Pharmacology Made Simple : Combination of Antihypertensives : Zestoretic

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Zestoretic

This medication is used to treat high blood pressure.

Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

This product contains two medications: lisinopril and hydrochlorothiazide.

Lisinopril is an ACE inhibitor and works by relaxing blood vessels so that blood can flow more easily.

Hydrochlorothiazide is a "water pill" (diuretic) that causes one to make more urine, which helps body get rid of extra salt and water.

This product is used when one drug is not controlling blood pressure.



Lisinopril

Lisinopril is a drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of high blood pressure, heart failure, and after heart attacks and diabetic nerve pain.

It is also used for preventing kidney and eye complications in people with diabetes. Its indications, contraindications, and side effects are as those for all ACE inhibitors.


Caution should be used in the following populations, as dose adjustments may be required.

Kidney problems

The dose must be adjusted in those with poor kidney function. Dose adjustments may be required when creatinine clearance is less than or equal to 30mL/min.

Pregnancy and breastfeeding

Lisinopril has been assigned to pregnancy category D by the FDA. Animal and human data have revealed evidence of lethal harm to the embryo and teratogenicity associated with ACE inhibitors.

Birth defects have been associated with use of lisinopril in any trimester. However, there have been reports of death and increased toxicities to the fetus and newly born child with the use of lisinopril in the second and third trimesters.

The label states, "When pregnancy is detected, discontinue Zestril as soon as possible.Mothers should not breastfeed while taking this medication because of the lack of safety data that currently exists.


Contraindications

Treatment with lisinopril should be avoided for people who have a history of angioedema (hereditary or idiopathic) or who have diabetes and are taking aliskiren.

Adverse effects

People taking lisinopril for the treatment of hypertension may experience the following side effects:

Headache
Dizziness
Cough (
Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
Hyperkalemia
Fatigue
Diarrhea
Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens-Johnson syndrome.

Thiazide

Thiazide  is a type of molecule and a class of diuretics often used to treat hypertension (high blood pressure) and edema (such as that caused by heart failure, liver failure, or kidney failure).

When administered acutely thiazides lower blood pressure by causing diuresis, a fall in plasma volume and a reduction in cardiac output. However, after chronic use thiazides cause a reduction in blood pressure by lowering peripheral resistance (i.e. vasodilation).

The mechanism of this effect is uncertain but it may involve effects on 'whole body' or renal autoregulation, or direct vasodilator actions either through inhibition of carbonic anhydrase or by desensitizing the vascular smooth muscle cells to the rise in intracellular calcium induced by norepinephrine.

Other Uses :

Thiazides also lower urinary calcium excretion, making them useful in preventing calcium-containing kidney stones. This effect is associated with positive calcium balance and is associated with an increase in bone mineral density and reductions in fracture rates attributable to osteoporosis.

By a lesser understood mechanism, thiazides directly stimulate osteoblast differentiation and bone mineral formation, further slowing the course of osteoporosis.

Because of their promotion of calcium retention, thiazides are used in the treatment of

Dent's disease
Hypocalcemia
Nephrolithiasis (idiopathic hypercalciuria)
Bromide intoxication
Nephrogenic diabetes insipidus


Contraindications

Hypotension
Allergy to sulphur-containing medications
Gout
Renal failure
Lithium therapy
Hypokalemia
May worsen diabetes

Thiazides reduce the clearance of uric acid since they compete for the same transporter, and therefore raise the levels of uric acid in the blood. Hence they are prescribed with caution in patients with gout or hyperuricemia

Chronic administration is associated with hyperglycemia.

Thiazides cause loss of blood potassium, while conserving blood calcium.

Thiazides can decrease placental perfusion and adversely affect the fetus so should be avoided in pregnancy.

Side Effects

Hypokalemia

Thiazide diuretics reduces potassium concentration in blood through two indirect mechanisms: inhibition of sodium-chloride symporter at distal convoluted tubule of a nephron and stimulation of aldosterone that activates Na+/K+-ATPase at collecting duct.

Inhibition of sodium-chloride symporter increases availability of sodium and chloride in urine. When the urine reaches the collecting duct, the increase in sodium and chloride availability activates Na+/K+-ATPase, which increases the absorption of sodium and excretion of potassium into the urine.

Reduction of Total Body Volume

Long term administration of thiazide diuretics reduces total body blood volume. This activates the renin–angiotensin system, stimulates the secretion of aldosterone, thus activating Na+/K+-ATPase, increasing excretion of potassium in urine. Therefore, ACE inhibitor and thiazide combination is used to prevent hypokalemia.

Other Side Effects : 

Hyperglycemia
Hyperlipidemia
Hyperuricemia
Hypercalcemia
Hyponatremia
Hypomagnesemia
Hypocalciuria