Cadura XL tablets

Indications

• Hypertension
• Benign prostatic hyperplasia
• Acute urinary retention associated with benign prostatic hyperplasia

Dosage

Adults: For hypertension, the initial dose is 1 mg once daily, which may be increased to 2 mg after 1 to 2 weeks based on response. The maximum dose is 16 mg once daily. For benign prostatic hyperplasia, the initial dose is 2.5 mg once daily, titrated as necessary, with a

Mechanism of action

Doxazosin selectively inhibits the postsynaptic alpha-1 receptors on vascular smooth muscle by nonselectively blocking the alpha-1a, alpha-1b, and alpha-1d subtypes. This action decreases systemic peripheral vascular resistance, reducing blood pressure with minimal effects on heart rate. It also relaxes smooth muscle in the prostate and bladder neck, relieving urinary obstruction symptoms associated with benign prostatic hypertrophy.

Pharmacodynamics

Doxazosin decreases both standing and supine blood pressure and relieves urinary symptoms of BPH through alpha-1 receptor inhibition. It may induce hypotension, particularly upon standing, which can lead to dizziness or lightheadedness. The risk of these effects is heightened with dose adjustments or prolonged intervals between doses. Initial treatment should start at a low dose, with gradual titration to the effective dose. Doxazosin has also been shown to positively influence plasma lipid levels.

Pharmacokinetics

Doxazosin is well absorbed after oral administration, with peak plasma concentrations occurring within 2 to 3 hours. It undergoes extensive hepatic metabolism and has a half-life of approximately 22 hours, allowing for once-daily dosing. The drug is primarily excreted in the urine, with about 4% unchanged. Caution is advised in patients with liver impairment, as clearance may be reduced.

Contra-indications

• History of postural hypotension
• Severe hepatic impairment
• History of micturition syncope

Adverse effects

• Dizziness
• Asthenia
• Dry mouth
• Headache
• Malaise
• Nausea
• Postural hypotension
• Priapism
• Gastrointestinal discomfort

Interactions

• Cobicistat increases exposure to doxazosin
• Idelalisib increases exposure to doxazosin
• Clarithromycin increases exposure to doxazosin

Precautions

• Care with initial dose due to risk of postural hypotension
• Monitor for dizziness, especially upon standing
• Use caution in patients with heart failure or pulmonary edema
• Monitor in patients undergoing cataract surgery due to risk of intra-operative floppy iris syndrome

Pregnancy

Doxazosin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines.

Breast-feeding

Doxazosin is not recommended during breastfeeding; caution is advised.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Immediate-release tablet (2.5 mg, 5 mg, 10 mg)
• Modified-release tablet (4 mg, 8 mg)

Indications

• Hypotension
• Vasopressor support during anesthesia
• Management of shock states

Dosage

Children: Refer to specific clinical guidelines or resources for dosing information.

Adults: Refer to specific clinical guidelines or resources for dosing information.

Mechanism of action

Mesyltate exerts its effects by selectively stimulating alpha-1 adrenergic receptors on vascular smooth muscle, leading to vasoconstriction. This increases systemic vascular resistance and elevates blood pressure. Additionally, it has some indirect effects on the release of norepinephrine, enhancing sympathetic tone.

Pharmacodynamics

The activation of alpha-1 adrenergic receptors results in smooth muscle contraction and vasoconstriction, which effectively increases blood pressure. The drug's sympathomimetic activity can also stimulate heart rate through reflex mechanisms, although its primary action is on vascular smooth muscle.

Pharmacokinetics

Mesyltate is administered intravenously or intramuscularly and is rapidly distributed throughout the body. It has a short half-life due to its metabolism by catechol-O-methyltransferase and monoamine oxidase. The drug is primarily eliminated through hepatic metabolism and renal excretion of metabolites.

Contra-indications

• Hypersensitivity to mesyltate or any component of the formulation
• Severe myasthenia gravis
• Acute respiratory failure
• Glaucoma

Adverse effects

• Dry mouth
• Blurred vision
• Constipation
• Confusion
• Dizziness
• Nausea
• Urinary retention

Interactions

• Anticholinergic agents may increase side effects
• CNS depressants may enhance sedation
• Antihistamines may have additive anticholinergic effects

Precautions

• Use with caution in patients with cardiovascular disease
• Caution in patients with renal impairment
• Monitor for signs of urinary retention
• Assess for potential drug interactions

Pregnancy

Use in pregnancy only if the potential benefit justifies the potential risk to the fetus, as animal studies have shown adverse effects.

Breast-feeding

Caution is advised. Limited data suggest that mesyltate may enter breast milk, and effects on the nursing infant are not known.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Formulations

• Tablets
• Oral solution

Mechanism of action

Doxazosin selectively inhibits the postsynaptic alpha-1 receptors on vascular smooth muscle by nonselectively blocking the alpha-1a, alpha-1b, and alpha-1d subtypes. This action on blood vessels decreases systemic peripheral vascular resistance, reducing blood pressure, exerting minimal effects on the heart rate due to its receptor selectivity. Norepinephrine-activated alpha-1 receptors located on the prostate gland and bladder neck normally cause contraction of regional muscular tissue, obstructing urinary flow and contributing to the symptoms of benign prostatic hypertrophy. Alpha-1 antagonism causes smooth muscle relaxation in the prostate and bladder, effectively relieving urinary frequency, urgency, weak urinary stream, and other unpleasant effects of BPH. Recently, doxazosin was found to cause apoptosis of hERG potassium channels in an in vitro setting, possibly contributing to a risk of heart failure with doxazosin use.

Pharmacodynamics

Doxazosin decreases standing and supine blood pressure and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors. Doxazosin may cause hypotension due to its pharmacological actions. This frequently occurs in the upright position, leading to a feeling of dizziness or lightheadedness. The first dose of doxazosin may lead to such effects, however, subsequent doses may also cause them. The risk of these effects is particularly high when dose adjustments occur or there are long intervals between doxazosin doses. Treatment should be started with the 1 mg dose of doxazosin, followed by slow titration to the appropriate dose. Patients must be advised of this risk and to avoid situations in which syncope and dizziness could be hazardous following the ingestion of doxazosin. Interestingly doxazosin exerts beneficial effects on plasma lipids. It reduces LDL (low-density lipoprotein) cholesterol and triglyceride levels and increases HDL (high-density lipoprotein) cholesterol levels. A note on priapism risk In rare cases, doxazosin and other alpha-1 blockers may cause priapism, a painful occurrence of persistent and unrelievable penile erection that can lead to impotence if medical attention is not sought as soon as possible. Patients must be advised of the priapism risk associated with doxazosin and to seek medical attention immediately if it is suspected.