Endocrine

pharmacology
SYLLABUS
Anterior Pituitary Hormone (P. 493)
GH and its analogues (P. 493) and inhibitors- Uses and adverse effects
Growth hormone inhibitors (P. 494)
Prolactin analogues and inhibitors (P. 494)- Uses and adverse effects
Gonadotropins preparations (P. 495), Uses and adverse effects
GnRH agonists (P. 495) and antagonist (P. 496) preparations, uses and adverse effects
Thyroid and Antithyroid Drugs: (P. 496)
Review biosynthesis and physiology of thyroid hormones (P. 496)
Consequences of excess and deficiency of thyroid hormones
Drugs for treating hypo and hyperthyroidism.
List the drug that can cause hyper or hypothyroidism.
Drugs affecting calcium balance and Bone Turnover: (P. 498)
Integrated physiological role, therapeutic implications of parathormone (P. 499), calcitonin (P. 499) and
vitamin –D (P. 499)
VI
Bisphosphonates (P. 500) – classification, mechanism of action, uses and adverse effects.
Adrenocorticosteroids and Synthetic Analogues: (P. 501)
Review of synthesis, regulation and physiological actions, enumerate the preparations and compare the salient
features. Mechanism of action, indications, adverse effects and contraindications.
Drugs Therapy for Diabetes Mellitus: (P. 505)
Diabetes-review, pathogenesis
Principles of management, role of insulin (P. 507), oral hypoglycemics (P. 506)
List the various preparations and compare the salient features.
Discuss the commonly used preparations under mechanism of action, indications, adverse effects,
contraindications
Glucagon (P. 512)-Explain the uses and rationale
Enumerate other drugs that may alter the blood sugar level

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VI

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PHARMACOLOGY

ANTERIOR PITUITARY HORMONES Mechanism of Action:

 These hormones are peptide in nature and they act 1. Direct action
on extracellular receptors on target cells. GH acts on cell surface JAK – STAT protein kinase
 They act under the influence of the hypothalamus receptor (present in all cells)
and produce and secrete several peptide 
hormones that regulate many physiological Activates cytoplasmic JAK-STAT tyrosine protein
processes including stress, growth, and kinase.
reproduction. 
 Following are hormones of anterior pituitary: Metabolic effects (i.e glycogenolysis, lipolysis,
glucose utilization & regulation of gene
- Growth Hormone (GH)
expression by muscle)
- Prolactin 2. Indirect action:
- Thyroid Stimulating Hormone (TSH) GH acts on liver cells
- Follicle Stimulating Hormone (FSH) 
- Lutenizing Hormone (LH) Liver produce somatomedin – C /Insulin like Growth
- Adrenocorticotropic hormone (ACTH) Factors – 1 (IGF – 1)

- Beta-Endorphin 
Promotes nitrogen retention and protein synthesis
Growth hormones (GH)
and lipogenesis in target cells. VI
 Single chain polypeptide of 191 aminoacids

secreted by pituitary gland.
Hyperplasia of target cells & growth (i.e Insulin like
 Growth hormone is secreted from anterior anabolic effect).
pituitary. Uses:
 Intermittent release of growth hormone releasing 1. Pituitary dwarfism:
hormone (GHRH) from the hypothalamus - (0.03-0.06) mg/kg  3 times a week in subject
stimulate the GH-secreting cells to synthesize and of age (20-25) years before epiphyseal fusion.
release GH. - Used in catabolic conditions eg. Severe burn,
 The level of growth hormone is: bed ridden patient, osteoporosis.
High in children 2. In patients with AIDS related wasting
3. Replacement therapy for children with GH deficiency.
Maximal during adolescence
4. In children with constitutional short stature (if
Lowest during adulthood
epiphyses are open)
 Growth hormone is: Preparations:
Stimulated by: Growth Hormone Releasing - Rt – GH is prepared by Recombinant DNA
Hormone (GHRH) technology & are in 2 forms:
Inhibited by: By Somatostatin i. Somatrophin – 191 AAs
ii. Somatrem – 192 AAs

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 Pharmacology

Adverse effects: Prolaction (PRL) & its analogues

- Pain at site of injection.  It is a 199 amino acid quite similar to GH.
- Lipodystrophy.  Causes growth and development of breast in
- Immunogenic responses like allergy with presence of oestrogen & progesterone during
recombinant- GH. pregnancy.
- Glucose intolerance, myalgia, headache  Synthesis of milk proteins and lactoses & its
- Hypothyroidism secretion during lactation.
- Hand stiffness  Inhibits hypothalamo-pituitary-gonadal axis during
- Salt and water retention & after pregnancy causing lactational amenorrhea
GH Inhibitors & infertility.
 Includes Somatostatin & Octreotide.  Hyperprolactinaemia is responsible for
I. Somatostatin galactorrhoea-amenorrhoea- infertility syndrome.
- Inhibits GH secretion and including TSH,  In males it causes loss of libido and depressed
prolactin from pituitary. fertility.
- Inhibits insulin and glucagon secretion from  It is regulated by inhibitory influence of
pancreas. hypothalamus via dopamine acting on D2 receptor
- Inhibits GI secretion including gastrin & HCI. of lactotrophs. So,
- Constricts splanchnic, hepatic and renal i. Dopamine antagonists: Haloperidol,
blood vessels. Metaclopromide  es PRL secretion
Uses: ii. Dopamine depleters: Reserpine, Methyl –
 Control of bleeding oesophageal varices. DOPA  es PRL level.
 Control of bleeding peptic ulcer. iii. Dopamine agonist: Bromocryptine, Cabergolin
VI
 Diabetic ketoacidosis  es PRL secretion.
Adverse effects: Prolactin inhibitors
 Steatorrhoea I. Bromocryptine
 Diarrhoea - Synthetic ergot derivative.
 Hypochlorhydria - It is a potent dopamine agonist with greater
 Dyspepsia action on D2 receptors
II. Octreotide
- On D1 receptors, it acts as partial agonist or
- 40 times more potent than somatostatin &
antagonist
longer acting.
Mechanism of Action:
- Action similar to somatostatin except it is
weak insulin inhibitor.  Acts on D2 receptor on lactotrophs   es
Uses: PRL secretion.
 Acromegaly  Acts on CNS  shows levo-dopa like action.
 In esophageal variceal bleeding So, useful in treatment of Parkinsonism.
 Diarrhea associated with carcinoid, AIDS,  Acts on CTZ  nausea, vomiting  early
cancer chemotherapy etc. adverse effect.
Adverse effects:  Suppress postural reflex.
 Abdominal pain  Weak peripheral -blocker – Vasodilation &
 Steatorrhea, diarrhea, gall stones. hypotension.
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Uses: b. LH
 Hyperprolactinemia  Induces preovulatory swelling of the ripe
Females – infertility and amenorrhoea graafian follicle and triggers ovulation
followed by luteinization of the ruptured
Males- gynecomastia, impotence and
follicle and sustains corpus luteum till the
sterility
next menstrual cycle.
 Hepatic coma
 Induces progesterone secretion.
 Parkinsonism- as adjunct to Levodopa
 Stimulates testosterone secretion by the
 Acromegaly due to small pituitary tumors in interstitial cells so it is also called
inoperable cases Interstitial cell stimulating hormone (ICSH).
 Hepatic coma Receptor:
Adverse Effects:  In testis- Interstitial (Leydig) cells
 Early effect:  In ovaries- Interstitial cells, theca cells,
 Vomiting, Constipation, Postural preovulatory granulosa cells & luteal cells
hypotension  Preparations
 Late effects: i. Menotropin (FSH + LH)
 Behavioural alteration, Confusion, ii. Urofollitropin/menotropin (pure FSH).
Hallucination, Psychosis iii. Human Chorionic Gonadotropin (HCG)
II. Cabergolin iv. Recombinant FSH (rt-FSH)/Follitropin  &
- Newer, more potent, selective, longer acting D2 Follitropin )
v. Recombinant LH (rt-LH)/Lutropin
agonist than bromocryptine.
 Uses:
Uses:
i. Amenorrhea & infertility VI
 Hyperprolactinemia. ii. Hypogonadotrophic hypogonadism
 Acromegaly iii. Cryptorchidism
 Parkinsonism  only in high doses iv. Polycystic ovary
 Hepatic coma v. Invitro fertilization
 Adverse effects:
Gonadotropins (Gns)
i. Ovarian hyperstimulation resulting polycystic
 Following are the gonadotropins: ovary, pain in lower abdomen & ovarian bleeding.
a. FSH –Follicle stimulating hormone ii. Precocious puberty.
b. LH –Luteinizing Hormone iii. Allergic reaction.
a. FSH iv. Breast & prostate tumors.
 Induces follicular growth, development of GnRH agonist
ovum and secretion of estrogens in females.  Preparations:
 Supports spermatogenesis in male. - Gonadorelin, Goserelin, Nafarelin, Triptorelin,
 Absence of FSH leads to ovarian and Leuprolide.
testicular atrophy.  Uses:
Receptor: i. To help in timely ovulation
In testis- Seminiferous (Sertoli) cells ii. Uterine fibroid/leiomyoma
iii. Endometriosis
In ovaries- Granulosa cells
iv. Central precocious puberty
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 Pharmacology

 Adverse effects: 4. List three antithyroid drug. Explain the mechanism

i. Hot flushes of action of one of them. Write the limation of uses
ii. Loss of libido of radioactive iodine (2+3+2=7) [04]
iii. Osteoporosis 5. Mention (32=6) [04]
iv. Emotional disorders a. The important adverse effects of radioactive
GnRH antagonists iodine
 Ganirelix, Cetrorelix Thyroid homones
 Uses:  Thyroxine (T4) & triiodothyronine (T3).
- Inhibits gonadotropin secretion from pituitary
 (For synthesis, transport, metabolism,
esp. inhibits LH surges during controlled
MOA & actions, refer Physiology.)
ovarian stimulation.
Preparations of thyroxine:
 Adverse effect:
L-thyroxine [10]
- Arises due to histamine release.
 Oral bioavailability  75%
THYROID & ANTITHYROID DRUGS  Administered in empty stomach (since food
Past Questions: interteres with absorption)
1. Write short notes: Uses of L-thyroxine:
a. Carbimazole (3) [03, 02] 1. Cretinism:
b. Indications of carbimazole (3) [03]  L-thyroxine 8–12 g/kg/day started as early
as possible. Physical growth & development
c. Radio-active iodine (3) [08, ]
is restored & further mental retardation is
2. Write the pharmacological basis for the use of:
prevented.
a. L-thyroxine in therapy (3) [10]
2. Adult hypothyroidism:
VI b. Carbimazole (3) [05]
 L-thyroxine started with low dose 50 g &
c. Carbimazole in hyperthyroidism (3) [09]
increased every 2 – 3 weeks to an optimum
d. Propylthiouracil in hyperthyroidism (3) [09] of 100 – 200 g/day. Increase in dose in
e. Iodides prior to surgery of thyroid gland usually needed in pregnancy.
(3) [07, 08] 3. Myxoedema coma:
f. Lugol's iodine prior to surgery of thyroid gland
 It is an emergency due to acute hypothyroidism.
(3) [04]
 Drug of choice is L-thyroxine 200-500 g
g. Iodine is used prior to surgery in case of
i.v. followed by 100 g i.v. OD till oral
thyrotoxicosis (3) [03]
therapy can be started.
h. Iodide used prior to surgery of thyroid gland
4. Nontoxic goiter & thyroid nodules:
in cases of thyrotoxicosis (3) [10]
 L-thyroxine decreases TSH levels & hence
i. Potassium iodide before thyroidectomy
goiter/nodule regresses.
(3) [04]
5. Other uses:
j. I-131 is the prefered treatment for most
 Include papillary carcinoma of thyroid &
patients over 21 year of age with Graves’
refractory anaemia.
disease (3) [02]
k. Iodine in thyroid diseases (4) [01] Thyroid inhibitors
3. List antithyroid drugs. Describe the mechanism of Classification: [04, 06]
action and adverse affect of carbimazole. 1. Antithyroid drugs: Propylthiouracil, Methimazole,
(2+3+2=7) [06] Carbimazole.
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2. Ionic inhibitors (inhibit iodide trapping): Adverse effects: [06]

Thiocyanates, Perchlorates, Nitrates.  Hypothyroidism and goiter
3. Drugs inhibiting hormone release: Iodine,  GI intolerance
iodides of Na & K.
 Skin rashes & joint pain.
4. Drugs destroying thyroid tissue (Radioactive
 Loss or graying of hair.
iodine): I131,I125 ,I123
 Loss of taste, fever, liver damage.
1. Antithyroid drugs: [02,03,05,09]
 Rarely, agranulocytosis
- Inhibit thyroid hormone synthesis by binding with
thyroid peroxidase i.e. inhibit oxidation of iodide, 2. Ionic inhibitors:
iodination, & coupling of tyrosine residues. - Inhibits Na+-I- symporter (NIS) and inhibits
iodide trapping.
- Propylthiouracil in addition inhibits peripheral
conversion of T4 to T3. - Perchlorate is 10 times more potent than
- Propylthiouracil is highly plasma protein thiocyanate.
bound hence less transferred across placenta - Nitrates are weak inhibitors of NIS.
& milk as compared to carbimazole & - These are toxic to organs like liver, kidney,
methimazole. i.e. propylthiouracil is preferred bone marrow and brain.
during pregnancy & lactation to prevent foetal Adverse effects:
hypothyroidism.  Gastric irritation
- They are quickly absorbed orally, widely
 Fever
distributed in body, metabolized in liver &
 Skin rashes
excreted in urine. Methimazole is active
metabolite of carbimazole.  Agranulocytosis
Dose:  Aplastic anemia
It is not used nowadays. VI
Drugs Initial Dose Maintenance
Dose 3. Iodine & iodides (inhibit hormone
Propylthiouracil 50- 150 mg TDS 25- 50 mg BD release):
- These are the fastest acting thyroid inhibitors.
Methimazole 5- 10 mg TDS 5- 15 mg BD
- Inhibits hormone release leading to the
Carbimazole 5- 15 mg TDS 2.5- 10 mg BD
condition called as thyroid constipation and
Uses: also inhibits proteolysis of thyroglobulin.
 In Grave's disease and toxic mutinodular - Excess iodide inhibits its own transport by
goiter as: decreasing expression of NIS on cell membrane
a. Definitive therapy (but recurrence is and also inhibits iodination of tyrosil and thyronil
high upto 50% of patient of Graves residue of thyroglobulin (by altering redox
disease but recurrence is rare in toxic potential of thyroid cell) resulting in reduced T3
nodular goiter).
and T4 synthesis (Wolff-Chaikoff’s effect)
b. Pre-operative preparation: To bring
back thyroid function to normal before - Peak effects are seen within 10 – 15 days, after
subtotal thyroidectomy. which thyroid escape occurs & thyrotoxicosis
c. Along with I131: For older patient requiring may return i.e. worsening of hyperthyroidism
prompt control of severe hyperthyroidism. occurs in toxic multinodular goiter.
 Propylthiouracil is also used in thyroid Preparation
storm (since blocks peripheral T4 to T3  Lugol’s solution (5% iodine in 10%
conversion). potassium iodide solution)
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 Pharmacology

Dose:  Not suitable for young patient (age < 25

 Na iodide or K iodide – (100-300) mg/day. years) since more likely to develop
Uses: [01,03,04,07,08,10] hypothyroidism and then may require life
i. Pre-operative preparation: For long therapy of thyroxine and also prone to
thyroidectomy in Graves disease(since get genetic damage or cancer.
these drugs make thyroid gland firm, less Other drugs:
vascular and easier to operate on and also
a. Beta blockers: Propranolol, Metoprolol,
decreases thyroid hormone level).
Atenolol
ii. Thyroid storm: Lugol’s iodine- (6-10) drops
Mechanism of Action:
orally or Iopanoic acid /Ipodate (iodine
a. Membrane-stabilizing action: inhibits T4 to T3
containing radiocontrast media) orally.
b. Blocking beta receptors
iii. Antiseptic: Tincture iodine, Povidone
iodine. Uses:
Adverse effects: - Grave’s disease, Thyroid storm
b. Lithium:
 Acute reaction: swelling of lips, eyelids,
angioedema of larynx, fever, joint pain,  It interferes with iodination of tyrosine but
is too toxic for therapeutic use.
thrombocytopenia.
Drugs causing hypothyroidism:
 Iodism (due to chronic overdose):
Inflammation of mucous membranes, - Antithyroid drugs, radioactive iodine, lithium,
salivation, rhinorrhoea, sneezing, lacrimation. p-amino salicylic acid.

4. Radioactive iodine: [04,08] Drugs causing hyperthyroidisim:

- I131 (commonly used), I123 & I125. - Amiodarone, Iodine, L-thyroxine
VI
- I emits X-rays (used for tracer studies) & 
131
Drugs used for hypothyroidisim:
particles. a. Synthetic:
-  particles have destructive effect on thyroid i. Levothyroxine
tissue & penetrate only (0.5–2) mm of the
ii. Liothyronine
tissue leading to pyknosis, necrosis & fibrosis of
thyroid follicles. iii. Liotrix (combination of L-thyroxine and
liothyronine)
- Therapeutic dose is 3–6 µ curie. Response is
slow, starts after 2 weeks, gradually increases, b. Animal origin: Desiccated thyroid
peaking at about 3 months. DRUGS AFFECTING CALCIUM
131
Advantages of I :
BALANCE AND BONE TURNOVER
 Simple, convenient, inexpensive &
Past Questions:
permanent treatment.
 No surgical risk, scar or injury to parathyroid 1. Write short notes calcium preparation (3) [07]
gland or recurrent laryngeal nerves. 2. Write the pharmacological basis for the use of
131 bisphosphonates in osteoporosis (3) [08]
Disadvantages of I : [02,04]
 Contraindicated in pregnancy (as it can  Calcium homeostasis is maintained by 3
destroy fetal thyroid leading to cretinism if hormones: parathormone, calcitonin and calcitriol
given in first trimester). (active form of Vit D3)

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Parathormone Preparation:
Mechanism of action & physiological role:  Synthetic salmon calcitonin:
2+
Low plasma Ca level  activates Ca sensing Adverse effects:
receptor (CaSR) on parathyroid cells (Chief cells)  Bad taste, nausea, allergy, tingling of finger.
 Uses:
Release parathormone (PTH) and shows its
effects on 3 organs:  Hypercalcemic states e.g. Hyper
i. In small intestine, it increases calcitriol production parathyroidism, Hypervitaminosis D.
and thus increases calcium absorption.  Post menopausal osteoporosis  along
ii. In kidney, it increases calcium reabsorption & with Ca and Vit D.
phosphate excretion.
 Paget’s disease of breast (but
iii. In bone, it binds PTH receptor in osteoblast.
bisphosphonates preferred).
Osteoblast releases RANK-L (Receptor for
Activation of Nuclear Ligand KB). RANK-L binds Calcitriol (1,25-Dihydroxy cholecalciferol)
its receptor in osteoclast and increases  It has steroid nucleus & is active form of vitamin
proliferation of osteoclast & increases acid & D3.
proteolytic enzyme secretion. Thus, formation
of remodeling pit due to bone dissolution Physiological role & MoA:
occurs and increases Ca level in plasma. I. In Small Intestine
Note: After remodeling pit formation, osteoblast Binds cytoplasmic Vit.D receptor (VDR)
produce osteoprotegerin (OPG)  binds RANK – L & 
prevents binding with RANK-L receptor & thus Form complex which is translocated to nucleus.
decreases osteoclast activity. 
Use: es mRNA transcription
VI
- Human recombinant parathormone (Teriparatide) 
is used in treatment of osteoporosis as 20 IU/day  protein synthesis esp. calcium binding
s.c. protein (CBP) or calbindin.
Calcitonin 
 Polypeptide chain of 32 AAs (aminoacids)  calcium & phosphate absorption.
produced by C-cells or parafollicular cells of II. On bone
thyroid gland & is regulated by serum Ca2+ level.
It acts on Vit. D receptor of osteoblast
Mechanism of action & physiological role:

Binds to G-protein receptor Laying down of osteoid


cAMP production
Calcium deposition resulting mature bone formation.

And its effects arises III. On kidney:
 es renal tubular reabsorption of calcium.
Bone Kidney Preparations:
- Inhibits bone - Inhibits calcium & i. Calciferol (Ergocalciferol/Vit D2)
resorption by directly phosphate ii. Cholecalciferol
acting on osteoclast & reabsorption from PCT iii. Calcitriol
decreasing their directly iv. Alfa-calcidiol
surface area v. Dihydro-tachysterol (DHT)
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 Pharmacology

Uses: ii. Second generation bisphosphonates:

i. Prophylaxis & treatment of nutritional vitamin Pamidronate, Alendronate, Ibandronate.
D deficiency. iii. Third generation (more potent and higher
ii. Metabolic rickets efficacy) bisphosphonates: Risedronate,
iii. Postmenopausal/Senile osteoporosis Zoledronate
iv. Hypoparathyroidism Mechanism of action: [08]
v. Fanconi’s syndrome - Binds with calcium ion in bone with high
vi. Plaque type psoriasis affinity.
Calcium 
 (1-1.5)kg calcium store in adult. During resorption calcium ions along with
 Physiological roles: refer physiology of bisphosphonates are also released and
endocrine system. endocytosed by osteoclasts.

Uses: 
- Tetany: Apoptosis of osteoclast and disruption of
cytoskeleton in osteoclast.
 (10-20) ml calcium gluconate slow i.v.
infusion along with supportive treatment & - Inhibits prenylation of certain G-binding
oxygen. protein involved in cytoskeleton of osteoclast.
- As dietary supplement: 
 To fracture patient, pregnancy, lactating Inactivation and apoptosis of osteoclast.
mothers, children. 
VI - Osteoporosis Decrease in bone resorption (useful in
 Along with raloxifene and calcitriol for osteoporosis)
treatment & prevention. Uses: [08]
Adverse effects: - Hypercalcemia of malignancy
- Constipation, bloating, flatulence.
- Osteolytic bone metastasis
Calcium preparations: [07]
- Osteoporosis especially with 2nd and 3rd
- Calcium chloride – 27% Ca generation drugs) for post menopausal
- Ca gluconate – 9% Ca women.
- Ca lactate – 13% Ca - Paget’s disease (disordered bone remodeling
- Ca dibasic phosphate – 23% Ca and honeycomb appearance of bone
- Ca carbonate (40% Ca) architecture).
Bisphosphonates Adverse effects:
 These are pyrophosphate analogues - Gastric irritation, flatulence
 Anti-resorptive drugs which inhibits bone - Bone pain
resorption. - Headache, metallic taste
Classification: - Pyrexia, hypersensitivity
i. First generation (least potent) - Flu like symptoms
bisphosphonates: Etidronate, Tiludronate

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ADRENOCORTICOSTEROIDS AND c. Prednisolone as anti-inflammatory (3) [09]

SYNTHETIC ANALOGUES d. Glucocorticoids as anti-inflammatory (3) [03]
Past Questions: e. Glucocorticoids in inflammatory disorder
1. List commonly used glucocorticoids. Write the (3) [05]
important adverse effects and contraindications f. Corticosteroids as anti-inflammatory (3) [04]
of Prednisolone (2+3+2=7) [10] g. Corticosteroids are gradually withdrawn by
2. Describe the important therapeutic uses and tapering dose (3) [03]
adverse effects of glucocorticoids. (4+4=8) [09] h. Glucocorticoids as anti-inflammatory agent
3. Describe the mechanism of anti-inflammatory (3) [01]
action of Corticosteroids. (3) [08]  These includes 21 carbon compound having
4. a. List the important adverse effects of steroid nucleus and synthesized from cholesterol
glucocorticoids. (2) [08] by adrenal cortex under influence of ACTH.
b. List corticosteroids. ( 2) [08]
 These compounds contain
c. Describe the mechanism of anti-inflammatory cyclopentanoperhydrophenanthrene (steroid)
action of Corticosteroids. ( 3) [08] nucleus.
5. List important adverse effects of glucocorticoids.  Review of synthesis, regulation and
(2) [08] physiological action:- refer to physiology of
6. List corticosteroids. List therapeutic uses and endocrine system
adverse effects of glucocorticoids on prolonged Classification: [02,08,10,11]
use. (7) [11 July]
Name of Drugs Ratio of
7. List glucocorticoids. Write the indications and glucocorticoid &
contraindications of corticosteroids. mineralocorticoid
(2+3+2=6) [07]
VI
activity.
8. List two glucocorticoids and two 1. Glucocorticoids
mineralocorticoids. [1+1=2] [02]
a. Short acting: (T1/2 < 12 hr) (1:1)
9. Explain the anti-inflammatory and Hydrocortisone / cortisol
immunosuppresive effect of glucocorticoids and
b. Intermediate acting (T1/2 = 12
their therapeutic uses. (2+2+2=6) [02]
– 36 hr)
10.Add a note on special precautions to be taken
i. Prednisolone 4:0.8
during therapy with adrenocorticosteroids.
(2) [02] ii. Methyl–prednisolone 5:0.5
11. Explain the mechanism of action of glucocorticoids iii. Triamcinolone 5:0
as anti-inflammatory agent. (3) [01] c. Long acting (T1/2 > 36 hr)
12.Mention the adverse effects of corticosteroids. i. Dexamethasone 25:0
(3) [01] ii. Betamethasone 25:0
13.Mention the danger of sudden stoppage of
2. Mineralocorticoids
glucocorticoides after prolonged therapy.
i. Deoxy corticosterone 0:100
14.Short notes:
acetate (DOCA)
a. Contraindications of corticosteroids (3) [03]
b. Gradual withdrawal of corticosteriod after ii. Fludrocortisone (10:150)
prolonged use (3) [05] iii. Aldosterone (0.3 :3000)

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 Pharmacology
Mechanism of action:
Corticosteroid penetrates the cell membrane

Binds cytoplasmic receptor forming hormone -
Receptor complex (H - R)

Complex enters nucleus
 e. Anti-inflammatory action
Binds
Glucocorticoid Response Element (GRE) or
Mineralocorticoid Response Element (MRE)
 circulation to lymphoid tissue. Increase blood
Activates transcription of required genes

Regulation of protein synthesis
 to combat stress.
Required biochemical functions
 ln many tissues, overall effect is catabolic due
to steroid directed synthesis of an inhibitory
protein.
Actions of Mineralocorticoid (Aldosterone):
VI - The main action of mineralocorticoid is to
enhance Na+ reabsorption in DCT; it causes
increase in K+ & H+ excretion.
- The action of aldosterone is expressed by gene
mediated increased transcription of mRNA
which directs the synthesis of aldosterone
induced proteins (AIPs)
Actions of Glucocorticoid:
- The level of secretion of glucocorticoid is
influenced by stress & circulating steroids.
a. It stimulates protein catabolism (except in
liver) & lipolysis, thus providing building
blocks & energy for glucose synthesis.
b. Increases gluconeogenesis by increasing
amino acid uptake by liver & kidney; it
increases the activities of gluconeogenic
enzymes.
c. Glucocorticoids augment the action of
growth hormone on adipocytes, causing
increase in activity of hormone-sensitive
-502- FAST TRACK BASIC
lipase and cause lipolysis. Redistribution of
body fat occurs as the fat depots in
different areas respond differently.
d. The tissues over the extremities loses fat
and it is deposited over face, neck &
shoulder resulting in moon face, fish mouth,
buffalo hump (in case of increased
secretion).
f. Alteration of blood cell levels in plasma:
Decrease in eosinophils, basophils, monocytes,
& lymphocytes by redistributing them from
levels of haemoglobin, erythrocytes, platelets
& polymorphonuclear leukocytes.
g. Increases resistance to stress by raising
plasma glucose levels. They provide energy
h. Cause a modest rise in BP (vasoconstrictor
action via adrenergic stimuli) on small vessels.
Pharmacokinetics:
- Orally effective except DOCA  then
undergoes 1st high pass metabolism. So, oral
bioavailability is less than in parenteral route.
- 90% in plasma bounds to Transcortin/Cortisol
Binding Globulin while rest 10% is free active
form.
- Metabolised by microsomal enzyme in liver
into 17-Ketosteroids.
- Undergoes glucuronidation & sulfate
conjugation & excreted in urine.
Hydrocortisone:
- Has short duration of action and it acts rapidly.
- Also has significant mineralocorticoid activity.
Uses:
a. Replacement therapy: 20 mg morning+10
mg afternoon PO
b. Shock
c. Status asthmaticus
d. Acute adrenal insufficiency
e. Suspension for enema in ulcerative colitis
(topically)
SCIENCE MBBS

Prednisolone:
- It is 4 times more potent than hydrocortisone
and is a more selective glucocorticoid.
- It has intermediate duration of action.
- At higher dose, fluid retention occurs.
- Causes less pituitary-adrenal suppression with
single morning dose/ alternate day treatment.
Uses:
- Allergic, inflammatory, autoimmune diseases &
in malignancies
Dose:
- 5-60 mg/day PO, 10-40 mg IM, intraarticular;
also used topically.
Methylprednisolone:
- It is slightly more potent & more selective than
prednisolone.
- Pulse therapy
 High dose methylprednisolone used.
 1 g infused IV every 6-8 weeks
 In nonresponsive active rheumatoid
arthritis, renal transplant etc with good
results & minimal suppression of pituitary-
adrenal axis.
 Initial effect of pulse therapy is due to its
antiinflammatory action
 Long term benefit may be due to temporary
switching off of immune damaging
processes due to lymphopenia & decreased
Ig synthesis.
Dose: 4-32 mg/day oral.
Triamcinolone:
- Slightly more potent than prednisolone but
highly selective glucocorticoid.
- Dose: 4-32 mg/day PO, 5-40 mg IM, intra-
articular injection; topical application
Dexamethasone:
- Long acting, very potent & highly selective
glucocorticoid.
- Causes marked pituitary-adrenal suppression
but fluid retention & hypertension not a
problem.
FAST TRACK BASIC
Endocrine
Uses:
- Inflammatory & allergic conditions:
- 0.5-5 mg/day PO Shock, cerebral oedema 4-20
mg/day IV infusion/IM inj; topical application
Betamethasone:
- Similar to dexamethasone; topical application
- Dexamethasone/betamethasone are preferred
in cerebral edema.
- Fluid retention must be avoided.
Desoxycorticosterone acetate (DOCA):
- Only mineralocorticoid activity.
- Used occasionally for replacement therapy in
Addison's disease.
Fludrocortisone:
- Orally active potent mineralocorticoid having
some glucocorticoid activity as well.
Uses:
- Replacement therapy in Addison's disease
- Congenital adrenal hyperplasia with muscle
wasting
- Idiopathic postural hypotension
VI
Aldosterone:
- Most potent mineralocorticoid.
- Not used clinically because of low oral
bioavailability & difficulties in regulating doses.
Uses: [02,07,09,11]
i. Replacement therapy
ii. Pharmacotherapy
i. Replacement therapy.
a. Acute adrenal insufficiency:
 Hydrocortisone – 100 mg i.v. bolus
followed by 100 mg i.v. infusion with
saline & glucose solution.
b. Chronic adrenal insufficiency /Addison’s
disease:
 Hydrocortisone – 20 mg morning oral &
10 mg afternoon.
 Fludrocortisone – (50 – 200)  g daily to
prevent salt wastage.
SCIENCE MBBS -503-
 Pharmacology

c. Congenital adrenal hyperplasia k. Brain conditions:

(Adrenogenital syndrome):
 Hydrocortisone- 0.6 mg/kg/day in divided
dose  to give negative feedback to
suppress pituitary ACTH & thus prevent
hyperplasia of adrenal cortex.
ii. Pharmacotherapy: [@ 4A collagen LIES in
Brain MOSTLY]
a. Arthritides:
 e.g Rheumatoid arthritis, osteo-arthritis,
rheumatic fever, gout  used only to
control acute exacerbation or when
other NSAIDS fails to provided relief.
b. Allergic conditions:
 e.g., Anaphylaxis, urticaria, serum
sickness, angioneurotic edema, allergic
conjunctivitis.
c. Autoimomune diseases:
 e.g. SLE, Myasthenia gravis, Hemolytic
anemia, Idiopathic Thrombocytopenic
Purpura.
d. Asthma (bronchial asthma):
VI  Status asthmatius, Acute exacerbation of
asthma, chronic asthma.
e. Collagen diseases:
 e.g. SLE, Poly arteritis Nodusa, Nephrotic
syndrome, Glomerulonephritis.
f. Lung diseases:
 e.g. Aspiration pneumonia, pulmonary
edema, ARDS.
g. Infective diseases:
 e.g TB, Lepra reaction, bacterial
meningitis etc.
h. Eye diseases:
 Keratitis, allergic conjunctivitis, iritis but
not in HSV keratitis & occular injury.
i. Skin diseases:
 Pemphigus vulgaris, exfoliative dermatitis.
j. Intestinal diseases:
 Crohn’s disease, Ulcerative colitis.
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 Cerebral edema as in tumor, tubercular
meningitis esp. Dexamethasone and
Betamethasone are preferred.
l. Malignancies:
 Leukemia, lymphomas, Hodgkin’s
lymphoma.
m. Organ transplant and skin allograft.
n. Septic shock
o. Thyroid storm
Mechanism of anti- inflammatory action:
[01,02,03,04,05,08,09]
- Corticosteroid induces annexin formation in
macrophages, endothelium and fibroblasts.

Annexin inhibits phospholipase A2 (i.e. indirect
inhibition of phospholipase-A2).

Decreased production of prostaglandins(PG),
leukotrienes(LT) and Platelet Activating
Factors(PAF).
- Corticosteroid downregulates expression of
genes for cytokines and COX-2 in inflammatory
cells leading to decrease in PG, IL1, IL2,IL3, IL6,
TNF-, IFN- and thus suppress fibroblast
proliferation and chemotaxis.
- Thus, action is non-specific and blocks all
stages of inflammation including healing and
scar formation.
Note: Corticoids are only palliative and do not remove
cause of inflammation but suppress cardinal signs of
inflammation and also decreases capacity of immune
cells to remove microbes and foreign body.
Special precautions to be taken during
corticosteroid therapy: [02,03,05,]
1. Single high dose or short course of high
dose therapy are not likely to be harmful in
absence of contraindications.
2. In case of severe illness, start with high dose
and gradually decrease dose after symptoms
subside till correct dose is attained.
3. In case of mild illness, start with lowest
dose and gradually increases till correct
doses is attained.
SCIENCE MBBS

4. No sudden withdrawl of therapy after
having given for (2-3) weeks or else may
precipitate adrenal insufficiency.
5. In case if severe trauma or stress
superimpose during corticoid therapy then
increase the dose.
6. Use local therapy as far as possible e.g.
cutaneous, inhaled, intranasal route, etc.
Adverse effects: [01,08,09,10,11]
a. Adverse effects of mineralocorticoids:
 Hypernatremia  volume overload & HTN,
edema.
 Hypokalemia  cardiac arrhythmia
 Metabolic alkalosis  es neuronal
excitability & lowers seizure threshold
b. Adverse effects of glucocorticoids:
 Cushing habitus  moonface, buffalo
hump, fish mouth.
 Fragile skin, purple striae esp in lower
abdomen & thigh.
 Hyperglycemia (due to  hepatic
gluconeogenesis), DM.
 Muscular weakness (due to  muscle
protein catabolism)
  susceptibility to infection (due to 
lymphoid tissue) TB, fungal & viral
infections.
 Delayed wound healing.
 Peptic ulcer with perforation
hemorrhage.
 Cataract & glaucoma
 Growth retardation (because es GH
secretion & early epiphyseal fusion) in
children
 Psychosis and nervousness
 IUGR, gestational DM & hypertension, pre-
eclampsia in pregnancy
 Negative calcium balance and osteoporosis
Contraindications of corticosteroids:
[01,08,09,10,11]
- DM (Diabetes mellitus)
FAST TRACK BASIC
Endocrine
- Osteoporosis
- Viral fungal , TB, infection
- Epilepsy
- CHF (Congestive Heart Failure)
- HTN (Hypertension)
- Renal failure
(@ DOVE got CHF)
Corticosteroid synthesis inhibitors:
- Metyrapone  inhibits 11– hydroxylase  
cortisol synthesis
- Aminogluthimide
- Ketoconazole  non–selective inhibitor of
adrenal & gonadal steroid synthesis.
- Mitotaine  causes necrosis of adrenal cortex
- Mifepristone  in large doses, blocks
glucocorticoid receptor i.e. glucocorticoid
antagonist. So, used in cushing syndrome.
DRUG THERAPY FOR DIABETES
MELLITUS
Past Questions:
1. a. Enumerate the preparations of human insulin. VI
(3)
b. Mention the advantages of human insulin.
(3)
c. Mention the conditions of diabetes mellitus
where insulin must be used. (2)[09]
and 2. Enumerate the antidiabetic drugs. Describe the
mechanism of action and adverse effects of
sulfonylureas. (3+2+2=7) [09]
3. List antidiabetics. Give the mechanism of action
and side effects of metformin. (2+3+2=7) [05]
4. List oral antidiabetic drugs. Describe the
mechanism of action and adverse effects of
sulphonylureas. (2+3+2=7) [10]
5. Enumerate anti-diabetic drug. Describe the
mechanism of action of oral hypoglycemic agent
(3+4=7) [05]
6. Classify anti-diabetic drug. Explain the mechanism
of action of metformin in diabetic mellitus.
SCIENCE MBBS -505-
 Pharmacology

(4+3=7) [04]  Diabetes – review & pathogenesis  refer

7. Name the drug of choice in following condition Pathology of Endocrine system.
giving reasons: A. Classification of insulin as per duration
a. Type II diabetes mellitus with later month of of action:
pregnancy (3) [04] 1. Rapid/Ultrashort acting:
8. List insulin obtained from various sources.  Insulin lispro
Mention the advantages of human insulin. What  Insulin glulisine
are the adverse effects of insulin?
 Insulin aspart
(2+3+2=7)[03]
2. Short acting:
9. Compare and contrast human and other insulin.
 Regular insulin or crystalline Zn insulin.
(303]
10.Name the drug of your choice in the following  Semilente insulin
condition, giving reasons 3. Intermediate acting:
a. Diabetic ketoacidosis (3) [02]  Neutral protamine Hagedorn (NPH) or
11.Mention the drug therapy at maturity onset Isophane insulin
diabetes. (2) [02]  Lente insulin (Insulin zinc suspension)
12.Classify the drug used in diabetes mellitus. 4. Long acting:
Describe the mechanism of action and adverse  Protamine zinc insulin (PZI)
effects of sulphonylureas. (2+3+2 =7) [01]
 Ultralente insulin
13. Describe briefly the mechanism of action,
therapeutic uses and side effects of insulin B. Oral hypoglycemic drugs: [01,04,05,09,10]
preparations. (32+2=7) [08] 1. Insulin secretagogues:
VI 14.Write short notes: a. Sulfonyl ureas:
a. Drug therapy of maturity onset diabetes(2) [02]  1st generation: Tolbutamide,
b. Chlorpropamide (3) [02] Chlorpropamide.
c. Oral antidiabetics (3) [07]  2nd generation: Glipizide, Glimeperide,
Glibenclamide (Glyburide), Gliclazide.
d. Anabolic effects of insulin (3) [11]
b. Meglitinide derivatives/D—phenylalanine
e. Difference among insulin preparations (3) [08]
derivatives:
f. Sulphonylurea compound (3) [04]
 Repaglinide,Nateglinide
15.Write the pharmacological basis for the use of:
2. Biguanides: Metformin, Phenformin.
a. Glipizide in diabetes mellitus (3) [09]
3. Thiazolidinediones: Rosiglitazone, Piaglitazone.
b. Sulphonylurea as antidiabetics (3) [08]
4. -glucosidase inhibitors: Acarbose, Miglitol.
c. Biguanides in diabetes (3)10, 01]
Goals of therapy:
d. Metformin as anti-diabetics (3) [03]
- Avoid symptoms due to hyperglycemia
e. Metformin in type II diabetes mellitus (3) [11] (FBG≤100)
f. Metformin in diabetes mellitus (3) [06] - Prevent short term complications (infections,
g. Metformin in obese elderly diabetic without ketoacidosis)
complication (3)(03,07) - Prevent long term complications ( micro- &
16.Write about the sources, preparations, uses and macro-vascular)
adverse effects of insulin. [1+2+2+1=6](013) - Improve quality of life & occupation
- Bring HbA1C < 7.0%

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 Endocrine

Treatment: glycogen synthase and inhibiting glycogen

Type 1 DM:
- Replacement therapy with insulin
- Addition of insulin sensitizer
Type 2 DM:
- Oral hypoglycemic agents
- Insulin in some selected cases
Insulin:
- Banting and Best discovered it in 1921.
Preparations of human insulin: [03,09]
- Prepared by recombinant DNA technology in
E.coli or yeast or by enzymatic modification of
porcine insulin.
1. Human actrapid: Human regular insulin.
2. Human monotard: Human lente insulin.
3. Human insulatard: Human isophane insulin.
4. Human actraphane: Human soluble insulin
and isophane insulin.
5. Huminsulin.
6. Human mixtard.
Action:
- It is hypoglycemic hormone reducing blood
sugar to normal level especially after meal.
- It is anabolic in nature.
i. On Glucose metabolism (esp. in liver)
a. es glycogenesis (in liver & muscle) & es
glycogenolysis (in liver) by activating
Mechanism of Action:
phosphorylase respectively.
b. es gluconeogenesis in liver via decreasing
gene mediated transcription of PEPCK enzyme.
c. es glucose uptake & utilization by tissue via
ing synthesis and translocation of GLUT1 and
GLUT4 from cytoplasm to cell membrane.
ii. On lipid metabolism (esp in adipose tissue):
a. Insulin activates phosphodiesterase enzyme

es cAMP level

Prevents activation of hormone sensitive lipase

es lipolysis

es free fatty acid and glycerol level in blood.
b. Insulin  es transcription of Lipoprotein
lipase (LPL) in endothelium.

es clearance of VLDL and Chylomicron.
iii. On protein metabolism (esp. in muscle):
a. es AAs uptake and protein synthesis by
cells.
b. Inhibits protein breakdown esp. in muscle VI
so anabolic & positive nitrogen balance.
Insulin

Binds insulin receptor which consists of 2 extracellular  subunits (insulin binding site) and
2 transcellular  subunits (having tyrosine protein kinase activity)

Activates tyrosine protein kinase

Phosphorylation of insulin Receptor substrate

Secondary messengers (PIP3) Phosphorylation and

dephosphorylation of several enzymes

Rapid metabolic Activates MAP kinase and increases mRNA Translocation of GLUT1 & GLUT4
action on glucose, transcription of enzymes & carriers from cytoplasm to cell membrane
lipid & protein
Increases cellular proliferation &
Glucose entry into cytoplasm
differentiation
FAST TRACK BASIC SCIENCE MBBS -507-
 Pharmacology

Preparations of Insulin [013] - High 1st pass metabolism

Preparations Source Plasma t1/2 is (5-9) min

Insulin delivery systems:
a. Rapid acting
- Disposable insulin syringe
- Regular insulin - Bovine pancreas
- Portable pen injector
- Human actrapid - Human pancreas - Continuous subcutaneous insulin infusion
(by Rt-DNA (CSII):
technology using
 Regular insulin, insulin Lispro, aspart &
E.coli) glulisine
- Actrapid - Highly purified (HP)  Abdomen, flanks, thigh
porcine insulin  Physiological, excellent glycemic control,
b. NPH (Natural Protamine Hagedorn) insulin: expensive
- Inhaled insulin
- Insulin Isophane - Bovine pancreas
 To control mealtime hyperglycemia
- Insulatard - HP porcine insulin
- Implantable pump & external artificial
c. Lente insulin pancreas
- Insulin Zn (Lente) - Bovine pancreas Uses: [02,03,08,09]

- Monotard - HP porcine insulin. i. Diabetes mellitus:

d. Protamine Zn insulin
VI - Insulin protamine Zinc - Bovine pancreas
Advantages of human insulin over other insulin:
[08]
1. More water soluble than porcine or bovine
insulin.
2. More rapid subcutaneous absorption.
3. Earlier onset of action and more defined
action.
4. Greater stability and consistency especially in
recombinant form of insulin e.g. insulin lispro.
5. Lower incidence of hypoglycemic episodes
especially with recombinant form of insulin.
Pharmacokinetics:
- Orally inactive (since completely digested)
- Given parenterally. Injected or naturally
released insulin is metabolized in liver mainly
and some portion in kidney & muscle.
- Type – I  (0.4 -0.8) U/kg/day s.c. before
each major meal.
- Type –II  (0.2 – 1.6) U/Kg/day depending
on severity of diabetes.
- Prevents hyperglycemia, glycosuria and
complications of diabetes mellitus.
- Also used in DM controlled by diet &
exercise only when there is:
a. Pregnancy, surgery, trauma.
b. Perioperative period and labour pain.
c. Complications of DM e.g., Diabetic
ketoacidosis, coma and wet gangrene of
foot.
d. Post pancreactomy
ii. Diabetic ketoacidosis & coma [02]
- Common in type – 1 DM and arise due to
infection, trauma, pancreatitis and acute
stress.

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 Endocrine

Mechanism of diabetic ketoacidosis & coma:

Deficiency of insulin

Hyperglycemia Ketosis

Glycosuria Vomiting & loss of Compensatory Impaired

electrolytes hyperventilation glucose entry
into brain
Osmotic diuresis & loss of
electrolytes
DEHYDRATION

Plasma hyperosmolarity
&  blood volume

Hypoperfusion to tissue Intracellular dehydration

SHOCK Impaired consciousness

and COMA
Treatment: Conditions of Diabetes mellitus where
1. Diabetic ketoacidosis: insulin must be used. [09] VI
a. Insulin injection: 1. Type-1 Diabetes mellitus.
 (0.1-0.2)U/kg i.v. bolus dose of regular 2. Post-pancreactomy diabetes & gestational
insulin followed by 0.1U/kg/hr infusion. diabetes.
b. Intra venous fluids containing normal saline: 3. Primary or secondary failure of oral
 Infused at the rate of 1 lt/hr & gradually hypoglycemics or intolerance.
reduce to 0.5 lt/hr. After blood glucose level 4. Underweight patient.
falls to 300 mg/dl, 5% glucose in ½ N saline 5. Temporarily to tide over infections, trauma,
is infused. surgery, pregnancy.
c. KCl, NaHCO3, phosphate: 6. Peri-operative period of labour.
 To replace electrolytes lost in urine, 7. Complications of diabetes e.g. Diabetic
vomiting and acidosis. ketoacidosis, non-ketotic hypersmolar coma,
d. Antibiotics: gangrene of extremities.
 To treat infection precipitating emergency Adverse effects of Insulin: [03,08]
condition. - Hypoglycemia:
2. Non-ketotic hyperosmolar coma:
 Most severe adverse effect arises due to
- Common in Type -2 DM of elderly age. higher insulin dose or omission of meal
- Mechanism : similar to DKA after insulin injection.
- Management: Similar to DKA but NaHCO3 is not  Leads to counter regulatory sympathetic
required in it but heparin therapy is to be stimulation (palpitation tremor, anxiety)
added to prevent thrombosis due to and neuroglucopenic symptoms (confusion,
hyperviscosity of blood & sluggish blood flow. convulsion & coma).
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 Pharmacology

- Allergy – urticaria, angioedema. - Not effective in pancreactomised patient (since

- Lipodystrophy, swelling & erythema at site of no -cells) or Type – 1 DM (since > 70%  cells
injection. are non –functional)
- Edema temporarily - Other actions:

- Obesity.  es serum glucagon level.

Insulin resistance:  Upregulation of insulin receptors in target

tissue.
- It is the decreased response of cells of the body
Adverse effects: [01,09,10]
to insulin
i. Hypoglycemia
- May be due to:
 Especially in elderly patient with hepatic
 Anti-insulin antibodies
and renal dysfunction.
 Decreased number of insulin receptors
Note:
 Reduced binding of insulin
- Chlorpropamide causes more severe hypoglycemia
 Mutations of GLUT4
than other SU
Types:
a. Acute- Infection, trauma, surgery, ketoacidosis ii. Non-specific side effects:

b. Chronic- Pregnancy, OCP, Cushing syndrome,  Nausea, vomiting, diarrhea, constipation,

acromegaly headache.
Treatment: iii. Hypersensitivity.
- Lifestyle change (fibrous diet, regular exercise) iv. Specific side effect:
- Medication (purified insulin, human insulin +  Chlorpropamide  Cholestatic jaundice,
biaguindes/thiazolidinediones) dilutional hyponatremia, alcohol intolerance.

VI Oral hypoglycemic drugs: [07]  Tolbutamide   I- uptake by thyroid tissue

Indication of oral hypoglycemic agents: Contraindications:
- Age > 40 yrs at onset of disease  Renal failure
- Obesity  Pregnancy (since traverse placenta)
- Duration < 5yrs  Nursing mother (since secreted in milk)
- FBG < 200mg/dl ii. Meglitinides/D-phenylalanine
- No complications when starting the treatment analogues:
i. Sulfonyl urea (SU): [02,04] 1. Repaglinide:
Mechanism of action: [01,05,09,10] Mechanism of action:
- Binds to SUR 1 (Sulfonyl Urea Receptor 1) on  Similar to SU
cell membrane of  cells Use:
  Due to rapid onset & shorter duration of
Blocks ATP sensitive K+ channels action, it is taken ½ hour before major meal &
 reduce POST-PRANDIAL HYPERGLYCEMIA. It is
Depolarization given only in type 2 DM as alternative to
 sulfonyl urea (SU).
 intracellular calcium level [MCQ 2013]
 2. Nateglinide:
Release of insulin into circulation from  cells  Given (10-20) min before meal.

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 Endocrine

Adverse effects: - es glucose level in blood but not effective as

i. Dizziness sulphonyl urea and Metformin.
ii. Flu like symptoms - Also, es serum TAG level & es HDL level
iii. Nausea, arthralgia without change in LDL.
iii.Biguanides – Metformin & phenformin Adverse effects:
Mechanism of action: [04,05]  Plasma volume expansion
- Mainly suppresses hepatic glycogenolysis and  Edema
glucose output from liver into blood.  Weight gain
- Translocates GLUT1 (not GLUT4) to cell  Headache, myalgia & mild anemia
membrane unlike insulin.  CHF & liver dysfunction.
- es insulin mediated glucose uptake in muscle Use:
& adipocytes.  As adjuvant to SU or Metformin in Type II to
- es glucose absorption from intestine. overcome insulin resistance.
Adverse effect: [05] Contraindication:
 Metallic taste.  Pregnancy
 Lactic acidosis (since interferes mitochondrial v.  - Glucosidase inhibitors:
respiratory chain and es anerobic glycolysis) Mechanism of action:
esp in alcoholics, hepatic & renal disease, CVS It is complex oligosaccharide
and respiratory disease and hypotensive 
patient. So, Phenformin is not used. Reversibly inhibits intestinal brush border enzyme
called as  -glucosidase enzyme
 Abdominal pain, anorexia, nausea

 Vit B12 deficiency. Prevents digestion of carbohydrate & sucrose
Contraindications: 
 Alcoholics Less absorption of glucose VI
 Patient of hepatic renal, CVS or respiratory 
disease. No post-prandial rise in blood glucose level
 Patient of hypotension Use:
 Pregnancy  As adjuvant to SU.
Uses: Adverse effects:
 1st line drug for Type–II DM esp in obese patient.  Flatulence, Abdominal discomfort, diarrhea.
 Can be combined with other antidiabetic drugs. Summary of treatment of diabetes:
 Polycystic ovary. 1. Non-pharmacological
iv. Thiazolidinediones: - Dietary control (more fibrous & less
Mechanism of action: carbohydrate diets)
- Selective agonist for nuclear receptor PPAR- - Regular exercise
(Peroxisome proliferate activated receptor- )
2. Pharmacological

Type 1 DM:
Enhances gene transcription of cytokines
increasing insulin sensitivity cytokines eg. - Insulin
Adiponectin - Insulin ± Insulin sensitizers (Bigaunides/
 Thiazolidinediones)
es insulin resistance and es insulin sensitization - Insulin- 2 doses of intermediate acting insulin/
in tissues single dose long acting insulin to maintain basal
 level + Insulin Lispro/Aspart/Glulisine/ regular
 glucose entry to adipose tissue & muscle insulin to control post meal hyperglycemia

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 Pharmacology

Type 2 DM:  Increasing glycogenolysis

nd
- Sulfonylureas (2 generation)  Decreasing glycogenesis
- Sulfonylurea + Biguanide  Decreasing glucose uptake by cells
- Sulfonylurea + Biguanide + Thiazolidinedione c. In intestine, relaxes smooth muscles &
inhibits gastric acid production.
- Postprandial hyperglycemia
Uses:
 Sulfonylurea/Biguanides + Meglitinides/ - -blocker overdose resulting cardiogenic
Acarbose shock.
- Insulin ± Sulfonylurea/ Biguanide/ Meglitinide - Radiology of Bowel.
Glucagon - Severe hypoglycemic emergency. (common in
 Single polypeptide chain of 29 Aas secreted by  - Type – 1 DM) where patient is unconscious &
islet cells. oral glucose feeding is impossible (0.5 -1) mg
Mechanism of action: i.v or i.m.
Binds it own receptor (G protein coupled) on - Used in endocrine diagnosis as in
target cells
pheochromocytoma.

Activates adenylyl cyclase Other hypoglycemic drugs
  Diazoxide (K+ channel opener)  inhibits insulin
 CAMP level in liver adipocyte, heart and shows release (opposite to SU action).
following effects:
 Thiazide diuretics & phenytoin.
a. In heart, es inotropic & chronotropic
 Somatostatin  inhibits insulin release.
effect
 Streptozocin  selectively destroys  -cells.
b. In blood es glucose level by:
 Increasing gluconeogenesis
VI

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 Endocrine

SPECIAL POINTS FOR MCQs

1. Drug of choice for hyperprolactinemia is Bromocryptine & cabergolin.
2. Use of phenformin is associated with development of Lactic acidosis and megaloblastic anemia.
3. Oral hypoglycemic causing Cholestatic jaundice is Chlorpropamide.
4. Hyperprolactinemia is adverse effect of Metaclopromide.
5. Newer insulin are Monomers .
6. Insulin having longest duration of action is Protamine zinc insulin.
7. Best insulin preparation for i.v. injection is Regular insulin.
8. Tolbutamide acts via production of insulin from pancreas.
9. Anti-diabetic used safely in renal failure is Rosiglitazone.
10. Insulin casues K+ entry into cells.
11. Deoxy corticosterone acetate is the corticosteroid without any glucocorticoid activity.
12. Mifepristone is glucocorticoid receptor blocker.
13. Metyrapone is useful in congenital adrenal hyperplasia because it inhibits 11 -  -hydroxylase
enzyme.
14. Thyroid hormones sensitize heart to catecholamines.
15. High dose of iodine is used preoperatively for thyroidectomy to make the gland firm & less VI
vascular.
16.  adrenergic blockers are drug of choice for thyroid storm.
18. β particles emitted by I131 pierce only 0.5 - 2 mm of tissue.
19. Most important adverse effect of antithyroid drugs or radioactive iodine is hypothyroidism due to
overdose.
20. Propylthiouracil inhibits peripheral T4 to T3 conversion.
21. GH controls growth of almost all organs of body except brain & eye.
22. GnRH agonists stimulate gonadotropin secretion when given in a pulsatile manner whereas
inhibit the release when continuous administration is given.
23. Liothyronine (T3) is short acting and useful in emergency situations like myxedema coma.
24. L-thyroxine (T4) is long acting, less potent and useful in long term use in hypothyroidism.
25. Propylthiouracil is the drug of choice for hyperthyroidism during 1st trimester or pregnancy
whereas for non-pregnant woman and male, methimazole is preferred.
26. Iodides are the fastest acting antithyroid drugs.
27. 2 receptor stimulation inhibits insulin secretion whereas β2-agonists and vagal stimulation
enhances insulin release.

FAST TRACK BASIC SCIENCE MBBS -513-

 Pharmacology

28. Hypoglycemia is the most common complication of insulin therapy.

29. Metformin is the only oral agent that has been demonstrated to reduce macrovascular events in
type II DM.
30. Dexamethasone suppression test is used to test the intactness of hypothalamo-pituitary-adrenal
axis function and diagnosis of Cushing’s syndrome.
31. Bisphosphonates are used for treatment of :
i. Post-menopausal osteoporosis
ii. Steroid induced osteoporosis
iii. Paget’s disease
iv. Hypercalcemia of malignancy.
32. Tolbutamide is the shortest acting sulfonylurea whereas chlorpropamide is the longest acting
sulfonylurea.
33. Metformin and phenformin are biguanides which are preferred for obese patients since they also
causes weight loss.
34. Fludrocortisone is the most potent mineralocorticoids used clinically while Betamethasone is the
most potent glucocorticoids.
35. Long term use (>2weeks) of corticoids can lead to hypothalamo-pituitary adrenal axis suppression.
36. Steroids are contraindicated in psychosis due to CNS stimulatory action and in epilepsy due to
lowering of seizure threshold.
VI 37. Ketoconazole is an anti-fungal agent used for treatment of Cushing syndrome.
38. Spironolactone & Eplerenone are aldosterone receptor antagonists that are used as K+ sparing
diuretics.
39. Drospirenone, a progestin also antagonizes the effects of aldosterone.
40. Cinacalcet acts as calcimimetic drug by directly activating calcium sensing receptors (CaSR) on
parathyroid gland. So, used in secondary hyperparathyroidism.
41. Selective glucocorticoid action with no mineralacroticoid activity is shown by Methyl
prednisolone, Triamcinolone, Dexamethasone and Betamethasone.

-514- FAST TRACK BASIC SCIENCE MBBS