Hydrochlorothiazide / reserpine Side Effects
Some side effects of hydrochlorothiazide / reserpine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
For the Consumer
Applies to hydrochlorothiazide / reserpine: oral tablet
If you experience any of the following serious side effects, stop taking hydrochlorothiazide and reserpine and seek emergency medical attention:
an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives);
a very irregular heartbeat;
heart failure (shortness of breath, swelling of ankles or legs, sudden weight gain of 5 pounds or more);
abnormal bleeding or bruising;
yellow skin or eyes;
little or no urine.
Other, less serious side effects may be more likely to occur. Continue to take hydrochlorothiazide and reserpine and talk to your doctor if you experience
fatigue or drowsiness;
dizziness (avoid standing up too quickly and use caution when performing hazardous activities);
anxiety, depression, or nightmares;
diarrhea, nausea, vomiting, or an acid stomach (take hydrochlorothiazide and reserpine with food or milk if it upsets your stomach);
stuffy nose or a dry mouth (sucking on ice chips or sugarless hard candy may relieve a dry mouth);
tingling or numbness in your arms, legs, hands, or feet;
muscle weakness or cramps;
increased hunger or thirst;
sensitivity to sunlight; or
impotence or difficulty ejaculating.
Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.
For Healthcare Professionals
Applies to hydrochlorothiazide / reserpine: oral tablet
Psychiatric problems related to reserpine therapy can be serious. Depression occurs in 2% to 28% of patients, is more likely when daily doses exceed 0.5 mg, and can present at any time during therapy. Suicidal ideation has been reported. Reserpine-induced depression is quickly reversible if therapy is withdrawn as soon as the syndrome is recognized, but can persist for several months after drug discontinuation if the syndrome fully develops. Reserpine withdrawal psychosis has been reported.
The depressive syndrome usually consists of melancholy, loss of self confidence, early morning awakening, loss of libido, and reduced appetite.
A case of reserpine withdrawal psychosis has been reported. This uncommon condition may be due to dopamine receptor supersensitivity, which may develop during chronic reserpine therapy.
Since HCTZ may increase total serum cholesterol by 11%, LDL lipoprotein cholesterol by 12%, and VLDL lipoprotein cholesterol levels by 50%, and may reduce insulin secretion, HCTZ should be used with caution in diabetic patients and in those with hypercholesterolemia.
Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.
Metabolic side effects are commonly associated with hydrochlorothiazide (HCTZ), especially when doses greater than 50 mg per day are used. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50%, and may predispose patients to cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia, hyperglycemia, and elevated serum uric acid levels are also relatively common. HCTZ may increase serum cholesterol.
Hypersensitivity reactions to HCTZ, manifest as nausea, vomiting, diarrhea, and rash, are reported in less than 1% of patients. Case reports of acute pulmonary edema, interstitial cystitis, and interstitial nephritis, and anaphylaxis are associated with HCTZ.
A 68-year-old man with a history of myocardial infarction (MI) developed dyspnea, chest tightness, a low grade fever, dizziness, sweating, and vomiting associated with cyanosis, a mild leukocytosis, radiographic evidence of pulmonary edema, clinical evidence of hypovolemia, and respiratory acidosis. MI and infection were ruled out. The patient recovered after restoration of his intravascular volume with saline and albumin. The only precipitating factor per history was the ingestion of HCTZ, which the patient had taken without incident for two years. Rechallenge resulted in recurrent acute pulmonary edema. Other signs of hypersensitivity, such as rash and eosinophilia were absent.
Rare reports of reserpine-induced bronchospasm are believed to be due to inactivation of beta-adrenergic receptors, which can result in a marked potentiation of the bronchoconstrictive effect of histamine.
Respiratory side effects including nasal congestion are reported in 8% of patients who are receiving reserpine. Other respiratory system side effects are rare, and include approximately 30 case reports of acute noncardiogenic pulmonary edema associated with HCTZ and less than 10 case reports of bronchospasm associated with reserpine.
Nervous system side effects commonly associated with reserpine include sedation, lethargy (different from the psychiatric syndrome of depression), drowsiness, weakness, vertigo, insomnia, or headache in approximately 1% to 5% of patients. While reserpine is used to treat tardive dyskinesia, extrapyramidal movements may worsen upon withdrawal of therapy. A case of CNS hypertension, believed to be due to cerebral edema, is associated with reserpine. A single report of cerebrovascular insufficiency is associated with HCTZ-induced plasma volume contraction.
Increased parkinsonian movements upon reserpine withdrawal (as with neuroleptics) may be due to supersensitivity to dopamine as a result of increased dopamine receptors that developed during reserpine therapy.
Dermatologic reactions associated with HCTZ include case reports of erythema annular centrifugum, acute eczematous dermatitis, morbilliform and leukocytoclastic vasculitis. Thiazides may induce phototoxic dermatitis. In addition, a rare, distinct entity with clinical and laboratory features indistinguishable from those of subacute cutaneous lupus erythematosus is associated with HCTZ.
A 67-year-old white woman with hypothyroidism, hypercalcemia, depression, and hypertension developed facial erythema, headaches, tremors, confusion, and personality changes associated with a new positive ANA and anti-nRNP, and skin biopsy consistent with lupus erythematosus while taking HCTZ, levothyroxine, and amitriptyline. The eruption resolved upon discontinuation of HCTZ, but she later developed a higher ANA titer associated with symptomatic diffuse interstitial pulmonary infiltrates. She was successfully treated with corticosteroids.
Although HCTZ has been used to treat nephrogenic diabetes insipidus, a case report in which the drug was believed to have caused this condition has been reported.
Renal side effects including new or worsened renal insufficiency may occur due to HCTZ-induced intravascular volume depletion. Rare cases of interstitial nephritis are associated with HCTZ.
Cardiovascular side effects include hypotension in 8% and bradycardia (and rare cases of syncope with bradycardia) in 3% of patients. HCTZ-induced hypokalemia and hyponatremia may predispose patients to ventricular ectopy or complete AV heart block. A rare case of paroxysmal atrial tachycardia with block associated with reserpine in a patient who was not taking a digitalis preparation has been reported.
A woman with paroxysmal atrial tachycardia developed sinus pauses during reserpine therapy which were reproducible by carotid massage, except when isoproterenol was given. Reserpine is known to increase vagal tone and deplete cardiac catecholamines.
One patient, in a series of 231, had emergent hypertension, stroke, and thyrotoxic crisis. Reserpine 1 mg intramuscularly resulted in a blood pressure drop from 180/100 to an unmeasurable level. The patient recovered after isoproterenol therapy.
Gastrointestinal side effects due to unopposed parasympathetic activity produced by catecholamine depletion may lead to increased gastrointestinal motility and secretory activity. Because of this, new diarrhea or worsening of existing diarrhea or increased salivation are reported in 2% of patients. Increased appetite, abdominal pain, or vomiting are rarely reported. Rare cases of pancreatitis and acute cholecystitis have been associated with HCTZ.
Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in increased risk of cholesterol gallstone formation. Reports of bowel strictures associated with thiazide ingestion have been reported in the 1960's, although these patients were on a combination HCTZ-potassium product.
Genitourinary complaints are limited to impotence, reported in approximately 1% of male patients.
Immunologic side effects are rare. A single case of angioimmunoblastic lymphadenopathy has been associated with reserpine. In one study of 231 patients who were taking reserpine, only one case of a lupus-like syndrome was recorded. The patient has previously received hydralazine.
A 79-year-old woman with hypertension, who was taking reserpine, potassium, HCTZ, and ibuprofen, developed fatigue, anorexia, fever, night sweats, and weight loss. Associated laboratory findings showed anemia, lymphocytosis, thrombocytopenia, IgA kappa paraproteinemia, positive ANA, and a positive Coombs' test. Bone marrow biopsy, lymphangiography, and lymph node biopsy showed bone marrow lymphocytosis, enlarged foamy abdominal lymph nodes with irregular filling, and angioimmunoblastic lymphadenopathy, respectively. Within four days after discontinuation of reserpine (her other medications were continued), the paraprotein level normalized and the platelet count rose. After an additional nine months of prednisone therapy, all signs and symptoms resolved.
A 53-year-old man with hypertension developed nausea, vomiting, diarrhea, and progressive anorexia and weakness associated with scleral icterus, anemia with spherocytosis, dark red urine with proteinuria, bilirubinuria, and hemoglobinuria, and elevated lactic dehydrogenase levels 18 months after beginning HCTZ and methyldopa. Haptoglobin was less than 50 mg per dL. Direct and indirect Coombs tests were positive. The patient died suddenly. Autopsy revealed no obvious cause of death, left ventricular hypertrophy, and mild coronary atherosclerosis.
Hematologic side effects are rare. Cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with HCTZ.
Endocrinologic problems associated with thiazide diuretics include glucose intolerance and a potentially deleterious effect on the lipid profile. This may be important in some patients with or who are at risk for diabetes or coronary artery disease. Reserpine can induce hyperprolactinemia, resulting in gynecomastia in men, breast engorgement in women, and pseudolactation.
A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed an increased mean fasting blood glucose level after treatment. Withdrawal of thiazide therapy for seven months in 10 of the patients resulted in mean reductions of 10% in fasting blood glucose and 25% in the 2-hour glucose tolerance test value. A control group was not reported.
Musculoskeletal side effects are unusual. Myalgias and chills are occasionally reported during HCTZ-induced diuresis.
Oncologic concerns were raised after a large drug surveillance center in Boston reported an association between reserpine, a stimulator of prolactin, and breast cancer in 1974, which was partially, but not completely, confirmed in two similar centers in Europe. A critical review of the these studies elucidated several design flaws. Subsequent, controlled studies failed to show an association between reserpine and an increased incidence of breast carcinoma.
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