Yendluri R. Bharadwaj, Ranjith Anishetty, Krishnaharsha Adusumelli, Spoorthy Paladi and Sravani Kethireddy. Vignan Pharmacy College, Hyderabad, India.
| Generic name: | Amiodarone |
| Brand name: | Cordarone, Pacerone, Aratac , Arycor, Atlansil |
| Category: | Potassium Channel Blocker |
| Indications: | Increases the refractory period via sodium and potassium channel effects and slows intra-cardiac conduction of the cardiac action potential |
| Safety trials: | Maternal oral amiodarone seems to be effective and relatively safe to treat Fetal tachycardia [1][10]. Treatment with amiodarone was associated with an increased risk of death from circulatory failure [2]. Amiodarone was more effective in the restoration of sinus rhythm in the recent onset of atrial fibrillation [3] and in patients where AF developed after elective CABG(coronary artey bipass grafting) [4]. Meta-analysis showed amiodarone to be associated with an increased risk of developing bradycardia and hypotension when used for the prophylaxis of postoperative atrial fibrillation [5]. It is ineffective for the acute termination of sustained ventricular tachycardia [6]. |
| Pk/pd studies: | Pretreatment with amiodarone and repeat DC cardio version results in sinus rhythm restoration in patients with persistent AF after an initial unsuccessful attempt [7] Amiodarone,given as an intravenous bolus is relatively safe and more effective for heart rate control [9][8]. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans [11]. |
| Clinical trials/animal studies: | Reduction in heart rate, prolongation of corrected QT interval and accumulation of corneal micro deposits are 3 clinical effects studied for making kinetic-dynamic comparisons because they occur in virtually all patients receiving amiodarone [12]. Correlation of amiodarone dosage, heart rate, QT interval and corneal micro deposits with serum amiodarone and desethylamiodarone concentrations studies helped in further studies [13]. |
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| References: | Amiodarone: 1) Arch Cardiovasc Dis. 2008 Oct; 101(10):619-27. PMID: 19056068 |
| Generic name: | Aspirin |
| Brand name: | Supac,Zorpin,Gelprin,Ascription |
| Category: | Anti-Coagulant |
| Indications: | It works by stopping the production of certain natural substances causing blood clots. |
| Safety trials: | Effective anticoagulation can prohibit thrombembolic events and is thusessential for the prognosis of patients suffering from atrial fibrillation [1]. the risks associated with addition of aspirin toanticoagulation in patients with AF outweigh the benefit [6].Oral anticoagulation therapy is superior toclopidogrel plus aspirin for prevention of vascular events in patients withatrial fibrillation at high risk of stroke [7] |
| Pk/pd studies: | Inhibition of serum TxB2 generation and ofthromboxane metabolite urinary excretion by the lower dosage of aspirin, althoughsubstantial, still appeared incomplete [3].ibuprofen, indomethacin, naproxen, and tiaprofenic acid all block the antiplatelet effect of aspirin [4]. |
| Clinical trials/animal studies: | Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk ofmajor bleeding [2]. significant inhibition of aspirin antiplatelet effects is seen in the presence of a typical ibuprofen dosing regimen [5]. |
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| References: | Aspirin: 1) Hamostaseologie. 2008 Oct; 28(4):213-6. PMID: 18836647 |
| Generic name: | Atenolol |
| Brand name: | Temormin (Tablets), Tenormin (I.V Injection) |
| Category: | Beta-Blocker |
| Indications: | It is a ß1-selective drug, which exerts greater blocking activity on myocardial ß1-receptors |
| Safety trials: | Constant dosages of atenolol result in higher heart rates during pregnancy compared with the postpartum period [4]. |
| Pk/pd studies: | hyperlipidemia affects pharmacodynamic properties of hydrophilic atenolol [2]. The pharmacodynamic effects of propranolol and atenolol in obese andlean subjects were of similar magnitude [3]. With respect to pharmacodynamics, a single dose of Atenololattenuates the increase in plasma ANG II and PRA in response to a single dose of Valsteran [5]. |
| Clinical trials/animal studies: | Oral administration of atenolol at a mediandose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats inducedeffective plasma concentrations at 2 hours after treatment in most cats [1].only (S)-atenolol, but not (R)-atenolol, contributes to the beta-blocking effect [6]. |
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| References: | Atenolol: 1) Am J Vet Res. 2008 Jan; 69(1):39-44. PMID: 18167085 |
| Generic name: | Azimilide |
| Brand name: | |
| Category: | |
| Indications: | slow down the spontaneous discharge frequency of automatic pacemakers by depressing the slope of diastolic depolarization |
| Safety trials: | Azimilide did not demonstrated statistically significant efficacy in reducing the risk of arrhythmia recurrence in patients who were in atrial fibrillation and converted to sinus rhythm [1]. Azimilide reduces the occurrence of the asymptomatic or silent arrhythmia [2]. Azimilide does not exhibit reverse-use dependence, that is, its binding characteristics and effectiveness are not related to the heart rate [3]. |
| Pk/pd studies: | when azimilide is coadministred with ketoconazole or CYP3A4inhibitors there are no expected changes in the pharmacokineticsof azimilide [5]. Azimilide pharmacokinetic parameters are dependent on bodyweight, gender, smoking status, and bilirubin and are independent of theco administration of digoxin, warfarin, and cytochrome P4503A4 inhibitors andinducers [6]. Azimilide shows a nonsignificant trend toward efficacy inmaintaining sinus rhythm in patients with paroxysmal atrial fibrillation in the presence and absence of structural heart disease [7]. |
| Clinical trials/animal studies: | The clinical trials showed that doses of azimilide 100 and 125 mg once daily prolonged the time of arrhythmia recurrence in patients [4].
post infarct survival evaluation (ALIVE)trial concluded that azimilide was safe and effective atrial fibrillation therapy in patients with depressed left ventricular function after an myocardial infarction [8]. |
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| References: | Azimilide: 1)Am Heart J,2006 May;151(5):1043-9. PMID-16644334 |
| Generic name: | Bisoprolol |
| Brand name: | Ziac, Zebeta |
| Category: | Beta-Blockers |
| Indications: | It is a selective type ß1 adrenergic receptor blocker. |
| Safety trials: | Perioperative bisoprolol therapy did not affect cardiovascular outcome in elderly at-risk patients undergoing surgery with spinal block [1]. |
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| Clinical trials/animal studies: | The low-dose combination of bisoprolol and hydrochlorothiazidemay be an appropriate alternative for elderly patients with systolichypertension [2]. |
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| References: | Bisoprolol: 1) Anesthesiology. 2007 Jul; 107(1):33-44. PMID: 17585213 |
| Generic name: | Clopidogrel |
| Brand name: | Iscover,Plavix,Clopilet,Ceruvin |
| Category: | Anticoagulant |
| Indications: | It acts by irreversible blockade of the adenosine diphosphate receptor on platelet cell membrane |
| Safety trials: | Has less efficacy compared to prasugrel [1]. A 600 mg clopidogrel bolus prior to initiating regular dose clopidogrel in the setting of acute ischemic stroke was safe [2]. efficacy of the combination of clopidogrel and aspirin therapy was effective and safe [3]. clopidogrel, was found to be effective in treating coronary artery disease [4] clopidogrel therapy is safe and effective in pediatric population [5]. |
| Pk/pd studies: | Clopidigrel has less pharmacodynamic response compared with prasugrel [11]. Pharmacokinetics of clopidogrel is affected by factors such as smoking [12]. CYP2C19 genotype affects the plasma levels of clopidogrel [13]. |
| Clinical trials/animal studies: | no attenuation of clopidogrel's effects on platelet aggregation with long-term administration [6]. After acute coronary syndrome, patients who undergo coronary artery bypass graft surgery within 5 days of receiving clopidogrel are at increased risk for reoperation, major bleeding [7]. PRI as a P2Y(12)-specific assay detected significantly more patients with impaired response than onventional platelet aggregation [8]. Clopidogrel intake was best shown by ADP induced aggregation [9]. A new loading dose of 900 mg improves IRPA and reduces poor and/or slow response to clopidogrel [10] |
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| References: | Clopidogrel: 1) Expert Rev Cardiovasc Ther. 2009 Jan; 7(1):17-23. PMID: 19105763 |
| Generic name: | Digoxin |
| Brand name: | Digitek (Tablets), Lanoxin (Injection), Lanoxicaps |
| Category: | Cardiac Glycoside |
| Indications: | Digoxin acts on a subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes) and decreases its function. |
| Safety trials: | digoxin can be safely administered with varenicline without the need for dose adjustment [1]. digoxin can be safely given to patients with left ventricular dysfunction or CHF who need additional treatment for angina pectoris or hypertension[2]. digoxin today illustrates principles of modern pharmacology that have helped make drugs safer and more effective [3]. |
| Pk/pd studies: | Digoxin pharmacokinetics has no report in the inflammation induced by bacterial DNA containing unmethylated CpG motifs (CpG-DNA) [4]. digoxin has been widely used to restore sinus rhythm and requires the addition of another rate-limiting agent[5]. Digoxin pharmacokinetics are significantly different between individuals with the TTT-TTT haplotype and those with TGC-CGC [6]. Digoxin remains useful in the management of chronic heart failure [7]. |
| Clinical trials/animal studies: | Therapeutic effects of digoxin in the fetus with multiple etiologies for CHF can be assessed with the help of CVPS score [8]. E-codes for digoxin have poor PPVs, a result that might produce misclassification in studies based solely on discharge coding [9]. digoxin is effective in reducing one year mortality in chronic heart failure in digitalis [10]. |
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| References: | Digoxin: 1) Eur J Clin Pharmacol. 2008 Nov; 64(11):1101-9.PMID: 18661125 |
| Generic name: | Diltiazem |
| Brand name: | Cardiazem, Diltiazem |
| Category: | Calcium Channel Blocker |
| Indications: | effects directly on coronary dilation |
| Safety trials: | Magnesium sulfate represents a safe, reliable and cost-effective alternative treatment strategy to diltiazem [3]. Diltiazem in monotherapy is effective in the control of hypertension [4] Ventricular rate control occurs more rapidly with intravenous diltiazem [5] |
| Pk/pd studies: | The protective effect of diltiazem on both histopathological injury and neurological function is significant [7]. Diltiazem decreases left atrial appendix flow rate velocity [7]. |
| Clinical trials/animal studies: | Exercise hemodynamic and neurohormone responses are sensitive biomarkers which could be used for safety and efficacy evaluation of DTZ [1] A lower incidence of atrial fibrillation following coronary artery bypass grafting was observed in patients treated prophylactically with diltiazem [2]. |
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| References: | Diltiazem: 1) J Pharm Pharm Sci. 2006; 9(2):245-51. PMID: 16959194 |
| Generic name: | Dofetilide |
| Brand name: | Tikosyn |
| Category: | Potassium Channel Blocker |
| Indications: | Blocks the rapid component of the delayed rectifier outward potassium current. |
| Safety trials: | Dofetilide had an unusually high pharmacological conversion rate, demonstrated an incremental dose response, and was well tolerated and safe, [1] dofetilide is a strong candidate for first choice treatment when the aim is to achieve sinus rhythm [2].The pooled survival analysis provided reassurance regarding the safety of dofetilide in patients with supraventricular arrhythmias [3] |
| Pk/pd studies: | Dofetilide is more effective than quinidine to terminate atrial flutter in this animal model [4] dofetilide exposure comparable to that in humans, QT(c) responses in dogs were greater than those reported in humans [5]. quinidine and dofetilide might cause the reverse frequency-dependent prolongation of action potential duration through distinct mechanisms with regard to blocking and unblocking kinetics [6]. The QT responsiveness to dofetilide is greater on day 1 than on day 5 [7]. |
| Clinical trials/animal studies: | Oral magnesium l-lactate raises intracellular magnesium concentrations and lowers the QTc interval of patients receiving sotalol or dofetilide [8].
Dofetilide is a well-tolerated antiarrhythmic drug with a high conversion rate of AF to sinus rhythm[9] Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease [10]. |
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| References: | Dofetilide: 1) Pacing Clin Electrophysiol. 2007 Dec; 30(12):1527-30.PMID: 18070309 |
| Generic name: | Dronedarone |
| Brand name: | Multaq, Sr33589 |
| Category: | Anti Arrhythmic |
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| Safety trials: | Dronedarone may increase the risk of mortality in patients with congestive heart failure [1].dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients [3]It is likely the first amiodarone congener that will be used in the control of atrial fibrillation [4]In patients with severe heart failure and left ventricular systolic dysfunction, treatment withdronedarone was associated with increased early mortality [6] |
| Pk/pd studies: | Dronedarone was well tolerated with no evidence oforgan toxicities or proarrhythmias [5]Amiodarone and Dronedarone have similar effects on the expression ofThyroid harmone receptor isoforms in the RA, which could partly contribute to their ability to decrease heart rate [7].Dronedarone treatment results in cardio protection by selectively mimicking hypothyroidism. [10] |
| Clinical trials/animal studies: | in patients with permanent AF, dronedarone was highly effective at controlling ventricular rate [2]Dronedarone and amiodarone display similar antiarrhythmic efficacy post-myocardial infarction, partly by preventing repolarization in homogeneity [8].a unique antiarrhythmic compound seemingly devoid ofthe side effects mediated by iodine in amiodarone [9]. |
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| References: | Dronedarone: 1) Ann Pharmacother. 2007 Apr; 41(4):599-605. PMID: 17389667 |
| Generic name: | Esmolol |
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| Safety trials: | Esmolol can be administered safely to patients younger than 6years after repair of coarctation of the aorta [1]. Intravenous esmolol was safe and well tolerated in the early phase of NSTEMI in patients presenting with symptoms of heart failure and ongoing ischaemia [2] esmolol is effective by attenuating hemodynamic responses from sympathetic activation or endogenous catecholamine release [3]. Esmolol is effective for rate control in a majority of postoperative cardiothoracic surgery patients with atrial fibrillation or flutter [4]. |
| Pk/pd studies: | The pharmacokinetics of esmolol and its efficacy in terminating SVT in children is similar to that observed in adults [5].
pharmacokinetic profile of esmolol allows the drug to provide rapid pharmacological control and minimises the potential for serious adverse effects [6] The most prevalent adverse effect during esmolol infusion was hypotension [7] esmolol is effective and well tolerated for the treatment of SVT [8]. |
| Clinical trials/animal studies: | using esmolol before extubation following coronary artery bypass graft surgery prevents undesirable haemodynamic responses [9]The dosage required to control hypertension in patients after repair of aortic coarctation was higher than patients who underwent repair of other congenital heart defects [10]Esmolol and alfentanil both significantly reduced the increases in heart rate and mean arterial pressure associated with endotracheal intubation and incision [11].conversion to sinus rhythm is significantly more likely with esmolol compared to verapamil [12] |
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| References: | Esmolol: 1) J Thorac Cardiovasc Surg. 2008 Aug;136(2):321-8..PMID: 18692637 |
| Generic name: | Flecainide |
| Brand name: | Tambacor, Almarytm, Apocard, Ecrinal And Flecaine. |
| Category: | Sodium Channel Blocker |
| Indications: | Flecainide blocks the Nav1.5 sodium channel in the heart, causing prolongation of the cardiac action potential. |
| Safety trials: | The single dose oral load in regimen of flecainide appears to be effective for cardio version of recent-onset trial fibrillation [1] the use of flecainide in patients with supraventricular arrhythmias is safe and, because of its proven efficacy, advisable [2] Flecainide is well tolerated and effective in maintaining sinus rhythm in patients without significant cardiac disease but with AF [3]. Intravenous flecainide has effective and rapid action in the conversion of PAF and its administration is safe in the treatment of this arrhythmia in the ER [4]. |
| Pk/pd studies: | flecainide may have additive or synergistic effects in maintaining sinus rhythm in atrial fibrillation [5] anti-arrhythmic efficacy of flecainide differed between males and females because of gender-associated differences in pharmacokinetics [6]. Flecainide is rapidly distributed in the mother and fetus following a single intravenous dose with a maternal volume of distribution similar to that reported in normal healthy human adults [7].The probability of cardio version after an oral loading dose of flecainide in patients with AF is dependent on ka [8]. |
| Clinical trials/animal studies: | Flecainide-induced QRS prolongation did not differ between the new controlled-release form and the immediate-release form [9]
The saturating dependency of human repolarization on cycle length, described by the proposed function, is differently affected by amiodarone and flecainide [10] flecainide exerted a significant dose-dependent effect on the prevention of symptomatic PAF/PAFL(paroxymal atrial fibrillation [11] |
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| References: | Flecainide: 1) Int J Cardiol. 2003 Feb; 87(2-3):121-8.PMID: 12559528 |
| Generic name: | Heparin |
| Brand name: | Heparin, Lovenox |
| Category: | Anti Coagulant |
| Indications: | Prevents the formation of clots and extension of existing clots within the blood. |
| Safety trials: | low molecular weight heparin is a safe andeffective method in restoring and maintaining sinus rhythm and enables us to make earlier cardio version in atrial fibrillation [2]. |
| Pk/pd studies: | LowMolecularWeightHeparin is as effective, is safer, and may be more cost-effective than unfractionated heparin [1]. Unfractionated heparin administered by means of a 3-hour continuous infusion for hemodialysis anticoagulation provided an efficient and safe effect that quickly disappeared after the end of the session [3]. The molecular weight properties and the disaccharide composition of orally administered unfractionated heparin/SNAC and parenterally administered unfractionated heparin are identical and consistent with the starting pharmaceutical standard heparin [5]. |
| Clinical trials/animal studies: | haemodialysis patients receiving the LMWH enoxaparin during dialysis are at risk of bleeding up to 10 h after the injection [4]. LMWHs offer important benefits to children with symptomatic thromboembolic events and poor venous access [6]. |
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| References: | Heparin: 1) Pharmacotherapy. 2003 Jan; 23(1):57-63. PMID: 12523460 |
| Generic name: | Ibutilide |
| Brand name: | Corvert |
| Category: | Potassium Channel Blocker |
| Indications: | induces of specific inward sodium current, which prolongs action potential and refractory period of myocardial refractoriness |
| Safety trials: | ibutilide can be an effective tool in selected patients for cardio version of atrial flutter [1]. The use of IB in patients receiving amiodarone or propafenone for AFL or AF is equally effective and safe as the use of IB alone [4]. Ibutilide is more effective than amiodarone in converting recent-onset Af to SR [2][3][10] Ibutilide is more effective than intravenous propafenone for the cardio version of recent onset AF, [5] There were no adverse effects associated with ibutilde administration [6]. |
| Pk/pd studies: | PK properties of ibutilide are linear with respect to dosing [12] in conscious dogs, racemic, R-, and S-ibutilide similarly prolong QTc independent of appreciable cardiovascular changes,[13] Menstrual cycle and sex differences exist in QTc responses to ibutilide, with the greatest increase in QTc corresponding to the first half of the menstrual cycle [14]. |
| Clinical trials/animal studies: | Concurrent use of magnesium enhanced the ability of ibutilide to successfully convert atrial fibrillation (AF) or flutter (AFl [7] Ibutilide is highly effective for rapidly Terminating atrial flutter. [8][9] caution must be observed while using ibutilide in women [11]. |
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| References: | Ibutilide: 1) Pacing Clin Electrophysiol. 2007 Aug; 30(8):1003-8.PMID: 17669084 |
| Generic name: | Lidocaine |
| Brand name: | Xylocaine |
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| Safety trials: | Drug-related hypotension with aqueous amiodarone was less frequent than with lidocaine [2]. As compared with lidocaine, amiodarone leads to substantially higher rates of survival to hospital admission in patients with shock-resistant out-of-hospital ventricular fibrillation [3]. |
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| Clinical trials/animal studies: | Vagally associated AF in Germnshepard dogs is terminated with lidocaine [1]. a bolus of 100 mg of lidocaine administered 2 minutes before release of the ACC can safely decrease the incidence of reperfusion ventricular fibrillation and is associated with better hemodynamics after weaning from cardiopulmonary bypass [4]. |
| Side effects: | burning or discomfort in the place you applied the patch,redness or swelling of the skin under the patch |
| Contra indications: | Liver disease. |
| Drugs that interact: | disopyramide (Norpace), flecainide (Tambocor), medications applied to the skin or mouth to treat pain, mexiletine (Mexitil), moricizine (Ethmozine), procainamide (Procanabid, Pronestyl), propafenone (Rhythmol), quinidine (Quinidex), and tocainide (Tonocard) |
| References: | lidocaine: 1) J Vet
Intern Med. 2008 Nov-Dec;22(6):1274-82. PMID: 18798790
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| Generic name: | Metoprolol |
| Brand name: | Dutoprol, Lopressor, Tropol Xl,Novartis And Toprol-Xl (In The Usa), Selokeen (In The Netherlands), Minax By Alphapharm (In Australia), Metrol By Arrow Pharmaceuticals (In Australia), Betaloc By Astrazeneca, Neobloc By Unipharm (In Israel) And Corvit |
| Category: | Beta-Blockers |
| Indications: | it selectively blocks the beta 1 receptors in the heart |
| Safety trials: | metoprolol in patients with Acute myocardial infarction and Left ventricular dysfunction, resulted in better long-term quality of life and favorable early safety profile [1]. Cautious use of titrated metoprolol appears to be safe and beneficial when added to standard heart failure therapy in patients with dilated cardiomyopathy associated with coronary artery disease [6]. Controlled release metoprolol formulations offer the potential to maximize the confirmed benefits of this agent in the management of hypertension and angina [7] Metoprolol IR is inferior to metoprolol XL in its effects on heart rate variability, autonomic balance, and blood pressure in patients with heart failure [12]. |
| Pk/pd studies: | Extended release metoprolol is an effective and well-tolerated treatment for hypertension in children (6 to 16 years of age) [2]. The results of the double-blind, placebo-controlled study in patients after cardio version of persistent atrial fibrillation showed that metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter [4]. for potential therapeutic use, monolithic drug matrix films MF-3, composed of EC: PVP (3:2), may be suitable for the development of a transdermal drug delivery system of Metaprolol Tartarate [8]. A greater chronotropic response to metoprolol was found in the hypertensive group, suggesting that, at least in part, the greater cardiac effect of metoprolol explained the enhanced hypotensive response of the beta blocker in the SH animals [10]. On average, metoprolol plasma concentration is doubled after an amiodarone loading dose (1.2 g/day over a period of 6 days) [14]. |
| Clinical trials/animal studies: | Metoprolol CR/XL was easily instituted, safe and well tolerated in elderly patients with systolic heart failure [3]. There was no significant difference with regard to reduction of chest pain in the patients randomly assigned to metoprolol compared with placebo [5]. A greater potency to metoprolol in vivo chronotropic effect was found in fructose-fed rats [9]. Deviation from the intended exposure and proportion of intended exposure achieved by the patient are valid adherence measures for immediate-release metoprolol and are associated with health care utilization [13]. |
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| References: | Metaprolol:
1) Am Heart J. 2007 Jul; 154(1):116-22. PMID: 17584563 |
| Generic name: | Phenytoin |
| Brand name: | Dilantin,Eptoin,Epanutin |
| Category: | Antiepileptic |
| Indications: | Prevents the seizures |
| Safety trials: | Phenytoin should be avoided due to the high risk of congenital malformations and limited role as an antiarrhythmic drug during pregnancy [1] Phenobarbital regimen is rapidly effective, comparable in safety, and enjoys certain practical advantages in comparison with phenytoin regimen [2]. careful infusion of phenytoin sodium in 0.9% sodium chloride injection is safe [3] |
| Pk/pd studies: | etoricoxib alters the pharmacokinetics of phenytoin [4].
Pharmacokinetic-pharmacodynamic model of chronic phenytoin increases the clearance of rocuronium but has no effect on the k(e0), IC(50) or gamma parameters [5]. Pharmacokinetics studies suggests that phenytoin has widely been used for neuralgia in diabetic neuropathy in rats [6] central pharmacokinetics of phenytoin is altered in mercaptopropionic acid epileptic rats in a refractory epileptic model [7] |
| Clinical trials/animal studies: | Single dose studies states that, the bioavailability of the prompt-release phenytoin was higher than the corresponding doses of the extended-release product [8]. Sodium valproate preferred in convulsive status epileptics because of its higher efficacy compared to phenytoin [9] |
| Side effects: | Drowsiness, redness, irritation, bleeding, and swelling of the gums. upset stomach ,vomitingconstipation,stomach pain, loss of taste and appetite, weight loss, difficulty swallowing, mental confusion, blurred or double vision,insomnia,nervousness,muscle twitching,headache,increased hair growth |
| Contra indications: | Problems with your blood sugar; a blood disorder; or heart, kidney, or liver disease. |
| Drugs that interact: | acetaminophen (Tylenol), antacids such as Mylanta anticoagulants such as warfarin ,chloramphenicol (Chloromycetin), cimetidine (Tagamet), disopyramide (Norpace), doxycycline (Vibramycin), fluconazole (Diflucan), heart medications such as digoxin, ibuprofen (Advil), isoniazid (INH), lithium, medications ,chlorpheniramine (Chlor-Trimeton), medications for depression such as amitriptyline (Elavil), meperidine (Demerol), omeprazole (Prilosec), oral contraceptives, pyridoxine (vitamin B6), quinidine, rifampin, sedatives such as phenobarbital, sucralfate (Carafate), theophylline (Theo-Dur), tranquilizers such as chlorpromazine (Thorazine) |
| References: | Phenytoin:
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| Generic name: | Procainamide |
| Brand name: | Procan, Pronestyl, Procanbid |
| Category: | Na+,K+ Channel Blocker |
| Indications: | It blocks Open Na+ channels and outward K+ currents. It prolongs the cardiac action potential and decreases rate rise of the action potential |
| Safety trials: | Procainamide acts faster in the loading phase of atrial fibrillation of recent onset [1].procainamide is faster in treating atrial fibrillation [2] and more effective than propafenone for the treatment of AF of short duration [5]. it reduces arrhythmias in the early postoperative period after coronary artery bypass surgery [7]The single 2 mg/kg and 3.5 mg/kg cumulative pericardial procainamide doses prolonged atrial refractoriness [3]Intravenous procainamide is an effective and safe means for the rapid termination of atrial fibrillation of recent onset and that its success rate is inversely related to the size of the left atrium [4]. |
| Pk/pd studies: | Administration of Procanbid tablets every 12 hours is essentiallyequivalent to administration of procainamide extended-release tablets (Procan SR)every 6 hours with respect to pharmacokinetics of procainamide [6] Accumulation of NAPA [N-acetylprocainamide] during procainamide therapy can alter both procainamide elimination as well as its electrophysiologic actions [8].In most patients, the electro pharmacologic effect of procainamideis rapid and proportional to plasma concentration [9]. |
| Clinical trials/animal studies: | procainamide issuperior to lidocaine in terminating spontaneously occurring monomorphic VT [10].at high plasma concentrations, lidocaine and procainamide adversely affect defibrillation energyrequirements consistent with an adverse, concentration-dependent effect of sodiumchannel blockade [11]encainide and tocainide are more likelythan procainamide to cause hemodynamic and clinical deterioration.[12] |
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| References: | Procainamide: 1) Minerva Cardioangiol. 2007 Aug; 55(4):433-41. PMID: 17653020 |
| Generic name: | Propafenone |
| Brand name: | Rhythmol |
| Category: | Sodium Channel Blocker |
| Indications: | Causes the influx of sodium ions into the cardiac muscle cells to be slowed down. |
| Safety trials: | oral loading with propafenone in a patient on concurrent carvedilol treatment may lead to a pharmacokinetic interaction, [1] propafenone was more effective in the restoration of sinus rhythm [2][4]. Concurrent administration of propafenone plus ibutilide for pharmacological cardio version of persistent AF is safe and more effective than ibutilide alone [3]. Its adverse effects are similar to placebo [5]. propafenone SR has important and statistically significant antiarrhythmic effects in patients with AF [6]. |
| Pk/pd studies: | Plasma propafenone concentrations were markedly influenced by CYP2D6 genotype-derived phenotype [10]. The bioavailability of intravenous dose was consistent with Previous reports for solid dosage forms [11]. depletion assay with plasma incubation gave insights into the nonlinear pharmacokinetics of propafenone [12]. For racemic propafenone, stereo selectivity was observed at low substrate concentration and was not seen at high substrate Concentration. [13] The antiarrhythmic efficacy of propafenone depends on the oxidation phenotype [14] |
| Clinical trials/animal studies: | Plasma propafenone concentrations were markedly influenced by CYP2D6 genotype-derived phenotype [7]. Adjunctive use of single oral bolus propafenone is safe and effective in patients with an ICD [8] Ibutilide but not propafenone decreases the duration of AF after cardiac surgery and neither appears to affect LOS or rhythm at discharge [9]. |
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| References: | Propafenone: 1) Int J Cardiol. 2008 Dec 3. PMID: 19062111 |
| Generic name: | Quinidine |
| Brand name: | Quinidex |
| Category: | Sodium Channel Blocker |
| Indications: | Quinidine primarily works by blocking the fast inward sodium current (INa) and causes the phase 0 depolarization of the cardiac action potential to decrease |
| Safety trials: | Oral quinidine was safe and effective in the conversion of persistent atrial fibrillation to sinus rhythm [1]. The combined standard dose of propafenone and quinidine may be used to maximize efficacy and tolerability [2]. In recent-onset AF, sotalol was more effective, whereas in Chronic AF, quinidine had a better result [3]. Quinidine was more efficacious and as well tolerated [4] |
| Pk/pd studies: | extremely long quinidine elimination half-life and reillustrates the importance of drug pharmacokinetics in patient care [9]. Quinidine concentration-effect relations describing ventricular repolarization are associated with antiarrhythmic efficacy in patients with ventricular tachycardia [10]. Combination quinidine-mexiletine therapy suppressed episodes of ventricular tachycardia [11] quinidine and its metabolites may have different electrophysiologic effects [12]. |
| Clinical trials/animal studies: | The QTc values in Caucasians were higher than those in Koreans at the same quinidine concentrations, especially at higher quinidine concentrations and in Female subjects [5]. C Total body clearance of quinidine was decreased dose-dependently By the DEX (dexamethasone )treatment, although the decrease was not Statistically significant [6]. Oral quinidine is effective in suppressing the gain of function in IKr responsible for some cases of short QT syndrome with a mutation in HERG and thus restoring normal rate dependence [7]. quinidine, can be absorbed rapidly at the proximal intestine, escaping the barrier function of P-gp, [8] |
| Side effects: | diarrhea, stomach, pain and cramps, dizziness or lightheadedness, headache, fatigue, weakness, rash, vision changes, difficulty, sleeping, tremor |
| Contra indications: | infection, Myasthenia gravis, heart, kidney, or liver disease, or muscle weakness. Surgery, including dental surgery, pregnancy, Drug may make you dizzy. Do not drive a car or operate machinery, alcohol can add to the dizziness caused by this drug. Cigarettes and caffeine products may increase the irritability of heart and interfere with the action of quinidine. |
| Drugs that interact: | anticoagulants such as warfarin (Coumadin); antidepressants; cimetidine (Tagamet); codeine products;diltiazem (Cardizem, Dilacor, Tiazac); medication for heart disease or high blood pressure; Medications for seizures, sleep, or an infection; and vitamins. |
| References: | Qunidine: 1) J
Cardiol. 2001 Dec;38(6):351-4.PMID: 11806093 |
| Generic name: | Recainam |
| Brand name: | |
| Category: | |
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| Safety trials: | recainam can be safely administered as a loading dose followed by a continuous infusion in patients with stable cardiac disease without significant ventricular dysfunction [6]. The antiarrhythmic efficacy and safety of intravenous recainam was tested in 10 hospitalized patients with frequent (greater than 30/h) complex ventricular ectopic beats. There were seven men and three women of average age 57 years (range 21 to 74.More than 90% suppression of repetitive beats occurred in all 10 patients (100%) and more than 90% suppression of total arrhythmic occurred in 9 patients (90%) during the maintenance period [7]. Adverse experiences were reported in 4 of the 18 patients, possibly drug-related in 2; none was considered severe or required discontinuation of recainam [8]. Oral recainam at dosages of 300 to 600 mg every 8 hours is effective in some drug-resistant ventricular arrhythmias and is well tolerated [11]. |
| Pk/pd studies: | The pharmacokinetics, antiarrhythmic activity and safety of intravenously administered recainam were evaluated in 15 men and 3 women. Adverse experiences were reported in 4 of the 18 patients, possibly drug-related in 2; none was considered severe or required discontinuation of recainam [1]. The absolute bioavailability of orally administered recainam increased proportionally to the quantity of drug [2]. The pharmacokinetic profile of recainam in dogs most closely resembled that of man [3]. |
| Clinical trials/animal studies: | Oral recainam at dosages of 300 to 600 mg every 8 hours is effective in some drug-resistant ventricular arrhythmias and is well tolerated [4]. The data suggest that recainam plasma levels may serve as a useful guide in monitoring electrophysiologic response [5]. Recainam produced a generalized slowing of intracardiac conduction [9]. recainam caused less electrophysiological change than expected, had modest antiarrhythmic efficacy, and might have significant arrhythmogenic potential [10]. This selective binding during action potential was further augmented by depolarization and is likely to play a significant role in the control of ventricular arrhythmias by the drug [12]. Recainam can be safely administered as a loading dose followed by a continuous infusion in patients with stable cardiac disease without significant ventricular dysfunction [13] |
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| References: | Recainam: 1) Am J Cardiol. 1993 Mar 15;71(8):686-94. PMID: 8447266 |
| Generic name: | Sematilide |
| Brand name: | |
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| Safety trials: | Sematilide, when administered prolonged repolarization but did not alter hemodynamic variables in patients with heart failure [1]. Neutral form of sematilide may penetrate the cardiac cell membrane via hydrophobic pathway. Sematilide prolonged the interburst interval and reduced the opening probabilities of the IK1 channel [8]. |
| Pk/pd studies: | The pharmacokinetics, effect (QTc interval), and tolerability after intravenous and oral administration of 25 mg of the drug were studied. Sematilide HCl was well tolerated [2]. QT dispersion and QRS and RR intervals were compared in patients before and after treatment with amiodarone (n = 26), sematilide (n = 26), and sotalol (n = 26). QT, QRS, and RR intervals, and QTc values were calculated for each complex, and their mean values were calculated for each lead Amiodarone, sematilide, and sotalol all significantly prolonged the QT interval and the QTc value [3]. Sematilide inhibits rapidly activating Ik in guinea pig atrial myocytes, resulting in the prolongation of action potential duration and refractoriness [9]. |
| Clinical trials/animal studies: | Sematilide, a close structural analog of N-acetylprocainamide, prolongs cardiac action potentials in vitro, whereas it does not depress maximum action potential upstroke slope, a "class III" action [5]. inhibition by amiodarone with its additional ion channel blocking action may contribute to the prevention of TdP [6]. Sematilide selectively blocks the rapidly activating delayed rectifier K+ current in atrial myocytes and provide evidence supporting the usefulness of the drug as a class III antiarrhythmic agent [7]. sematilide prevented only the induction of ventricular arrhythmias [10]. Sematilide HCI was studied to investigate: a) whether there existed interspecies correlations and b) whether reliable animal-to-human predictions were possible for the main pharmacokinetics parameters. There were no important species differences observed in the in vitro determined parameters, fraction unbound in plasma, and blood-to-plasma concentration ratio between rats, dogs, and humans [11]. |
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| References: | Sematilide: 1) J Am Coll Cardiol. 1995 Dec;26(7):1679-84. PMID: 7594103 |
| Generic name: | Sotalol |
| Brand name: | Betapace, Betapace Af, Sotalex, Sotacor-T |
| Category: | K+ Channel Blocker, Beta Blocker |
| Indications: | It blocks potassium channels and prolongs repolarization It is a beta blocker and slows atrioventricular nodal conduction |
| Safety trials: | sotalol was successful and safe in the treatment of fetal tachycardia [3] The combination of flecainide and sotalol can safely and effectivelycontrol refractory supraventriculartachycardia in children [4].sotalol should be considered a drug of first choice to treat fetal AF [5] |
| Pk/pd studies: | d,l sotalol has moderate efficacy to convert and maintain normal sinus rhythm, Sotalol reduced the overall VTA recurrence rate [6][8] sotalol-induced changes of the T-loop morphology in healthy individuals based on novel vectocardiographic parameters [7]. A rapid and sensitive ion-pair HPLC method using a monolithic column and fluorescence detection has been developed for quantification of sotalol in plasma [9]. |
| Clinical trials/animal studies: | Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans [10]. Oral low-dose sotalol decreases the occurrence of atrial fibrillation after cardiac surgery [11]. Body surface area is the best predictor for the PK ofSotalol [12]. The cardiovascular safety pharmacology assessment of drugs prior tofirst-in-human testing, and its findings may serve as a reference source for the dose [1] |
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| References: | Sotalol: 1) Br J Pharmacol.2008 Aug; 154(7):1439-45.PMCID:PMC2492091.PMID:18516073 |
| Generic name: | Verapamil |
| Brand name: | Covera-Hs, Isoptin, Verelan,Calan, And Bosoptin. |
| Category: | Calcium Channel Blocker |
| Indications: | Blocks the voltage-dependent calcium channels, which are concentrated in the sinoatrial and atrio-ventricular nodes |
| Safety trials: | Plasma concentration of racemic verapamil differ with different routes of drug administration [5]. lower incidence of angina pectoris and stroke in the verapamil-SR-based group [6]. Anti-arrhythmic treatment after DC cardio version of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol [7]. Intraluminal Calcium channel blockers like verapamil may constitute an effective endovascular treatment for mechanically-induced vasospasm [8]. However, because of its favorable adverse effect profile, verapamil is recommended for optimizing visualization of the peripheral arterial vascular system [9]. |
| Pk/pd studies: | S-verapamil is cleared more rapidly than R-verapamil in healthy volunteers [1].high plasma verapamil concentrations (617 to 2970 ng/mL) produce frequent but well tolerated hemodynamic and electrocardiogram changes [3]. |
| Clinical trials/animal studies: | There are sex-specific differences in the drug metabolism of verapamil [2] Verapamil produces marked blood pressure reductions when combined with diuretics and/or ACE inhibitors, beta-blockers and vasodilators such as prazosin [4]. |
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| References: | Verapamil: 1) Biopharm Drug Dispos. 2002 Jan; 23(1):17-31.PMID: 11891670 |
| Generic name: | Vernakalant |
| Brand name: | Kynapid |
| Category: | Investigational Drug |
| Indications: | |
| Safety trials: | vernakalant was found to be efficacious and safe in converting recent-onset AF to sinus rhythm [1][4].controlled-release formulation of vernakalant is expected to help prevent or slow the recurrence of atrial fibrillation [7]. |
| Pk/pd studies: | Vernakalant has the electrophysiological properties of a multiple ion channel blocker |
| Clinical trials/animal studies: | Intravenous vernakalant has the potential to be an important agent in the conversion of atrial fibrillation and oral vernakalant may be a useful drug for the suppression of atrial fibrillation recurrences [2][6]. vernakalant dose-dependently prolonged atrial refractoriness, prolonged AV nodal conduction and refractoriness, and slightly prolonged QRS duration, but it had no effect on ventricular refractoriness[5]. |
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| References: | Vernakalant: 1) Ann Pharmacother. 2008 Apr; 42(4):533-42. PMID: 18334607 |
| Generic name: | Warfarin |
| Brand name: | Coumarin, Antoven, Marevan, Waran |
| Category: | Anti-Coagulant |
| Indications: | Decreases the clotting ability of the blood. |
| Safety trials: | short-term tolerability of warfarin likely contributes to its underutilization [1]. Anticoagulation controlvaries widely among patients taking warfarin for AF [6]. |
| Pk/pd studies: | warfarin (INR 2.0 - 3.0) is effective and safe for the moderate to high risk nonvalvular atrial fibrillation patients [3].INRs of 3.5 or greater should be avoided [4]. warfarin pharmacokinetics and pharmacodynamics are not altered with concomitant administration of ciprofloxacin PR [5]. |
| Clinical trials/animal studies: | fixed dose oral ximelagatranIs effective as adjusted dose warfarin in stroke prevention [2]. patients with a CHADS(2)=1 had a low risk ofstroke, yet still derived a modest (<1% per year) but statistically significantabsolute reduction in stroke with OAC and had low rates of major hemorrhage onOAC [7]. |
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| References: | Warfarin: 1) Circulation. 2007 May 29; 115(21):2689-96.PMID: 17515465 |
ISLAA 2022-Left Atrial Appendage
Dr. Dhanunjay Lakkireddy, MD, F.A.C.C, FHRS, The Kansas City Heart Rhythm Institute (KCHRI), KS, USA.
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