Usage
Hydrochlorothiazide + Quinapril is prescribed for the treatment of hypertension (high blood pressure). Lowering blood pressure reduces the risk of stroke, heart attack, and other cardiovascular complications. It is not indicated for initial therapy, and patients should generally be titrated on individual components before switching to the fixed combination if it suits their determined dosages.
Its pharmacological classification is a combination of a thiazide diuretic (hydrochlorothiazide) and an angiotensin-converting enzyme (ACE) inhibitor (quinapril).
Mechanism of Action:
Quinapril blocks the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This vasodilation helps lower blood pressure and reduces cardiac workload. Hydrochlorothiazide increases the excretion of sodium and water by the kidneys, further contributing to blood pressure reduction.
Alternate Names
This combination does not have an international nonproprietary name (INN). It is often referred to simply as quinapril/hydrochlorothiazide or hydrochlorothiazide/quinapril.
Brand Names: Accuretic (discontinued), Quinaretic
How It Works
Pharmacodynamics: Quinapril’s primary effect is vasodilation through the inhibition of angiotensin II formation. Hydrochlorothiazide increases sodium and chloride excretion in the distal renal tubule, causing diuresis, which also lowers blood pressure.
Pharmacokinetics:
- Absorption: Quinapril is rapidly absorbed after oral administration and is converted to its active metabolite, quinaprilat. Hydrochlorothiazide is also well-absorbed orally.
- Metabolism: Quinapril is metabolized to quinaprilat in the liver. Hydrochlorothiazide is not extensively metabolized.
- Elimination: Quinaprilat is primarily excreted renally. Hydrochlorothiazide is excreted unchanged by the kidneys.
Mode of Action: Quinapril competitively binds to and inhibits ACE, thereby decreasing the production of angiotensin II. This results in vasodilation, decreased aldosterone secretion, and reduced sodium and water retention. Hydrochlorothiazide acts on the distal convoluted tubule, inhibiting sodium reabsorption, leading to increased excretion of sodium, chloride, and water.
Receptor Binding/Enzyme Inhibition: Quinapril directly inhibits ACE. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule.
Elimination Pathways: Quinapril (as quinaprilat) is primarily excreted renally. Hydrochlorothiazide is also excreted renally.
Dosage
Standard Dosage
Adults:
Initial dose: Quinapril 10 mg/Hydrochlorothiazide 12.5 mg once daily. Dosage can be adjusted based on blood pressure response, up to a maximum of Quinapril 80 mg/Hydrochlorothiazide 50 mg daily. Dose adjustments should typically occur at intervals of 2-4 weeks or as directed by a physician.
Children:
Use in children is not recommended as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Initial dose of quinapril should be lower, typically 10 mg daily, with careful titration based on response.
- Patients with Renal Impairment: Use with caution; dosage adjustment may be necessary based on creatinine clearance. Not recommended for patients with CrCl < 25mL/min.
- Patients with Hepatic Dysfunction: Use with caution.
- Patients with Comorbid Conditions: Consider potential interactions with other medications and conditions like diabetes, heart failure, etc.
Clinical Use Cases Dosage guidelines for clinical use cases such as intubation, surgical procedures, mechanical ventilation, and other emergency situations are not specifically established for Hydrochlorothiazide + Quinapril. In these situations, blood pressure management should be individualized based on patient needs and under the close supervision of a healthcare professional.
Side Effects
Common Side Effects
- Cough
- Headache
- Dizziness
- Fatigue
- Upper respiratory tract infections
Rare but Serious Side Effects
- Angioedema (swelling of the face, lips, tongue, throat)
- Hypotension
- Renal failure
- Electrolyte imbalances (hyperkalemia, hypokalemia)
- Liver dysfunction
- Blood disorders (agranulocytosis, neutropenia, thrombocytopenia)
Long-Term Effects
May cause chronic complications such as renal impairment with prolonged use. Close monitoring of renal function and electrolyte levels is essential in long-term use.
Adverse Drug Reactions (ADR)
Serious ADRs include angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis. These conditions warrant immediate discontinuation of the drug and prompt medical intervention.
Contraindications
- Hypersensitivity to quinapril, hydrochlorothiazide, or any component of the formulation
- History of angioedema related to ACE inhibitor therapy
- Anuria (no urine output)
- Concurrent use of sacubitril/valsartan
- Pregnancy
Drug Interactions
- Other antihypertensive medications (additive hypotensive effects)
- Potassium supplements or salt substitutes (risk of hyperkalemia)
- Lithium (increased lithium levels)
- NSAIDs (may reduce antihypertensive effect and increase risk of renal impairment)
- Alcohol (may increase risk of hypotension)
Pregnancy and Breastfeeding
Pregnancy Safety Category: D (contraindicated)
Hydrochlorothiazide + Quinapril can cause fetal harm and is contraindicated during pregnancy. It should be discontinued as soon as pregnancy is detected.
This medication is excreted in breast milk and may cause adverse effects in the nursing infant. It is generally recommended to discontinue breastfeeding or the medication.
Drug Profile Summary
- Mechanism of Action: ACE inhibition (quinapril) and diuresis (hydrochlorothiazide)
- Side Effects: Cough, headache, dizziness, fatigue, angioedema, hypotension, renal impairment
- Contraindications: Hypersensitivity, angioedema history, anuria, pregnancy, concurrent use of sacubitril/valsartan
- Drug Interactions: Other antihypertensives, potassium supplements, lithium, NSAIDs, alcohol
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; caution advised during breastfeeding.
- Dosage: Initial: Quinapril 10mg/HCTZ 12.5mg; Max: Quinapril 80mg/HCTZ 50mg
- Monitoring Parameters: Blood pressure, renal function, electrolytes
Popular Combinations
Hydrochlorothiazide + Quinapril is already a combination product. Combining it with a third antihypertensive agent may be done in some cases under close monitoring, but is generally not recommended.
Precautions
- General Precautions: Monitor renal function, electrolytes (especially potassium), and blood pressure regularly.
- Specific Populations: Caution in elderly and patients with renal or hepatic impairment. Contraindicated in pregnancy.
- Lifestyle Considerations: Limit alcohol intake; avoid excessive sun exposure.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydrochlorothiazide + Quinapril?
A: The initial dose is typically Quinapril 10 mg/Hydrochlorothiazide 12.5 mg once daily. The maximum dose is Quinapril 80 mg/Hydrochlorothiazide 50 mg daily.
Q2: What are the common side effects?
A: Common side effects include cough, headache, dizziness, and fatigue.
Q3: Is Hydrochlorothiazide + Quinapril safe during pregnancy?
A: No, it is contraindicated during pregnancy due to the risk of fetal harm.
Q4: What are the serious side effects I should watch out for?
A: Angioedema, hypotension, renal impairment, and electrolyte imbalances are potential serious side effects.
Q5: Can this drug be used in children?
A: Safety and effectiveness in children have not been established, so use is not recommended.
Q6: What should I do if a patient develops angioedema?
A: Discontinue the drug immediately and provide supportive care. Angioedema can be life-threatening and requires prompt medical attention.
Q7: How does renal impairment affect the dosage of this combination?
A: Use with caution in renal impairment. Dosage adjustment may be required based on creatinine clearance.
Q8: Are there any drug interactions I should be aware of?
A: Yes, clinically significant interactions can occur with other antihypertensives, potassium supplements, lithium, and NSAIDs.
Q9: What monitoring is required during treatment?
A: Monitor blood pressure, renal function tests (BUN, serum creatinine), and electrolyte levels (especially potassium) regularly during treatment.
