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Polythiazide / reserpine Side Effects

Applies to polythiazide / reserpine: oral tablet.

Cardiovascular

Cardiovascular side effects include hypotension in 8% and bradycardia in 3% of patients. Some patients who develop hypotension or bradycardia experience syncope. This may be more likely in elderly patients. Cardiac arrhythmias, including ventricular ectopy and complete AV heart block, have been associated with thiazide-induced hypokalemia. 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.[Ref]

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 to deplete cardiac catecholamines.[Ref]

Metabolic

Metabolic side effects of polythiazide, as with other thiazide diuretics, include hypokalemia, hyponatremia, hypochloremia, hypercalcemia, hypercholesterolemia, and hyperuricemia. Significant reductions in the serum potassium concentration (decreases of 0.5 mEq/L or more) have been observed in up to 50% of patients who are taking moderate doses of thiazide diuretics. This reduction in serum potassium can predispose some patients to develop cardiac arrhythmias.[Ref]

Some of the metabolic changes associated with thiazide diuretics may be significant in patients with underlying cardiac arrhythmias (hypokalemia), coronary artery disease (hypercholesterolemia), gout (hyperuricemia), or liver disease (hyponatremia and hypokalemia).[Ref]

Respiratory

Respiratory side effects including nasal congestion occurs in 8% of patients who are taking reserpine. A rare respiratory system side effect associated with reserpine is bronchospasm.[Ref]

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.[Ref]

Nervous system

Nervous system side effects 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, has been associated with reserpine.[Ref]

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.[Ref]

Hypersensitivity

Hypersensitivity reactions to thiazide diuretics have been reported in less than 1% of patients. While most allergic reactions present as rash with nausea and vomiting, rare cases of acute pulmonary edema, interstitial cystitis, interstitial nephritis, and anaphylaxis have been associated with some thiazide diuretics.[Ref]

Psychiatric

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 reserpine therapy.[Ref]

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. Reserpine-induced suicidal ideation and withdrawal psychosis have 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. Limited data suggest an association between psychiatric depression and thiazide diuretics. These data are uncontrolled observations and have not been substantiated.[Ref]

Dermatologic

Dermatologic reactions to thiazides include erythema annular centrifugum, acute eczematous dermatitis, and 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 has been associated with a related drug, hydrochlorothiazide.[Ref]

Gastrointestinal

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 have been reported in 2% of patients. Increased appetite, abdominal pain, or vomiting have rarely been associated with reserpine. There have been rare cases of pancreatitis and acute cholecystitis associated with thiazide diuretics.[Ref]

Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in increased risk of cholesterol gallstone formation. Cases of bowel strictures associated with thiazide ingestion were reported in the 1960's, although these patients were on a combination hydrochlorothiazide-potassium product.[Ref]

Renal

Renal side effects including new or worsened renal insufficiency may occur due to polythiazide-induced intravascular volume depletion. Rare cases of interstitial nephritis have been associated with some thiazide diuretics.[Ref]

Endocrine

Endocrinologic problems have been associated with both drugs. Reserpine-induced hyperprolactinemia can result in gynecomastia in men and breast engorgement or pseudolactation in women. Thiazide diuretics can induce glucose intolerance and produce 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.[Ref]

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 7 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.[Ref]

Genitourinary

Genitourinary complaints are limited to impotence, reported in approximately 5% of male patients who are taking reserpine.[Ref]

Hematologic

Hematologic side effects are rare. Cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated either with polythiazide or related thiazide agents.[Ref]

A 2.5-year-old male with anasarca developed cyanosis and oral ulcerations associated with laboratory evidence of pancytopenia 15 days after beginning polythiazide (dose not available). A bone marrow aspiration revealed general hypoplasia with absence of megakaryocytes and blast cells. The child died from persistent hemorrhaging and infections despite prednisolone and antimicrobial therapy.[Ref]

Immunologic

Immunologic side effects are rare. A single case of angioimmunoloblastic lymphadenopathy has been associated with reserpine. In one study of 231 patients, only one case of a lupus-like syndrome was observed. The patient had previously received hydralazine.[Ref]

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. 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 of her signs and symptoms resolved.[Ref]

Oncologic

Oncologic concerns were raised after a large drug surveillance center in Boston reported an association between reserpine, a stimulator of prolactin, and breast cancer. These data were partially, but not completely, confirmed in two similar centers in Europe. A critical review of these studies elucidated several design flaws. Subsequent, controlled studies failed to show an association between reserpine and an increased incidence of breast carcinoma.[Ref]

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