Calcium Channel Blockers ACEM 2003

  • View
    215

  • Download
    0

Embed Size (px)

Text of Calcium Channel Blockers ACEM 2003

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    1/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Calcium channel blockersCalcium channel blockers

    Professor Ian Whyte

    Hunter Area Toxicology Service

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    2/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Calcium channel blockersCalcium channel blockers

    Phenylalkylamines

    verapamil

    Benzothiazepines diltiazem

    Dihydropyridines

    nifedipine, felodipine, nimodipine,nicardipine, amlodipine, lercanidipine

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    3/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Calcium channel blockersCalcium channel blockers

    Block calcium channels (L-type) in

    heart and blood vessels

    prolong depolarisation QRS width

    block SA and AV node conduction

    heart block

    asystole

    vasodilators

    cerebral protection

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    4/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Calcium channel blockersCalcium channel blockers

    Hypotension

    peripheral vasodilatation and myocardial

    depression Bradycardia

    AV and SA node block

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    5/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    AntidotesAntidotes

    Correction of acidosis

    Calcium loading

    Glucagon Insulin-dextrose euglycaemia

    Atropine

    Inotropic agents Cardiac pacing

    Bay K 8644 (calcium channel agonist)

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    6/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Correction of acidosisCorrection of acidosis

    Correct acidosis to a pH within the normal

    range

    L calcium channel function is impaired when the

    pH falls outside the physiological range

    acidosis enhances the effect of verapamil and

    decreases the effect of calcium

    sodium bicarbonate significantly improved

    myocardial contractility and cardiac output in aswine model of verapamil poisoning

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    7/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Calcium loadingCalcium loading

    Calcium loading is the most logical

    and appears to be the most effective

    agent to use in calcium channelblocker poisoning

    It is primarily indicated in patients

    with heart block (who have usually

    taken verapamil or diltiazem)

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    8/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    GlucagonGlucagon

    Glucagon is a well-accepted antidote

    for beta-blocker poisoning

    The rationale for its use in CCBpoisoning is that it activates myosin

    kinase independent of calcium flux

    Clinical experience suggests it is lesseffective in this setting than in beta-

    blocker poisoning

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    9/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    InsulinInsulin--dextrose euglycaemiadextrose euglycaemia

    Insulin infusions should be used to treathyperglycaemia or hyperkalaemia

    Insulin-dextrose euglycaemia is more

    effective in animal models than calcium,adrenaline or glucagon

    Effective in a case series of clinicallyserious poisonings

    Hypotension that is refractory to volumeloading, correction of acidosis and calciumsalts

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    10/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    InsulinInsulin--EuglycaemiaEuglycaemia

    Insulin as an inotrope

    myocardial ischaemia/infarction

    endotoxic shock cardiogenic shock post cardiopulmonary bypass

    CCB andFblocker induced myocardial depression Yuan TH, Kerns WP, Tomaszewski CA,Ford MD, Kline

    JA. Insulin-glucose as adjunctive therapy for severe calciumchannel antagonist poisoning. J Tox Clin Tox 1999; 37(4):

    463474

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    11/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    InsulinInsulin--EuglycaemiaEuglycaemia

    Rationale

    In unstressed, aerobic state the

    myocardium relies primarily on free fattyacids (FFAs) for mechanical energy

    During shock, substrate preference shifts

    from FFAs to carbohydrate oxidation

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    12/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    InsulinInsulin--EuglycaemiaEuglycaemia

    In the presence of

    inhibition of insulin release

    insulin resistance poor tissue perfusion

    impaired glycolysis and carbohydrate

    delivery

    Systemic hyperglycaemia and

    inefficient myocardial energy transfer

    myocardial depression

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    13/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    InsulinInsulin--EuglycaemiaEuglycaemia

    Hypokalaemia

    Shift of extracellular K+ to intracellular via

    Na+/K+pump

    Na+ shift means resting membrane potential

    becomes more negative (hyperpolarisation)

    decrease arrhythmias

    Prolongs plateau phase of action potential increases calcium entry

    Aim for K+ 2.83.2

    Replace if K+ < 2.5

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    14/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    AtropineAtropine

    Vagal tone is increase by vomiting andgastrointestinal decontamination

    Atropine should be given to allpatients who are vomiting or havingGI decontamination

    Atropine should be given to all

    patients with bradycardia A response may only occur after

    calcium loading

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    15/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Inotropic agentsInotropic agents

    Dopamine is the initial pressor agent ofchoice (75% response) for diltiazemoverdose

    Isoprenaline produces a therapeutic responsein 50% of patients

    Action is predominantly through increasingthe frequency of impulses originating in theSA node

    These agents are often ineffective aschronotropic agents when there is a highdegree of conduction block

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    16/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Cardiac pacingCardiac pacing

    Ventricular rather than atrial pacing

    In severe poisoning the heart may fail

    to capture and pharmacologicaltherapy will still be required

  • 8/8/2019 Calcium Channel Blockers ACEM 2003

    17/17

    Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

    Calcium channel agonistsCalcium channel agonists

    Calcium channel agonists (eg. Bay K

    8644) would appear to be a logical

    antidote Animal studies using these compounds

    have not been very promising