Amlodipine Causes Ecchymosis and Hematuria

 

ABSTRACT:

A 48-year-old male,  was diagnosed with essential hypertension and was treated with  amlodipine 5 mg once a day, and candesartan 16 mg once a day.  After two months of starting of  treatment by amlodipine, the patient complained flat,  brownish black patches  and some time associated with small local  edema  on different parts of body. There was no history of  any other illness  during the above period. General and clinical examinations revealed no abnormalities. Clotting time, bleeding time, fibrinogen  level, and platelet function test are normal. The antihypertensive therapy changed from amlodipine to another class of antihypertension drugs. Over a period of 4 weeks, the ecchymosis and hematuria  resolved.

 

 

 

INTRODUCTION:

Calcium channel blockers are heterogenous group of drugs  thatblock cellular  entry of Ca²⁺ through calcium channel rather than its intracellular actions¹. They decrease myocardial contractile force, which reduce myocardial oxygen demands. Calcium channel blockers in arterial smooth muscle cause generalized arterial dilatation and decrease arterial blood pressure. Amlodipine is widely prescribed to treat hypertension². It is dihydropyridine L-type calcium channel blocker.In addition to angina pectoris, amlodipine  has well  documented efficacy in hypertension^3,4.

 

Rajinikanth B. andVenkatachalam V.V. reportedthat amlodipine possess significant reduction in inflammation against induced ulcerative colitis in mice^5. Minor adverse effects of amlodipine include flushing, dizziness, nausea, constipation, and peripheral edema². Rare  adverse reactions have been reported such as gingival overgrowth^6,7,8, hyperpigmentation^9,10, petechial rash¹¹, and gastrointestinal bleeding¹². In this report, the first case of ecchymosis and hematuria associated with amlodipine is reported.

 

Case study:

A 48-year-old male, was diagnosed with essential hypertension and was treated with  amlodipine 5 mg once a day, and candesartan 16 mg once a day. After two months of starting of  treatment by amlodipine, the patient complained flat, brownish black patches  and some time associated with small local  edema  on different parts of body [Figure:1]. This patch disappeared after approximately 2 weeks and reappeared in another part of the body such as chest, abdomen, back, brows, and behind the auricle of the ear.There was no history of  any other illness during the above period. General and clinical examinations revealed no abnormalities. Clotting time, bleeding time, fibrinogen level, and platelet function test are normal.

 

   

Figure 1: Amlodipine-induced ecchymosis in the chest, brows, and behind the auricle.

There were no others  serious symptoms, but the ecchymosis   were  made the patient anxious.The patient was reassured and the antihypertensive therapy changed  toModuretic tablet (amiloide 5mg and hydroclorthiazide 50mg)  once daily. Within two months, the suspension of amlodipine and candesartan resulted in a significant improvement  of his condition. Because the failure  to control the hypertension,   amlodipine 10mg  was re-prescribe once daily.  After few weeks, the ecchymosis returned with hematuria. Re-investigation of clotting time, bleeding time, fibrinogen  level, and platelet function test revealed no abnormalities. CT scan showed normal kidneys.  The antihypertensive therapy changed from amlodipine to candesartan 16mg once daily and metoprolol 50mg once daily. Over a period of 4 weeks, the ecchymosis and hematuria  resolved.

 

DISCUSSION:

The dihydropyridines are a potent vasodilators in vitro and vivo.The  hemodynamic effect of the  drugs  of this group shows selective dilatation of arterial vessels and causes an  increasing  in blood flow with little effects on venous pooling. Calcium channel blockers cause relaxation of arterial smooth muscles with less effects on venous beds.Reduction of the blood pressure causes sympathetic reflexes including compensatory increases in heart rate.

 

Amlodipine has slow absorption  and prolonged duration of effect The plasma half life is 35-50 hours, so plasma level and effects increase over 7-10 days.Amlodipine  causes both peripheral arterial  and coronary dilation¹³. Unwanted responses may occur such as excessive vasodilatation which expressed as hypotension, headache, dizziness, flushing and nausea. Amlodipine, also,  may causes peripheral edema, pulmonary edema, and gingival overgrowth. In this case, amlodipine caused ecchymosis and hematuria. The  severity of ecchymosis  is strongly influenced by dosage and duration amlodipine administration. The exact pathogenesis of amlodipine–induced ecchymosis and hematuria is not well understood. Explanation of this adverse effects might be due to  an increasing of intracapillary hydrostatic pressure, relaxation of the precapillary sphincter,  and capillary permeability may increase the leakage of erythrocytes from capillary into the interstitum and cause ecchymosis and hematuria⁶. The second explanation for ecchymosis and hematuria by amlodipine is an increase in tissue plasminogen activator level¹⁴.

 

Pahor et al and Kaplan et al identified that calcium channel blockers were associated with a increased risk of gastrointestinal and life threatening bleeding^15,16. Kuoet al reported a case of patient who presented with nonthrombocytopenicpurpura following the administration of diltiazem and nifedipine. When this side effect occurs following administration of these drugs, caution is advised in using other drugs of calcium channel blockers¹⁷. Sirkeret al reported acase of hyperpigmentation of the legs with petechial rash, areas of erythema and hyperpigmentation, and marked leg edema which had followed nifedipine administration¹⁸.

 

CONCLUSION:

Ecchymosis and hematuria could occur within therapeutic dose of amlodipine.This adverse reactions might cause anxiety to the patient and specific treatment dose not required. Drug withdrawal and reassurance to the patient are necessary. Physicians need to be aware of the amlodipine that can induce ecchymosis and hematuria to arrive right diagnosis and obtain the best management.

 

REFERENCES:

1.     Murdoch D, Rennie CH. Amlodipine, a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease. Drugs 1991;41:478-505.

2.     Palanisamy S, Sumathy A. Intervention to improve patient adherence with antihypertensive medications at a tertiary care teaching hospital. International Journal of PharmTech Research, 2009, 1( 2): 369-374.

3.     Hedner T. Calcium channel blockers: spectrum of side effects and drug interactions. Acta.  Pharmacol. Toxicol. 1986; 58(suppl 2): 119-130

4.     Stafford RS, Monti V, Furberg CD, Ma J. Long-term and short-term changes in antihypertensive prescribing by office-based physicians in the United States. Hypertension. 2006; 48(2):213–218.

5.     Rajinikanth B, Venkatachalam VV. Study on the effect of Amlodipine on chemically induced inflammatory bowel disease using animal model. International Journal of PharmTech Research, 2014-2015, 7( 1): 119-124.

6.     VericaP, Nina Z, Sanja I, and Tijana A. Case report: untypical amlodipine-induced gingival hyperplasia. (HindawiPublishing Corporation)  Case reports in Density; Volume 2015: Article ID 756976.

7.     Ambika S, Chakshu A, Vijay P, and Divesh S.  Case report: severe gingival enlargement with coexisting erosive Lichen Planus in severe chronic periodontitis patient.  (Hindawi Publishing Corporation)  Case reports in Density; Volume 2015: Article ID 538538.

8.     Vishal DJ, Akash PD, Ashok PS. Adverse Effects Associated with the Use of Antihypertesive Drugs: An Overview. International Journal of PharmTech Research, 2010, 2( 1): 10-13.

9.     Franz H M, and Ehud G. Pedal edema-not all dihydropyridine calcium antagonists are created equal. A J H 2002; 15: 1019-1020

10.  Zulal E. Amlodipine associated hyperpigmentation. Saudi Med J 2004; Vol.25 (1): 103-105.

11.  MurthMB, and Murthy B. Amlodipine-induced petechial rash.J Postgrad Med 2011;57(4):341-2.

12.  William P, Linda B P, Jeff D W, Jeffrey W, Syed ZA, Charles E, Paula T, Suzanne O, Curt D, Richard HG, Michael HA, Barry RD,Jeffrey LP. Risk of hospitalized gastrointestinal bleeding in persons randomized to diuretic, ACE-Inhibitor, or calcium-channel blocker in ALLHATJ ClinHypertens (Greenwich) 2013 November ; 15(11).

13.  Taylor SH. Usefulness of amlodipine angina pectoris. Am. J. Cardiol., 1994, 73: 28A-33A.

14.  Fogari R, Lazzari P, Corradi L, Zoppi A, Preti P, Rinaldi A, Mugellini A. Effect of benazepril amlodipine combination on fibrinolysis in hypertensive diabetic patients.Eur. J. Clin. Pharmacol., 2003,  59 (4), 271-275.

15.  Pahor M, Guralink JM, Furberg CD, Carbonin P, Havlik R. Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet, 1996, 347 (9008): 1061-1065.

16.  Kaplan RC, Heckbert SR, Koepsell TD, et al. Risk factors for hospitalized gastrointestinal bleedingamong older persons. Cardiovascular Health Study investigators. J. Am.Geriatr. Soc.,  2001; 49(2):126–133.

17.  Kuo M, Winiarski N, Garella S. Nonthrombocytopenicpurpura associated sequentially with nifedipine and diltiazem. Ann. Pharmacother., 1992, 26; 1089-1090.

18.  Sirker A, Missouris CG, Mac Gregor GA. Dihydropyridine calcium channel blockers and peripheral side effects. J. Hum. Hypertens. 2001, 15:745-6.

 

 

 

Accepted on 24.05.2018           © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(9): 3799-3801.