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Pharmacology


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Pharmacology

A Book of Achieving Knowledge For Drugs

By

Amit Kishor Srivastava

EDUCREATION PUBLISHING (Since 2011)

www.educreation.in


iv


v

DEDICATED TO GOD AND SPECIAL

REGARDS TO MY FAMILY

“The price of success is hard work, dedication to the

job at hand, and the determination that whether I win

or lose, I have applied the best of myself to the

task at hand”


vi

Acknowledgement

I am extremely thankful to Dr. Satyawan Singh,Director General, Goel Institute of Pharmacy & Sciences Lucknow & Dr. Amresh Gupta, Associate Professor & HOD, (Pharmacognosy dept.)U.P.University of Medical Sciences, Saifai for giving me an opportunity to carry out written book.

I express my gratitude to Dr. Vinay Kumar Khanna, Scientist, Development Toxicology and Neurotoxicology Division, Indian Institute of Toxicology Research, Lucknow for his co-guidance with his incessant moral support, valuable suggestions and versatile expertise shared with me during this study. I whole heartedly thank for his extensive support and for allowing me to carry out part of my work under his supervision.

I express my sincere thanks to Prof. (Dr.) S.K. Saraf, Director BBDNIIT, Lucknow for his kind cooperation during my work.

I would like to express my sincere gratefulness and humble regards to my friend Mr. Saroj Kumar, Assistant Professor, Goel institute of Pharmacy & Sciences, Lucknow, for his cooperation, guidance, supervision, critical views and stimulating constructive suggestions, and useful insights throughout the work.

I would like to express my sincere gratefulness and humble regards to my friend Mr. Rohit singh, Mr.Bidhyut Dubey, Assistant Professor. His truly guidance has made him as a constant oasis of ideas and passions in science. I remain indebted to him and a heartfelt thank to him.

I would like to record my great debts of gratitude toDr. Neeraj Verma, Mr. Akash Ved, Mrs. Arpita Singh, Mr. J. P. Singh sir , Mr. Amit K. Nigam sir, Mr. B. P. Singh sir, Mr. O. P. Verma, Mr. Salil Tiwari, Mr. Rajesh, Ms. Shweta , Ms. Ruchi, Mr. Prabhat, Mr.vikash, Mr. varun, Who has nurtured and moulded me during my work. It is due to their keen interest, encouragement and fruitful suggestion that enabled me to conclude my work.

I would like to thank my Beloved, mother Mrs. Laxmi Srivastava and Brother Mr. Vimal Srivastava. Theyreceive my deepest gratitude and love for giving me life, for educating me with aspects from both arts and sciences, for providing the strength to stand on my feet, for inseparable support and prayers and for all the sacrifices and efforts. They always remained inclined to enlighten my glimmering future and this book the complete reflection of their efforts.

I would like to thank my wifeMrs. Kalyani Srivastavafor her dedication, words of encouragement and love. I would like to thank my Beloved son Akki and Daughter NikkiAs well as Harshit, Shivam , Shradha. They receive my deepest gratitude and love for giving me life, for providing the strength to stand on my feet.

I would be failing in my duty if I do not acknowledge the sustained encouragement and good wishes of my beloved father who made it possible for me to see this day.

Thanking you all

Amit Kishor Srivastava


vii

Preface

This text book is designed to provide the fundamentals of pharmacology to students of pharmacy and other health sciences. An important goal of this book is to enhance student’s perception of the relevance of pharmacology to pharmacy practice.

This book includes important concept described in sufficient detail so that the students integrate and understand these principles and then be able to apply them in subsequent course work in pharmacology and therapeutics.

The book begins with an overview of the fundamental aspects of medicine. This is followed by a detailed discussion of the Hormonal therapy, Antibiotics & Naturopathy. The book then continues with the basic pharmacology of the Antibiotics drugs. Emphasis has been given to describe treatment of different diseases and in depth presentation of various mechanism of action, adverse drug reaction, drug interaction as well as its uses.

An attempt has been made to cover all the topics in a balanced manner neither skip essential details nor overloading with unnecessary details. My major objective to write this book is to present the information in a lucid, condensed and cohesive form to cover specifically the needs of pharmacy students.

I hope that this book will serve the possible needs in better understanding of all the aspect for the knowledge of special pharmacology topics.

For further improvement of this book, any suggestion and critics from students, teachers will be greatly appreciated.

Amit K. Srivastava


viii

Contents

Serial No. Title Page no.

A. Chapter 1: Hormones and its related drugs 1

1. Hormones 1

2. Anterior Pituitary Hormone 2

3. Growth Hormones 2

4. Gonadotropins 3

5. Thyroid Hormones and Thyroid Inhibitors

4

6. Insulin, Oral Hypoglycemic Drugs and Glucagon

6

7. Diabetes Mellitus (DM) 6

8. Insulin 7

9. Oral Hypoglycemic Drugs 8

10. Biguanides 9

11. Glucagon 10

12. Corticosteroids 11

13. Gonadal Hormones and their Antagonist 15

14. Androgens (Male Sex Hormones) 15

15. Estrogens (Female Sex Hormones) 17

16. Progesterone 19

17. Antiprogestin (Mifepristone):- 20

18. Uterine stimulants (Oxytocics, Abortifacients) 22

19. Oxytocin 22

B. Chapter: 2 Chemotherapy 24

20. History of chemotherapy 24

21. Antibiotics 25

22. Antibiotic resistance 26

23. Sulfonamides 28

24. Quinolones 30


ix

25. Beta lactum antibiotics

32

26. Penicillin

32

27. Semisynthetic Penicillins 34

28. Beta-lactamase inhibitors 35

29. Clavulanic acid & Sulbactam 35

30. Cephalosporins 36

31. Tetracyclines 38

32. Chloramphenicol 40

33. Aminoglycoside 41

34. Macrolide 42

35. Erythromycin 43

36. Antitubercular Drug 45

37. Isoniazid H (lsonicotinic acid hydrazide) 46

38. Antileprotic Drugs 47

39. Dapsone (DDS) 47

40. Antifungal Drugs 48

41. Amphotericin B(AMB) 48

42. Heterocyclic Benzofuran:- Griseofulvin 49

43. Anti Viral drugs 50

44. Anti-herpes virus drugs: Idoxuridine 50

45. Acyclovir 51

46. Anti Retro Virus 52

47. Anti Influenza virus drugs 53

48. Anti Malarial drugs 54

49. Chloroquine 55

50. Quinine 56

51. Cinchonism 56

52. Artemisinin derivatives 57


x

C. Chapter: 3 Naturopathy 58

53. Naturopathy 58

54. Hydrotherapy 59

55. Mud Therapy 61

56. Mud bath 63

57. Chemotherapy 65

58. Aromatherapy 66

59. Therapeutic Massage 69

60. Acupressure 70

61. Chromotherapy 71

D. Chapter 4: Adverse drug reaction and Drug interaction 73

62. Adverse drug reaction 73

63. Drug induced disease 75

64. Drug interaction 78

65. Adverse drug reaction (ADR) general terms 83

66. Monitoring of ADR 84

67. Management of ADR 89

68. Fixed drug dose combinations 91

E. Chapter 5: Pharmacoepidemiology 93

69. Pharmacoepidemiology 93

70. Rational drug therapy 95

71. Therapeutic index 96

F. Chapter 5: Case control studies &Risk 98

72. Cohort study and Case control studies 98

73. Relative risk 102

74. Attributable and Relative risk 103

75. Bibliography 104


Pharmacology: A book of achieving knowledge for drugs Page 1

Hormones and its related drugs

Hormone:-

Hormone is derived from Greek word (hormoein = to stirrup). This substance

having intense biological activity which is produced by, specific cells in the body

and is transported through circulation to act on its specific target cells.

Hormones having programmed pattern of life event which regulate body function

to maintain homeostasis in the changed extent / internal environment.

Hormones are secreted by the endocrine or ductless gland in to the blood stream.

Different types of endocrine glands and their secretion are as follows-

1) Pitutary gland:-

Anterior- Growth hormone (GH), Prolactin hormones Adrenocorticotropic

hormone (ACTH, throid stimulating hormone (TSH), Follicle stimulating

hormone ( FSH) and Luteinizing hormone (LH).

Posterior- Oxytocin, Antidiuretic hormone (ADH, Vasopressin).

2) Thyroid:- Thyroxine(T3),Triiodothyronine(T4), Calcitonin.

3) Parathyroid:- Parathormone(PTH).

4) Pancrease:- (Iselets of Langerhans) Insulin, Glucagon

5) Adrenals:- Cortex Glucocorticoids(hydrocortisone) Mineralocorticoids (aldosterone), Sex

steroids (dehydroepiandrosterone)

Medulla:-Adrenaline, Noradrenaline

6) Gonads:- Androgens (testosterone) Estrogens (estradiol) Progestins

(progesterone)

Sites and mechanisms of hormone action:-

The hormones act on their target receptor into response in a variety of mechanism.

1. At cell membrane receptors

(A) Through alteration of intracellular cAMP alteration of protein kinase A

regulation of cell function Ca2+ acting as third messenger in some situations

Exp: - Estrogens, Progestin, Adrenaline, Glucagon, ACTH, Calcitonin

(B) Through IP3/DAG Pathway release of intracellular Ca2+ and protein kinase C

activation.

Exp:-Oxytocin, Vasopressin

(C) Direct transmembrane activation of tyrosine protein kinase phosphorylation cas

cade; Regulation of various enzymes.

Exp: - Insulin, Prolactin, Growth hormone.



(D) At Cytoplasmic receptors Penetrating cell membrane, hormone combines with a cytoplasmic receptor exposed in a

DNA binding domain Migrates to nucleus and binds to specific genes DNA

mediated mRNA synthesis Synthesis of functional proteins.

Exp: - Steroidal hormones, Glucocorticoid, Mineralocorticoid, Estrogens, Progestins,

Androgens etc.

3. At nuclear receptor

The hormone Penetrates the nucleus combines with its receptor alters DNA-RNA

mediated Protein synthesis

Exp: - Thyroid hormones, Thyroxine, Tri-iodothyronin.

Anterior Pituitary Hormone:-

Anterior Pituitary (Adenohypophysis) is known as the master endocrine gland, having a

number of important regulatory hormones. Anterior Pituitary hormones are peptide in

nature and act at extracellular receptor located on their target cells. Their secretion is

controlled by the hypothalamo-hypophyseal portal system which is regulated through

feed-back Inhibition on target glands.

Growth Hormones:-

It is single chain peptides, 191 Amino acids, & its molecular wt is 22000.

Physiological function:-

GH promotes growth of all organs by inducing hyperplasia. In general, there is a

proportionate increase in the size and mass of all parts, but in the absence of

gonadotropins, sexual maturation does not take place. The growth of brain and eye is

independent of GH. It promotes retention of nitrogen and other tissue constituents: more

protoplasm is formed. GH promotes utilization of fat and spares carbohydrates: uptake of

glucose by muscles is reduced while its output from liver is enhanced; fat is broken

down.

Somatostain:-

This 14 amino acid peptide inhibits the secretion of GH, TSH and prolactin by pituitary;

insulin and glucagon in the pancrease and of almost all gastrointestinal secretions

including that of gastrin and HCl. The g.i. action produces steaporrhoea, diarrhoea,

hypochlorhydria, dyspepsia and nausea as side effect. Use of somatostatin is in

Acromegaly.

Prolactin:-

It is a 199 amino acid, single chain peptide of molecular wt. 23000; quite similar

chemically to GH.




Prolactin is the primary stimulus which in conjunction with estrogens, progesterone and

several other hormones, causes growth and development of breast during pregnancy. It

promotes proliferation of duct as well as acinar cells in the breast and induces synthesis

of milk proteins and lactose. After parturition, prolactin induces milk secretion, since the

inhibitory influence of high estrogen and progesterone levels is withdrawn. Prolactins

suppress hypothalamo-pituitary gonadal axis by inhibiting GnRH release.

Prolactin inhibitors:-

Bromocriptine:-

This synthetic ergot derivative 2-bromo-oergocryptine is a potent dopamine agonist; most

of its actions are based on this property.

Actions:-

1. Decrease sprolactin release from pituitary by activating dopaminergic receptors on

lactotrope cells-a strong antigalactopoietic.

2. Increases GH release in normal individuals, but decrease same from pituitarvy tumours

that cause acromegaly.

3. Has levodopa like actions in CNS-antiparkinsonian and behavioral effects.

4. Produces nausea and vomiting by stimuiating dopaminergic receptors in the CTZ.

5. Hypotension-due to central suppression of postural reflexes and weak peripheral

adrenergic blockade.

6. Decreases gastro intestinal motility.

Gonadotropins(GNS):-

The anterior pituitary secretes two GNS viz.FSH & LH. both are glycoprotein containing

22-28% sugar and consist of two peptide chains having a total of 207 amino acid

residues. Molecular wt. 32,000 for FSH and 30,000 for LH.

Physiological functions:-

FSH and LH act in, concert to promote gametogenesis and secretion of gonadal

hormones.

FSH:- In the female it induces follicular growth, devlopment of ovum and secretion of

estrogens.

In the male it supports spermatogenesis and has influence on seminiferous tubules.

LH:- It induces preovulatory swelling of the ripe graphian follicle and triggers ovulation

followed by luteinization of the ruptured follicle and sustains corpus luteum till the next

menstrual cycle. It is also probably responsible for atresia of the remaining follicles.



Uses:-

1 Amenorrhoea and infertility

2 Hypogonadotrophic hypogonadism

3 Cryptorchism

4 To aid in vitro ferlilization

Thyroid Stimulating Hormone (TSH, Thyrotropin):-

The thyroid gland facilitates normal growth and maturation by maintaining the level of

metabolism in the tissues that is optimal for their normal function. It is a 210 amino acid,

two chain glycoprotein, MW 30000. The two major thyroid hormone is triiodothyronine

and Thyroxin.


TSH stimulates thyroid to synthesize and secrete thyroxine (T4) and triiodothyronine (T3).

Its actions are:

It Induces hyperplasia and hypertrophy of thyroid follicles and increases blood

supply to the gland.

It Promotes trappingof iodide by thyroid.

It Promotes organification of trapped iodine and its incorporation into T3 and Ta

by increasing peroxidase activity.

It enhances endocytotic uptake of thyroid colloid by the follicular cells and

proteolysis of thyroglobulin to release more of T3 and T4.

Adreno corticotropic hormone (ACTH, Corticotropin):-

It is a 39 amino acid single chain peptide. It is derived from a larger peptide, proopio

melanocortin (M.wt. 30,000) which also gives endorphins, two lipotropins and two

MSHs.


ACTH promotes stroidogenesis in adrenal cortex by stimulating c AMP. So that

formation in cortical cells (through specific surface G protein coupled receptors). It

increases the availability of cholesterol for conversion to pregnenolone, which is the rate

limiting step in the production of gluco, mineralo and weakly androgenic steroids.

Thyroid Hormones and Thyroid Inhibitors:-

Thyroid hormone

The thyroid gland secretes 3 hormones-thyroxine (T4), triiodothyronine (T3) and

calcitonin. The Former two are produced by thyroid follicles, have similar biological

activity and the term 'thyroid hormone' is restricted to these only. Calcitonin produced by

interfollicular 'C' cells is chemically and biologically entirely different. It is considered

along with parathormone, with which it regulates calcium metabolism.



Chemistry and Synthesis:-

Both T4 and T3 are iodine containing derivatives of thyronine which is a condensation

product of two molecules of the amino acid tyrosine. Thyroxine is 3, 5, 3', 5' tetra

iodothyronine while T3, is 3, 5, 3'triiodothyronine. The thyroid hormones are synthesized

and stored in the thyroid follicles as part of thyroglobulin molecule-which is a

glycoprotein synthesized by thyroid cells, MW 660 KD, contain, sugar.

The synthesis, storage and release:-

1. Iodide uptake (Trapping)

2. Synthesis of thyroglobin

3. Oxidation and iodination

4. Iodination of Tyrosine

5. Coupling of T1 and T2

6. Pinocytosis & digestion of Colloids

7. Secretion of thyroid hormones

8. Transport in the blood

Fig:-The synthesis, storage and release of Thyroid

hormone

Thyroid inhibitors:-

These are drugs used to lower the functional capacity of the hyperactive thyroid gland.

Thyrotoxicosis:-

Thyrotoxicosis is due to excessive secretion of thyroid hormones. The two main causes

are Graves’s disease and toxic nodular goiter. Graves’s disease is an autoimmune

disorder.

Classification:-

1) Inhibit hormone synthesis (Antithyroid drugs):- Propyl thiouracil,Methimazole,

Carbimazole.

2) Inhibit iodide trapping (lonic inhibitors):- Thiocyanates (-SCN), Perchlorates (-

ClO4), Nitrates.

3) Inhibit hormone release: - Iodine, Iodides of Na and K, Organic iodide.

4) Destroy thyroid tissue: - Radioactive iodine (131

I, 12 5

I, 12 3

I).

Mechanism of action:-

Antithyroid drugs bind to thyroid peroxidase and prevent oxidation of iodide/ iodo

tyrosyl residues, thereby;

(i) Inhibit iodination of tyrosine residues in thyroglobulin



(ii) Inhibit coupling of iodotyrosine residues to form T3 and T4.

Pharmacokinetics:- All antithyroid drugs are quickly absorbed orally, widely distributed in the body, enter

milk and cross placenta; are metabolized in liver and excreted in urine primarily as

metabolites. All are concentrated in thyroid: intrathyroid t1/2 is longer: effect of a single

dose lasts longer than would be expected from the plasma t1/2. Carbimazole acts largely

by getting converted to methimazole in the body.

Adverse effects:- Hypothyroidism and goiter can occur due to overtreatment, but is

reversible onstopping the drug. It is indicated by enlargement of thyroid, and is due to

excess TSH production. Important side effects are: gastrointestinal intolerance, rashes,

joint pain, loss or graying of hair, loss of taste, fever & liver damage are infrequent.

Uses:-

i. As definitive therapy: - Remission occurs in up to half of the patients of Graves

disease after 1- 2years of treatment.

ii. Preoperatively Surgery in thyrotoxic patients

iii. Expectorant

iv. As an Antiseptics

Iodine and iodides:-

Though iodine is a constituent of thyroid hormones, it is the fastest acting thyroid

inhibitor. It is reduced in the intestines to iodide and the response to iodine or iodides is

identical. The gland, if enlarged, shrinks, becomes firm and less vascular. The thyroid

status starts returning to normal at a rate commensurate with complete stoppage of

hormone release from the gland.

Uses:-

l. Preoperative preparation

2. Thyroid storm

3. Prophylaxis of endemic goiter

4. Antiseptic

Insulin, Oral Hypoglycaemic drugs and Glucagon:-

Diabetes Mellitus (DM):- It is a metabolic disorder characterized by hyperglycaemia,

glycosurea, hyperlipaemia, negative nitrogen balance and sometimes ketonaemia.

Two major types of diabetes mellitus are:-

Type -1 Diabetic Mellitus (Insulin dependent DM):- There are beta cells destruction in

pancreatic iselets, majority of cases of auoimmune antibodies that destroyed beta cells are

detectable in blood. In all type1 cases circulating insulin level low or very low & patient

are suffer from ketosis.

Type -2 Diabetic Mellitus (Non Insulin dependent DM):- There is no loss or moderate

reduction in beta cells mass, insulin circulation is low, normal or even high no antibody is

detectible in the body.



Over 90% cases of Type DM causes are may be-

Abnormality in glycoreceptors to beta cells so that they response at high

concentration.

Reduce sensitivity of peripheral tissues to insulin that is reduction in no. of insulin

receptor (down regulation).

Excess of hyperglycemic hormones like Glucagon.

Insulin:-

Insulin was first discovered in 1921 by Banting and Best who demonstrated the

hypoglycaemic action, of an extract of pancreas prepared after degeneration of the

exocrine part due to ligation of pancreatic duct. It was first obtained in pure crystalline

form in 1926 and, the chemical structure was fully worked out in 1956 by Sanger. Insulin

is a two chain polypeptide having 51

amino acids and MW about 6000. The A-chain has 21 while B-chain has 30 amino acids.

There

are minor differences between human, pork and beef insulins. The A and B chains are

held together by two disulfide bonds.

Mechanism of Action:-

Flow chart of MOA of Insulin:-

lnsulin receptors Heterotetrameric glycoprotein consisting of 2 extracellular

and 2 transmembrane p subunits linked together by disulfide bonds. lnsulin receptors

Binding of insulin to alfa subunits induces aggregation and intemalization of the receptor

This activates tyrosine kinase activity of the beta subunits Auto phosphorylation /

phosphorylate trosine residues of lnsulin receptors Substrate proteins (IRSI, IRS2 etc).



Insulin stimulate glucose transporter (GLUT) across cell membrane.

Result Glucose transported by GLUT1& GLUT2 to the plasma.

Oral Hypoglycemic Drugs:-

These drugs lower blood glucose levels and are effective orally. The chief drawback of

insulin is-it must be given by injection.

Classification:-

Sulfonyl ureas (ATP channel Blocker):-

First generation:- Tolbutamide, Chlorpropamide

Second generation:- Glibenclamide (Glyburide), Glipizide Gliclazide Glimepiride

Meglitinide / phenyl alanine analogues:- Repaglinide, Nateglinide

Dipeptidyl Peptidase 4 Inhibitors:- Sitagliptin, Vidaligliptin, Saxagliptin, Allogliptin,

Linogliptin

Overcome Insulin Resistance:-

Biguanides:- Metformin, Phenformin

Thiazolidinediones:- Pioglitazone, Rosiglitazone,

Miscellaneous Drugs:-

α Glucosidase inhibitors:- Acarbose, voglibaose, Miglitol

Amyline Analogues:- Pramlinitide

Dopamine D2 Receptor agonist:- Bromocriptine

Na+ Glucose Co-transport inhibitors:- Dapagliflozine

Sulfonyl ureas:-

All have similar pharmacological profile significant action being lowering of blood

glucose level in normal subjects and in diabetics, but not in type 1 diabetics.

Mechanism of action:-

They act on the sulfonylurea receptors which are Present on the pancreatic B cell

membrane

Causes depolarization of K+ channels by reducing conductance

Inhances Ca++ ion Influx

Degranulation of insulin from pancreas

The rate of insulin secretion and glucose concentration is increased



Pharmacokinetics:-

All sulfonylureas are well absorbed orally, and are 90% or more bound to plasma

proteins. it have low volumes of distribution (0.2- .4 L/kg). Some are primarily

metabolized-may produce active metabolite; are mainly excreted unchanged in urine.

Drug Interactions:-

A. Drug that enhances sulfonylurea action:-

Displace from protein binding: Phenylbutazone, sulphinpyrazone, salicylates,

sulfonamides, Para Amino Salicylic acid, Clofibrate.

Inhibit Metabolism/excretion:- Sulfonamides, Phenylbutazone, warfarin,

chloramphenicol, acute alcohol intake

Synergised with or prolong pharmacodynamic action:- Salicylates, Lithium,

Theophylline

B. Drugs that decrease sulfonylurea action:-

Induce metabolism: Phenobarbitone, phenytoin, Rhiphampicin, Chronic

alcoholism.

Opposite action/suppress Insulin release: Coritcosteroids, Diazoxide, thiazides,

furosemide.

Adverse effect:-

Hypoglycemia

Non specific side effects:- Nausea, vomiting, flatulence, diarrhoea or constipation,

headache, paresthesias and weight gain.

Hypersensitivity: - Rashes, photosensitivity, transient leukopenia, rarely

agranulocytosis.

Biguanides:-

They differ markedly from sulfonylurea causes little or no hypoglycaemia in nondiabetic

subjects, and even in diabetics’ episodes of hypoglycemia due to metformin are rare.

They do not stimulate pancreatic β cells. Metformin is reported to improve lipid profile as

well in type 2 diabetics.

Mechanism of Action:-

Their hypoglycemic action are-

Suppress hepatic gluconeogenesis and glucose output from liver.

It inhances insulin mediated glucose disposal in muscles and fat.

It interferes with mitochondrial respiratory chain.

It inhibits intestinal absorption of glucose, other hexose, amino acids and vitamin

B12 .

Adverse effects:-

Abdominal pain, anorexia, nausea, metallic taste, mild diarrhea and tiredness are the

frequent side effects.Lactic acidosis and vitamin B12 deficiency are also reported.



Meglitinide / D – phenylalanine analogues:-

These are recently developed quick and short acting insulin releases.

Repaglinide

It is a meglitinide analogue oral hypoglycaemic designed to normalise meal-time glucose

excursions. Though not a sulfonylurea, it acts in an analogous manner by binding to

sulfonylurea receptor as well as to other distinct receptors. Closure of ATP

dependent K+ channels depolarisation Release of ca++ result insulin

release.

Thiozolidinediones:-

This novel class of oral antidiabetic drugs is selective agonists for the nuclear

peroxisome proliferator-activated receptor (PPARγ) which enhances the

transcription of several insulin responsive genes.

They tend to reverse insulin resistance by stimulating GLUT4 expression and

translocation so that entry of glucose into muscles and fat is improved.

α- Glucosidase inhibitors: - (Acarbose)

It is complex oligosaccharide which is reversibly inhibits α -glucosidases, the

enzymes for the digestion of carbohydrates in the brush border of small intestine

mucosa.

It slow down and decreases digestion and absorption of polysaccharides and

sucrose.

Glucagon:-

A hyperglycaemic principle was demonstrated to be present in the pancreatic

islets was named 'glucagon'.

Glucagon is a single chain polypeptide containing 29 amino acids, MW 3500

Beef and pork glucagon are identical to human glucagon. It is secreted by the

cells of the islets of Langerhans.

Like insulin, glucagon is also derived by cleavage of a larger peptide prohormone.

lts secretion is regulated by glucose levels, other nutrients, paracrine hormones

and nervous system.

Glucose has opposite effects on insulin and glucagon release, i.e. high glucose

level inhibits glucagon secretion and it is more sensitive to orally administered

glucose:

Mode of Actions:- Glucagon is hyperglycaemic; most of its actions are opposite to that of insulin.

Glucagon causes hyperglycaemia primarilv by enhancing glvcogenolvsis and

gluconeogenesis in liver; suppression of glucose utilization in muscle and fat

contributes modestly.



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