Diuretics postural hypotension

Q91 Lower initial doses of diuretics should be used in the elderly. The elderly are particularly susceptible to postural hypotension. 

Elderly patients must be started on the lowest possible dose of diuretics as they tend to be more susceptible to their side-effects, such as postural hypotension. 

Although less of a problem than with phenoxybenza-mine or phentolamine, symptoms of postural hypotension, such as dizziness and light-headedness, are the most commonly reported side effects associated with prazosin therapy. These effects occur most frequently during initial treatment and when the dosage is sharply increased. Postural hypotension seems to be more pronounced during Na+ dehciency, as may occur in patients on a low-salt diet or being treated with diuretics, (3-blockers, or both. 

Volume depletion of some degree occurs with all diuretics following prolonged use. This can cause problems, such as postural hypotension, in those with poor cardiac function. Volume depletion also causes a fall in glomerular filtration that can trigger homeostatic reflexes such as increased aldosterone and antidiuretic hormone secretion. This contributes to electrolyte disturbances, such as hypokalaemia and metabolic alkalosis. 

Livedo reticularis sometimes occurs in patients taking amantadine and usually clears within 1 month after the drug is withdrawn. Other dermatologic reactions have also been described. Peripheral edema, another well-recognized complication, is not accompanied by signs of cardiac, hepatic, or renal disease and responds to diuretics. Other adverse reactions to amantadine include headache, heart failure, postural hypotension, urinary retention, and gastrointestinal disturbances (eg, anorexia, nausea, constipation, and dry mouth). 

Therapeutic uses Thiazide diuretics decrease blood pressure in both the supine and standing positions postural hypotension is rarely observed, except in elderly, volume-depleted patients. These agents counteract the sodium and water retention observed with other agents used in the treatment of hypertension (for example, hydralazine). Thiazides are therefore useful in combination therapy with a variety of other antihypertensive agents including (3-blockers and ACE inhibitors. Thiazide diuretics are particularly useful in the treatment of black or elderly patients, and in those with chronic renal disease. Thiazide diuretics are not effective in patients with inadequate kidney function (creatinine clearance less than 50 mls/min). Loop diuretics may be required in these patients. 

Prazosin, oxazosin and terazosin (see p. 73) produce a competitive block of oci adrenoceptors. They decrease peripheral vascular resistance and lower arterial blood pressure by causing the relaxation of both arterial and venous smooth muscle. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Therefore, long-term tachycardia and increased renin release do not occur. Postural hypotension may occur in some individuals. Prazosin is used to treat mild to moderate hypertension and is prescribed in combination with propranolol or a diuretic for additive effects. Reflex tachycardia and first dose syncope are almost universal adverse effects. Concomitant use of a p-blocker may be necessary to blunt the short-term effect of reflex tachycardia. 

Neither drug causes much postural hypotension, but water retention may warrant concomitant diuretic use. 

Answer E. In approaching the answer to this question, try to sort out the incorrect statements. Spironolactone does not cause hypokalemia, but hyperkalemia. Although loop diuretics may cause hyperuricemia, there is no connection between elevations of uric add and fainting episodes. When used with ACEIs in the treatment of heart failure, spironolactone is reported to increase survival, but there is no evidence of similar efficacy in patients with HTN. Obviously, statement B is erroneous (never choose never ). Although postural hypotension from the combination of antihypertensive drugs is most likely responsible for the fainting episode in this patient, there could also be alternative explanations ... 

Phenothiazine derivatives cause postural or orthostatic hypotension. This may be more pronounced in patients with reduced vascular volume resulting from acute hemorrhage or dehydration, and when used with diuretic agents. Hypotension is more frequent with phenothiazine derivatives having either an aliphatic substitution on NIO (e.g., chlorpromazine) or a piperidine substitution on NIO (e.g., mesoridazine or thioridazine). It occurs less frequently with compounds containing a piperazine substitution (e.g., trifluoperazine). The hypotension is due to direct vasodilation and an alpha-adrenergic-receptor-blocking effect. The pressor effects of epinephrine can be reduced, blocked, or reversed by appropriate doses of chlorpromazine. 

Prazosin, (1 mg t.i.d.) alone or in combination with other drugs such as a diuretic, is indicated in the management of moderate hypertension. It is a direct vasodilator and is nsed for long-term therapy. Its side effects are sedation, postural hypotension, and headache (due to vasodilation). As much as 91% of prazosin is bound to plasma protein. When used for the first time or in larger-than-recommended doses, prazosin may cause pronounced hypotension, faintness, dizziness, and palpitations. These effects, which have been labeled first-dose phenomena, are seen especially in salt-and water-depleted patients. Therefore, the initial dose of prazosin is small, and it is given at bedtime. 

The case history suggests that the syncope (fainting) is associated with diuretic use. Complications of diuretics that can result in syncope include both postural hypotension (which this patient exhibits) due to excessive reduction of blood volume and arrhythmias due to excessive potassium loss. Potassium wasting is more common with thiazides (because of their long duration of action), but these drugs rarely cause reduction of blood volume sufficient to result in orthostatic hypotension. The answer is (C). 

Toxicity Behavioral effects include restlessness, agitation, insomnia, confusion, hallucinations, and acute toxic psychosis. Dermatologic reactions include livedo reticularis. Miscellaneous effects may include gastrointestinal disturbances, urinary retention, and postural hypotension. Amantadine also causes peripheral edema that responds to diuretics. 

Prazosin (Minipress) Peripheral alpha-1 adrenergic antagonist. Dilates both arteries and veins. Hypertension and hypertension with congestive heart failure. Hypotension (postural hypotension on first dose is sudden and severe). Sodium depletion (often caused by diet or diuretic therapy in hypertensive patients) worsens the hypotensive episodes. Edema, dry mouth, congestion, headache, nightmares, sexual dysfunction and lethargy may also be observed. 

This active metaboiite of methyidopa decreases total peripheral resistance, with little change in cardiac output and heart rate, through its stimulation of central inhibitory a2-adrenoceptors. A reduction of plasma renin activity also may contribute to the hypotensive action of methyidopa. Postural hypotension and sodium and water retention also are effects related to a reduction in blood pressure. If a diuretic is not administered concurrently with methyidopa, tolerance to the antihypertensive effect of the methyidopa during prolonged therapy can result. 

Starting with a low dose of the ACE inhibitor reduces the risk of first-dose hypotension. In a study in 8 patients with hypertension, treated with a diuretic (mainly furosemide or hydrochlorothiazide) for at least 4 weeks, captopril was started in small increasing doses from 6.25 mg. Symptomatic postural hypotension was seen in 2 of the 8 patients, but was only mild and transient. ... 

A few patients taking some antihypertensives feel dizzy or begin to blank out or faint if they stand up quiekly or after exereise. This orthostatie and exertional hypotension may be exaggerated in some patients shortly after drinking alcohol, possibly beeause it ean lower the eardiae output (noted in patients with various types of heart disease ). For other reports of postural hypotension with alcohol, see alpha bloekers , (p.42), and ealeium channel blockers , (p.57). Some manufacturers of antihypertensives e.g. ACE inhibitors and thiazide diuretics" warn that acute alcohol intake may enhance the hypotensive effects, particularly at the start of treatment, and this could apply to any antihypertensive. Patients just beginning antihypertensive treatment should be warned. 

Dose Initial 0.25 mg PO tid, wkly 10.25 mg/dose, to 3 mg max max 4 mg for RLS Caution [C, /-] Sev e CV, renal, or hepatic impair Contra Component allergy Disp Tabs SE Syncope, postural X BP, NA, HA, somnolence, dosed-related hallucinations, dyskinesias, dizziness Interactions t Risk of bleeding W/ ASA, NSAIDs, fevCTfew, garlic, ginger, horse chestnut, red clover, EtOH, tobacco t effects OF amitriptyline, Li, MTX, theophylline, warfarin t risk of photosensitivity W/ dong quai— use sunscreen, St. John s wort X effects W/ antacids, rifampin X effects OF ACEIs, diuretics EMS t Bleeding risk w/ concurrent EtOH, tobacco, ASA, and NSAID use t effects of warfarin OD May cause N/V, drowsiness, hypotension, and CP symptomatic and supportive... 

Orthostatic hypotension, although often loosely referred to in older literature (SED-10, 370) (159), is in fact only likely to become a problem in very old subjects, aged 90 years or more, even if a potent loop diuretic is used this was the clear conclusion of a good prospective study published in 1978 (159). In 843 independent hving men and women aged 60-87 years, postural fall in systolic blood pressure was not related to treatment with diuretics, after correction for initial blood pressure (160). At currently recommended doses, older subjects do not generally experience particular problems from hjrpokalemia and do not appear to be at special risk of cardiac dysrhythmias in the face of diuretic-induced hjrpokalemia (SEDA-15, 218). 

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