Calcium channel blockers

Professor Ian Whyte

Hunter Area Toxicology Service

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 Cardiac arrhythmia
 Primary
– quinidine–like drugs, sympathomimetic
drugs, calcium channel blockers, β–
blockers, digitalis, chloroquine
 Secondary to metabolic/electrolyte
abnormalities
– salicylates, methanol, ethylene glycol

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 Cardiotoxic drugs
 All patients should have
– oxygenation and protection of airway
– decontamination of the GIT
 atropine pre–medication
– correction of electrolyte abnormalities
 acid base balance
– cardioversion when appropriate
– consultation
 PIC 131126

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 Cardiac arrest
 Successful resuscitation has been well
documented after 8 hours of CPR
 Overdose patients usually have
– a reversible cause for their arrest
– good general health
– novel treatments for arrhythmias
– cerebral protection

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 Calcium 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
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
 Calcium channel blockers
 Hypotension
– peripheral vasodilatation and myocardial
depression
 Bradycardia
– AV and SA node block

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 18 yo female admitted 3 hours after self–
poisoning with
– 3.5 g of slow release verapamil (Isoptin SR)
– 6 g of paracetamol
– 4.5 g of tetracycline
– 1 g of pseudoephedrine

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 On arrival in ED
– PR 120, BP 110/80, RR 20, afebrile
– drowsy but oriented and cooperative

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 GI decontamination
– emesis before arrival
– lavaged with return of green tablets
– 50 g of charcoal with sorbitol repeated 4 h later

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Investigations
– ECG
 sinus tachycardia with normal QRS width
– serum paracetamol at 4 h was 38 µmol/l
 hepatotoxicity > 1300 µmol/l at 4 hours

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 16 hours post overdose
– BP fell to 70/40 and then 50/30
– PR 50
– oxygen saturation dropped to 75 %

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 16 hours post overdose
– ECG
 absent p waves
 prominent u waves

 normal QRS duration and QT interval

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Treatment
– IV atropine 0.6 mgs – no response

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Treatment
– IV calcium gluconate
 6 g over 20 minutes
 further 6 g over the next hour
– pr 60, sinus rhythm, BP 100/80
– oxygen saturation > 95 %
– infusion of 10% calcium gluconate at 2
G/h for 10 hours
– she was also given 2.5 L IV fluids

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
 CCB case
 Outcome
– non–cardiogenic pulmonary oedema
– twenty four hours post admission
 largely recovered , sinus rhythm PR 60, BP
115/70

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Outcome
– peak serum Ca was 4.8 (2.18–2.47
mmol/l)
– serial verapamil levels at 6, 18, 22 and 46
hours were 616, 2374, 2518 and 1006
ng/ml
 range during usual therapy
– 100–300 ng/ml

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 A thirty one-year-old female is brought
to the Emergency Department by
relatives
 She states that she ingested 25 x 240
mg sustained-release diltiazem tablets
approximately one hour earlier as a
suicide attempt

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 The tablets do not belong to her and
she has no significant intercurrent
illnesses
 She appears upset but otherwise well
 Her pulse is 70/minute, her blood
pressure 125/70 mmHg and her ECG
shows normal sinus rhythm

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Outline your initial management

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Despite the relatively benign
presentation, this is a life-threatening
overdose
 Aggressive gastrointestinal
decontamination using whole bowel
irrigation before clinical effects of
poisoning develop

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Give oral polyethylene glycol solution
(GoLYTELY) at a rate of 15–20
mL/kg/h
 Few patients can drink it this fast so it
is best to place a nasogastric tube
(premedicate with atropine!)

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Then sit the patient on a commode
chair and continue until the rectal
effluent looks like the GoLYTELY
solution
 This may take several hours

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Institute appropriate monitoring
 This includes establishing IV access,
continuous ECG monitoring and
frequent non-invasive blood pressure
monitoring
 This patient will need a minimum of
16 hours monitoring even if she
remains completely asymptomatic

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Admission should be to a monitored
bed and personnel should be available
who are capable of placing an arterial
line, transvenous pacemaker and
Swan-Ganz catheter

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Some six hours later, the patient is
noted to be drowsy with a pulse rate of
45/minute (first degree heart block)
and blood pressure of 80/40 mmHg
 How do you respond now?

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB case
 Despite the excellent decontamination,
sufficient drug has been absorbed to
result in a toxic syndrome
 There is no way of knowing at present
how severe it is going to be
 Best to assume the worst
 Management at this point includes

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 CCB treatment
 Normal saline bolus (10–20 mL/kg)
 Calcium
– 5–10 mL of 10% calcium chloride or 10–20 mL of
10% calcium gluconate over 5 minutes
– repeat every 3–5 minutes up to 3 to 5 doses
– if response institute calcium infusion of 1–10 mL/h
of 10% calcium chloride
– monitor serum calcium after 30 mL of calcium
chloride or equivalent
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
 CCB treatment
 Glucagon 0.05 mg/kg IV
– repeat every 5–10 minutes as needed
– if response consider infusion of 0.075–
0.15 mg/kg/h
 Atropine, isoprenaline and/or pacing
may be tried if associated symptomatic
bradycardia
 Dopamine infusion if still persistent
hypotension
Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
 CCB treatment
 If no response to the above consider
– insulin bolus 1 unit/kg with glucose 25
mL of 50% dextrose IV followed by
– insulin infusion of 0.5 units/kg/hr with
50% dextrose infusion at 0.5 g/hr
adjusted according to hourly glucose
checks

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 25mL (12.5g)
Insulin 1 U/kg AND 50% glucose

Insulin 0.5 0.5 g/h 50%

U/kg/h glucose

SBP<90 after 1h BSL<5.5 mmol/L BSL>11 mmol/L

Insulin 1 U/kg/h glucose glucose

SBP>100 for 6h

Stop insulin Off insulin, eating, BSL>5.5 mmol/L

Stop glucose

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 Cardiopulmonary bypass
 As a last resort extracorporeal blood
pressure support eg cardiopulmonary
bypass may be considered

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

 Antidotes: asystole &
bradycardia
 Atropine everything
 Bicarbonate tricyclic antidepressants
 Calcium calcium channel blockers
 Diazepam chloroquine, organochlorines
 Epinephrine everything, β–blockers
 Fab fragments digoxin
 Glucagon β–blockers, CCBs

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital