Nitrates include -
Erythrityl tetranitrate, Isosorbide dinitrate, Isosorbide mononitrate, nitroglycerin ,
 pentraerythritrol, tetranitrate, glyceryl trinitrate
Refer - Isorbide 5- mononitrate

Interacting drugs- summary

 + Isosorbide -

Alcohol 
 severe  hypotension and cardiovascular collapse  occur.

Aspirin  
 Increased nitrate serum concentrations and actions  occur
    
Calcium Chl blkrs
 Marked orthostatic hypotension occur. Dosage adjustment of either
 agent   necessary

Dihydroergatamine 
  Increased  bioavailability of dihydroergotamine with resultant increase
  in mean standing systolic blood pressure, or functional antagonism
   between these agents,  decreasing the antianginal effects.

Nitroglycerine  + heparin
 Pharmacological effects of heparin  decreased. 
            
              

Angina pectoris

Nitrates include

Erythrityl tetranitrate, Isosorbide dinitrate, Isosorbide mononitrate, nitroglycerin , pentraerythritrol, tetranitrate, glyceryl trinitrate

Refer - Isorbide 5- mononitrate

Cardiovascular-
Chest pain ( 1% or more ) acute MI, angina pectoris, apoplexy,  arrhythmias, atrial fibrillation, bradycardia, hypotension, hypertension, pallor, palpittions, postural hypotension, premature  ventricular contractions supraventriculat tachcardia, syncope. tachcardia ( less than 1% )

CNS-

Dizziness, emotional lability, fatigue, headache, ( 1% or more ), agitation, anxiety, confusion, depression, hypersthesia, hypokinesia, impaired concentration, insomnia, nervousness, nightmares, restlessness, tremor, vertigo ( less than 1% )

Dermatologic- 

Pruritus drug rash  ( 1% or more ) , sweating ( less than 1% )
 
GI- 

Abdominal pain, Nausea, vomiting, diarrhea,  ( 1% or more ) anorexia, decreased weight, dry mouth, dyspepsia, tenesmus, thirst, tooth disoder,( less than 1% )

GU-

Dysuria, impotence, urinary frequency, prostatic disorder ( less than 1% )

Musculoskeletal -

Arthalgia, muscle cramps, ( less than 1% )

Respiratory -

Incresed cough, upper respiratory tract infection ( 1% or more ) .
asthma, dyspnea, sinusitis ( less than 1% )

Miscellaneous-

Allergic reaction,  flushing, pain ( 1% or more ) ,amblyopia, asthenia, back pain,
bitter taste, blurred vision, cod sweat, diplopia, increaed appetite, malaise, neck pain,
neck stiffness, paresthesia, rigors, susurrus aurium ( less than 1% )

Acute MI when shock is present.Marked anaemia, Cerebral haemorrhage, Hypotension.

Special precautions:

Glaucoma, elderly, hypothyroidism, malnutrition.

Tolerance- to vascular and antianginal effects of nitrates may develop.

Glaucoma- intraocular pressure may be increased, therfore caution isequired in administering to patients with glaucoma.

Excessive dosage- may produce severe headache. Lowering the dosage and using analgesics will help control the headaches, which diminish or disappear as therapy continues.

Volume depletion/hypotension- severe hypotension (particularly upright posture ) may occur witrh even small doses of isosorbide mononitrate.

Excercise caution in patients who may be volume depleted or hypotensive for any reason. Withdrawl- in terminating of angina gradually reduce the dosage to prevent withdrawal reactions.

Drug abuse and dependence- amyl nitrate is abused for sexual stimulation. The effect of inhaltion is almost instaneous causing lightheadeness, dizziness, and euphoria.

Drug/Lab test interactons- nitrates may interfere with the Zlatkis-Zak color reaction causing a false report of decreased serum cholesterol.

Warnings-

MI- data supporting the use of nitrates during the early days of the acute phase of MI are insufficient to establish safety. In acute MI, use nitrates only under close clinical observation and with hemodynamic monitoring.

Arching- a cardioverter/defribrillator should be discharged through a paddle electrode that overlies a transdermal nitroglycerin system.

Postural hypotension- may occur even in small doses.Transcient episodes of dizziness, weakness, syncope or other cerebral ischemia diue to postural hypotension may develop following administration, particularly if the patient is standing or immobile.

Use measures which facilitate venous return (eg. head low posture, deep breathing, movements of the extremities) to hasten recovery. Angina- mitrates may aggravate angina caused by hypertrophic cardiomyopathy.

Nitroglycerin IV- the vailable preparations differ in concentration or voulme per vial or ampul. When switching from product to the another, pay attention to the dilution, dosage and administration instructions.

Hepatic or renal disease, severe- use with caution.

Hypotension- avoid excessive prolonged hypotension because of possible deleterious effects on the brain, heart, liver, and kidney from poor perfusion and the atendent risk of ischemia

Alcohol intoxification- has developed in patients on high dose IV nitroglycerin, Consider this complication when administering high doses for prolonged periods

Sublingal nitroglycerin- absorption is dependent on salivary secretion.

Dry mouth (including drug-indiced dry mouth) decreases absorption.

Transdermal nitroglycerin- is not for immediate relief of anginal attacks.

Pregnancy- use only when clearly needed and when potential benefits outweigh potential hazards.

Lactation- excercise caution when administering to nursing woman.

Children- safety and efficacy for use in children have not been established.

Dosage: 20mg twice daily,with 2 doses given 7 hours apart. Suggested regimen is to give first dose on awakening and seconf dose 7 hours apart.

Overdosage- Symptoms Treatment Toxic effects may result from inhalatiion of the drug,

1. Induce emesis or perform gastric lavage followed as dust,by ingestion or excessive absorption through the by charcoal administration, however, nitrates are intact skin or mucous membranes. rapidly and comletely absorbed Prolonged contact will produce skin eruptions.

2. Keep patient recumbent in shock position and Signs and symptoms result primariliy from comfortably warm or temporarily terminate the vasodilation and hemoglobinemia. infusion until the patients condition stabilizes. Manifestations include hypotension, tachycardia,

3. Gastric lavage may be of use if the medication has flushing, perspirng skin (later becoming cold and only recently swallowed. cyanotic ) headache, vertigo, palpitations, visual

4. Passive movement of extremities may aid venous disturbances, diaphoresis, diziness, syncope, return. nausea, vomiting,(possibly with colic and bloody

5. Administer oxygen and artificial ventilation if diarrhea) anorexia, intial hyperpnea, dyspnea, and necessary . slow breathing, slow pulse, (dicrotic and intermittent )

6. Monitor methoglobin levels as indicated heart block, increased intracranial pressure with cerebral

7.Treat severe hypotension and reflex tachcardia by symptoms of confusion, moderate fever, and paralysis. elevating the legs and administering IV fluids. Tissue hypoxia, due to methoglobinemia can lead to

8.Since the duration of the hemodynamic effects cyanosis, metabolic acidosis, coma,convulsions and death following IV nitroglycerin administration is quite due to cardiovascular collapse. short additional corrective measures are usually not required

9.Consider an IV- alpha adrenergic agonist (eg. phenylephrine,methgoxamine)

10. Treat methoglobinemia

11. Ephinephrine is ineffective in reversing the severe hypotensive events associated with overdosage, ephinephrine and related compounds are contraindicated in overdosage

Missed dose

For patients using the ointment form of this medicine

1. If you miss a dose of this medicine, apply it as soon as possible, unless the next scheduled dose is within 2 hours.

2. Then go back to your regular dosing schedule.

3. Do not increase the amount used

For patients using transdermal (stick-on-patch) system

1. If you miss a dose this medicine appply it as soon as possible.

2. Then go back to your regular dosing schedule.

Hypotension

Drugs causing adverse reactions- ( 386 )

1. Nitroglycerine

2. Phenothiazines

3. Morphine

4. Diuretics

5. Citrated blood

6. Levodopa

As per US FDA guidelines as per USPDA 1997

It is the intention to bring out the salient features. Hence relevent details as prescribed by US FDA guidelines as per USPDA 1997  are brought out clearly in the following chapters. 

Descriptons are detailed only to the Group Head and the indiviual items can be seen by visiting the Web Site

ANTIANGINAL DRUGS-

Acebutol,Anlodipine,Atenol,Bepridil, Carteolol, Diltiazem,EthylTrtranitrate, Felodipine, Isosorbide,Dinitrate, Isosorbide Mononitrate, Isradipine, Labetilol, Nitriglycerin, xyprenol, Penbutiol, Pentraerthritol Pinodol,Verapramil

Refer - Isorbide 5- mononitrate

1.If you have been taking this medicine regularly for several weeks or more,do not suddenly stop using it. Stopping suddenly may bring back attacks of angina. Check with your doctor for the best way to reduce gradually.

2.Dizziness,lightheadedness,or faintness may occur especially when you get up quickly from a lying or sitting position. Getting up slowly may help. If you feel dizzy,sit or lie down.

3.While taking this medicine,be careful to limit the amount of alcohol you drink. Also extra care during exercise or hot weather or if you must stand for long periods of time.

4.After taking a dose of this medicine,you may get a headache that last for a short time. This is a common ide effect which should become less noticeable after you have taken medicine for a while.

5.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to nitrates or nitrites Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

6.Pregnancy - nitrates have been studies in pregnant women. Before taking these medicines make sure that your doctor knows if you are pregnant or if you may become pregnant.

7.Breast feeding- mothers who are taking this medicine and who wish to breast feed should discuss this with their doctor.

8. Children - no specific information comparing use of nitrates in children with use in other age groups

9.Elderly- dizziness or ligfhtheadedness may be more likely to occur in the elderly, who may be more sensitive to the effect of nitrates

10. Other medicines - Antihypertensives- or Otherv heart medicines- may increase the effects of nitrates on blood pressure

11. Other medical problems - Tell your doctor if you have any other medical problems especially

 Anemia -severe- Glaucoma - may be worsened by nitrates

Head injury or Stroke -recent- nitrates may increase pressure in the brain which can make problems worse Heart atack -recent- nitrates may lower blod pressure which can aggravate associated with heart attack.

12. Missed dose

If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose.

Do not use double doses.

13. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Not significant

Pregnancy

Use only when clearly needed and when potential benefits outweigh potential hazards.

Lactation

Excercise caution when administering to nursing woman.

Children- Safety and efficacy for use in children have not been established.