CALCIUM CHANNEL BLOCKERS

INOTROPIC AND CHRONOTROPIC ACTIVITY

 Calcium channel blockers decrease the force of
contraction of the myocardium (muscle of the heart).
This is known as the negative inotropic effect of
calcium channel blockers.
 Calcium channel blockers also slow down the
conduction of electrical activity within the heart, by
blocking the calcium channel during the plateau
phase of the action potential of the heart This results
in a negative chronotropic effect
 MECHANISM OF ACTION
 Calcium channel blockers work by blocking voltage-
gated calcium channels in cardiac muscle and blood
vessels. This decreases intracellular calcium leading
to a reduction in muscle contraction.
 In blood vessels, a decrease in calcium results in less
contraction of the vascular smooth muscle and
therefore an increase in arterial diameter (CCBs do not
work on venous smooth muscle), a phenomenon called
vasodilation
 With a relatively low blood pressure, the afterload on
the heart decreases.
CLASSIFICATION
Dihydropyridine
 They are often used to reduce systemic vascular

resistance and arterial pressure, but are not used

to treat angina because the vasodilation and
hypotension can lead to reflex tachycardia.
 Dihydropiridine calcium channel blockers can

worsen proteinuria in patients with

nephropathy.
 This CCB class is easily identified by the suffix

"-dipine".
NON-DIHYDROPYRIDINE
 Phenylalkylamine

 They are relatively selective for myocardium,

reduce myocardial oxygen demand and reverse

coronary vasospasm, and are often used to
treat angina.
 They have minimal vasodilatory effects

compared with dihydropyridines and therefore

cause less reflex tachycardia
 Eg: Verapamil, Gallopamil
 BENZOTHIAZEPINE
 They are an intermediate class between
phenylalkylamine and dihydropyridines in their
selectivity for vascular calcium channels.
 By having both cardiac depressant and vasodilator

actions, benzothiazepines are able to reduce arterial

pressure without producing the same degree of
reflex cardiac stimulation caused by
dihydropyridines.
Eg: Diltiazem
INDICATIONS
 High blood pressure
 Angina
 Abnormal heart rhythms
 Pulmonary hypertension
 Raynaud's syndrome
 Cardiomyopathy
 Subarachnoid hemorrhage.
 Prevention of migraine headaches.
 AMLODIPINE
 GENERIC NAME : Amlodipine
 TRADE NAME : Norvasc

ACTION

 Inhibits the transport of calcium into myocardial and vascular

smooth muscle cells, resulting in inhibition of excitation-
contraction coupling and subsequent contraction
 Systemic vasodilation resulting in decreased blood pressure
 Coronary vasodilation resulting in decreased frequency and
severity of attacks of angina
 INDICATIONS
Alone or with other agents in the management of
hypertension, angina pectoris, and vasospastic
(Prinzmetal's) angina
 PHARMACOKINETICS

Absorption: Well absorbed after oral administration (64-

90%)
Distribution: Probably crosses the placenta
Protein Binding: 95-98%
Metabolism and Excretion: Mostly metabolized by the
liver
Half-life: 30-50 hr (increased in geriatric patients and
patients with hepatic impairment
CONTRAINDICATIONS
 
 Hypersensitivity
  Blood pressure <90 mmHg

Use Cautiously in:

 Severe hepatic impairment (dosage reduction

recommended) 
 Geriatric patients (dosage reduction recommended;

increased risk of hypotension) 

 Aortic stenosis

  History of CHF

 Pregnancy, lactation, or children (safety not established)

ADVERSE REACTIONS

CentralNervous System: headache, dizziness,

fatigue,
Cardio Vascular : peripheral edema, angina,
bradycardia, hypotension, palpitations,
Gastro Intestinal: gingival hyperplasia, nausea,
Dermatology: flushing
ROUTE AND DOSAGE

Oral (Adults ): 5-10 mg once daily;

antihypertensive in fragile or small patients or
patients already receiving other antihypertensives--
initiate at 2.5 mg/day, increase as required/tolerated
(up to 10 mg/day) as an antihypertensive therapy
with 2.5 mg/day in patients with hepatic
insufficiency
 AVAILABILITY

Tablets: 2.5 mg, 5 mg, 10 mg 

 NURSE’S RESPONSIBILTY
 Monitor blood pressure and pulse before therapy, during dose
titration, and periodically during therapy. Monitor ECG periodically
during prolonged therapy
 Monitor intake and output ratios and daily weight. Assess for signs
of CHF (peripheral edema, rales/crackles, dyspnea, weight gain,
jugular venous distention)
 May be administered without regard to meal 
 Angina: Assess location, duration, intensity, and precipitating
factors of patient's anginal pain
 Lab Test Considerations: Total serum calcium concentrations are
not affected by calcium channel blockers
 Advise patient to take medication as directed, even if feeling well.
Take missed doses as soon as possible unless almost time for next
dose; do not double doses. May need to be discontinued gradually
VERAPAMIL
 GENERIC NAME : Verapamil
 TRADE NAME : Calan, Calan SR, Isoptin

ACTION
 Inhibits the transport of calcium into

myocardial and vascular smooth muscle cells,

resulting in inhibition of excitation-contraction
coupling and subsequent contraction 
 Decreases SA and AV conduction and prolongs

AV node refractory period in conduction tissue

 INDICATIONS
  Management of hypertension, angina pectoris, and/or
vasospastic (Prinzmetal's) angina
 Management of supraventricular arrhythmias and rapid
ventricular rates in atrial flutter or fibrillation
 PHARMACOKINETICS

Absorption: 90% absorbed after oral administration, but much

is rapidly metabolized, resulting in bioavailability of 20-25%
Distribution: Small amounts enter breast milk
Protein Binding: 90%
Metabolism and Excretion: Mostly metabolized by the liver
CONTRAINDICATIONS/PRECAUTIONS

 
 Hypersensitivity
  Sick sinus syndrome
  2nd- or 3rd-degree AV block (unless an artificial
pacemaker is in place)
  BP <90 mmHg
  CHF, severe ventricular dysfunction, or
cardiogenic shock, unless associated with
supraventricular tachyarrhythmias
  Concurrent IV beta blocker therapy
 ADVERSE REACTIONS
Central Nervous System: abnormal dreams, anxiety,
confusion, dizziness/lightheadedness, drowsiness, headache,
jitteriness, nervousness, psychiatric disturbances, weakness,
Eye, ENT: blurred vision, disturbed equilibrium, epistaxis,
tinnitus,
Respiratory : cough, dyspnea, shortness of breath,
Cardio Vascular : arrhythmias, CHF, bradycardia, chest
pain, hypotension, palpitations, peripheral edema, syncope,
tachycardia,
Gastro Intestinal : abnormal liver function studies,
anorexia, constipation, diarrhea, dry mouth, dysgeusia,
dyspepsia, nausea, vomiting,
CONT’D….
Genito Urinary : dysuria, nocturia, polyuria, sexual
dysfunction, urinary frequency,
Dermatology: dermatitis, erythema multiforme,
flushing, increased sweating, photosensitivity,
pruritus/urticaria, rash,
Endocrine: gynecomastia, hyperglycemia,
Hematology: anemia, leukopenia,
thrombocytopenia,
Metabolic: weight gain,
MusculoSkeletal : joint stiffness, muscle cramps,
Neurology: paresthesia, tremor
 ROUTE AND DOSAGE

Oral : 80-120 mg 3 times daily, increased as needed.

Extended-release preparations--120-240 mg/day as a
single dose; may be increased as needed (range 240-
480 mg/day)
 Intra Venous (Adults ): 5-10 mg (75-150 mcg/kg);

may repeat with 10 mg (150 mcg/kg) after 15-30 min

AVAILABILITY 
 Tablets: 40 mg, 80 mg, 120 mg

 Injection: 2.5 mg/m in 2- and 4-ml vials,

ampules, and syringes
 NURSE’S RESPONSIBILITY
 Monitor blood pressure and pulse before therapy, during dosage
titration, and periodically throughout therapy. Monitor ECG periodically
during prolonged therapy. Verapamil may cause prolonged PR interval
 Monitor intake and output ratios and daily weight. Assess for signs of
CHF
 Angina: Assess location, duration, intensity, and precipitating factors of
patient's anginal pain
 Arrhythmias: Monitor ECG continuously during administration.
Notify physician promptly if bradycardia or prolonged hypotension
occurs. Emergency equipment and medication should be available.
Monitor blood pressure and pulse before and frequently during
administration
 Lab Test Considerations: Total serum calcium concentrations are not
affected by calcium channel blockers
 CONT’D….
 Monitor serum potassium periodically. Hypokalemia
increases the risk of arrhythmias and should be corrected 
 Monitor renal and hepatic functions periodically during
long-term therapy. May cause increase in hepatic enzymes
after several days of therapy, which return to normal on
discontinuation of therapy
 Do not confuse verapamil with Virilon (testosterone). Do
not confuse Covera (verapamil) with Provera
(medrosyprogesterone)
 Oral: Administer verapamil with meals or milk to minimize
gastric irritation
 IntraVenous: Patients should remain recumbent for at least
1 hr after IV administration to minimize hypotensive effects
DILTIAZEM

 GENERIC NAME : diltiazem

TRADE NAME : Cardizem
 MODE OF ACTION
 Inhibits transport of calcium into myocardial and vascular
smooth muscle cells, resulting in inhibition of excitation-
contraction coupling and subsequent contraction 
 Systemic vasodilation resulting in decreased blood
pressure
 Coronary vasodilation resulting in decreased frequency
and severity of attacks of angina
 Suppression of arrhythmias
 INDICATIONS
 Hypertension 
 Angina pectoris and vasospastic (Prinzmetal's) angina

 Supraventricular tachyarrhythmias and rapid ventricular rates in atrial flutter or fibrillation  

 Management of Raynaud's syndrome 

PHARMACOKINETICS

Absorption: Well absorbed, but rapidly metabolized after oral administration

Distribution: Unknown

Protein Binding: 70-80%

Metabolism and Excretion: Mostly metabolized by the liver (CYP 3A4 enzyme system)

Half-life: 3.5-9 hr
 CONTRAINDICATIONS

 Hypersensitivity 
 Sick sinus syndrome
  2nd- or 3rd-degree AV block (unless an artificial
pacemaker is in place)
  Blood pressure <90 mmHg 
 Recent MI or pulmonary congestion
  Concurrent use of rifampin
 ADVERSE REACTIONS
Central Nervous System: abnormal dreams, anxiety, confusion, dizziness,

drowsiness, headache, nervousness, psychiatric disturbances, weakness,

Eye ENT: blurred vision, disturbed equilibrium, epistaxis, tinnitus,

Respiratory : cough, dyspnea,

CarddioVascular : ARRHYTHMIAS, CHF, peripheral edema, bradycardia,

chest pain, hypotension, palpitations, syncope, tachycardia,

Gastro Intestinal : abnormal liver function studies, anorexia, constipation,

diarrhea, dry mouth, dysgeusia, dyspepsia, nausea, vomiting,

Genito Urinary : dysuria, nocturia, polyuria, sexual dysfunction, urinary

frequency
CONT’D………

Dermatology : dermatitis, erythema multiforme,

flushing, increased sweating, photosensitivity,
pruritus/urticaria, rash,
Endocrine : gynecomastia, hyperglycemia,
Hematology: anemia, leukopenia,
thrombocytopenia,
Metabolic : weight gain,
MusculoSkeletal : joint stiffness, muscle
cramps,
Neuroolgy : paresthesia, tremor,
 ROUTE AND DOSAGE

Oral : 30-120 mg 3-4 times daily or 60-120 mg twice daily as SR

capsules or 180-240 mg once daily as CD or XR capsules or LA
tablets (up to 360 mg/day)
 IntraVenous : 0.25 mg/kg; may repeat in 15 min with a dose of

0.35 mg/kg. May follow with continuous infusion at 10 mg/hr

(range 5-15 mg/hr) for up to 24 hr

AVAILABILITY 
 Tablets: 30 mg, 60 mg, 90 mg, 120 mg
 Injection: 5 mg/ml in 10-ml vials, 25 mg ready-to-use syringes
(Lyo-Ject)
 NURSE’S RESPONSIBILITY
 Monitor blood pressure and pulse before therapy, during
dose titration, and periodically during therapy. Monitor
ECG periodically during prolonged therapy. May cause
prolonged PR interval
 Monitor intake and output ratios and daily weight.Assess
for signs of CHF (peripheral edema, rales/crackles,
dyspnea, weight gain, jugular venous distention)
 Arrhythmias: Monitor ECG continuously during
administration. Report bradycardia or prolonged
hypotension promptly. Emergency equipment and
medication should be available. Monitor blood pressure
and pulse before and frequently during administration
CONT’D….

 Lab Test Considerations: Total serum calcium

concentrations are not affected by calcium channel
blockers
 Monitor serum potassium periodically. Hypokalemia ↑
the risk of arrhythmias and should be corrected
 Monitor renal and hepatic functions periodically during
long-term therapy. May cause ↑ in hepatic enzymes
after several days of therapy, which return to normal on
discontinuation of therapy
 Do not confuse Cardizem (diltiazem) with Cardene
(nicardipine). Do not confuse Cardizem LA with
Cardene SR
THANK YOU