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Pharmacognosy

Central Nervous System and types of antiemetics

Central Nervous System: brain and its parts

types of antiemetics

The brain is one of the largest and most complex organs of the human body. It is the central organ of the nervous system, and along with the spinal cord, it makes up the central nervous system. Read more about CNS.

Antiemetics and types of antiemetics

Antiemetics are drugs effective against nausea and vomiting.
They are typically used to treat motion sickness. Antiemetics act on the brain by preventing the stimulation of the vomiting center (chemoreceptor trigger zone-CTZ). Examples

Classification: types of antiemetics

  • 5-HT3 receptor antagonists- Ondansetron, Granisetron, Dolasetron, etc.
  • Dopamine D2-receptor antagonists: Domperidone, Metoclopramide, Mosapride, etc.
  • Antihistamines or H1- histamine receptor antagonists: Diphenhydramine, Promethazine, etc.
  • Anticholinergics: Scopolamine, Hyoscine, Dicyclomine, etc.

Ondansetron

Ondansetron is an Antiemetic prescribed for nausea and vomiting. Antiemetics treat motion sickness, chemotherapy-induced nausea and vomiting, and the side effects of general anesthetics and opioid analgesics.

Domperidone

Domperidone is a specific blocker of dopamine receptors.  The antiemetic properties of domperidone are related to its dopamine receptor blocking activity at both the chemoreceptor trigger zone and at the gastric level.

Metoclopramide

Metoclopramide is Dopamine D2-receptor antagonists. It acts by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ), and causes antiemetic effects

Promethazine

Promethazine is a direct antagonist at the mesolimbic dopamine receptors and alpha-adrenergic receptors in the brain.

types of antiemetics: #Aushdhyey #औषध्येय #Pharma Aushdhyey_Series3

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Pharmacognosy

Metabolic pathways in plants and their determination

Metabolic pathways or Biogenetic pathways

Metabolic pathways or Biogenetic pathways are the pathways that lead to the formation of a chemical compound in plants. These chemical compounds are classified into two types: a) Primary metabolites and b) Secondary metabolites

File:Chemical damage.jpg - Wikipedia

a) Primary metabolites: are the metabolites/ chemical compounds which are essential for the growth, development, and reproduction in all organisms. Carbohydrates, fats, proteins, and nucleic acids are examples of primary metabolites.

b) Secondary metabolites: are the metabolites/ chemical compounds that are not essential OR not directly involved in the normal growth, development, and reproduction of living organisms. They are biosynthetically derived from primary metabolites. Thus, they are known as secondary metabolites. Alkaloids, tannins, terpenes, volatile oil, steroids, lignin, phenolic compounds, flavonoids are examples of secondary metabolites. Protection of the plants from UV rays, microbes, and pest infestation are the significant functions of secondary metabolites.

Building blocks: are required for the formation of secondary metabolites that are derived from primary metabolites. Surprisingly very few building blocks are required for secondary metabolite production. Acetyl coenzyme A (acetyl-CoA), Shikimic acid, Mevalonic acid, 1-deoxyxylulose 5-phosphate, and Amino acids are the most important building blocks involved in the biosynthesis of secondary metabolites are derived from.

The various Metabolic pathways which lead to the production of primary and secondary metabolites are listed below:

A) TCA Cycle

The TCA cycle is the central pathway in which various metabolites are formed. It mainly occurs in the matrix of mitochondria3. It is mainly responsible for the production of primary metabolites.

Significance of the TCA cycle:

1) The primary function of the TCA cycle is to provide energy in the form of ATP.

2) It is a significant pathway for the oxidation of carbohydrates, fats, lipids, and proteins3.

The steps involved in the TCA cycle are discussed below:

1) Two molecules of acetyl CoA and one molecule of oxaloacetate undergoes condensation to form a six-carbon compound known as citrate.

2) Citrate undergoes isomerization to form isocitrate.

3) Isocitrate undergoes oxidation in the presence of enzyme isocitrate dehydrogenase which results in the formation of α-ketoglutarate. During this step, CO2 is released and one molecule of NADH is formed.

4) α-ketoglutarate formed is further oxidized to form succinyl CoA. The CoA part comes from the acetyl CoA. Also, one NADH molecule is released in this step.

5) Succinyl CoA is converted to succinate. One molecule of GTP is released.

6) Further, succinate in the presence of succinate dehydrogenase is converted to fumarate, and simultaneously one molecule of FADH2 is formed.

7) Fumarate is converted to malate. This step is catalyzed by the enzyme fumarase.

8) Malate in presence of malate dehydrogenase is converted to oxaloacetate. Further oxaloacetate in presence of citrate synthase enzyme gets converted to citrate3

B) Calvin Cycle

The Calvin cycle is the cycle of chemical reactions which helps the plants in the process of carbon fixation. Through this cycle, the plants fix carbon from atmospheric CO2 into the form of three-carbon sugars2.

Steps in the Calvin cycle:

Step 1 Carbon Fixation: In this step CO2 from the atmosphere binds to the ribulose-1,5-bisphosphate (a five-carbon receptor molecule) which resulted in the formation of six-carbon compound. This step is catalyzed by the enzyme RuBP carboxylase/oxygenase. The six-carbon compound formed is further split into a three-carbon compound known as phosphoglyceric acid.

Step 2 Reduction phase: The phosphoglyceric acid compound formed in the first step is converted to glyceraldehyde-3 phosphate. The energy required for this step comes from ATP and NADPH.  NADPH donates electrons to the phosphoglyceric acid to form glyceraldehyde-3 phosphate, hence this step is known as reduction step.

Step 3 Carbohydrates formation/ regeneration phase: The glyceraldehyde-3 phosphate formed is converted back to sugar molecule such as glucose.

Step 4 Regeneration phase: Some of the glyceraldehyde-3 phosphate is converted to a five-carbon ribulose-1,5-bisphosphate compound that accepts the new carbon molecules.

Significance of the Calvin cycle:

Calvin cycle helps in the formation of three-carbon sugars in plants. These three-carbon sugars are used by the plants to build nucleotides, amino-acids, other sugars, and complex long-chain carbohydrates like glucose, starch, and cellulose2.

C) Embden Meyerhof Pathway

abbreviated as EMP pathway was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. In this pathway, glucose undergoes breakdown to generate energy in the form of ATP. Hence this pathway is also known as glycolysis (glyco: glucose; lysis: breakdown) pathway. The main site where glycolysis takes place is in the cytoplasm of all the living cells1.

The steps involved in the glycolysis are mentioned listed below:

Step 1: Glucose in presence of the enzyme glucokinase is converted to glucose-6-PO4. The latter undergoes isomerization in presence of the enzyme of isomerase to form fructose-6-PO4.

Step 2: Fructose-6-PO4 is converted to fructose-1,6-diphosphate in presence of the enzyme Phosphofructokinase.

Step 3: fructose-1,6-diphosphate in presence of the enzyme aldolase is converted to glyceraldehyde-3-PO4. The latter undergoes phosphorylation to form glyceraldehyde-1,3-biPO4.

Step 4: The glyceraldehyde-1,3-biPO4 undergoes dephosphorylation to form 3-phosphoglycerate.

Step 5: The 3-phosphoglycerate undergoes isomerization to form 2-phosphoglycerate. The 2-phosphoglycerate in presence of enolase enzyme gets converted to phosphoenolpyruvate.

Step 6: The phosphoenolpyruvate in presence of pyruvate kinase is converted to pyruvate.

Step 7: Pyruvate can undergo reactions to form either lactate or acetaldehyde or formate.

Step 8: If acetaldehyde is formed it further undergoes fermentation in presence of alcohol dehydrogenase enzyme to form ethanol.

Biosynthesis of carbohydrates in plants: The various Metabolic pathways for the production of carbohydrates in plants are mentioned below.

D) Gluconeogenesis

Gluconeogenesis is the pathway responsible for synthesis on new glucose molecules. The pathway works in the opposite direction of the glycolysis pathway. The gluconeogenesis pathway starts in the mitochondria and ends in the endoplasmic reticulum. The glyceraldehyde-3-PO4is the product of photosynthesis in plants. This product is stored inside chloroplasts in the form of starch or stored in other plant tissues in the form of glucose or sucrose. Similarly, stored fats are also converted to glucose and sucrose when seed germination occurs4.

E) Pentose Phosphate Pathway

It is a pathway that occurs in parallel to the glycolysis pathway. In this pathway energy in the form of ATP is not utilized. It is also known as hexose monophosphate shunt. The glucose pentose pathway consists of two important phases 1) oxidative phase and 2) non-oxidative pathway

1) The oxidative phase (irreversible reaction) is the phase in which NADPH is generated. The steps involved in the oxidative phase are mentioned below:

Step 1: Glucose-6-PO4 (intermediate product of glycolysis pathway) in presence of the enzyme glucose-6-PO4 dehydrogenase is converted to 6-phosphogluconolactone.

Step 2: 6-phosphogluconolactone is converted to 6-phosphogluconate. Gluconolactonase enzyme catalyzes this reaction.

Step 3: 6-phosphogluconate is converted to ribulose-5-PO4. The reaction is catalyzed by enzyme 6-phosphogluconate dehydrogenase.

Significance of the oxidative phase:

Results in the formation of 2 NADPH molecules which are utilized by the plant cells in various Metabolic pathways or biogenetic pathways.

2) Non-oxidative phase (reversible reactions): is the phase in which 5 carbon sugars moiety is formed. The steps are mentioned below:

Step 1: Ribulose-5-PO4 is converted into two different 5-carbon molecules (i.e. ribose-5-PO4 and xylulose-5-PO4

Step 2: Further depending upon the needs of the plant cell, 2 molecules of ribose-5-PO4 undergoes conjugation to form a C10 sugar moiety. The C10 sugar moiety formed can further undergo chemical interconversion to form C7 and C3 sugar molecules.

Significance of the non-oxidative phase: ribose-5-PO4 obtained from this phase is used for the building of DNA/RNA molecules12.

F) Glycogen Synthesis Pathway

The excess of glucose produced by plants is stored in the form of glycogen. The various steps involved in the glycogen synthesis are mentioned below:

1) Glucose undergoes phosphorylation to form glucose-6-PO4 in presence of the enzyme hexokinase/glucokinase.

2) Glucose-6-PO4 is converted to glucose-1-PO4 in presence of the enzyme phosphoglucomutase. The latter is converted to UDP-glucose in presence of the enzyme glucose-1-PO4 uridylyltransferase.

3) UDP-glucose is converted to glycogen in presence of the enzyme glycogen synthase5.

G) Shikimic Acid Pathway

The shikimic acid pathway is responsible for the metabolism of carbohydrates and amino acids. A combination of phosphoenolpyruvate, a glycolytic pathway intermediate, and erythrose 4-phosphate from the pentose phosphate pathway leads to the formation of Shikimic acid. The Shikimic acid formed is responsible for the production of a variety of secondary metabolites such as aromatic amino acids, phenols, cinnamic acid derivatives, lignans, and alkaloids.  Shikimic acid is an important intermediate that leads to the formation of Chorismic acid. Chorismic acid acts as a substrate for the formation of anthranilic acid and tryptophan.

The steps involved in the Shikimic acid pathway are discussed in brief:

Step 1: The phosphoenolpyruvic acid and erythrose-4-phosphate undergo condensation to form 2-keto-3-deoxy-7-phospho-D-glucoheptonic acid. The latter undergoes cyclization to form 3-Dehydroquinic acid.

Step 2: 3-Dehydroquinic acid undergoes dehydration to form 3-Dehydroshikimic acid. The latter undergoes keto-enol tautomerism to form Shikimic acid.

Step 3 Shikimic acid undergoes phosphorylation to form Shikimic acid 3-phosphate.

Step 4: Shikimic acid 3-phosphate undergoes dehydration and condensation to form chorismic acid.

Step 5: Chorismic acid acts as a substrate for the formation of anthranilic acid and tryptophan. Also, chorismic acid undergoes isomerization to form prephenic acid (a substrate for the formation of phenylalanine and tyrosine)11.

H) The acetate hypothesis

As per the acetate hypothesis, acetate occupies the central position concerning the general metabolism/ production of secondary metabolites in plants. The acetate pathway is an important pathway for the production of various secondary metabolites such as straight-chain and aromatic compounds. In the acetate pathway, acetate is the starting material. The acetate is utilized is in the form of acetyl CoA11.

I) Acetate mevalonate pathway/ Isoprenoid pathway

Acetyl CoA is the starting material for acetate mevalonate pathway. After a series of steps, it leads to the formation of mevalonate or mevalonic acid. Through this pathway, various isoprenoid compounds such as terpenes and steroids are obtained. Acetate mevalonate pathway contributes to the synthesis of 1/3rd of the total known secondary metabolites. This pathway occurs in eukaryotic cells such as plants, animals, and some bacterial cells.

The acetate mevalonate pathway leads to the biosynthesis of active isoprene units. The isoprene units obtained are considered as important active building blocks/ universal precursors. Examples of isoprene units are Isopentyl pyrophosphate and Dimethyl allyl pyrophosphate. These isoprene units contribute to the biosynthesis of many other secondary metabolites such as Anthraquinoes, naphthoquinones, terpenoids, glycosides, alkaloids.

The steps involved in the acetate mevalonate pathway are listed below:

  1. 2 molecules of Acetyl CoA (the end product of glycolysis) undergo condensation to form Acetoacetyl-CoA.
  2. Acetoacetyl-CoA undergoes condensation with 1 acetyl CoA to form HMG-CoA in presence of HMG CoA synthase.
  3. HMG CoA further undergoes a reduction in the presence of HMG-CoA reductase and NADPH to form Mevalonate (important intermediate).
  4. Mevalonate undergoes phosphorylation (twice) to form 5-pyrophosphomevalonate. The latter undergoes dehydration and decarboxylation and leads to the formation of Isopentyl pyrophosphate and Dimethyl allyl pyrophosphate.
  5. Isopentyl pyrophosphate and Dimethyl allyl pyrophosphate undergoes condensation to form geranyl pyrophosphate (a C10 monoterpene).
  6. Geranyl pyrophosphate undergoes condensation with isopentyl pyrophosphate to form farnesyl pyrophosphate (a C15 sesquiterpene)
  7. If farnesyl pyrophosphate undergoes condensation with isopentyl pyrophosphate, geranylgeranyl pyrophosphate (a C20).
  8. Squalene (C40 compound, important in cholesterol synthesis) is formed if farnesyl pyrophosphate undergoes condensation with farnesyl pyrophosphate11.

J) Biosynthesis of lipids in plants

The de novo synthesis is the main pathway in plants responsible for the synthesis of lipids or fatty acids. The most common fatty acids synthesized by the de novo pathway are palmitic, oleic, linoleic, and linolenic acids. The main site for de novo fatty acid biosynthesis is the plastid compartment in the plant cell.  Acetyl CoA is the substrate molecule for fatty acid synthesis.

There is two main enzyme system responsible for fatty acid synthesis. 1) acetyl CoA carboxylase and 2) fatty acid synthases.

The acetyl CoA obtained from TCA cycle has two fates:

1) Acetyl CoA is utilized as the starting material in plant cells for the synthesis of steroidal compounds (secondary metabolites) by the acetate mevalonate pathway.

2) Acetyl CoA can be utilized as a substrate molecule for the synthesis of complex fatty acids. Malonyl CoA, palmitate is some of the intermediates formed during the reaction. Fatty acid synthase is the class of enzyme utilized in fatty acid synthesis13.

K) Biosynthesis of volatile oils

Mevalonic acid pathway and 2-methylerythritol-4-phosphate (MEP) pathway are the major pathways by which plants biosynthesize the volatile oils. Various classes of terpenes (such as Monoterpenes, sesquiterpenes, diterpenes, triterpenes, tetraterpenes, and polyterpenes) are produced through this pathways5.  

Notations

  • Terpenes: are hydrocarbon compounds that are the most important constituents present in essential oils. Terpenes are made up of isoprene units (5 carbon atoms)6.
  • Monoterpenes: belongs to the class of terpenes containing 2 isoprene units (10 carbon atoms)6.
  • Sesquiterpenes: belongs to the class of terpenes containing 3 isoprene units (15 carbon atoms)6.
  • Diterpenes: belongs to the class of terpenes containing 4 isoprene units (20 carbon atoms)6.
  • Triterpenes: belongs to the class of terpenes containing 6 isoprene units (30 carbon atoms)6.
  • Tetraterpenes: belongs to the class of terpenes containing 6 isoprene units (40 carbon atoms)6.
  • Photosynthesis: is a process by which plants produce organic compounds such as carbohydrates using H2O, CO2, minerals, and light energy7
  • NADH: also known as Nicotinamide adenine dinucleotide which participates in various electron transfer chain reactions in the body8.
  • NADPH: also known as nicotinamide adenine dinucleotide phosphate is produced from the various biochemical process such as photosynthesis. It is also used in the biosynthesis of various compounds such as lipids, nucleotides, and amino acids9.
  • FADH2: known as Flavin adenine dinucleotide. It is an important energy molecule that is utilized by the plant cells in the process of cellular respiration.
  • ATP: is known as Adenosine triphosphate is an energy-carrying molecule present in the cells of all living things10.
  • ADP: Adenosine diphosphate also known as adenosine pyrophosphate (APP) is the metabolite of ATP. ADP can be converted to ATP or adenosine monophosphate (AMP)10.

References

  1. https://link.springer.com/referenceworkentry/10.1007%2F978-3-642-11274-4_503#:~:text=The%20Embden%2DMeyerhof%2DParnas%20(,as%203%2Dphosphoglycerate%20or%20pyruvate.
  2. https://biologydictionary.net/calvin-cycle/#:~:text=The%20function%20of%20the%20Calvin,turns%20them%20into%20plant%20matter.
  3. https://teachmephysiology.com/basics/atp-production/tca-cycle-2/
  4. http://www-plb.ucdavis.edu/courses/bis/105/lectures/Gluconeogenesis.pdf
  5. https://www.researchgate.net/figure/Glycogen-Synthesis-Pathway_fig6_318896009
  6. https://www.sciencedirect.com/topics/neuroscience/monoterpenes
  7. https://www.britannica.com/science/photosynthesis
  8. https://www.webmd.com/vitamins/ai/ingredientmono-1016/nadh#:~:text=People%20use%20NADH%20supplements%20as,chronic%20fatigue%20syndrome%20(CFS).
  9. https://study.com/academy/lesson/nadph-definition-structure-function.html#:~:text=NADPH%20is%20used%20in%20the,in%20the%20light%2Dindependent%20reactions.
  10. https://sciencing.com/what-does-adp-in-biology-do-12072977.html
  11. Evans, W. C. (2009). Trease and Evans’ pharmacognosy E-book. Elsevier Health Sciences. https://books.google.co.in/books?hl=en&lr=&id=l7pkTFyY428C&oi=fnd&pg=PT2&dq=trease+and+evans+pharmacognosy&ots=2nLv7q9jHi&sig=thg1yz6D9TDOwu33X0WuzMy7tik&redir_esc=y#v=onepage&q=trease%20and%20evans%20pharmacognosy&f=false
  12. https://www.khanacademy.org/test-prep/mcat/biomolecules/carbohydrate-metabolism/a/pentose-phosphate-pathway
  13. Aid, F. (2019). Plant lipid metabolism. In Lipid metabolism. IntechOpen. https://www.intechopen.com/books/advances-in-lipid-metabolism/plant-lipid-metabolism
Categories
Pharmacognosy

General introduction of Antitumour-Vinca

Are you aware of a particular antitumor or anticancer drug that is available in most gardens? That is nothing but Madagascar periwinkle or Vinca. Let us first have a basic idea about tumors, before delving into further information on Vinca.

Our human body is made of millions of cells. We know that these cells divide and multiply to form tissues, organs and so on. So, in short, this cell division has to cease at some point. But what if this continues without any break? Will we develop any symptoms or remain unaffected?

Well, this uncontrollable outgrowth of cells that serves no purpose is what doctors call tumors. Anybody can develop tumors. These may be silent and show no signs or may start showing symptoms at the initial stage itself. An important thing to know about this is that the term “tumor” is synonymous with “cancer”.

Madagascar periwinkle or Vinca:

Vinca

This plant is known for its salverform flowers that are usually violet or white in color. Due to its eye-catching appearance, this is commonly grown as groundcovers in gardens and hence is an easily available plant.

Occurrence:

Around B.C. 50, this plant was predominantly used in Europe for its wound healing and antihemorrhagic properties.  Later on, in the 1950s, Canadian scientists, Nobel and Beer, investigated this plant and discovered its antileukemic activity. This paved the way for other scientists to work on this plant and ultimately, alkaloids that were responsible for its anticancer activity were isolated.

Distribution:

This plant is indigenous to Madagascar. However, it is also cultivated in South Africa, India, U.S.A, Europe, Australia and the Caribbean islands both as an ornamental and medicinal plant.

Organoleptic evaluation:

Since the whole plant is considered to possess antitumor activity, it is vital to identify the right plant. The prominent macroscopic characters of the plant are:

  • Green, simple, petiolate, ovate and reticulate leaves
  • Leaves have an acuminate apex with a glossy appearance
  • Pale grey branched tap-roots
  • Violet pink-white to carmine-red flowers
  • Flowers are bracteate, pedicellate, complete and arranged in cymose clusters
  • Fruits are follicles with black seeds
  • The plant is a pubescent herb with characteristic odor and bitter taste

Chemical constituents:

The major constituents are indole alkaloids. Among them, about 20 dimeric indole-dihydroindole alkaloids possess anticancer activity. The most significant ones are vincristine and vinblastine. The other alkaloids are ajmalicine, lochnerine, serpentine and tetrahydroalstonine.

Mechanism of action:

Vincristine and vinblastine prevent cell division by binding to the mitotic spindles, thereby preventing the latter from joining together. This is how vinca alkaloids serve as anticancer agents.

Therapeutic use:

  • Vincristine sulphate – Treatment of acute leukemia
  • Vinblastine sulphate – Treatment of Hodgkin’s disease and choriocarcinoma
Categories
Pharmacognosy

Chaulmoogra oil: Antileprotics Drug

Chaulmoogra oil: Antileprotic agents

Bacterial infections have affected mankind for long. Pneumonia, otitis, upper respiratory tract infection and so on, are some of the commonly known ones. But have you ever heard of the term leprosy? Well, though not used in our daily conversation, we surely would have come across this at some point in our life. So, what is leprosy?

File:Hand showing leprosy Wellcome L0040719.jpg - Wikimedia Commons

Leprosy or Hansen’s Disease:

The causative organism of leprosy, Mycobacterium leprae was discovered in 1873. This bacterium spreads through contact with the nose and mouth droplets of an infected person. Thus leprosy is a contagious disease. It first affects the peripheral nerves and the skin of the target. Within a few weeks, the infected person develops skin sores, that are pale-colored and do not go away after months too. The next prominent symptoms are:

  • Nerve damage
  • Loss of sensation of the limbs
  • Muscle weakness

This disease, unfortunately, cannot be diagnosed easily as the symptoms develop only 3-5 years later. So, leprostatic agents like dapsone, clofazimine are commonly prescribed to treat them.

But, these agents again have their list of side effects and hence may not be suitable to all. Then how can this be treated? To answer this question, we just need to direct our attention to our ancient herbal remedies. And by doing so, we find a truly wonderful remedy for leprosy. Let’s now look into this antileprotic agent.

Chaulmoogra oil or Hydnocarpus oil

Chaulmoogra

Chaulmoogra oil is a fixed oil. So, how do we get this oil? Through the cold expression of the ripe seeds of the plant Hydnocarpus anthelmintic, this oil can be obtained. However, it needs to be filtered before use.

Occurrence:

This oil has been used for treating leprosy even before the 19th century when antibiotics were yet to make an appearance. This can be evinced by its mention in the ancient literature of both the Indian medicine and Traditional Chinese medicine.

Distribution:

The plant is native to Myanmar, Thailand and East India. But, it is also cultivated in Sri Lanka, Bangladesh and Nigeria.

Organoleptic evaluation:

The physical characteristics of the oil are evaluated as follows:

  • Semi-solid at room temperature
  • Crude oil is pale greenish-brown tinged
  • Filtered oil is yellow to brownish-yellow
  • Characteristic odor
  • Slightly acrid taste
  • At temperatures below 25ᴼC, it exists as a solid

Chemical constituents:

The fixed oil is chemically composed of esters of chaulmoogric acid, hydnocarpic acid and gorlic acid. The other constituents are proteins, cyanophoric glycosides and glycerides of palmitic and oleic acids. The therapeutically active ingredient is hydnocarpic acid.

Therapeutic efficacy:

Used externally for the treatment of:

  • Leprosy
  • Tuberculosis
  • Psoriasis
  • Rheumatism

It is also as subcutaneous or intramuscular injections with a dosage of 0.3 to 1 ml.

Leprosy is a devastating disease that can result in the affected people being ostracized from society. So, let’s stay alert and try to create awareness to ensure that none gets shunned by this disease.