Propranolol + Hydralazine Pharmacology
Propranolol + Hydralazine
Propranolol
In sympathetic over activity, it prolongs systole by retarding conduction. It increases oxygen supply and exercise tolerance in angina patients. It decrease automaticity and abbreviates refractory period of myocardial fibers and decreases rate of depolarization in SA node, Purkinje fibers, and other ectoptic foci. Prolong effective refractory period of AV node and AV conduction is delayed. At higher doses direct depressant membrane stabilizing action is exerted. The drug decreases BP in hypertensive individuals. Initially total peripheral resistance increases due to blockade of beta mediated vasodilatation and decrease in cardiac output; so little change in BP. But when treatment is continued due to adaptation of resistance vessels to decreased cardiac output total peripheral resistance decreases and systolic and diastolic BP falls.
Antimigraine action: Propranolol is useful in migraine due to its beta blockade action. Through beta blockade action it inhibits vasodilation and relieves migraine.
Distribution: Widely distributed in a plasma protein bound form.
Metabolism: Metabolized in liver.
Excretion: Excreted through urine.
2.Decreases coronary blood flow
3.Forgetfulness
4.Nightmares
5.Decreases exercise capacity
6.Decreases carbohydrate tolerance
7.Decrease insulin release
8.Increases free fatty acid levels and increase LDL to HDL ratio
9.Worsens chronic obstructive lung diseases
10.Gastrointestinal problems
11.Nausea
12.Sexual dysfunction
13.Cold extremities
14.Tiredness
15.Exacerbates prinzmetal`s angina
16.Bradycardia
17.Depression
18.Fever
19.Rash
2.Second or third degree heart block
3.Congestive heart failure
4.Cardiogenic shock
5.Bradycardia
6.Chronic obstructive pulmonary diseases
7.Hypoglycemia
8.Haemorrhage
.
2.Ischaemic heart disease
3.Congestive heart failure
4.Renal impairment
5.Hepatic impairment
6. Diabetes mellitus
7. The drug should be gradually withdraw with caution
8. Non allergic bronchospastic diseases
9. Thyrotoxicosis
10. Along with other antihypertensive drugs
2. Arrhythmias
3. Anxiety
4. Angina
5. Migraine
6. Prophylaxis of myocardial infarction
7. Tremors
8. Phaeochromocytoma
9. Hypertrophic sub aortic stenosis
Rifampicin, Phenobarbital, NSAIDs, Thyroid hormones, Smoking: Decrease antihypertensive action of propranolol.
Corticosteroids: Antagonism of hypotensive effect.
Sympathomimetics: Marked hypertension and bradycardia.
Insulin: Hypoglycemic effects prolonged by propranalol and masking of symptoms of hypoglycemia in diabetes.
Lidocaine: Increased levels of lidocaine may occur resulting in toxicity.
Calcium channel blockers: Severe bradycardia especially in those with impaired LV function.
Phenothiazines: Chlorpromazine increases plasma levels of propranolol.
Reserpine: Additive effect resulting in vertigo, syncope or postural hypotension.
Clonidine: May increase the postural hypotension. Severity of rebound hypertension caused by abrupt withdrawal of clonidine enhanced.
Haloperidol: Severe hypotension.
Prazosin: May increase first dose response (acute postural hypotension) of prazosin.
Theophylline: Propranolol antagonises effect of theophylline.
Alcohol: Enhanced hypotensive effect.
ACE inhibitors: Enhanced hypotensive effect.
Lab tests: May interfere with Glaucoma screening test due to reduction in intraocular pressure.
Hypertension: Starts with 80mg once daily or in 2 divided doses and gradually increases up to 320mg/day based on patient`s response in divided doses 12th hourly or 8th hourly.
Maximum daily dose: 640mg.
Sustained release formulations: 120 to 160mg/day. Once daily.
Children: 1mg/kg/day gradually increases to 4mg/kg/day based on patient`s response in 4 divided doses
Maximum dose: 5mg/kg/day.
Arrhythmias & Anxiety: 30mg to 150mg/day in 3 to 5 divided doses.
Children: 0.5 to 4mg/kg/day in 3 to 4 divided doses.
Angina: 40 to 80mg two times daily to 4 times daily.
Migraine: 80 to 120mg/day in divided doses in 12th hourly to 8th hourly. And gradually increases at 1 week intervals to 160mg/day.
Children: 1mg/kg/day four times daily and gradually increases up to 5mg/kg/day based on patient`s response.
Prophylaxis of myocardial infarction: Initiate the therapy with 20mg dose 5days after myocardial infarction. Then give doses of 40mg thrice daily and gradually increases at weekly intervals up to 80mg based on patients response.
Hydralazine
2. Tachyphylaxis
3. Edema
4. Palpitation
5. Dizziness
6. Dryness of mouth
7. Nasal congestion
8. Headache
9. Palpitation
10. Weakness
11. Orthostatic hypotension
12. Angina
13. Anxiety
14. Sleep disturbances
15. Reversible lupus erythmatosis
16. Paraeshesia
17. Tremor
18. Muscle cramps
2. Ischaemic heart disease
3. Coronary artery diseases
4. Valvular stenosis
5. Pericarditis
6. Aortic aneurism
2. Hepatic impairment
3. Cardiovascular disorders
4. Cerebro vascular disorders
5. Use with caution along with other antihypertensive drugs
6. Slowly withdraw the drug with caution
2. Congestive heart failure
3. Pregnancy associated hypertensive crisis
4. Hypertension associated with renal involvement
Sympathomimetics: Use these agents with great caution since hydralazine alone may cause tachycardia and angina.
Propranolol, Metoprolol: Oral bioavailability of these agents may be increased. Also they counteract reflex tachycardia.
Parenteral antihypertensive drugs: (e.g. Diazoxide): Profound hypotensive episodes may occur.
Alcohol: Hydralazine potentiates effect of alcohol.
Oral: Starts with 10mg 6th hourly. Increase the dosage up to 25mg 12th hourly to 6th hourly or 50mg 12th hourly to 6th hourly depending up on the patient`s response.
Maximum daily dose: 200mg
Maximum dose in fast acetylators: 300 to 400mg/day
I.V.: 10 to 20mg. Repeat if required by the patient
Children: Starts with 0.75mg/day. Increased up to 7.5mg/kg/day based on patient`s response.
Heart failure: Starts with 50 to 75mg. Increase the dosage up to 200 to 600mg/day in 2 to 4 divided doses based on patient`s response.
Maximum dose: 3gm/day
Pregnancy associated hypertensive crisis: Starts with 5mg I.V. Increases to 10mg at every half an hour until desired response is obtained.
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