CALCIUM CHANNEL BLOCKERS

All the associations  listed are incorrect except verapamil. This class IV drug increases PR interval.

Verapamil causes more constipation than other calcium channel blockers. Other common side effects include dizziness, and nausea, hypotension and headache.

Ref: Essentials of Pharmacology By K D Tripathi, 5th Edtion, Page 495.

Also know: LES pressure is higher in the supine position than in the upright position.

Drugs used in the management of SVT (act by slowing or blocking AV nodal conduction):

• Adenosine (1st choice)
• Beta blockers (2nd choice)
• Calcium channel blocker( verapamil)
• Diltiazem
• Esmolol
• Digoxin
• Amiodarone

Nitroprusside is prefered in aortic dissection, Phentolamine in aortic crisis, Hydralazine in eclampsia, nitroglycerine in hypertension associated with LV Failure and nicardipine in CVA

Ans. is ‘a’ i.e., Ritonavir; ‘c’ i.e., Verapamil

CYP3A4/3A5 inhibitors are

o Ritonavir                   o Erythromycin         o Itraconazole       o Troieandomycin o Verapamil

o Clarithromycin          o Azamulin              o Diltiazem           o Ketoconazole

o Grapefruit juice (Furano coumarins)

Ans. is ‘c’ i.e., Verapamil

o Amongst calcium channel blockers, verapamil has the most prominent cardiac electrophysiological action.
o CCBs primarily act on SA node and AV node (slow channel – Ca⁺² channel action potential) →↓ automaticity in SA node and decreased conduction in AV node.

Ans. is ‘d’ i.e., Verapamil

o You know that
1st choice drug for PSVT —› Adenosine
2nd choice drugs for PSVT –> CCBs or β-blockers
o However, adenosine may precipitate bronchospasm in asthmatics, so not preferred in asthmatics.
o β-blockers can also cause bronchoconstriction by inhibiting β-receptor mediated bronchodilatation.
o So, we are left only with CCBs (verapamil)

Ans. is ‘c’ i.e., Nifedipine causes reflex tachycardia

o DHPs (nifedipine) cause reflex tachycardia.
o Felodipine – it differs from nifedipine in having greater vascular selectivity, large tissue distribution and longer 0/2.

Ans. is ‘a’ i.e., Nimodipine

o Nimodipine is cerebroselective and is used as an anticonvulsant and calcium channel blocker of choice in subarachnoid hemorrhage.

Ans. is ‘b’ i.e., Calcium channel blocker

o Calcium channel blockers delay the recovery of `L’ type calcium channel from inactivated state to resting state —> depression of pacemaker activity and conduction – negative ionotropic, chronotropic and dromotropic effect.

o Amongst CCBs, recovery of Ca’ channel is delayed maximally by verapamil and to a lesser extent diltiazem.

o DHPs do not delay the recovery – no negative chronotropic, ionotropic or bathantotropic effect, infact short acting DHPs like nifedipine can cause tachycardia and paradoxically increase the frequency of angina short acting DHPs should not be used in angina.

Ans. is ‘c’ i.e., Verapamil

Ans. is ‘c’ i.e., Nifedipine causes reflex tachycardia

DHPs (nifedipine) cause reflex tachycardia.

o Felodipine – it differs from nifedipine in having greater vascular selectivity, large tissue distribution and longer t^1/2.

Ans. is ‘c’ i.e., Verapamil

” Verapamil is prescribed as a racemate, L-Verapamil is a more potent calcium channel blocker than is d­verapamil. However with oral therapy, the 1-enantiomer undergoes more extensive first – pass hepatic metabolism. For this reason, a given concentration of verapamil prolongs the PR interval to a greater extent when the drug is administered intravenously (where concentrations of the 1-and d-enantiomers are equivalent) than when it is administered orally.”

Ans. is ‘a’ i.e., Nimodipine

o Nimodipine is cerebroselective and is used as an anticonvulsant and calcium channel blocker of choice in subarachnoid hemorrhage.

Ans. is ‘c’ i.e., Ventricular tachycardia

Use of Verapamil as an antiarrhythmic

1. PSVT ‑
2. To control ventricular rate in Atrial flutter or Atrial fibrillation (May be used as an alternative to or in addition to Digitalis).

Verapamil is contraindicated in following arrhythmias

1.Ventricular arrhythmias — Injection of verapamil has precipitated ventricular fibrillation, therefore contraindicated.

2.Digitalis toxicity – Verapamil is contraindicated in Digitalis toxicity because additive A-V block may occur.

Heart block and sick sinus.

Ans. is ‘b’ i.e., Variant angina

“All CCBs are effective in reducing frequency and severity of classical as well as variant angina”.

Due to these cardiodepressant effects, it is C/I in the following conditions.

           Sick sinus syndrome (causes cardiac arrest)

           A- V block (Accentuate conduction defects)

           Congestive heart failure

           Hypotensive states

           Ventricular tachycardias

           AF with accessory pathway or WPW syndrome.

o Other conditions in which Verapamil is C/I.

           Digoxin toxicity —> Increases plasma digoxin level by decreasing its excretion, toxicity can develop.

           Quinidine and disopyramide —> Both these drugs have cardiac depressant action.

Verapamil is not used with β blockers because their depressant effect on SA and AV node may add up.

β

Ans. is ‘c’ i.e., Sick sinus syndrome

o Calcium channel blockers suppress SA node automaticity —> can cause cardiac arrest in sick sinus syndrome.

Ans. is ‘a’ i.e., Nitrates & ‘b’ i.e., CCBs

Ans. is ‘b’ i.e., To overcome increased sympathetic activity of Nifedipine

β-Blocker is given along with Nifedipine because

a)         Reflex tachycardia (Increased sympathetic activity) caused due to Nifedipine, is prevented by β-blocker.

b)         β-blockers cause dilatation of coronary arteries by unopposed a-mediated vasoconstriction. Nifedipine causes coronary vasodilatation and opposes the spasm caused by β-blockers.

The tendency of β-blocker to cause ventricular dilatation is counteracted by Nifedipine.

Ans. is ‘a’ i.e., Heart block

o CCBs (verapamil, diltiazem) have negative chronotropic effect (↓ SA node automaticity →↓ heart rate) and negative dromotropic effect (1AV node conduction).

o β-blockers have similar effect by blocking β₁ sympathetic receptors on heart (normally stimulation of β₁ receptors increases heart rate and conduction).

o Simultaneous use of these drugs can cause marked bradycardia and AV block.

Amongst CCBs, DHPs (nefidipine) can be used with β-blockers because DHPs have no direct negative chronotropic and dromotropic effect, rather they cause tachycardia by reflex sympathetic stimulation.

Ans. is ‘b’ i.e., Methyldopa; ‘c’ i.e., Clonidine

Rebound hypertension

o High blood pressure that is associated with the sudden withdrawl of various antihypertensive medications is called rebound hypertension.

o The increase in blood pressure may result in BP greater than when the medication was initiated.

o Depending on the severity of the increase in BP, rebound hypertension may result in hypertensive emergency.

o Rebound hypertension is avoided by gradually reducing the dose, i.e. “dose tapering”, thereby giving the body enough time to adjust to reduction in dose.

o Medications commonly associated with rebound hypertension include:

i) Centrally acting antihypertensive agents–clonidine, methyldopa (very less frequent than clonidine), moxonidine

ii) 0-blockers

Clonidine is the most common drug associated with rebound hypertension.

Ans. is ‘b’ i.e., Verapamil

Drugs causing constipation :

• Aluminium Hydroxide
• Ion exchange resins                
• Verapamil             
  
• Calcium carbonate
• Barium sulphate              
• Opiates                                     
• Ferrous sulphate
• Ganglionic blockers
• Phenothiazines               
• Tricyclic antidepresants

B i.e. Verapamil 

Intraoperative administration of intravenous blockers (atenolol, metoprolol, propranolol or esmolol)Q is done to avoid tachycardia during induction of anesthesia.

The onset of paroxysmal atrial tachycardia or fibrillation in perioperative period can be treated by the iv administration of drug that abruptly prolong the refractory period of AV node (adenosine) or lengthen the refractory period of accessory pathways (procainamide)Q Digitalis and verapamil may decrease refractory period of accessory pathways (in pre-excitation syndromes like Wolff-Parkinson-White syndrome) responsible for atrial fibrillation and thereby result in an increase in ventricular response rate during this dysrhythmia and thus should be avoided.

Ventricular tachycardia not a/ w hypotension is initially treated by iv administration of lidocaine, amiodarone or lidocaine, amiodarone or procainamide. Symptomatic VT is best treated by external electrical cardioversion.

A i.e. Calcium channel blockers; B i.e. Beta Blockers; C i.e. Aminoglycoside

– Aminoglycoside, Tetracycline & Polypeptide antibioticsQ (Mnemonic ATP) potentiate neuromuscular block

– B Blockers & Calcium channel blockerQ may cause Bradycardia & AV block with anesthesia

C i.e. Should be given in normal dose as they prevent MI & Angina

Calcium channel blockers potentiate neuromuscular-block, cause lowering of muscle tone of lower esophageal sphincter but there is no such indication of stoppage of this drug during anesthesia. CCB’s prevent MI & angina during anesthesia & should be given in normal doses (preoperatively)Q.

Ans. is ‘a’ i.e., Nefedipine 

Answer is A (Verapamil)

AV nodal blocking agents such as Calcium channel blockers, Beta blockers and Digoxin should not be used to treat Atrial Fibrillation in patients with WPW Syndrome. Use of these drugs may result in an acute increase in rate over the Accessory pathway placing the patient at risk for development of VF. Procainamide is the drug of choice for treatment of Atrial Fibrillation in patients with WPW Syndrome who are hemodynamically stable. Ibutilide and Amiodarone are also effective.

Treatment of Hemodynamically Stable Atrial Fibrillation in Patients with WPW Syndrome

• Procainamide is the drug of choice for treatment of Atrial Fibrillation in patients with WPW Syndrome who are hemodynamically stable.
• Ibutilide and Amiodarone are also effective.
• Avoid AV nodal blocking agents such as Calcium channel blockers, Beta blockers and Digoxin

The standard treatment of atrial fibrillation is to slow the ventricular rate with AV nodal blocking agents such as Calcium channel blockers, Beta blockers and Digoxin. In Patients with Pre-excitation (WPW Syndrome) the use of these agents should be avoided (contraindicated). Atrial Fibrillation in patients with WPW Syndrome is typically associated with rapid conduction over the AV node as well as the Accessory Pathway. AV nodal blockers slow down conduction and decrease the number of impulses entering the ventricles anterogradely through the AV node (but may increase the rate of conduction through the accessory pathway). This will reduce the number of impulses bombarding the ventricular end of the bypass tract or accessory pathway rendering the bypass tract less refractory. This may paradoxically increase the rate of conduction through the accessory pathway placing the patient at risk for development of VF.

‘Digoxin appears to shorten the refractory period of the Accessory pathway directly and thus increases the ventricular rate’ – Harrison

‘Verapamil appears to shorten the refractory period of the accessory pathway indirectly by causing vasodilatation and a reflex increase in sympathetic tone’ – Harrison

Answer is C (Nifedipine):

Presence of accelerated hypertension with blood pressures in excess of 200/100 mm Hg in a patient with high thoracic spinal cord injury (above T6) suggests a diagnosis of Autonomic Dysreflexia. Urgent management of the hypertensive crisis is paramount to prevent complications such as retinal haemorrhage, seizures, hypertensive encephalopathy or an intracerebral haemorrhage.

Oral Clonidine and/or Nifedipine are the most commonly used pharmacological agents to control hypertensive crisis in patients with autonomic dysreflexia

Autonomic Dysreflexia (AD) (Hypertensive Crisis following Spinal Cord injury above T6)

Bradvcardia in association with hypertension is another typical feature of AD and this results primarily from vagal compensation. Bradvcardia is however present in onl^y 50% of the cases.

What are the Triggering factors for AD

Autonomic Dysreflexia can be triggered by any painful/noxious stimulus in the clermatomes (skin), muscles or viscera below the level of cord injury.

What is the treatment of AD

Treatment of Autonomic Dysreflexia

Prevention of Trigger Factors

• Prevention of Trigger Factors
• Avoid Bladder Distension (leading cause) (prompt catheterization)
• Avoid Fecal Impaction (Second leading cause) (Manual evacuation, anal sphincter block, bowel programs)
• Anti-cholinergic Medicines are recommended

Management of Hypertensive crisis

Management of Hypertensive crisis

• Patient should be brought in a sitting position with legs dangling to take advantage of natural orthostosis.
• Pharmacological management with oral/transdermal medicine should be initiated

–  Transdermal Nitroglycerine

–  Oral Clonidine

–  Oral Nifedipine

–  Oral Phenoxybenzamine

– Oral Prazocin

• Pharmacological management with intravenous medicines may be considered in cases of hypertensive crises or encephalopathy or intraoperative hypertension

–  Nitroprusside

–  Diazoxide

–  Trimethaphan
–  Fenoldopam

Ans. A: Nimodipine

Nimodipine binds specificall^y to LAN/1)e voltage-gated calcium channels.

Nimodipine penetrates blood-brain barrier very effectively due to high lipid solubility. It effectively relaxes cerebral vasculature; approved for prevention and treatment of neurological deficit due to cerebral vasospasm following subarchnoid hemorrhage or ruptured congenital intracranial aneurysms.

Adverse effects particularly, in high dosage group (90 mg) includes itching, gastrointestinal hemorrhage, thrombocytopenia, neurological deterioration, vomiting, diaphoresis, congestive heart failure, hyponatremia, decreasing platelet count, disseminated intravascular coagulation and deep vein thrombosis.

Ans. C: Nifidepine

Sublingual nifedipine has previously been used in hypertensive emergencies. This was found to be dangerous, and has been abandoned.

Sublingual nifedipine causes blood-pressure lowering through peripheral vasodilation.

It can cause an uncontrollable decrease in blood pressure, reflex tachycardia, and a steal phenomenon in certain vascular beds

Ans. D: Amlodipine

Calcium channel blockers are suitable as first line antihypertensive agent for:

• Asthma/ COPD patients.
• Recurrent stroke prevention
• Elderly with poor arterial wall compliance
• Isolated systolic hypertension
• Raynaud’s/PVD patients
• Pregnant hypertensives
• Diabetes

Ans. is ‘d’ i.e., C or D

Pharmacological treatment of hypertension

Indications of drug therapy (the British hypertension society guidelines).

When sustained BP exceeds 160/100 mmHg or.

When BP is in the range of 140-159 / 90-99 mmHg and there is target organ damage or cardiovascular disease.

For diabetics when BP exceeds 140/90 mmHg.

The optimal target is to lower BP to or below 140/85 mmHg in nondiabetics and 140/80 mmHg in diabetics (WHO target is 130/85 mmHg).

Drug therapy

A simple stepped AB/CD regimen is used.

Ans. is ‘a’ i.e., Conduction block

Adverse effects of CCBs

• Nausea, constipation and bradycardia are more common with verapamil.
• Verapamil can accentuate conduction defect-should be avoided in 2^nd & 3^rd degree block, in sick sinus syndrome and along with 13-blocker.
• Most common side effects of DHPs are palpitation, flushing, hypotension, headache, ankle edema, drowsiness and nausea.
• Nifedipine can paradoxically increase the frequency of angina in some patients.
• Nifedine can cause voiding difficulty in elderly (relaxant effect on bladder) and glucose intolerance (decreases insulin release).

Ans. is ‘c’ i.e., Verapamil

Ans. is ‘c’ i.e., Ventricular tachycardia 

Ans. is ‘c’ i.e., Nitrates 

Ans. is `b’ i.e., Verapamil 

Drugs causing constipation :

• Aluminium Hydroxide
• Ion exchange resins  
• Verapamil       
• Calcium carbonate
• Barium sulphate       
• Opiates              
• Ferrous sulphate
• Ganglionic blockers
• Phenothiazines
• Tricyclic antidepresan 

Ans. is ‘a’ i.e., Nifedipine 

Ans. is ‘c’ i.e., Nifedipine causes reflex tachycardia 

Ans. is ‘c’ i.e., Sick sinus syndrome 

Ans. is ‘b’ i.e., Verapamil

Ans. is ‘c’ i.e., Nimodipine

• Nimodipine is shortest acting CCB. →Katzung 10/1/2 – 191
• Nimodipine selectively relaxes cerebral vasculature – can be used in subarachnoid haemmorrhage or ruptured congenital intracranial aneurism.
• Amlodipine is longest acting CCB.
• Amlodipine has maximum oral bioavailabilitv.
• Nisoldipine has minimum oral bioavailability.