Hydralazine Beta blockers

Vasodilators (e.g. hydralazine) Beta blockers + Hydralazine Diazoxide + Hydralazine Guanethidine + Minoxidil Nicorandil + Vasodilators... 

Hydralazine 4-8 hour Up to 30 minute 5-40 mg prn dosing Headache, tachycardia, lupus like syndrome, potential nephrotoxicity Often given with beta-blocker to counter reflex sympathetic drive, may increase ICP... 

Drugs that may affect beta blockers include aluminum salts, barbiturates, calcium salts, cholestyramine, cimetidine, colestipol, diphenhydramine, hydroxychloroquine, NSAIDs, penicillins (ampicillin), rifampin, salicylates, SSRIs, sulfinpyrazole, calcium blockers, oral contraceptives, flecainide, haloperidol, hydralazine, loop diuretics,... 

Drugs that may be affected by beta blockers include flecainide, gabapentin, haloperidol, hydralazine, phenothiazines, anticoagulants, benzodiazepines, clonidine, disopyramide, epinephrine, ergot alkaloids, lidocaine, nondepolarizing muscle relaxants, prazosin, sulfonylureas, and theophylline. 

Second and subsequent weeks Increase dosage to 50 mg 4 times daily. Maintenance Adjust dosage to lowest effective level. Twice daily dosage may be adequate. In a few resistant patients, up to 300 mg/day may be required for a significant antihypertensive effect. In such cases, consider a lower dosage of hydralazine combined with a thiazide or reserpine or a beta-blocker. However, when combining therapy, individual titration is essential to ensure the lowest possible therapeutic dose of each drug. 

Drugs that may interact with hydralazine include beta blockers (eg, metoprolol, propranolol) and indomethacin. 

ACE-I or ARB ACE-I or ARB in appropriate patients Beta-blockers in appropriate patients Rontine nse Dinretics for fluid retention ACE-I Beta-blocker In selected patients Aldosterone antagonist ARB DigitaUs Hydralazine/nitrates UsnaUy for palUation... 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

The primary vasodilators used in hypertension are hydralazine (Apresoline) and minoxidil (Loniten) (Table 21-5). These drugs are not usually the first medications used in patients with hypertension, but tend to be added to the drug regimen if other agents (diuretics, beta blockers) fail.89 Hydralazine is likewise used to lower blood pressure in emergency situations... 

At Cynthia s pharmacy, patients with heart disease are usually on several medications for their heart disease a diuretic, a beta blocker, and an angiotensin-converting enzyme (ACE) inhibitor. Patients with more severe disease may also be on an aldosterone inhibitor such as spironolactone, digoxin, hydralazine nitrate, and/or an angiotensin-receptor blocker (ARB). Some patients are... 

VASODILATOR ANTIHYPERTENSIVES BETA-BLOCKERS t hypotensive effect Additive hypotensive effect with diazoxide, hydralazine, minoxidil and sodium nitroprusside. In addition, hydralazine may T the bioavailability of beta-blockers with a high first-pass metabolism (e.g. propanolol and metoprolol), possibly due to alterations in hepatic blood flow or inhibited hepatic metabolism Monitor BP closely... 

The combination of isosorbide dinitrate with hydralazine is safe in systolic heart failure. Only headache and palpitation necessitated drug withdrawal and were more common than with enalapril (90). Headache and dizziness were more common with isosorbide dinitrate plus hydralazine than with placebo in patients taking ACE inhibitors and beta-blockers (5). 

The following drugs have been commonly associated with inducing, aggravating or unmasking SLE beta-blockers, carbamazepine, chlorpromazine, estrogens, griseofulvin, hydralazine, isoniazid (INH), lithium, methyldopa, minoxidil, oral contraceptives, penicillamine, phenytoin (diphenylhydantoin), procainamide, propylthiouracil, quinidine, and testosterone. 

In the treatment of hypertension, a major use of beta-blockers is in combination with hydralazine. The direct vasodilators bring about reflex cardiac stimulation, and beta-blockers prevent these adverse effects (see also Figure 67). Beta-blockers also reduce blood pressure by exerting a central effect or a peripheral action, or both, which decreases renin activity. Metoprolol and atenolol are beta selective, and they are safer agents in patients with asthma, diabetes mellitus, or low-renin hypertension. Some beta-blocking agents such as pindolol have intrinsic sympathomimetic activity and may be used in the treatment of pronounced bradycardia (sick sinus syndrome). Unlike propranolol, metoprolol is not a very lipid-soluble... 

MDL 899 (26) is a direct acting arteriolar vasodilator in man, but coadministration of a beta-blocker is necessary to prevent reflex-related side effects. A clinical study with cadralazlne (ISF 2469, 27) shows this compound similar to hydralazine with fewer side effects. Two other vasodilators, budralazine (28) and pinacidil (29) may owe some of their activity to calcium channel blockade.Anthranilamlde (WIN 48,049) lowers blood pressure in monkeys without accompanying tachycardia. This compound acts primarily as a direct vasodilator but also has sympatholytic and dopaminergic activities. Compounds and 32 also lower blood pres-... 

Another is the increase in bioavailability of high-extraction beta blockers with hydralazine , (p.847), possibly caused by altered hepatic blood flow, or altered metabolism. 

Uncertain. Hydralazine appears to increase the bioavailability only of those beta blockers that undergo high hepatic extraction and not those that are largely excreted unchanged in the urine. Hepatic extraction is discussed in more detail under Changes in first-pass metabolism , (p.4), and Table 22.1 , (p.833), lists the metabolic routes ofthe commonly used systemic beta blockers. It has been suggested that hydralazine may alter hepatic blood flow or inhibit hepatic enzymes, although other mechanisms may also be involved. - ... 

NSAiDs ACE inhibitors + NSAIDs Alpha blockers + NSAiDs Angiotensin II receptor antagonists + Aspirin or NSAiDs Beta blockers + Aspirin or NSAiDs Calcium-channel blockers + Aspirin or NSAiDs Guanethidine + NSAiDs Hydralazine + NSAiDs Thiazide and related diuretics + NSAiDs... 

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

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