Lisinopril hydrochlorothiazide long term side effects
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Long-Term Side Effects of Lisinopril-Hydrochlorothiazide Combination Therapy
Introduction to Lisinopril-Hydrochlorothiazide Combination
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide, a thiazide diuretic, are commonly combined to treat hypertension. This combination leverages the complementary mechanisms of both drugs to effectively lower blood pressure. However, understanding the long-term side effects is crucial for patient safety and treatment efficacy.
Common Long-Term Side Effects
General Adverse Events
In long-term studies, the most frequently reported side effects of lisinopril include headache, dizziness, cough, nausea, diarrhea, and fatigue. These side effects are generally mild and often not directly attributed to the medication 1. When combined with hydrochlorothiazide, the incidence of these side effects does not significantly increase, although the combination therapy can lead to a higher frequency of mild adverse events 3.
Metabolic Effects
Hydrochlorothiazide is known to affect metabolic parameters, including serum potassium and glucose levels. Long-term use of hydrochlorothiazide can lead to hypokalemia (low potassium levels) and hyperglycemia (high blood glucose levels) 27. In contrast, lisinopril tends to have a neutral or even beneficial effect on these metabolic parameters, making the combination therapy a balanced approach for managing hypertension without severely impacting metabolic health 8.
Electrolyte Imbalance
Hydrochlorothiazide can cause significant changes in electrolyte levels, particularly potassium. Long-term use of hydrochlorothiazide has been associated with decreased serum potassium levels, which can be mitigated by the potassium-sparing effects of lisinopril 47. This combination helps maintain a more stable electrolyte balance over extended periods 9.
Cardiovascular Effects
Lisinopril and hydrochlorothiazide both contribute to lowering blood pressure, but their combination has been shown to be more effective than either drug alone. Long-term studies indicate that this combination therapy effectively reduces systolic and diastolic blood pressure, with a significant reduction in total peripheral resistance 510. However, the combination therapy may also lead to a slight increase in heart rate, particularly during the initial phase of treatment 3.
Hemodynamic and Rheological Effects
Lisinopril has been observed to improve blood rheology by increasing erythrocyte aggregation time and decreasing disaggregation shear stress, which may reduce the risk of thrombotic complications. Hydrochlorothiazide, on the other hand, tends to have the opposite effect, potentially increasing blood viscosity 6. The combination therapy balances these effects, providing a comprehensive approach to managing hypertension while minimizing adverse hemodynamic changes.
Conclusion
The long-term use of lisinopril-hydrochlorothiazide combination therapy is generally well-tolerated and effective in managing hypertension. While common side effects such as dizziness, cough, and nausea may occur, they are typically mild. The combination therapy also helps mitigate the metabolic and electrolyte imbalances often associated with hydrochlorothiazide alone. Overall, this combination offers a balanced and effective treatment option for long-term hypertension management, with a favorable side-effect profile.
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Most relevant research papers on this topic
Clinical experience with lisinopril. Observations on safety and tolerability.
Lisinopril is well-tolerated for long-term treatment of hypertension and congestive heart failure, with a similar side-effect profile to other ACE inhibitors, but taste disturbance is rarely observed.
Observational StudyAntihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide combination. A large multicenter study. Lisinopril-Hydrochlorothiazide Group.
Low-dose lisinopril-hydrochlorothiazide combination effectively reduces blood pressure and is well-tolerated, with the best results achieved with L/H12.5 and L/H25.
RCTA 52‐Week Comparison of Lisinopril, Hydrochlorothiazide, and Their Combination in Hypertension
Lisinopril is more effective than hydrochlorothiazide as a step-one drug, and the combination of the two drugs is more effective and safer than either drug alone for controlling blood pressure.
RCTEffects of hydrochlorothiazide, amiloride, and lisinopril on the metabolic, hemodynamic, and electrocardiographic responses to increased plasma epinephrine.
Pretreatment with hydrochlorothiazide, amiloride, and lisinopril may exacerbate the metabolic and electrocardiographic effects of epinephrine infusions, potentially increasing the risk of malignant ventricular arrhythmias.
RCTComparison of long-term hemodynamic effects at rest and during exercise of lisinopril plus sodium restriction versus hydrochlorothiazide in essential hypertension.
Lisinopril combined with sodium restriction or hydrochlorothiazide effectively reduces blood pressure due to decreased peripheral vascular resistance both at rest and during exercise in essential hypertensive patients.
RCTEffects of lisinopril and hydrochlorothiazide on platelet function and blood rheology in essential hypertension: a randomly allocated double-blind study
Chronic treatment with lisinopril may improve blood rheology, while hydrochlorothiazide shows opposite effects, requiring further investigation.
RCTLisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group.
Lisinopril is as effective as hydrochlorothiazide in treating obesity-associated hypertension, with angiotensin-converting enzyme inhibitors showing greater efficacy at lower doses and faster response rates.
RCT
Highly CitedMetabolic effects of lisinopril versus hydrochlorothiazide plus amiloride in essential hypertension
Lisinopril is a better choice for treating essential hypertension due to its minimal metabolic effects compared to diuretics, which may cause lipid and uric acid metabolism disorders.
RCTLisinopril versus lisinopril plus hydrochlorothiazide in essential hypertension.
Lisinopril alone or combined with hydrochlorothiazide effectively lowers blood pressure in patients with essential hypertension without major side effects.
RCTControlled Multicenter Study of the Antihypertensive Effects of Lisinopril, Hydrochlorothiazide, and Lisinopril plus Hydrochlorothiazide in the Treatment of 394 Patients with Mild to Moderate Essential Hypertension
Lisinopril alone effectively reduces blood pressure, while hydrochlorothiazide and LIS + HCTZ effectively lower blood pressure, with LIS showing better long-term control than HCTZ.
RCT
Large Human TrialHighly Cited