Doxazosin hypotension caused

Doxazosin can cause a sharp fall in blood pressure at the start of therapy, and a modified-release formulation has been developed in an attempt to obviate this. In an open, non-comparative, sequential study in primary care, the ordinary formulation (1-16 mg/day for 3-6 months) was replaced by the modified-release formulation (4—8 mg/day for 3 months) in 3537 patients (8). The most common reasons for withdrawal from the study were loss to follow-up (37%) and adverse events (28%). Blood pressure fell from 160/95 to 139/82 mmHg with the ordinary formulation and to 135/79 mmHg when the modified-release formulation was used instead. The most common adverse events were weakness, headache, dizziness, and hypotension, all of which were more common with the ordinary formulation. However, these differences could have been due to a healthy survivor effect, in which those who had an adverse event early on (that is while taking the ordinary formulation) dropped out before taking the modified-release formulation, which would therefore appear to be safer. Thus, the lack of crossover in this study makes the results hard to interpret, although it appears that the two formulations were at worst no different from each other. 

Altered homeostasis in older persons can lead to important and common adverse drug effects the less robust homeostatic milieu may be stressed by drugs, causing adverse effects. Examples include orthostatic hypotension due to antihypertensives and other agents that cause a-adrenergic blockade (e.g. terazosin, doxazosin, tricyclic antidepressants and phenothiazines) in those with barorecep-tor dysfunction. Diuretics can cause hyponatraemia or hypokalaemia in older patients, whereas ACE inhibitors and NSAIDs can cause hyperkalaemia. 

Doxazosin, also a selective a i-blocker, resembles prazosin in most aspects, but it has a better pharmacokinetic profile, at least for long-term use as in essential hypertension. Owing to its slow onset of action, doxazosin causes far less orthostatic hypotension and reflex tachycardia than prazosin. As a result of its long duration of action, it can be administered once daily in the long-term treatment of essential hypertension. 

In the treatment of hypertension a selective O -adrenoceptor agent is preferable to the older, non-selective (ai - - a2)-blockers. Doxazosin is preferable to prazosin, because it has a slower onset and longer duration of action. It therefore causes less or no reflex tachycardia and orthostatic hypotension. 

Geriatric Considerations - Summary Alpha-adrenergic blockers are modestly effective alone, and in combination with 5-alpha reductase inhibitors (e,g, finasteride) in the treatment of urinary obstructive symptoms related to benign prostatic hyperplasia. Alfuzosin is a "uroselective" alpha-blockerwhich appears to cause less orthostatic hypotension than nonselective alpha-blockers such as terazosin, prazosin, and doxazosin. 

Prazosin Doxazosin Terazosin Block , but not a2 Lower BP Hypertension benign prostatic hyperplasia Larger depressor effect with first dose may cause orthostatic hypotension... 

Caution [C, ] CrCl <30 Contra Component sensitivity, asthma, severe COPD, sinus bradycardia Disp Soln SE Irritation, bitter taste, superficial keratitis, ocular allergic Rxn EMS Drug is absorbed systemically OD May cause electrolyte disturbances (K), acidosis and bradycardia monitor ECG Doxazosin (Cardura, Cardura XL) [Antihypertensive/Alpha Blocker] Uses HTN symptomatic BPH Action < [-Adrenergic blocker relaxes bladder neck smooth muscle Dose HTN Initial 1 mg/d PO may be T to 16 mg/d PO BPH Initial 1 mg/d PO, may T to 8 mg/d XR 2-8mg qAM Caution [B, ] Use w/ PDE5 inhibitor (eg, sildenafil) can cause 1 BP Contra Component sensitivity Disp Tabs SE Dizziness, HA, drowsiness, sexual dysfxn, doses >4 mg T postural BP risk Interactions T Effects W/ nitrates, antihypertensives, EtOH i effects W/ NSAEDs, butcher s broom -t effects OF clonidine EMS Concurrent EtOH use can T drowsiness syncope may occur w/in 90 min of initial dose OD May cause profound hypotension place pt in supine position, give IV fluids, use pressors if needed... 

Terazosin can often be given once daily, with doses of 5-20 mg/d. Doxazosin is usually given once daily starting at 1 mg/d and progressing to 4 mg/d or more as needed. Although long-term treatment with these -blockers causes relatively little postural hypotension, precipitous drop in standing blood pressure develops in a number of patients shortly after the first dose is absorbed. For this reason, the first dose should be small and should be administered at bedtime. While the mechanism of this first-dose phenomenon is not clear, it occurs more commonly in patients who are salt- and volume-depleted. 

Prazosin, terazosin, doxazosin, tamsulosin, and alfuzosin have been studied extensively and used widely in patients with benign prostatic hyperplasia. With the exception of tamsulosin, the comparative efficacies of each of these drugs, especially in comparison with relative adverse effects such as postural hypotension, appear similar, although direct comparisons are limited. Tamsulosin at the recommended dose of 0.4 mg daily is less likely to cause orthostatic hypotension than the other drugs. There is growing evidence that the predominant a,-receptor subtype expressed in the human prostate is the a,-receptor. Developments in this area will provide the basis for the selection of Ct receptor antagonists with specificity for the relevant subtype of aj-receptor. However, the possibility remains that some of the symptoms of BPH are due to aj-receptors in other sites, such as bladder, spinal cord, or brain. 

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