ANTIHYPERTENSIVE DRUG Vasodilator acting on smooth muscle


Generic name: 

Nitroglycerin

Brand name:


  • nitromak retard capsule
  •  Nitroderm TTS (Novartis)

Chemical name:

1, 2, 3-Trinitroxypropane

Molecular Formula:

C3H5N3O9 or C3H5(NO3)3


Chemical structure:

Nitroglycerin production:

The industrial manufacturing process often reacts with glycerin with a roughly 1: 1 mixture of Concentrated Vitriol and Concentrated Aqua Fortis.
This will be produced by mixing the aqueous white fumigation - a very expensive pure nitric acid in which nitrogen oxides are removed, as opposed to the aqueous red fumigation, which contains nitrogen oxides - and concentrated Negro.
Often, this mixture is obtained by the cheaper method of mixing the fumigant, which is also referred to as ole - sulfuric acid that contains excess sulfur dioxide - and anisotropic aqua fortis (consisting of about 70% forta aquis, and the rest water).

 The vitriol produces proton aqueous proton types, which are attacked by nucleophile oxygen atoms.
Thus the group is added as a C - O - NO2 ester and water is produced.
This is often different from the electrophoresis reaction where the neutronium ions are the electrode.

 The addition of glycerin leads to a chemical reaction (that is, heat is produced), as was common in mixed acid nitrates.
If the mixture becomes too hot, it leads to a runaway reaction, a state of accelerating nitrification amid oxidation of the organic materials destroyed by the last aqua fortis and thereby releasing toxic dioxide at a high risk of explosion.
Thus, the glycerine mixture is slowly added to the reaction vessel containing the mixed acid (not the glycerol acid).
The nitrate is cooled with cold water or another cooled mixture and kept throughout the period of adding glycerin at about 22 ° C (72 ° F), in which the esterification occurs very slowly so that it is not beneficial.
The nitrification vessel, which is often constructed of iron or lead and is usually stirred with compressed gas, has an emergency door at its base, suspended over a large group of extremely cold water which is often discarded by the entire reaction mixture (called the charge) to stop the explosion, It is a process that reminds drowning.
If the charge temperature exceeds about 30 ° C (86 ° Fahrenheit) (the actual value varies by country) or brown fumes appear in the nitrate ventilation opening, they are immediately drowned.

Class (nitroglycerin) (ATC coding system)

C01DA02 - Glyceryl Trinitrate
• C01DA - organic nitrate
• C01D - vasodilators used for cardiology
• C01 - Heart Therapy
• C - the cardiovascular system
C01DA52 - Glyceryl Nitrate Compositions, Formulations
• C01DA - organic nitrate
• C01D - vasodilators used for cardiology
• C01 - Heart Therapy
• C - the cardiovascular system
C05AE01 - Glyceryl Trinitrate
• C05AE - Muscle Relaxants
• C05A - Agents for treating hemorrhoids and anal fissures for topical use
• C05 - Vascular Endoscopes
• C - the cardiovascular system

Nitroglycerin indication

Nitroglycerin is indicated for various purposes.
It is indicated to prevent and treat angina or chest pain due to cardiovascular diseases, as well as to treat perinatal hypertension or cause hypotension during the operation.
Treatment for acute heart failure is also indicated in patients with myocardial infarction.
In the form of an ointment, nitroglycerin is indicated for the treatment of pain caused by anal fissures.
The transdermal shape is applied directly to the skin to prevent acute angular seizures.
The off-label venous form is used in emergency situations and is commonly used to treat acute coronary artery spasm caused by cocaine and hypertensive emergencies, as well as worsening acute congestive heart failure.
Some other off-label uses of nitroglycerin include managing variceal bleeding, managing esophageal spasm, and inducing uterine relaxation.

Dosage and administration

The dosage of this medicine will be different for different patients. Follow your doctor's orders or directions on the label. Subsequent information only includes typical doses of this medication. If your dose is different, do not change it unless your doctor tells you to try to do so.
The amount of medications you take is simply dependent on the power of the medications. Also, the number of doses you take each day, the time allowed between doses, and therefore the length of time you take medications depend on the medical problem you use.
To prevent or treat angina:
Oral dose (extended-release capsules):
Adults: 2.5 to 6.5 mg 3 to 4 times every day. Your doctor may increase your dose as needed.
 Children - the doctor must determine the use and dosage.
Sublingual dose (powder):
Adult ults: 1 or 2 sublingual packagings at the initial indication of an angina attack. One bundle can also be used every 5 minutes as needed, for up to fifteen minutes. Do not take 3 packages in a quarter of an hour.
 Children - the doctor must determine the use and dosage.
Sublingual dose (spray):
 adults: 1 or 2 sprays on or under the tongue at the initial indication of pain. Sprays can also be repeated every 5 minutes, as needed. You want to wait 5 minutes before giving a third spray if 2 sprays are used initially. Do not use 3 sprays in a quarter of an hour. To stop angina from exercising or pressure, use 1 or 2 sprays 5 to 10 minutes before the activity.
 Children - the doctor must determine the use and dosage.
Sublingual dose (tablets):
 adults: one tablet placed under the tongue or between the cheek and gums at the initial signal of an angina attack. One tablet can also be used every 5 minutes as needed, for up to fifteen minutes. Do not take 3 tablets in a quarter of an hour. To stop angina from exercising or stress, use one tablet 5 to 10 minutes before activity.
 Children - the doctor must determine the use and dosage.

pharmacophoric group :

  • nitro group
Nitroglycerin is nitroglycerol which is that the glycerin where the hydrogen atoms of all three hydroxy groups are replaced by the nitro groups. 

It acts as a primary medicine, releasing gas to open blood vessels and thus relieve heart pain. it's a task as a vasodilator, a gas donor, an explosive, a primary anesthetic, a tocolytic agent, a relaxant, and an antibiotic.

chemical mode of action on receptor site :

target:
Atrial natriuretic peptide receptor 1
action:
agonist
pub chem protein target :
P16066
pub chem gene target :
NPR1
general function :
Protein kinase activity

specific Function:
Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate cyclase activity upon binding of the ligand.

STRUCTURAL ACTIVITY RELATIONSHIP

In a cell-free system, the activity of organic nitrates to activate guanylate cyclase is decided mainly by the number of nitrate groups.• Since the activation of nitrates from guanylate cyclase involves the formation of free radicals of gas, the potency increases with the rise of the nitric group within the group.• Increased lipophilicity thanks to the esterification of the free OH group in isosorbide mononitrate had no significant effect on the activation of cyclase guanylate.

In their work on the muscles of the blood vessels, venous enlargement predominates over the expansion of the arteries. Venous enlargement reduces the return of veins as a result of intravenous aggregation and reduces the dimensions of the left diastolic and compression (preload)Smaller or smaller arterial enlargement reduces peripheral vascular resistance and left ventricular pressure upon contraction (posterior pregnancy). 
The effect on preload isn't shared by ß-blockers or calcium channel blockers.• Also, it's an enlarged effect of coronary vessels that improve regional coronary blood flow to ischemic regions resulting in improved oxygen supply to the guts muscle systemic effects of nitrates

future outlook of nitroglycerin :


The global nitroglycerin report on the angina market 2019 is comprehensively prepared with a primary focus on the competitive landscape, geographical and retail growth, and market dynamics, including drivers, constraints, and opportunities.
 Highlights key production, revenue, and consumption trends so players can improve their sales and growth in global nitroglycerin for the angina market. It provides a detailed analysis of the competition and the leading companies in the global nitroglycerin field for the angina market.

Here, it focuses on recent developments, sales, market value, production, gross margin, and other important factors for the business of major players working in the global nitroglycerin for the angina market.

References:

• https://www.ncbi.nlm.nih.gov/pubmed/12060725
• https://www.ncbi.nlm.nih.gov/pubmed/12048254
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021134s007lbl.pdf
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021134s007lbl.pdf
• https://www.ncbi.nlm.nih.gov/pubmed/9751938