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Clinical Pharmacology > 14.1 Poisoning > Flashcards

14.1 Poisoning Flashcards

1
Q

What can be poisonous?

A

Anything
Water can be poisonous at large volumes

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2
Q

Give some examples of pharmacological toxicity

A
  • Warfarin - excessive bleeding
  • Insulin - hypoglycaemia
  • Loop diuretics - electrolyte imbalance
  • ACEi - movement disorders
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3
Q

What is secondary pharmacological toxicity?

A

Secondary effects of a drug are toxic, not the drug itself

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4
Q

Give some examples of secondary pharmacological toxicity

A
  • Statins - myalgia/rhabdomyolysis
  • Thalidomide - teratogenic
  • B-agonist - tachycardia
  • B-blocker - bronchoconstriction
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5
Q

What are drugs with secondary effects usually prescribed with?

A
  • Chemotherapy drugs - often causes secondary vomiting, so anti-emetic given
  • Methotrexate - dihydrofolate reductase inhibitor, so folic acid given
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6
Q

What effects are often seen only with large overdoses of drugs?

A
  • Myocardial depression - B-blocker and CCB together
  • Respiratory depression - Opioid overdose, benzodiazepines, anti-epileptic (carbamazepine), barbiturates
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7
Q

What is biochemical toxicity?

A

Drug or metabolite which causes cellular damage eg macromolecules including structural proteins and enzymes

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8
Q

Are many drugs on the market biochemically toxic?

A

No - most drugs have been tested extensively for toxicity

At supra-therapeutic levels (overdose or high levels) toxic metabolites build up when they are usually converted to inactive metabolites

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9
Q

What dictates harm a drug can cause?

A

Balance of elimination of a drug or metabolites, can be toxic

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10
Q

How is biochemical toxicity caused by overdose treated?

A
  • Thiol groups on glutathione can prevent cell damage
  • Glutathione can get overwhelmed due toxic metabolite build-up
  • Can give n-acetylcysteine - replenishes thiols
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11
Q

What regime is n-acetylcysteine given in when treating paracetamol overdose?

A

Three successive infusions at different concentrations over 21 hours

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12
Q

What evidence is there for n-acetylcysteine working in the mechanism of donating thiols?

A
  • Studies shown n-acetylcysteine is beneficial in hepatic necrosis
  • CYP inducers which damage the liver can have their effect reduced by NAC if they are hepatotoxic
  • Patients with low hepatic reserves of glutathione
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13
Q

What part of metabolism does N-acetylcysteine work on in liver?

A

Phase 2

Increases production of glutathione by donating thiol groups

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14
Q

What is the biological toxicity of cyclophosphamide?

A
  • Highly toxic metabolites eliminated in urine
  • Can cause haemorrhagic cystitis due to damaging cells in bladder
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15
Q

When is cyclophosphamide prescribed?

A

Severe rheumatic disease

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16
Q

How do we prevent the biological toxicity of cyclophosphamide?

A
  • Use Mesna or excessive hydration
  • Mesna - thiol group and is polar so cannot cross tubular cells and is excreted in urine - protects bladder epithelia
17
Q

Where can you find information on managing poisoning?

A
  • BNF
  • Toxbase
  • UK National Poisons service information
  • Local guidelines - eg paracetamol
18
Q

What are the management principles for posioning?

A
  • Prevent absorption
  • Immediate actions - are they in danger?
  • Antidotes
  • Enhance elimination
  • Supportive measures
19
Q

What are some immediate actions for someone who has been poisoned?

A
  • Stop contact with poison
  • Vital signs and assess injury
  • History - from patient if possible, who they are with, evidence, packaging, written notes
20
Q

What are some supportive measures for poisoning?

A

Manage:
- Hypoxia
- Myocardial depression
- Cardiac toxicity
- Nephro/hepatotoxicity

21
Q

How can we prevent poison absorption?

A
  • Gastric lavage - stomach pumping, not reccomended due to risk of aspiration
  • Activated charcoal - need a lot, 10:1 of drug
22
Q

What are the problems with using activated charcoal?

A
  • Need to use a lot
  • Timing of overdose makes efficacy unpredictable
  • Not suitable for drowsy or if comatosed
  • Can affect absorption of therapeutic drugs
23
Q

How can we increase speed of poison elimination?

A
  • Continued activated charcoal - can be used up to 36hrs for some poisonings, normally needs to be used quickly
  • Sodium bicarbonate - causes alklaine diuresis by increasing pH (still <7.5 though), often used in aspirin poisoning
  • Haemodialysis -if drug has small Vd
  • Forced diuresis -not recommended as causes serious electrolyte imbalances
24
Q

What two examples of competitive antagonist antidotes?

A
  • Naloxone - opioid receptor antagonist
  • Atropine - muscarinic antagonist, organophosphate poisoning
25
Q

What happens in organophosphate poisoning?

A
  • Organophosphate binds to AChE and inhibits it
  • This severely reduces how much ACh broken down
  • ACh continues to bind to muscarinic receptors
  • SLUDGE
26
Q

What are some other examples of antidotes?

A
  • Chelating agents -forms a complex with poison, reduces free drug e.g. cyanide, lead and iron poisoning
  • Manipulating drug metabolism-Fomepizole, acetylcysteine
  • Antibodies-antivenom, digoxin-specific antibody
27
Q

How does Fomepizole work?

A
  • Inhibits alcohol dehydrogenase
  • Decreased toxic metabolites, formeldehyde (acidosis, retinal damage) and oxalic acid (acidosis, nephrotoxic)
  • These build up from methanol or ethylene glycol (anti-freeze) poisoning
28
Q

What is STOPP START?

A
  • Screening tool for the older peoples prescriptions (STOPP)
  • Screening tool to alert to right treatment (START)
29
Q

Why is medicine optimisation so important?

A
  • Polypharmacy
  • Every drug may be necessary- but check
  • Ensures right patient receives right drugs
  • Improves clinical outcomes
  • Economic
30
Q

What patients should be particularly targeted for review of medications (STOPP START review)?

A
  • Older people
  • Co-morbidities
  • Polypharmacy
  • High risk medications-narrow therapeutic index, known serious side effects
31
Q

What are some pharmacokinetic and pharmacodynamic changes that occur in older people meaning they need STOPP START review?

A
  • Body composition - increased fat, decreased body water and lean mass
  • Reduced renal function
  • Hepatic function
  • GI absorption/GI bleed risk
  • Baroreceptor sensitivity reduced - not as much response from HR
  • Reduced first pass metabolism
  • Protein binding
  • Receptor expression changes
  • Psychotropic drugs and extra pyramidal effects
32
Q

What needs to be considered in medication review STOPP START?

A
  • Is medication right for patient?
  • Time limited medications - used for discharge but not needed now
  • Age - life expectancy and risk/benefit if only short time left
  • Is medication effective - measurable outcome eg HbA1c, BP, cholesterol, symptomatic relief
  • Cost
  • ADRs and DDIs
33
Q

Who is STOPP START used for?

A

Older patients - 65 and above

34
Q

What is the aim of STOPP START?

A

Highlight and prevent inapproriate prescribing to reduce DDI and adverse reactions

Clinical Pharmacology (45 decks)

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