Viskazide

Viskazide Uses, Dosage, Side Effects, Food Interaction and all others data.

Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.

Pindolol is a first generation non-selective beta blocker used in the treatment of hypertension. Early research into the use of pindolol found it had chronotropic effects, and so further investigation focused on the treatment of arrhythmia. Research into pindolol's use in the treatment of hypertension began in the early 1970s.

Pindolol was granted FDA approval on 3 September 1982.

Pindolol is a nonselective beta blocker indicated in the management of hypertension and prophylaxis of angina. It has a short duration of action as it is given twice daily, and a wide therapeutic window as doses can range from 10-60 mg/day. Patients should be counselled regarding the risk of cardiac failure, exacerbating ischemic heart disease with sudden withdrawal, nonallergic bronchospasm, masking hypoglycemia in diabetics, and masking hyperthyroidism.

Viskazide
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Viskazide
Generic	pindolol + hydrochlorothiazide
Type
Therapeutic Class
Manufacturer
Available Country	Canada, United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Hydrochlorothiazide is used for-

Edema associated with congestive heart failure, hepatic cirrohosis, various forms of renal dysfunction and corticosteroid and estrogen therapy
Management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe form of hypertension
Management of diabetes insipidus
Management of proximal renal tubular acidosis
Idiopathic hypercalciuria and calcium nephrolithiasis, osteoporosis and exercise induced hyperkalemia

Pindolol is a beta adrenoceptor antagonist used to treat hypertension, edema, ventricular tachycardias, and atrial fibrillation.

Pindolol is indicated in the management of hypertension. In Canada, it is also indicated in the prophylaxis of angina.

Viskazide is also used to associated treatment for these conditions: Acidosis, Renal Tubular, Calcium Nephrolithiasis, Cirrhosis of the Liver, Congestive Heart Failure (CHF), Diabetes Insipidus, Edema, High Blood Pressure (Hypertension), Hypertension,Essential, Hypokalemia caused by diuretics, Nephrotic Syndrome, Premenstrual tension with edema, Sodium retention, Stroke, Prophylaxis of preeclampsiaAngina Pectoris, Atrial Fibrillation, Depression, High Blood Pressure (Hypertension)

How Viskazide works

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).

Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.

Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

The beta-1 adrenoceptor is a G-protein-coupled receptor. Agonism of the beta-1 adrenoceptor allows the Gs subunit to upregulate adenylyl cyclase, converting ATP to cyclic AMP (cAMP). Increased concentrations of cAMP activate cAMP-dependant kinase A, phosphorylating calcium channels, raising intracellular calcium, increasing calcium exchange through the sarcoplasmic reticulum, and increasing cardiac inotropy. cAMP-dependant kinase A also phosphorylates myosin light chains, increasing smooth muscle contractility. Increased smooth muscle contractility in the kidney releases renin.

Pindolol is a non-selective beta blocker. Blocking beta-1 adrenergic receptors in the heart results in decreased heart rate and blood pressure. By blocking beta-1 receptors in the juxtaglomerular apparatus, pindolol inhibits the release of renin, which inhibits angiotensin II and aldosterone release. Reduced angiotensin II inhibits vasoconstriction and reduced aldosterone inhibits water retention.

Beta-2 adrenoceptors located in the kidneys and peripheral blood vessels use a similar mechanism to activate cAMP-dependant kinase A to increase smooth muscle contractility. Blocking of the beta-2 adrenoceptor relaxes smooth muscle, leading to vasodilation.

Dosage

Viskazide dosage

Adults-

For Edema: The usual adult dosage is 25 to 100 mg daily as a single or divided dose.

For Control of Hypertension: The usual initial dose in adults is 25 mg daily given as a single dose. The dose may be increased to 50 mg daily, given as a single or two divided doses. Doses above 50 mg are often associated with marked reductions in serum potassium. In some patients (especially the elderly) an initial dose of 12.5 mg daily may be sufficient.

Infants and children-

For diuresis and for control of hypertension: The usual pediatric dosage is 1 to 2 mg/kg/day in single or two divided doses, not to exceed 37.5 mg per day in infants up to 2 years of age or 100 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 3 mg/kg/day in two divided doses may be required.

Side Effects

Generally, Hydrochlorothiazide is well tolerated. However, a few side effects may occur like weakness, restlessness, dizziness, headache, fever, diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia, and hypotension. In rare case hyperglycemia, glycosuria, hyperuricemia and muscle spasm may occur.

Toxicity

The oral LD₅₀ of hydrochlorothiazide is >10g/kg in mice and rats.

Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.

Patients experiencing an overdose may experience excessive bradycardia, cardiac failure, hypotension, and bronchospasm. Initiate treatment with symptomatic and supportive measures.

Precaution

Thiazides should be used with caution in patients with severe renal disease, impaired hepatic function or progressive liver disease and gout.

Interaction

Alcohol, Barbiturates, or Narcotics: Potentiation of orthostatic hypotension may occur.

Antidiabetic Drugs (oral agents and insulin): Thiazides can impair control of diabetes mellitus by diet and antidiabetic Drugs. Antihypertensive Drugs: Additive effect or potentiation.

Volume of Distribution

The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.

The volume of distribution of pindolol is approximately 2-3 L/kg.

Elimination Route

An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a T_max of 1-5 hours, and a C_max of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, C_max is 20% lower, and T_max increases from 1.6 to 2.9 hours.

The mean oral bioavailability of pindolol is 87-92%. A 5 mg oral dose reaches a C_max of 33.1 ± 5.2 ng/mL, with a T_max of 1-2 hours.

Half Life

The plasma half life of hydrochlorothiazide is 5.6-14.8h.

The half life of pindolol varies from 3-4 hours but can be as high as 30 hours in patients with cirrhosis of the liver.

Clearance

The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.

In otherwise healthy patients, the systemic clearance of pindolol is 400-500 mL/min. In patients with cirrhosis, the clearance of pindolol varies from 50-300 mL/min.

Elimination Route

Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide.

80% of an oral dose is eliminated in the urine, with 25-40% of the dose as the unchanged parent compound. 6-9% of an intravenous dose is eliminated in the feces. Overall, 60-65% of a dose is eliminated as glucuronide and sulfate metabolites.

Pregnancy & Breastfeeding use

Pregnancy: Evidence of fetal risk in hydrochlorothiazide therapy is found, but it is indicated if benefits outweigh risks. Thiazides are indicated in pregnancy when edema is due to pathologic causes.\

Lactation: Neonatal side effects have been seen incase of hydrochlorothiazide therapy and therefore it is not recommended.

Contraindication

Hydrochlorothiazide is contraindicated to the patients of anuria and those who are sensitive to hydrochlorothiazide or to other sulfonamide-derived drugs. Therapy is not to be initiated in diabetes mellitus.

Special Warning

Elderly: in some patients specially the elderly an initial dose of 12.5 mg daily may be sufficient.

Children: An initial dose for children has been 1 to 2 mg per kg body-weight in 2 divided doses. Infants under 6 months may need doses upto 3 mg per kg daily.

Acute Overdose

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. Rarely, autoimmune hemolytic anemia and other hypersensitivity reactions may complicate the picture.

In the event of over dosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. Hemodialysis can be used successfully to treat severe intoxication.