Class IV

Question 1

Class IV agents - general

Answer 1

Verapamil, Diltiazen

• Ca2+ channel antagonists (cardiac)

–> similar in utility to class II agents with priamry effects on nodal phase 0 depolarization

–> DEPRESSED SA nodal automaticity, AV nodal conduction, decreased ventriucalr contractility

Question 2

describe general of calcium channel blockers (CCBs)

Answer 2

• Ca2+ channel blockers interfere with the entry of Ca2+ into cells through voltage-dependent L- and T-type Ca2+ channels
• Major cardiovascular sites of action

–> vascular smooth muscle cells

–> cardiac myocytes

–> SA and AV nodal cells

- binding to specific sites in Ca2+ channel subuts, CCB DIMINISH THE DEGREE TO WHICH THE CA2+ CHANNEL PORES OPEN IN RESPONSE TO VOLTAGE DEPOLARIZATION

Question 3

describe L-type Ca2+ channel

Answer 3

• L-type Ca2+ channel alpha1 subunit
• alpha 1 contains pores
• NO CCB binds to all pores –> blockade is incomplete

Question 4

what are the main clases of CCB

Answer 4

• Dihydropyridine (DHP)
• NIFEDIPINE = effects mainly in the vasculature
• Non-dihydropyridine (NDHP)
• Verapamil = effects mainly HEART

- Diltiazem = effects mainly HEART

Question 5

describe the major cardiovascular actions of CCB

Answer 5

• VASODILATION = more makred in arterial and arteriolar vessels than on veins
• NEGATIVE CHRONOTROPIC AND DROMOTOROPIC EFFECTS (NDHP agents only)

–> seen on SA and AV nodal conducting tissue

• NEGATIVE INOTROPIC EFFECTS

–> seen on myocardial cells

–> in case of DHPs, this effect may be offset by REFLEX ADRENERGIC STIMULATION AFTER PERIPHERAL VASODIALTION

Question 6

describe non-cardiovascular effects of CCB

Answer 6

- Little or no effect on other smooth muscles

• Relax uterine smooth muscle and has been used in therapy for preterm contractions

- SKELETAL MUSCLE DOES NOT RESPOND TO CONVENTIONAL CCBS

Question 7

describe the main clinical applications of CCB

Answer 7

• Systemic hypertension
• angina pectoris
• supraventricular tachycardia
• post-infarct protection

Question 8

describe MoA VERAPAMIL

Answer 8

• Slow inward Ca2+ channels in nodal tissue are primarily affected

- DECREASE SA AUTOMATICITY –> DECREASED HR

- DECREASED AV CONDUCTION –> increased PR interval

- Cardiac depression (decreased ventricular contractility and HR)

• no effect on ventricular Na+ conduction = ineffective on ventricular arrhythmia

Question 9

Applications of verapamil

Answer 9

- supraventricular tachycardia (IV = conversion; PO = maintenance)

- RATE CONTROL in Atrial fibrillation

• angina pectoris
• hypertension

Question 10

describe the adverse effects of verapamil

Answer 10

• ADVERSE

–> headache, flushing, dizziness, ankle edema

–> CONSTIPATION

–> EXACERBATE CHF

• hypotension (IV)
• AV heart block in combo with Beta-blockers
• CONTRAINDICATIONS

–> WPW syndropme with Afib

–> VENTRICULAR TACHYCARDIA