Disease Overview And Pharmacological Basis Of Drug Therapies Biology Essay

The prevalence of atrial fibrillation in the population increases with age as it affects 0.5 % population in the elderly scope from 50-59 year-old and increasing to 8.8 % in the age ranged from 80-89 year-old.1 It was besides found that the hazard of shot is increased by 6-fold and is associated with a 2- fold addition in mortality. The prevalence of atrial fibrillation secondary to thyrotoxicosis has been estimated to run from 5-15 % 2 In another words, atrial fibrillation is developed in 5-15 % of patients with thyrotoxicosis.

Atrial Fibrillation is initiated by helter-skelter motion of electrical urges across the atria doing atria to fibrillate at a rate every bit high as 300 to 600 beats per minute. This will so take to deficient filling and voidance of the atria. At the same clip, ventricles lose their regular beat and get down to contract faster at rate of more than 100 beats per minute. This irregular whipping will so ensue in deficient blood supply to the organic structure. In add-on to that, the pooling of blood within the bosom can take to formation of blood coagulums and later increases the hazard of stroke.3 Underliing disease such as thyrotoxicosis is linked to the shortening continuance of action potency resulting in an addition in cardiac contractility later triping development of atrial fibrillation.4 This consequence was shown in a survey conducted by in which the continuance of action potency is significantly lower in patients with hyperthyroidism.5 The thyroid endocrine is structurally similar to catecholamines which histories for change of the action possible continuance, sweetening of automaticity and activity.5

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Atrial fibrillation is diagnosed by electrocardiogram demoing absence of P moving ridges and irregular QRS composites. 3 Urine and electrolyte trial, thyroid map trial and cardiac enzyme trial are usually carried out excessively. Thyroid map trials are evaluated by mensurating the degree of thyroid exciting endocrine and free tetraiodothyronine ( T3 ) , liothyronine ( T4 ) as high thyroid endocrine degree ( thyrotoxicosis ) is one of the hazards factor of AF. Therefore, a rise in T3, T4 and a decrease in TSH degree indicates AF.4 The serum concentration of cardiac enzyme such as troponin I is measured to find the grade of harm to bosom. 3

In this instance scenario, the patient was diagnosed with paroxysmal atrial fibrillation secondary to thyrotoxicosis. Paroxysmal atrial fibrillation is defined as return of episode of AF which usually resolves in less than 7 days.6 The direction of atrial fibrillation in this patient comprised of the usage of Coumadin for thromboprophylaxis and the usage of anti thyroid drugs ( carbimazole and polythiouracil ) for intervention of implicit in hyperthyroidism. Warfarin is a vitamin K adversary which acts by suppressing enzymic decrease of vitamin K to its active hydroquinone signifier therefore interferes with the station translational & A ; Icirc ; ?- carboxylation of glutamic acid residues in coagulating factors II, VII, IX and X taking to a lack in coagulating factors in blood.6 Both carbimazole and polythiuracil are chemically related to thiourea and the thicarbamide group ( S-C-N ) histories for anti thyroid activity. They act by suppressing the thyroperoxidase-catalysed oxidization reactions by moving as substrates for the postulated peroxide-iodinium composite, hence competitively suppressing the interaction with tyrosine. It was found that propylthiouracil has extra consequence of cut downing the deionation of T4 to T3 in peripheral tissues.7

Evidence Based Surveies

Harmonizing to NICE guidelines, direction of paroxysmal atrial fibrillation should be initiated with the purposes of stamp downing fits of atrial fibrillation and keep long-run fistula beat and to forestall the complications associated with paroxysmal AF such as shot. 6First line drugs that are recommended are beta blocker such as Tenormins but if patients are still sing symptoms of fits, drugs from different drug category such as Class Ic antiarrhythmic drug ( flecainide, propafenone ) and Class III antiarrhythmic drug ( sotalol, Cordarone ) should be considered. Warfarin is used to cut down the happening of shot. The appropriate and effectual direction of the implicit in disease ( hyperthyroidism ) is indispensable in this patient in order to cut down the frequence paroxysms.6

A survey conducted by Steeds shown that both sotalol and Tenormin had similar and important efficaciousness in decrease diagnostic happening of paroxysmal atrial fibrillation. The dosage used in this peculiar survey was 80mg Bachelor of Divinity for sotalol and 50mg daily for atenolol.8 On the footing of consequences at 1 twelvemonth, Cordarone would be preferred with regard to category I and other category III drugs, as it was more effectual in forestalling returns of atrial fibrillation, produced fewer backdowns, no important proarrhythmia, and caused no addition in all-cause mortality.

Two surveies conducted by Kochiadakis GE and his colleges have shown that Cordarone was more effectual in cut downing the rate of atrial fibrillation return and able to reconstruct sinus beat more efficaciously compared to sotalol.9,10 In add-on to that, low dosage of Cordarone was found to be more effectual than sotalol in reconstructing normal fistula beat. The efficaciousness of amidorone was farther proven by a meta analysis condutced by Lafunte and his colleges. In this survey, Cordarone ( category III antiarrhythmic drug ) was concluded to hold higher efficaciousness over category Ia antiarrhythmic drug ( disopyramide, Quinidex ) , category Ic antiarrhythmic drug ( flecainide and propafenone ) and other category III drug ( sotalol ) in forestalling the backsliding of atrial fibrillation. In add-on to that, it was shown that Cordarone resulted in fewer inauspicious effects compared with other drug class.11

Antithrombolytic therapy is of import to understate the hazard of shot. The chief drug used is warfarin. In two surveies comparing efficaciousness of Coumadin against placebo concluded that Coumadin was able to cut down the hazard of ischemic shot significantly. 12,13 However, a meta analysis conducted by Aguilar and his colleges showed that the usage of Coumadin resulted in an increased hazard of bleeding but overall mortality is non significantly different from those who are taking anti thrombocyte agent such as aspirin.14 Similarly, this meta analysis besides showed that Coumadin was more efficacious than placebo for primary shot bar with moderate grounds of more major hemorrhage. This meta analysis included analysis of antiplatelet agent such as acetylsalicylic acid and its efficaciousness in cut downing the hazard of shot and it was found that acetylsalicylic acid was more effectual than placebo for primary shot bar ( 1.9 % hazard decrease for shot ) with grounds of major shed blooding. By comparing Coumadin and acetylsalicylic acid, it was found that the usage of Coumadin accounted for fewer instance of shot compared to patient on acetylsalicylic acids but with a higher hazard of bleeding. This meta analysis besides depicted that low dose Coumadin or a combination of low dose Coumadin and acetylsalicylic acid were less effectual for shot bar than adjusted-dose warfarin.13,14 This determination is supported by another meta analysis conducted by HART. In the analysis, adjusted dose Coumadins and antiplatelet ( acetylsalicylic acid ) was able to cut down incidence of shot by 64 % and 22 % severally. Another meta analysis justifies that adjusted dose Coumadin is more advantageous in cut downing the incidence of shot in patient with atrial fibrillation when compared to efficaciousness of low dosage or fixed dose Coumadin with aspirin.12 However, there was no difference observed in footings of overall mortality, vascular or hemorrhagic decease, or major bleeding between these two groups. Hence, it is sensible to reason that adjusted dose Coumadin was more effectual compared to antiplatelet in shot hazard decrease. 12 In add-on to that, a survey conducted by Van Walraven showed similar findings warranting that adjusted dose Coumadin was able to bring forth a more predictable and important decreases in shot for patients with atrial fibrillation.15 The survey conducted by Aguilar indicated that the usage adjusted-dose Coumadin to protract INR ranged from 2 to 3 was able to cut down incidence of shot decease for patients with AF well and the haemorrhage side effects were non dominant as the patients were carefully monitored.14

The patient in this instance scenario was diagnosed with atrial fibrillation secondary to thyrotoxicosis. As mentioned earlier, NICE guidelines province that appropriate direction of underlying disease such as hyperthyroidism is indispensable in cut downing the frequence of paroxysms periods in another term a better control of atrial fibrillation.6 This patient was non given any types antiarrhythmic medicine including beta blockers, Class Ic antiarrhythmic drug ( flecainide, propafenone ) and Class III antiarrhythmic drug ( sotalol, Cordarone ) . These types of drugs were found to hold important curative consequence on patients with atrial fibrillation as explained antecedently. Appropriate direction of hyperthyroidism correlatives with better direction of atrial fibrillation as shown in this patient. In peculiar, her atrial fibrillation was good controlled with the usage of anti thyroid agent as she merely developed one episode of palpitation since the past two old ages which was relieved by remainder. The antithyroid agents that were prescribed to the patient include carbimazole and polythiouracil.

The direction of thyrotoxicosis purposes to take down the serum concentration of thyroid endocrine in the organic structure. There are three chief interventions presently available for intervention of thyrotoxicosis. These include the usage of anti thyroid agents such as carbimazole, methimazole and polythiouracil, radioactive I and thyroid surgery.16,17 The usage of anti thyroid agents in the direction of thyrotoxicosis is proven to be good in pull offing atrial fibrillation. This statement is justified by a survey conducted by Berker.D and his colleges. The survey showed that both mehimazle and polythiouracil are effectual in cut downing P moving ridge continuance and scattering. Prolonged P wave continuance and scattering was shown to be correlated with development of episodes of atrial fibrillation in patient with hyperthyroidism.4 Hence it is sensible to reason that shortened P wave continuance and continuance resulted from anti thyroid therapy plays a function in cut downing negative effects of thyroid endocrines on atrial electrophysiology.4 Backslidings due to halting of anti thyroid drug can be estimated in 40 % to 60 % in patients with thyrotoxicosis ( Graves & A ; acirc ; ˆ™s disease in peculiar ) .18

Anti thyroid drug therapy can be divided into two typical drug regimens which include block-replace regimen and titration regimen. Block-replace regimen involves the usage of high and fixed dosage of anti thyroid drug to suppress production of thyroid endocrine followed by a replacing dosage of thyroid endocrine. Contrastingly, titration regimen involves decrease in dosage of antithyroid drug by titrating intervention against thyroid endocrine concentrations in the organic structure. 19,20 A meta analysis conducted by Abraham.P and his college indicated comparing of these regimens in forestalling backsliding one twelvemonth after halting the therapy and optimum continuance for both block-replace and titration regimen. 19 In this survey, titration regimen with therapy continuance of 18 months and 6 months were compared and it was shown that longer continuance therapy resulted in lower incidence of backslidings ( 37 % ) compared to 6 month therapy ( 58 % ) . Similar comparing was made for block regimen therapy but consequences indicated that there is no important difference between the efficaciousnesss of 6 month and 12 month block- replace regimens. When comparing the efficaciousness of both regimens in forestalling backslidings, it was found that both regimens had similar efficaciousness ( 54 % ) . However, block-replace regimen was reported to do more side effects taking to higher incidence of backdown compared to titration regimen. The most common side consequence reported was roseolas. In short, groundss showed that the optimum therapy continuance for titration regimen ranged from 12-18 months and 12 months for block-replace regimen and noted that that titration regimen produces fewer side effects. 19 In this instance scenario, patient had been taking carbimazole 20mg daily for 18 months but her thyroid degrees were elevated upon withdrawing of carbimazole taking to atrial fibrillation. Relapse occurred and another drug, polythiouracil 100mg tds was prescribed to her. Her atrial fibrillation was good controlled ( normal fistula beat ) with the usage of this anti thyroid drug. Evidence showed that carbimazole to be taken 20mg day-to-day is more effectual than dosing of 40mg day-to-day. The usage of lower dosage is associated with fewer side effects lower hazard in developing hypothyroidism.21 This is farther supported by a survey conducted on accessing the principle of utilizing carbimazole dosage of 100mg day-to-day and it was found that high dose carbimazole resulted in higher hazard of side effects such agranulosis. 22


The patient in this instance scenario was given appropriate direction. Harmonizing to NICE guidelines and relevant surveies, it was found that direction of underlying disease which is hyperthyroidism in this circumstance is indispensable in cut downing the frequence of atrial fibrillation episodes. Patient was admitted to hospital due to an lift in thyroid endocrine degree triping paroxysmal atrial fibrillation. The patient was so prescribed an anti thyroid drug and her atrial fibrillation was resolved over clip. In add-on to anti thyroid medicine, patient was given Coumadin for thromboprophylaxis as formation of blood coagulums in patients with atrial fibrillation is common. Warfarin was proven to be a better pick of anti coagulator as it has shown to cut down the hazard of shot significantly.


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