Antidotes Flashcards
Discuss indications and contraindications to the use of atropine
Indications
- poisoning by agents that impair AV conduction such as cardiac glycosides, B blocker and Ca blocker
- Organophosate and carbomate poisoning
Contraindications
- Closed angle glaucoma
- Obstructive disease of the GIT
- Obstructive uropathy
Discuss PD and PK of atropine
PD: competitive antagonist of ACh at muscarinic receptors. It reverses excessive parasympathetic stimuation that resutls from inhibition of acetylcholinesterase. Does not act at nicotinic receptors
PK: Poor bioavailability, hepatic metabolism with half life of 2-4 hours. Crosses BBB and placental barries
Discuss administration of atropine and side-effects from excess
Bradycardia caused by drug induced AV conduction blockade
-IV bolus of 600mic repeated doses to 1.8mg
Organophoshate and carbamate poisoning
- IV blolus of 1.2mg with further dsoes every 2-3 minutes doubling the dose each time until drying of resp secretions is ahcieved. HR is not a useful end point as tachy may persist due to nicotinic effects
- Very large doses can be administered >100mg in severe tox
Excess –> anticholinergic syndrome
Paeds dose initially is 20mic/kg
Discuss calcium as antidote, indications and contraindications
Calcium gluconate (0.22mmol Ca ions/ml) Calcium cholride (0.68mmol calcium ions/ml)
Indications
- Calcium channel blockade
- hydrofluoric acid skin exposure
- hypocalcaemia of systemic flurosis secondary to ingestion of or extensive skin exposure to hydrofluoric acid
- Hypocalcaemia secondary to ethylene glycol poisoning
- iatrogenic hypermagnesaemia
- hyperkalaemia
Contra
- Hypercalcaemia
- Digoxin toxicity
Discuss calcium PD and PK
PD: Calcium acts as a physiological antaonist to the effects of hyperkalaemia and hypermagnesaemia on the cardiac conducting system and skeletal muscel. Administration of calcium in hypocalcaemic states restores or maintains ionised calcium at a concentration sufficient to prevent cardiac dysthythmias. In hydrofluroic acid poisoning calcium ions bind to fluride ions and prevent further tissue penetration.
Changes preferred sourec of energey in cardiac tissue to glucose from fatty acids – impairs uptake of glucose due to impaired insuling
PK: 99% of the bodies calcium is concentrated in bones. Of the calcium in plasma about half is ionised and physioogically active while the other half is bound to albumin. Plasma concentration is maintained at close to 2.5 mmol/L by a number of hormonal homeostatic mechanisms
Discuss administration of caclicum
Hypocalcaemia/hyperK/HyperMG
- Administer 10-20ml of 10% calcium gluconate IV over 5-10 minutes or 5-10 mls clacium chloride
- Cardaic monitoring is essential
Ca blockade
- 2g (20mls) of calcium chloride or 60mls of gluconate over 5-10 minutes -
- Repeat the dose every 20 minute up to 3 times until effect is seen
Hydrofloric acid skin exposure
#Topical 2.5% gel
–Minor burns
–For hands palce gel in a glvoe and place the hand in the glove
#local injection of calcium gluconate
-consider if topical application fails
-inject 0.5ml/cm2 intradermally and subcut
-not suitable for finger
-do not inject calcium chloride as this can cause tissue injury
# Bier’s block (foreamr reginal intravenous injection)
-Consider for alrge HF exposure to fingers han or forearm or if gel application to hese regions ahs failed
-insert IV distal in affected arm
-dilute 10mls calcium gluconate in 40mls of normal saline
-inject solution IV with beirs up
-release after 20 minutes
#intraarterial infusion
-insert art line into radial brachial or femoral artery of the affected limb
-dilute 10m of calcium gluconate into 40mls of normals slaine
-infuse over 4 hours
Hydrofloric acid inhalation injury
-give neb 2.5% gluconate solution
END POINTS
- Hypocalcaemia, hypermag or hyper K normalisation
- Ca Channel blocker - HD improvement
- Hydrogluroic acid exposure - resolution of pain
Paeds
- 1ml/kg of calcium gluconate
Discuss HIET, indications and contraindications
HIET may allow the heart to overcome the metabolic starvation that results from Ca channel blocker toxicity
Indications:
- severe Ca channel overdose
- propanalol overdose
Contraindications
-Nil
Discuss mechanisms of action of HIET
- Increased glucose and lactate uptake by myocardial cells
- improved myocardial function wihtout increased o2 demand
- Increased pyruvate dehydrogenase activity thus hastening myocadial lactate oxidation and clear the cystosol of glycotic byproducts that can impair calcium handling and cause diastolic dysfunction
Promotes excitation contraction coupling and contractility because increased glucose availability results in
- increased SR associated calcium ATPase activity
- Increased ctyoplasmic calcium concentration
- enhanced calcium entrance into mitochondira and sarcolemma
HIET is best used adjunctively with catecholamines
- insulin mediated inotropy is not catecholamine mediated and is not affected by b blockers so addtive effects are likley
- Although insulin appears to improve contractility it has not chronotropic affect and may cause vasodiliation
Discuss administration of HIET
Commence therapy with
- glucose 25 grams (50ml 50%) IV bolus unless marked hyperglcyaemia >22mmol present
- short acting insuling 1U/KG bolus to maximally saturate insulin receptors
Continue with
- Insulin infusion at 0.5 IU/KG/H and titrated every 30 minutes to a max of 5IU/kg/hr
- dextrose 25g/h infusion to maintain euglycaemia - CVC access may be required to allow concentrated solutions to be used
Monitor
- glucose- every 2o minutes for first hour then hourly
- potassium replace only if <2.5mmol and there is a source of K loss - total body stores are not depleted and K will shift back to the extracellular compartment once insulin discontinued
- Check K hourly during initiation and tiration - 6 houlry once stable
Peak effect usually reached at 1 hour most effective if started early
Discuss intravenous intralipid indications and contraindications
Sterile emulsion of soya been oiloil in water used in parenteral nutrition. Novel antidote that requires further study but ay have a role to play in the resus of patients with refractory cardiac instability or arrest due to LA or other lipophil agents
Indication
- LA induced cardiovascular collapse resistant to standard resus protocols
- Consider in other toxic caused refractory cardiac instability or arrest ie: TCA, antidepressant, propanolol, Ca channel blockade
Contrindications
- Inadequate standard resus
- egg soya or peanut hypersensitivity
Discuss MOA of Intralipid
Introduction of an intravascular lipid phase that extracts agent from tissue binding sites, increased myocardial ATP synthesis due to reversal of inhibition of fatty acid delivery to mitochondira and restoration of myocyte funciton by activation of caclium and potassium channels and an increase in intracellular calcium
Discuss admin of intralipid + adverse effects assocaited with its use
Give 1-1.5ml/Kg IVLE 20% over 1 minute
Can repeat bolus once or twice at 3-5 minute intervals if required then
-infuse IVLE 0.25ml/kg/min until HD stable
-increase to 0.5ml/kg/minute if hypotension persists
-increasing above 8ml/kg is unlikley to be beneficial
Adverse effect
- Anaphylaxis
- pulmonary HTN, Acute lung injury, haematuria, pnacreatitis and hypertriglyceridaemia have been described
Nil data for pregnancy or kids should not be withheld if life threatening situation
Discuss methylene blue its indications and contraindicaitons
Treatment of choice for symptomatic drug induced methaemoglobinaemia. It has been proposed as a potential adjunct in the treatment of shock states
Indications
- symptomatic drug induced methaemoglobinaemia (signs of hypoxaemia with chest pain, dyspnoea or confusion)
- Consider in asymptmatic patients with methaemoglobin levels >20%
- Used in refractory anaphylactic and toxic shock states where hypotension persists despite vasopressor administration
Contraindications
- G6PD deficiency: lack of NADPH in this condition causes methylene blue to be ineffective as it cannot be reduced to leucomethylene blue - haemolysis may also occur
- renal impairment: dose needs to be reduced
- methaemoglbinaemia reductase defieincy
- nitrate induced matehaemoglobinaemia following the treatment of cyanide poisoning
- hypersensitivity
Discuss mechanism of action of methylene blue
Dramatically increases the antural rate of reduction of metHb to haemoglobin. Methylene blue is reduced to leucomethylene blue then reduces MetHb to HB.
Inhibits the nitric oxide synthase and guanyalte cylclase and scavenges endotherial nitric oxide. In shock states it appears to ahve both vasoconstricitve and inotropic effect.
Discuss administration of methylene blue
- Administer 1-2 mg/kg (0.1-0.2 ml/kg of 1% solution) IV slowly over 5 minutes. Follow with a normal saline flush to minimise venous irritation
- MetHb levels should be measured hourly until a consistent fall is documentede
- Methaeoglobinaemia usually responds to a single dose howevere a further 1-2mg/kg may be repeated after 30-60 minutes if inadequate response
- in rare cases such as dapsone poisoning when methaemoglobin formation may continue for days repeat dosing every 6-8 hours may be necessary
END POINTS
- reoslution of symptoms of hypoxaemia
- repsonse is confirmed by repeat MetHb estimation
- Stabilisation of HD parameters
Pulse oximetry reading will be unreliable as Met HB and methylene blue interfere with reading
Discuss adverse effects of methylene blue
- Local pain and irritation commonly occur at the site of administration and extravasation can result in local tissue necrosis
- Common non-specific adverse effects include headache, dizziness, restlessness nausea vomiting chest discomfort and shortness of breath
- blue staining of mucous membranes (may mimic cyanosis) and urine
- Methylene blue may paradoxically cause methaemoglobinaemia when given in high doses (>7mg/kg) secondary to a direct oxidative effect on HB
- Acute haemolytic anaemia may occur in G6PD deficient individiauls with large doses of methylene blue
Discuss NAC indications and contraindications
The most widely used sulfhydryl donor in the treatment of paracetamol poisoning. It is almost completley protective against paracetamol induced hepatotoxicity when administered within 8 hours of overdose.
Indications
- Acute paracetamol overdose
- repeated supratherapeutic paracetamol ingestion
- paracetamol induced fulinant hepatic fialure
Discuss mechanisms of NAC
NAC prevents NAPQI induced hepatotoxciicyt when given within 8 hours of an acute paracetamol overdose. It ameliorates the clinical course of toxicity when given after that time or following repeated supratherapeutic ingestion. Four possible mechainsms contribue to this acution
1) increased glutathione availabiolity
2) direct binding to NAPQI
3) provision of inorganic sulfate
4) reduction of NAPQI back to paracetamol
The antioxidant properties of NAC may offer beneift in a number of other poisoning in which oxidiative stress is an imporatnt toxic mechanism and may also explain its beneficial effects in liver failure
PK
-NAC metabolism is complex with a variety of sulfur contianingn compoungs being prouced. PLasma half life follwoing IV amdinistration is 6 bours and 30% is eliiminated unchanged in the urine
Discuss administration of NAC
The results of a large retrospective study inidcates that nonallergic anaphylactic reaction during treatment with IV NAC can be reduced using a two bag regime instead of the tradiional three bag
First bag given at 200mg/kg over 4 hours
second bag given at 100mg/kg over 16 hours
Discuss Non-allergic anaphylactic reactions seen in NAC
Mechanism is non igEmediated histamine release or direct complement activation `
Unlike true anaphylaxis prior exposure to NAC is not needed, nor is continued or future treatment contraindicated
-Incidence of 10-50% including hypotension, flushign rash and angio-oedema
- These usually occur during or shortly after the intiail dose and can be treated with an oral H1 blocker (loratadine) or promethazine 12.5 mg IV
- The infusion need only be ceased if the reaction is severe in whcih case it may be restarted as soon as the reaction is settling .
For moderate to severe reactions treat as per anaphylaxis and stop the infusion. Acetylcysteine can then be recommenced once symptoms settle at half rate for 30 minutes and then recommenced as per normal protocol.
Discuss indication for Digibind
Cardiac glycoside poisoning where there is an imminent threat to life or where the risk assessment such suggest such a risk.
Acute
- cardiac arrest
- life threatening dysrhythmia
- ingested dose >10mg or >4mg child
- serum dig >15nmol/L
- serum K >5mmol/L
Chronic
- Cardiac arrest
- life threatening dysrhythmia
- cardiac dysrhythmia or increased automaticity not likely to be tolerated for a prolonged period
- moderate to severe GIT symptoms
- any symptoms in presence of impaired renal function
Discuss administration and dose of digifab
Place the patient in a monitored area where equipment drugs and personnel are available to provide full resus.
Calculate dose required dilute in 100ml of NaCl and admin over 30 minutes
CALCULATION Acute
1) Known
- number of ampoules = ingested dose (mg) x 1.6
2) Unknown
- 5 ampoules if the patient is HD stab
- 10 ampoules if unstable
- 20 amp if arrested
- repeat doses of 5 amp every 30 minutes until reversal of dig toxicity is achieved
Chronic
1) Number of ampoules = (serum dig (ng/ml) x bodyweight) / 100
2) alternatively commence 2 ampoules and observe for response if there is no reversal after 30 minutes repeat dose
OTHER
1) stable 5 ampoules every 30 minutes
Be aware that dig level after treatment may be very high as most serum dig assays measure both free and Fab-bound dig
Hyper K due to dig poisoning is treated with Fab and not IV calcium as dig causes elevation in intracellular myocardial calcium levles.
Describe MAO of digi bind
40mg of Fab binds 0.5mg of digoxin. Digoxin immune fab binds directly to the free intravascular and interstitial digoxin with much greater affinity than the Na/K ATPase receptor. A concentration gradient is created and intracellular digoxin dissociates from tissues and moves to the intravascular space where binding to immune FAB continues.
Discuss adverse drug reaction associated with digifab
Rare - very safe drug
- hypokalaemia
- allergy
- exacerbation of underlying cardiac failure
- loss of rate control of pre-exisiting AF
