Action and Spectrum

Mechanism of action

hydrochlorothiazide is a thiazide diuretic that works by inhibiting the reabsorption of sodium and chloride ions in the renal tubules, leading to increased excretion of these electrolytes and water. This leads to a decrease in blood volume, which helps lower blood pressure

On the other hand, aliskiren is a direct renin inhibitor that works by inhibiting the activity of the renin enzyme in the renin-angiotensin-aldosterone system (RAAS). This system plays a crucial role in regulating blood pressure, and by inhibiting renin, aliskiren reduces the formation of angiotensin I, which is a precursor to the vasoconstrictor angiotensin II. By reducing the levels of angiotensin II, aliskiren leads to vasodilation and a decrease in blood pressure

Spectrum

hydrochlorothiazide is a diuretic that increases the excretion of sodium and water, leading to a decrease in blood volume and a subsequent reduction in blood pressure. hydrochlorothiazide is also used to treat edema (swelling), and heart failure
aliskiren is a direct renin inhibitor that blocks the activity of renin, an enzyme that regulates blood pressure.

By inhibiting renin, aliskiren reduces the production of angiotensin II, a potent vasoconstrictor that can increase blood pressure. aliskiren is primarily used to treat hypertension and is sometimes used in combination with other antihypertensive medications
Both aliskiren and hydrochlorothiazide have a specific spectrum of activity related to their mechanism of action.

While hydrochlorothiazide directly affects the renal tubular mechanisms of electrolyte reabsorption, leading to sodium and chloride excretion, aliskiren directly inhibits the renin-angiotensin system by blocking the activity of renin. As such, the spectrum of activity of these medications is focused on their ability to lower blood pressure, reduce edema, and treat heart failure

Drug Interaction

Adverse Reaction

Frequency defined:

10%

Increased BUN

1-10%

Vertigo (1%)

Increased uric acid level (2%)

Diarrhea (2%)

Flu-like syndrome (2%)

Weakness (1%)

Dizziness (2%)

Hypokalemia (2%)

Hyperkalemia (1%)

Increased ALT (1%)

Cough (1%)

Cough (1%)

Aliskiren

Diarrhea (2.3%)

Rash (1%)

Increased BUN (≤ 7%)

Cough (1.1%)

Increased creatinine kinase (1%)

Hyperkalemia (≤1%)

<1%

Decreased hemoglobin

Decreased hematocrit

Frequency undefined

Hydrochlorothiazide

AnorexiaEpigastric distress

Orthostatic hypotension

Anaphylaxis

Confusion

Stevens-Johnson syndrome

Dizziness

Hyperuricemia

Post-marketing reports

Aliskiren

Hyponatremia

Vomiting

Hydrochlorothiazide

Non melanoma skin cancer

Black Box Warning

Black box warning

Drugs that have an immediate effect on the renin-angiotensin system can harm or even kill a growing baby. If pregnancy is found, stop taking the medication as soon as possible

Contraindication / Caution

Contraindications

Hypersensitivity to aliskiren, hydrochlorothiazide, or sulfonamides: Patients with known hypersensitivity to any of these medications should not take them

• Anuria: aliskiren and hydrochlorothiazide should not be used in patients with anuria, where the kidneys cannot produce urine
• Concomitant use with ACEIs or ARBs in patients with diabetes: In patients with diabetes, the concomitant use of aliskiren with ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is not recommended. This is because the combination may increase the risk of renal impairment, hypotension, and hyperkalemia

Caution

• Hypotension: Both aliskiren and hydrochlorothiazide can cause a decrease in blood pressure, which may be more pronounced in patients who are volume-depleted or have low blood pressure, to begin with. Patients should be monitored for signs of hypotension, and the dose may need to be adjusted if necessary.
• Hyperkalemia: aliskiren and hydrochlorothiazide may cause an increase in serum potassium levels, which can be dangerous in patients with impaired renal function, diabetes, or other conditions that increase the risk of hyperkalemia. Patients should monitor their serum potassium levels regularly, and the dose may need to be adjusted if necessary
• Renal impairment: aliskiren and hydrochlorothiazide may impair renal function, especially in patients with pre-existing renal impairment or those taking other medications that affect the renin-angiotensin-aldosterone system. Renal function should be monitored closely in these patients
• Electrolyte imbalances: hydrochlorothiazide can cause electrolyte imbalances, especially hypokalemia, which may increase the risk of arrhythmias. Patients should have their electrolyte levels monitored regularly, and the dose may need to be adjusted if necessary
• Gout: hydrochlorothiazide may exacerbate gout or increase the risk of developing gout, especially in patients with a history of gout. Patients should be monitored for signs and symptoms of gout
  Pregnancy and breast-feeding: aliskiren and hydrochlorothiazide should not be used during pregnancy or breast-feeding unless the potential benefits outweigh the potential risks

Pregnancy / Lactation

Pregnancy consideration:

aliskiren and hydrochlorothiazide should not be used during pregnancy or breast-feeding unless the potential benefits outweigh the potential risks

Lactation: Excretion of the drug in human breast milk is unknown

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology

aliskiren is a direct renin inhibitor, which blocks the activity of renin, an enzyme involved in the production of angiotensin II, a hormone that causes vasoconstriction and increases blood pressure. By inhibiting renin, aliskiren reduces the levels of angiotensin II, leading to vasodilation and a decrease in blood pressure. aliskiren is taken orally and is rapidly absorbed, reaching peak plasma concentrations in 1-3 hours. It is primarily eliminated through faeces.

hydrochlorothiazide is a thiazide diuretic that increases the kidneys’ excretion of sodium and water. hydrochlorothiazide works by inhibiting the reabsorption of sodium and chloride ions in the distal tubules of the kidney, leading to increased excretion of sodium, chloride, and water, and ultimately reducing blood volume and blood pressure. hydrochlorothiazide is also taken orally and is rapidly absorbed, reaching peak plasma concentrations in 1-2 hours. It is primarily eliminated through urine.

aliskiren and hydrochlorothiazide can be used in combination therapy to achieve better blood pressure control than either drug alone. Combining the renin inhibition of aliskiren and the diuretic effects of hydrochlorothiazide, the drugs work together to lower blood pressure by reducing blood volume and systemic vascular resistance

Pharmacodynamics

As a direct renin inhibitor, aliskiren blocks the conversion of angiotensinogen to angiotensin I, which ultimately reduces the production of angiotensin II. This decreases vasoconstriction and reduces aldosterone production, resulting in a decrease in blood pressure. aliskiren also increases the activity of the vasodilator, bradykinin hydrochlorothiazide, as a thiazide diuretic, inhibits sodium and chloride reabsorption in the kidney’s distal tubules. This increases the excretion of sodium and chloride and reduces blood volume, which in turn decreases blood pressure. When used in combination, aliskiren, and hydrochlorothiazide work synergistically to lower blood pressure by reducing blood volume and systemic vascular resistance. The combination is more effective than either drug alone, making it a useful option in the treatment of hypertension

Pharmacokinetics

Absorption

Rapidly absorbed after oral administration with a bioavailability of 2.5-3%

Distribution

Widely distributed in the body

Metabolism

Metabolized by CYP3A4 in the liver to inactive metabolites

Elimination/Excretion

Excreted primarily in the urine (about 25% as unchanged drug) and faeces. Both aliskiren and hydrochlorothiazide have a long half-life, with aliskiren having a half-life of 24 hours and hydrochlorothiazide having a half-life of 6-15 hours. They are eliminated primarily by the kidneys

Adminstartion

Administration

aliskiren and hydrochlorothiazide are commonly used to treat hypertension (high blood pressure). aliskiren is a direct renin inhibitor that helps to relax blood vessels, while hydrochlorothiazide is a diuretic that helps to reduce the fluid volume in the body

Patient Information Leaflet

Patient information leaflet

Generic Name: hydrochlorothiazide/ aliskiren

Pronounced: [ HYE-droe-KLOR-oh-THYE-a-zide-and-a-LIS-ke-rin ]

Why do we use hydrochlorothiazide/ aliskiren?

aliskiren and hydrochlorothiazide are combined to treat hypertension (high blood pressure). Aliskiren is a direct renin inhibitor that helps to relax blood vessels, while hydrochlorothiazide is a diuretic that helps to reduce the fluid volume in the body. By working together, they can help lower blood pressure and reduce the risk of hypertension-related complications, such as heart attack and stroke.