Anitarrythmics Flashcards
Discuss risk assessment of amiodarone
Acute oral overdose is usally benign regardless of the dose ingested
Delayed cardiac effects, including hypotension a flutter and t-wave inversion have bee reported
-Features observed with chronic toxicity are not observed followign acute overdose
-No fatalities from acute oral overdose
- Chronic toxicity is common and clinical manifestations include:
- pulmonary toxicity,
- CVS effects (bradycardia, AV blocks, Torsades de pointes, hypotension and -ve inotropy)
- Thyroid dysfunction
- Liver toxciity
- COrneal microdeposits
Discuss toxic mechanism and toxicokinetics of amioderane
Toxic mechanic - Vagh williams class 3 predominant with all other class action. K blockade prolongs phase 4 of the cardiac action potential and the regractory period of atrial and ventricular tissue
Toxicokinectics: Oral bioavailability is vairable by generally poor.
Almost completely protein bound
Large VD
Undergoes first pass metabolism by Cp450
Elimination is rpedominantly bilary and very slwo up tol 80nyours following acute infestion and up to 100 hours for chronic therapy
Discuss IX and management of amioderaone
Screening test as per all Tox nil specific
Management
Resus -
Bradycardia may be resistant to atropine and may require adrenaline, isoprenaline or pacing
D: activated charcoal if within 2 hours
E: nil
A: nil
D: 24 hour of cardiac monitoring. May be medically cleared if asymptomatic and have a normal ECG
Discuss risk assessment of acute digoxin poisoning
Manifest with early onset of vomiting and hyperkalaemia and can progress to life threatening cardaic dysrhtyhmias and cardiovascular collapse.
Cardaic complications are refractory to converntional resus measures. Dioxing immune Fab is highly effective
Acute dig toxciity occurs if more tha 10 times the daily defined does is ingested
Potentially lethal digoxin intoxication is predicted by
-dose ingested >10mg (adult) or >4mg (child)
-serum digoxin level >15 nmol/L at any time
-serum potassium >5.5 mmol/L
Children- ingestion up to 75mic/kg is sage and does not require hosptialisation or invvestigation
Discuss TM and TK of digoxin
TM: inhibits the membrane Na/Katpase pump leading ot a reduced sodium gradient and reduced calcium extrusion from the cell.
Results in increased concetration of intracellualr caclium (enhanced automaticity and positive inotropic effect) and increased extracellular potassium
-Dig also enahcnes vagal tone, reuslting in decreased sinoatrail and AV conduciton velocities
TK: Well absrobed after oral administration with bioavailability of 60-80%. Peak effects usually occur after 6 hours. Its VD is large 5-10L/kg
Dig undergoes minimal heaptic metabolism and is eliminated unchagned by the kidneyus.THe elimination half life is 30-40 horus and prolonged in renal impairment
Discuss Clinical features of acute digoxin overdose
Nausea and vomiting are early clinical features of acute digoxin poisoning and develop wihtin 2-4 hours of ingestion. Peak serum dix levels are reached at approxiamty 6 hours and death secondary to CVS collapse may follow at the 8-12 hours mark
GIT
-nasuea vomting and abdominal pain
CVS #bradycardia -(1st 2nd and 3rd degree AV block) -AF with ventricular response <60 #increased automaticity -ventricular extopic beats or bigeminy -SVT with AV block -VT #Hypotension
CNS
-lethargy, confusion and delirium
Normal DIG ECG features
- downsloping ST depression with a characteristic reverse tick sign
- flattened inverted or biphasic t-wave
- shortened QT interval
- prominenet U waves
- J point depression
Discuss IX of acute digoxin toxicity
Serum Digoxin levels
- confirming poisoning
- provide indication for antibody treatment
- perform level 4 hours post ingestion and then every 2 hours until definitive treatment or toxicity resoving
- do not repeat levels after digbiund - most labs measure both bound and unbound digoxin resulting in alarmingly high serum levels
EUC
-hyperkalaemia of any magnitdue is an important early sign of severe digoxic toxicity
ECG:
- Downsloping ST depression with characteristic reverse tick appearance
- flattend or biphaisc t-waves
- shortend QT interval
- mild PR interval prolongation
- prominent u waves
- peaking of the terminal portion of the t wave
- j point depression
Discuss Management of acute dix toxciity
RESUS
ABCD
Potential life threats include
-hypotension
-cardiac dysrhytmia
-cardiac arrest: - in cardaic arrest standard resus mesaures are futile. ALS is initiated while 20 ampoules (or as many as are available) of digoxin immune fab are sourced and administered. - THis may be life saving- Attempts at resus should continue for at least 30 mintues after the administration of digoxin immune Fab
-If digoxin Fab is not immediately available temporising measures are instituted to deal with life threats
#hyperkalaemia
-administer sodium bicarbonate 100mEq IV bolus (1mEg/kg for children)
-insulin dextrose( 0.1units/kg and 2ml/kg of 10% dex)
-Calcium is contra-indicated in the treatment of digoxin or cardiac glycoside induced hyperkalaemia
#AV block -give 600 mic IV atropine repeat until desired effect or max dose of 1.8mg -external pacing rarely effective #ventricualr tachydysthytmias -administer lignocaine 1mg/kg IV over 2 mintues
D: Oral charcoal if wihtin the 1st horu E: nil A: digi fab - indicated for the followin -cardiac arrest -life threatening cardiac dysrhtymia -ingested dose >10mg or 4 mg for children -serium dix >15nmol/ml (12ng/ml) -seruym K >5mmol
Discuss risk assessment of chronic digoxin
Underdiagnosed condition that carries signifaicnt mortality and morbidity. Dig has a narrow therapeuytic index and intoxication commonly develops in elederly patients with multiple co-morbidities
Untreated mortality within a week is 15-30%
Probability of dig intoxication is predicted by considering serum dig levels and clinical features
Probability of dig toxicity #bradycardia only -serum dig level 1.9 mmol/l -10% -Serum dig level 3.2nmol/L -50% #GI Symptoms only -serum dig level 1.9 mmol/l -25% -Serum dig level 3.2nmol/L -60% #GI symptoms and brady -serum dig level 1.9 mmol/l -60% -Serum dig level 3.2nmol/L -90% #Automataicity alone -serum dig level 1.9 mmol/l -70% -Serum dig level 3.2nmol/L -90% #automaticity + any other feature -serum dig level 1.9 mmol/l ->80% -Serum dig level 3.2nmol/L -100%
Discuss clinical features of chronic toxicity of digoxin
Same as acute for CVS, GIT and CNS
Visual
- decreased VA
- aberration of colour vision
- yellow haloes
COnsider chronic digoxin intoxication in any pateint on digoxin who presents with collapse, hypotension, bradycardia, dysrhythima, GI complaints altered mental state or general deterioration.
DIscuss IX of chronic digoxin toxicity
Dig level - taken 6 or more hours post last ingestion of digoxin
Same management as acute
Discuss risk assessment of quinine
Characterised by cinchonism consisting of nausea vomiting, tinnitus vertigo and deafness. Larger overdoses may result in life threatening cardiotoxicity and severe potentially permanent visual disturbance
All cases of deliberate self poisoning should be regarded as having the potential to cause cardiotoxicity and delayed visual distrubacne
-Ingestion of >1g usually produces some degree of cinchonism.
CVS, CNS and blindness are more commonly observed when the ingested dose is >5g and almost universal if 10 g
Ingestion of 2 tablets by a child <6 is potentially life threatening
Discuss TM of quinine
Class 1a antidysrhythmic with corresponding sodium channel and K chennel blockade. Results in both QT and QRS prolongation. In overdose quinine is directly toxic to the retina.
Discuss clinical features of quinine overdose
CINCHONISMS
- characterised by nausea, vomiting alterations in hearing, tinnitus and vertigo
- occurs early following OD and resolves as blood quinine levels falls
CVS
- hypotension, sinuc tachy and QRS widening and polongation of the QT and PR intervals
- Wide complex tachycardia and torsades are reported
- these effects usually occur relatively early and resolve as blood quinine concentration fllas
CNS
- Drowsiness and confusion are observed with large ingestion
- coma and seizures are rare
Eyes
- onset of visual disturbance is delayed and usually not apparent until 6-8 hours post ingestion
- manifestations include blurring disturbances in colour perception pupillary dilation and visual filed constriction
- Recovery of visual disturbance usually occurs over days to weeks although permanent risidual deficits do occur. These are more likley in patients who develop complete blindness
Discuss management of quinine overdose
RESUS
- COMA
- Wide complex tachy - as per Na channel
- Torsades de pointes - correct hypoxia, and hypokalaemia and admin mg sulfate 10mmol IV over 15 minutes. If heart rate is <100 beats commence isoprenaline infusion at 1-10 mic/min (0.05-2.0 mic/kg/min) or overdrive pacing to maintain heart rate at 100-120 BPM
- Seizures
- General supportive measures
D: charcoal to all aptients who are awake and able to drink charocal slurry themselvs.
E: MDAC –> 5g of quinine or who has any degree of visual disturbance
