User:Thomas6607/Doxazosin

Post Traumatic Stress Disorder

Doxazosin has been used in some studies as a potential treatment for post traumatic stress disorder associated nightmares but this indication is not currently by Health Canada or the Food and Drug Administration.

Contraindications
Doxazosin use is avoided in people who are allergic to quinazolines or any other components of the medication. Medications thats contain quinazoline include doxazosin and terazosin.

Adverse Effects
The most common side effects that were seen with the use of this medication included fatigue (8% versus 1.7% in placebo), dizziness (15.6% vs 9.0), edema (2.7% vs 0.7%), and orthostatic hypotension which most often occurs on the first dose or with subsequent dose changes. The rates of side effects are similar between people who use the medication for benign prostatic hyperplasia and those who use it for high blood pressure. Other less common side effects that are reported with this medication are runny nose, dyspnea, and weight gain. An extremely rare but serious side effect is priapism, permanent sexual dysfunction can occur if medical assistance is not received promptly. Some α1-adrenergic receptors blockers have shown potential liver toxicity such as alfuzosin however doxazosin is seen to have a low risk of causing liver damage.

Overdose
Overdoses result in extremely low blood pressure and heart rate which can lead to excessive dizziness and falls. If an overdose occurs it is advised to seek medical care or contact a poison control centre.

Interactions
This medication should not be used at the same time as other α1-adrenergic receptors blockers since this would lead to cumulative side effects, such as excessive dizziness. Rates of orthostatic hypotension and dizziness may increase when combining the use of doxazosin with phospodiesterase-5 inhibitors such as tadalafil and sildenafil. The use of strong CYP3A4 inhibitors such as clarithromycin or ketoconazole can reduce the metabolism of doxazosin resulting in higher plasma drug levels and increased risk of side effects.

Pharmacology
Doxazosin is an α1-adrenergic receptor blocker, it can help lower blood pressure by inhibiting epinephrine and norepinephrine from binding to α1-adrenergic receptors in the blood vessels. Epinephrine and norepinephrine are hormones produced in the medulla of the adrenal glands which act on the adrenergic receptors throughout the body to produce various effects. Normally when norepinephrine binds to the α1-adrenergic receptors in the blood vessels, vasoconstriction will occur which raises the blood pressure. Doxazosin has no activity on adrenergic receptors so when it binds to adrenergic receptors it only results in less epinephrine binding leading to vasodilation of blood vessels, the relaxation of the blood vessels throughout the body in turn helps to reduce blood pressure.

Benign prostatic hyperplasia is a condition where a benign growth is developed on the prostate that presses against the urinary tract and bladder, this increases pressure in the area leading to decreased urine output, increased urinary frequency, nocturia and sometimes urinary retention. It is important to first rule out prostate cancer before initiating treatment. Doxazosin can help with benign prostatic hyperplasia by blocking epinephrine and norepinephrine from binding to α1-adrenergic receptors the receptors in the neck of the bladder and prostate, this reduces the constriction in the smooth muscle present in the urethra which allows for urine to flow through more freely.

Pharmacokinetics
Doxazosin has a known oral bioavailability of 60-70%, following ingestion it reaches peak plasma concentrations in 2-3 hours. This medication is predominantly metabolized by the CYP450 enzymes of the liver then excreted in the feces (63%). The major CYP enzyme responsible for its metabolism is CYP3A4, a small portion of the medication is excreted in the kidneys via the urine (9%). The protein binding is 98% so during an overdose this medication will not be removed by dialysis. Pharmacokinetic parameters of doxazosin do not appear to be greatly impacted by decline in renal function or aging. Elimination half life is estimated to be 22 hours. A small study open label study looked at the impact of mild/moderate liver dysfunction and the impact on elimination, it showed higher total drug remained in the body but the overall half life did not go up significantly (24 hours).