Hydralazine

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Hydralazine
Systematic (IUPAC) name
phthalazin-1-yl hydrazine
Identifiers
CAS number	86-54-4
ATC code	C02DB02
PubChem	3637
Chemical data
Formula	C8H8N4
Mol. weight	160.176 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	Oral, intravenous

Hydralazine hydrochloride (1 -hydrazinophthalazine monohydrochloride; Apresoline®) is a medication used to treat high blood pressure. A vasodilator, hydralazine works by relaxing blood vessels (arterioles more than venules) and increasing the supply of blood and oxygen to the heart while reducing its workload. It is commonly used in the condition of pregnancy called preeclampsia.

[edit] Administration

Oral, in tablets and suspension, or intravenous. In most adults, oral doses range from 40 mg to 200 mg a day, divided in 2 to 4 doses, while intravenous doses range from 5 to 40 mg, repeated as necessary.

Patients given hydralazine over a period of six months or more may develop a lupus-like syndrome or other immune related diseases that generally are reversible with withdrawal. Hydralazine is differentially acetylated by fast and slow acetylator phenotypes thus incidence of lupus-like disease in slow acetylators.

[edit] Side effects

Common side effects include:

• Diarrhea
• Tachycardia due to baroreceptor reflex
• Headache
• Loss of appetite
• Nausea or vomiting
• Pounding heartbeat
• Drug-Induced Lupus Erythematosus

[edit] Notes

• A directly acting arteriolar vasodilator with little action on venous capacitance vessels;  TPR
• It causes greater reduction of diastolic than systolic blood pressure
• Reflex compensatory mechanisms are evolved which cause tachycardia, increase in CO & renin release - increased aldosterone - Na+ & water retention

• Disproportionate cardiac stimulation appears to involve direct augmentation of NA release & myocardial contractility as well

1. Thus, a hyperdynamic circulatory state is induced-angina may be precipitated due to increased cardiac work as well as steal phenomenon
2. There is no reduction in renal blood flow despite fall in blood pressure
3. However, fluid retention & edema may occur by above mechanism

• Tolerance to hypotensive action develops unless diuretics or -blockers or both are given together to block compensatory mechanisms
• Mechanism of vascular smooth muscle relaxant action is not clearly known
• It is partly endothelium dependent - may involve generation of NO (nitric oxide) & stimulation of cGMP
• Direct effects on membrane potential & on Ca2+ fluxes have also been proposed
• Hydralazine is well absorbed orally, peak occurs in 1-2 hours & is subjected to first pass metabolism in liver
• Chief metabolic pathway is acetylation which exhibits a bimodal distribution in population – slow & fast acetylators
• Bioavailability is higher in slow acetylators but these patients are more prone to develop lupus syndrome

• Hydralazine is completely metabolized both in liver & plasma; metabolites are excreted in urine, t1/2 1-2 hours

1. However, hypotensive effect lasts longer (12hours), probably because of its persistence in vessel wall
2. Adverse effects are frequent & mainly due to vasodilatation
3. Facial flushing, conjunctival injection, throbbing headache, dizziness, palpitation, nasal stuffiness, fluid retention, edema, CHF
4. Angina & MI may be precipitated in patients with coronary artery disease
5. Postural hypotension is not prominent because of little action on veins - venous return & CO are not reduced
6. Paresthesias, tremor, muscle cramps, edema, rarely peripheral neuritis

• Lupus erythematosus or rheumatoid arthritis like symptoms develop on prolonged use of doses above 100mg/day

1. It is more common in women & is slow acetylators
2. It is slowly reversible on stopping treatment
3. Hydralazine is used in moderate to severe hypertension not controlled by first line drugs
4. Usually, low doses are added to diuretics & -blockers already being administered
5. It is not used alone
6. Large doses are not recommended for long periods
7. Hydralazine can be used in patients with renal involvement, but is contraindicated in older patients & in those with ischaemic heart disease
8. It is one of preferred antihypertensives during pregnancy
9. It can also be used parenterally in hypertensive emergencies
10. Arteriolar dilator action of hydralazine can be employed in management of CHF

Antihypertensives (C02) and diuretics (C03) edit
Antiadrenergic agents (including alpha):	Clonidine, Doxazosin, Guanethidine, Guanfacine, Lofexidine, Mecamylamine, Methyldopa, Moxonidine, Prazosin, Rescinnamine, Reserpine
Vasodilators:	Diazoxide, Hydralazine, Minoxidil, Nitroprusside, Phentolamine
Other antihypertensives:	Bosentan, Ketanserin
Low ceiling diuretics:	Bendroflumethiazide, Chlorothiazide, Chlortalidone, Hydrochlorothiazide, Indapamide, Quinethazone, Mersalyl, Metolazone, Theobromine
High ceiling diuretics:	Bumetanide, Furosemide, Torasemide
Potassium-sparing diuretics:	Amiloride, Eplerenone, Spironolactone, Triamterene