q
What poisons have an affect on the liver?
A
Paracetamol
- eliminated by conjugation with glutathione =makes it stable + inactive
- high doses saturate pathway - not enough glutathione to inactive paracetamol. Paracetamol is oxidised
- reactive oxidised paracetamol binds covalently to thiol groups in cell proteins + kills cells
- acetylcysteine or methionine used in overdose by boosting production of glutathione in the liver
- pts taking enzyme inducing drugs (including alcohol) + those with glutathione depletion (pts with eating disorders) are at increased risk.
Magic mushrooms
24
Q
What poisons have an affect on the respiratory system?
A
- Opiates
- paraquat (causes pulmonary oedema, and O2 increases its toxicity)
- cyanide (cellular toxin) found in almonds, pips/seeds
- agrochemical (paralyse resp system)
25
What poisons affect the kidneys?
- paracetamol
| - aspirin
26
What are the main 2 types of poisons?
Carrosive (see damage on tissue + clothes)
- battery acid
- bleech
Non-carrosive (NO burning or irritation action)
-have systemic reaction
27
Initial assessment of poisoned pt ABCDE additional only...
Airway
- is it protected e.g. was mask used
- clue in airway regarding poison
- smell (alcohol)
- colour (methaemaglobinaemia) usually dark in colour
- tablet residue
- Brutus (acid or alkalis)
Breathing
- rate (opiates)
- patten (kussmauls breathing -hyperventilation + aspirin intoxication)
- efficiency (organophosphates + paraquat) - caused by pulmonary oedema
Circulation
-signs of IVDA
Disability
- pin point pupils = opiates, organophosphates, other cholinergics
- large pupils = alcohol, anti-cholinergics, amphetamines, beta blockers
Exposure
- removal of clothes - main side effect of most drugs = hypothermia (be careful)
- injection sites
- use protection (some drugs can penetrate skin + from concealed needles)
- clues in pts pockets
28
When taking the PC what should be noted?
- what they took
- how much taken (dosage)
- when taken
- where taken
- why taken -intensional?
- anyone else involved?
29
When taking history of presenting complaint what should be noted?
- taken before? -tolerance or allergy
- other medications -interactions (serotonin syndrome)
- underlying diseases
- family history
30
Why is it important to note when the pt last ate/drank?
To note absorbtion of drug
31
Who do you call to find the antidote?
TOXBASE
32
What are the treatments useful in hospital for elimination + reduction of absorption?
- activated charcoal
- gastric aspiration + lavage
- whole bowel irrigation
- emisis
- haemodialysis + haemoperfusion
- alkaline diuresis
33
What’s the advantage of using activated charcoal?
- has a large surface area in relation to weight
- effective up to one hour post-ingestion - won’t work if drugs already been absorbed
- useful in paracetamol overdose, carbamazepine, theophylline + digoxin
☹️doesn’t absorb iron, lithium, corrosive agents or organic solvents
☹️contraindicated in pts with unprotected airway e.g. drowsiness or comatose due to risk of aspiration
34
Why is gastric aspiration + lavage used?
- orogastric tube is passed into stomach, which is washed out with 30-600ml water (repeated 3-4 times until effluent is clear).
- ET tube needed if pts unconscious
- only removes small amount of poison - early lavage within 60min of ingestion may benefit to pts who have taken life threatening amount
- contraindicated in poisoning with corrosives or petroleum compounds
35
How does haemodialysis- haemoperfusion work?
- in haemodialysis, drug passes down concentration gradient through dialysis machine + is removed in dialysis fluid e.g. lithium, methanol, salicylates
- in haemoperfusion, blood passed through column of activated charcoal or resin to which the drug is absorbed e.g. theophylline, barbiturates
- needs to be small molecules to pass across the semi-permeable membrane
36
What are the side effects of haemodialysis + haemoperfusion?
- haemorrhage
- air embolism
- infection
- loss of peripheral artery
37
How does alkaline diuresis work?
- urine is made alkaline (pH 7.5-8.5) by administration of IV NaHCO3
- this ionises weak acids e.g. aspirin in renal tubes + reduced reabsorbtion
- useful in basic drugs e.g. amphetamines, ecstasy, salicylates + phenobarbitals
- no longer used - as uses large IV volumes of water containing NaHCO3
38
What is the antidote for BZs?
Flumazenil
39
N-acetylcystine or parvolex is used for the overdose of what?
Paracetamol
40
What is the antidote to beta-blocker overdose?
Glucagon
Adverse effects
- vomiting
- hyperglycaemia
- hypokalaemia
- hypocalcaemia
41
What is the antidote to organophosphate overdose?
Atropine
42
Sodium nitrate + dicobalt edetate is used in the treatment of beta overdose?
Cyanide
43
What is the antidote to heavy metal poisoning?
Sodium calcium
44
What are reactive oxygen species (ROS)?
They are chemically reactive chemical species containing oxygen. They are caused by the reduction of molecular oxygen to a superoxide anion.
E.g. peroxides, superoxide
45
What are immunosuppressant drugs used for?
- to prevent rejection of transplanted organs + tissues
- treat diseases that have an autoimmune component to their pathogenisis e.g. rheumatoid arthritis, myasthenia gravis, Crohn’s disease
46
Th2 responses predominate when?
In allergic conditions e.g. asthma
47
When do Th1 responses predominate?
In multiple Diseases e.g rheumatoid arthritis
48
What is rheumatoid arthritis?
Characterised by chronic erosive arthritis of synovial joints.
Associated with circulating autoantibodies to reheumatoid factors + extracarticulate manifestatioms e.g. vasculitis.
Characterised by acute flares that cause increased pain + functional impairments due to active synovitis.
49
What else is corticosteroids used in treatment of?
E.g. prednisolone used in treatment of cancer + are powerful immunosuppressants.
They inhibit action of transcription factors + reduces transcription of may cytokines genes
50
What are antiproliferative drugs?
E.g. azatyioprine used to prevent tissue rejection in transplant surgery + in autoimmune disease e.g. myasthenia gravis (prevents induction phase of immune response)
Mycophenolate mofetil used for prophylaxis of acute rejection following cardiac or renal transplantation
51
What are calcineurin inhibitors?
E.g. cyclosporine
Used to prevent + treat rejection of transplanted organs
Side effects
- nephrotoxixity (damage to kidneys)
- hypertension
- hepatotoxicity (damage to liver)
Tacrolimus similar actions but more potent
52
What ar monoclonal antibodies?
E.g. basiliximab
IL-2 antagonist + prevents T-cell growth
Used for the prophylaxis of acute rejection in allogenic renal transplantation
53
What are disease-modifying antiheumatoid drugs (DMARDs)
Given after RA diagnosis
- methotrexate used in cancer + RA
- sulfasalazine suppresses inflammatory action of RA
- Gold
- penicillamine
- hydroxychloroquine
54
What are examples are delayed-action poisons?
- aspirin
- iron
- paracetamol
- tricyclic antidepressants
- paraquat
55
Overdose sign of coma - what could have been taken?
Usually due to CNS depression e.g.
- hypnotics
- antidepressants
- anticonvulsants
- tranquillisers
- opioid analgesics
- alcohol
DOENST occur with paracetamol poisoning unless another drug has all’s been taken
56
Overdose sign of convulsions - what could have been taken?
Caused by CNS stimulation by;
- anticholinergics
- sympathomimetics
- tricyclic antidepressants
- MOAI
57
Overdose sign of respiratory features - what could have been taken?
- cough, wheeze, SOB can occur after inhalation of irritant gases e.g. ammonia, chlorine + smoke
- cyanosis could be due to methaemoglobineamia caused by poisons such as Chlorates, nitrates, nitrites, herbicides
- hypoventilation common in CNS depressant
- reduction in RR = opioids
- hyperventilation = salicylate poisoning, CNS stimulants + cyanide
- pulmonary oedema = inhaled poisons or herbicides e.g. paraquat
58
Overdose sign of cardiovascular features- what could have been taken?
- tachycardia = anticholinergic, sympathomimetics + salicylates
- bradycardia = digoxin or beta blockers
- dysrhythmias = tricyclic antidepressants, antihistamines, antiarrhymics (if taken in excess) + antipsychotics
- hypotension (systolic <70mmHg can lead to irreversible brain da,age or acute tubular necrosis) = CNS depressants, diuretics
- hypertension uncommon but may occur following sympathomimetics e.g. amfetamine
59
Overdose sign of changed body temp - what could have been taken?
- hypothermia = following phenothiazines or barbiturates
| - hyperthermia = CNS stimulant e.g. amfetamines
60
What drugs induce liver enzymes?
- anticonvulsants
- rifampicin
- st Johns wort
- alcohol
61
What are the features of hepatic failure?
- vomiting
- abdo pain
- confusion
- hyperventilation
- hypoglycaemia
- cerebral oedema
- bleeding
62
What are the symptoms of aspirin overdose?
- tittinus, N+V, deafness, sweating, vasodilation, hyperventilation, lethargy + dehydration
- salicylate centrally stimulates respiratory system producing hyperventilation
- respiratory alkalosis follows with compensatory metabolic acidosis + dehydration. Hypokalemia may occur
- lactic acidosis also occurs
- overdose of salicylate increases heat production, oxygen + glucose use = high temp, tachycardia + hypoglycaemia
- alters platelet function + may result in bleeding
63
What are the features of tricyclic antidepressant overdose?
- anticholinergic symptoms e.g. dry mouth, dilated pupils, urinary retention
- dry + warm skin
- tachycardia + hyperthermia
- jerky limb movements
- hypotension-they block the alpha-adrenergic receptor on blood vessels, resulting in vasodilation.
- increased muscle tone + reflexes
- respiratory depression
- LOC
- convulsions
- cardiac arrhythmias - drug has a sodium channel-blocking effect = widened QRS (width linked to severity), VT, torsades de pointes + atrioventricular dissociation.
64
What are the features of SSRI overdose?
- N+V
- agitation, tremor + nystagmus (rapid movement of eyes)
- drowsiness
- sinus tachy
- convulsions
- occasionally serotonin syndrome with hyperthermia
65
Why cant flumazenil be taken with tricyclic antidepressants?
May precipitate seizures
66
What are the features of a beta-blocker overdose?
- bradycardia + hypotension
- AV block, conduction delay, Ventricular arrhythmias + cardiac arrest
- pulmonary oedema, bronchoconstriction + hypoglycaemia
- convulsions + coma (if lipid-soluble drug e.g. propranolol)
67
What are the features of calcium channel blocker overdose?
- verapamil is a negative inotrope = decreases cardiac contractivity = complete heart block + asystole. Causes hypotension + vasodilation
- N+V
- dizziness, agitation + confusion
- metabolic acidosis
- hyperglycaemia (due to blocking calcium channels on beta cells causing decreased insulin release).
- cardiogenic shock
