Endocrine Pharmacology

703
 .__ \ C' l - f' ' ' \ \.

Defmjtion : Diabetes mellitus is a clinical syndrome characterized by hyperglycemi a due to abso lute or re lative defic iency c,f
II {~Jlrn. ·
(Ref: Davie/son \ -22nd)
Classification : Most cases of OM can be separated into 2 types-
!. Type-/ diabetes or Insulin dependent diabetes mellitus (JDDM) (Juvenile onset diabetes): Occurs before age 20
yrs due to lack of insulin.
2. Type-2 diabetes or No11-i11.m/i11-depe11de11t diabetes mellitus (NJDDM) (Adult-onset diahete.\) : occurs after age 40
yrs due to decreased sensitivity of tissue to insulin. It is more common.

Features
' I Type •·DM I Type II DM -
• Age at onset Usuall y< 20 years Usually> 40 years
• Body weight at time of disease onset Normal or low Obese
• Plasma insulin Low or absent Normal or high
• Insu lin sensitivity Normal Reduced
• Therapy Insulin Weight loss, oral hypoglycemic agent
• Ketonuria Yes No
• Rapid death without insulin thera py Yes No
• Family history of diabetes No Yes
• Autoantibodies Yes No
• Diabetic complications at diaimosis No 20%
(Ref Guyton- 12th: Davidson 's-22'"')
Clinic.)fii/4atures of DM
.JI/ Polyuria (frequent urination)
L. Polydrpsta (excessive thtrst)
3. Po lyphagia (excessive hunge,)
4. Rapid weight loss
5. Nocturia (abnormally excessive urination during the night.)
6. Weakness

Insulin
Structure of insulin : Insulin is a polypeptide contain ing two chai ns of amino acids (A & B) linked by disulfide bridges (S-
S). It contains 51 am ino ac ids, 2 1 in A chain & 30 in B chai n. When the two chains are split apart, the function al activity of
the insulin is lost.
(Ref Ganong-2-lth edition)
thesis & secretion:
• Gene-+ mRNA -+ Preproinsulin -+ Proinsulin -+ Insulin & C peptide
• C peptide can be measured by radioimmunoassay, and its leve l provides an index of B cell func tion in patients
receiving exogenous insulin.
(Rel Ganong-24th edition)
Storage of insulin: Granules within the B ce lls store the insulin in the fo rm of crystals consisting of two atoms of zinc and
six molecules of insu li n.
Secretion of insulin: Insulin secretion stimu lated by-
1. Glucose (main stimul us) c:_ j C1
1

, rs::.·+- C f'- pk J
2. Other sugars (eg, mannose)
(.• -/ ( 'r,---=:; , (\.( 5)5f (. ' L'---
3. Certain amino acids (eg, leucine, argini ne)
4. Hormones such as glucagon-like polypeptide- I
5. Yagal activity
(Rel Kat::1111g-l Jth}
ulin de radation:
Endogenous insulin
• Liver- 60%
• Kidney- 35-40%
 705 Endocrine Pharmacology
Exogenous insulin
• Kidney- 60%
• Liver- 30-40%.
Half-life of insulin : The half-life of circulating insulin is 3- 5 minutes.
(Ref Kat::11ng- I 3th)

Q. Give the mechanism of action of insulin . (CU-l 6J, I 0Ju,09J)

An
M chanism of action of insulin:
Insulin binds to the a-subunit of its receptor
,!,
Autophosphorylation of the ~-subunit of the insulin receptor
,!,
Activation of tyrosine kinase activity of the intracellular portion of the ~-subunit
,!,
Phosphorylation of some cytoplasmic enzymes & dephosphorylation of others
,!,
Activation of some of these enzymes & inactivation of others
,!,
Effects of insulin including:
• Translocation of glucose transporters (especially GLUT 4) to the cell membrane with a resultant increase in
glucose uptake;
• Increased glycogen synthase activity and increased glycogen formation;
• Multiple effects on protein synthesis, lipolysis, and lipogenesis;
• Activation of transcription factors that enhance DNA synthesis and cell growth and division .
(Ref Katzung-l 3th; Guy!On-l 2th: Ganong-24th)

Insulin

Insulin
a. S-S receptor
s-s-- S-S

Glucose

I
J I
Cell membrane

I
Tyrosine Tyrosine
kinase kinase
Insulin receptor substrates (IRS)
Phosphorylation of enzymes

,_ ~l~t-s:- -I----F~~ ----r- --~~!w-t:-

transport synthesis and gene
, expression

''' ,0 Protein
synthesis
Glucose
synthesis

Figure: l\lleclw11is111 uf'ins11/i11 action (Ref Ci11ytu11)

 Bl ueprmt
. T ·\ I Pharmaco loi;,')' 706
Q. How does glucose sti mulate insuli n release'? (CU- I5Ju )
Ans.
HQ.U: glucose stimu lates insul in release:
Presence of glucose in the gut
t
Secretion of gut horm ones ' or incretin s' eoo , 0olucagon-like pe1Jtide (GLP-1)
~

t
lncretins stimulate insulin secretion in a glucose-dependent mann er; thu s hypoglycemia does no~occ ur.
(Ref: Katzung-/ Ji!,;

Q. )Yl tare the pharmacological actions of insuli n? (RU-07Ju)

A lS :
abolic effects of insulin / Actions of insuli n:
Type - '. IL'1ver : .·, ·.·· :~- ' ,,. . ISkeletalmuscle>.~.'-' .• ,:_ IAdiposeTissue'··: .,. ·,, ."
• Carbohydrate i Glycogenesis i Glucose uptake i Glucose uptake
metabolism i Glycolysis i Glycolysis i Lipogenesis from glucose
,J, Glycogeno lysis i Glycogenesis
,J, Gluconeogenesis ,J, Glycogenolysis
• Protein i Protein synthesis i Amino acid uptake
metabolism i Am ino acid uptake i Protein synthesis
,J, Protein catabolism
,J, Re lease of
gluconeogenic amino acids
• Fat metabolism i Lipogenesis i Ketone uptake i Fatty acid synthesis
,J, Ketogenesis i Glycerol phosphate synthesis
i Triglyceride deposition
EB Lipoprotein lipase
(-) Hormone sensiti ve lipase
• K+ uptake t t
• General i Cell growth
(Ref Ganong-24th; Guyton-1 2th)

Q. Mention how insulin lowers blood glucose level. (DU- IJJ, IIJ, CU-l5J , RU -17J, 15J, 12Ju , IIJ, SU-
17J, l 6J u/J, I JJ, 121 u)
Q. Explain antidiabetic effects of insu lin . (SU-l 3Ju,08Ju)
Q. Elaborate antidiabetic role of insulin glargine. (SU -I4J)
Q. Explain hypoglycemic role of insulin . (SU-07 J u,06S)
Q. x ain the mechanism of action of insulin. (CU -14J, 12J, l0Ju)
E lain blood glucose controlling action of insulin. (SU-I 2Ju)
. ow do the insulin preparations lower elevated glucose level? (RU- I 4J)
A s.
of insulin / insulin glargine: Insulin lowers blood glucose leve l by the fo ll ow ing
mechanisms-
i Glycogenes is
iG lucose uptake
iG lyco lysis Decreases blood glucose
tG lycogenolys is
tG luconeogenes is
 707 Endocrine Pharmacology
rce
1 to 110111 . . . .
. '' .s O 'irisu/i11: According 10 so urce ins ulin is o/'3 ty p es.
~ /. Bovine insulin: Obta inedji·om c o 1I•. It cli(l'ers/i·o111 hum an insulin hy_l.1.1.1A-irro acids & it is more (.tnti,(!,e nic.
J. Porcine j:1.5,ufi: 1 :_ Obrnine dfr o m pork: It d[f/ersfi ·om ln1111011_insul{n b), / ll/111110 ~1c id & thush.'SS i11111111n :'·1!,l:!l1il'.
3. Human msulm . This ts made e ithe , hy e11::.y 111 e mod!ftc a/1011 oj porc in e ,nsu/111 o r hy 11s111g recomb111,111I D NA 10
\ !lynth es i::.e th e Promsulin. This is don e by introducing the DNA int o e ith er £. co il or J1e as1.
· (R e{ !J enn ell & /Jrown-! Ith)

Q. Classify _aytidiabetic drugs. (SU- l 6Ju , 16J)

Q. Catego ~ e the drugs_ for DM? (DU-06M ; C U-0SJ ; RU-06S)
Q. Classy y hypoglycemic agents. (SU-17J)
Ans. /
A.oi'ict<a betic drugs accordin g to mode of action:
K Parenteral hypoglycemic agents: In s ulin
B. Oral hypoglycemic agents (OHA): See be low

Parenteral hypoglycemic·agent· ., Insulin

Q. Enumerate different insulin preparations. (CU-06S ; RU- l 4J,07 Ju ; SU- l 2J ,06J)
Q. Name the different preparations of human insulin. (CU-06M)
Q. Classify insulin preparations according to duration of action . (DU-1 SJu, I 4Ju , 1 I Ju , CU-08Jan)
Q. Name the different insulin preparations on the basis of kinetic properties . (SU-1 SJu)
Q. Mentio the duration of action of different insulin preparations . (RU-07.Ju ,06M )
Q. Wl)'at ·s lispro Insulin ? (SU-06S)
Q. Wha are the insulin analogues? (CU-07Jan,06M)
Q. n 1st currently used insulin analogues? (RU- I SJ)
A
insulin preparations/ insulin analogues: In s ulin preparations are the on ly parente ral hypoglyce mic agent. Fo ur
principal ty pes of injected insulin s are av a ilabl e:
l. Rapid-actin g, w ith very fast o n set and short durati o n ;
2. Short-acting, with rapid o n set of acti o n;
3 . Intermediate-actin g; and
4. Long-acting, with s low o n set of act io n
An inha led fo rm o f rapid-actin g insulin a lso is m arkete d .
/

// //
Types Preparation of ins ulin ~ -setof LI>1uration of -=z!Route of
action action administration
1. Rapid acting or ,.-'I n s u lin Li s pro Within 15 min 3 -4 ho urs IV
ultra short i,Y1!1s ulin aspart
acting insulin • In s ulin Glulisine
•
Hum a n in s ulin reco mbin a nt inhaled
2. Short acting ,, ~
Regul a r in s ulin Within ½ to l 1/2 5 - 8 ho urs IV
insulin •
N a tu ra l in s ulin ho urs
So lubl e in s ulin
•
3. Intermed iate i~
NPH (Ne utral Protamine Hage dorn) or Within l-2 l 8-24 ho urs S ub c uta n~o us
acting insulin isop ha ne in sulin ho urs
• In s ulin z inc s uspe ns io n ( Le nte in s ulin )
4. Long acting v• C rysta llin e in s ulin z inc s uspe ns io n Within 3-4 2 0-36 ho urs S ub c utan eo us
insulin/ Insu lin (U ltral e nte in s ulin ) ho urs
Analogues L.,.(Prota min e z in c in s ulin s us pe ns io n
• In s ulin g la rg in e
• In s ulin cl ete mir
 ~
. CI.Ml"'- V"~\1
. -.....r
~\
.. - 0 ,J:-7
Blul'print 11 PharmacolOg)' 708
M'1xtures. of insulin·
1. Mixture of regular &
Insulin ,,..
NPH y' 20% regular & 8011/ci NPH insulin .
30% regular & 70% NPH insulin .
40% regular & 60% NPH insulin.
,.,. 50% regular & 50% NPH insulin .
-
2. Mixture of lispro & NPH Insu lin ,.,. 25% Lispro & 75% NPI-I insulin .
1•
/ 50% Lispro & 50% NPH 1nsu
. 1·111 .

(Ref Kotzung-!3th: Ciooclmun & Gil111u11·s-l2thJ

Nice to know
Insulin analog: An insulin analog is an a/teredflmn of insulin, d!fferen1.fi·o111 any occurring in nalure, bw .1·1ill uvai/ah/e In
th e human hody for perfcmning the sume action as human insulin in /erms c!fglycemic conlrol. Through genelic engineering
of 1he underly ing DNA, !he amino acid sequence cf insulin can be changed lo a/fer ifs ADkfE (absorplion , dislrihu1ion.
me1abolis111, and excretion) characteristics.

Th ese modijications have been used to create two types of insulin analogs:
I. Rapid-acting injected insulin analog: those !hat are more readily absorbed_ji-om the iniection site and lherefore uct
faster than natural insulin injected subcwaneously, in/ended 10 supply !he bolus level of insulin needed u/ meal!ime
(prandial insulin i.
2. long-acting injected insulin analogs: !hose thal are released slowly over a period c?f" between 8 and 24 hours,
inlencled to supply the basal level o_f'insulin during the day and particularly at nighttime (basal insulin).
(Re( WikipeJia)

Nice to know
• Soluble and neutral insulin are the same; the British National For11111lwy favours 1hefiJrm er term, but neu1ra/ is
the INN (imernationally approveclj name. Human, porcine and beef are available.
• lsoplHme insulin is the only approved name for suspensions of' insulin with protamine. Human, porcine and beef
are available; the lat/er is rarely used
• Biphasic insulins are, with one ex<.:eption, proprietwy mixtures of soluble (neutral) insulin and isophane insulin,
which provide soluble (neu tral) insulin at concenlrations between I 0% and 50% of' the to/a/ insulin concentration.
These preparations rem ove the need for potients to mix soluble and isophone insulins, without losing the flexible
administration of the right amount r?fso/11hle (ne 111ral) insulin 10 cover the meal following the dose.
• Mixed insulin zinc su.,pension is proprietw y mixtures of c,ystalline and amorphous ::.inc suspension.
(R ef Bennett & Brown-I Ith)

Nice to know
Insulin delivery n•stem:
I. Portable pen injectors: To facilitate multiple SIC inj. of insulin, particular()' during intensive insulin 1herap_r.
portable pen-size injectors have been develop ed. These contain cartridges of' insulin & replw:eah/e n!!edles.
2. Continuous insulin infusion devices (CSI/) or insulin pumps : The devices have a user-programmable pump 1hut
delivers individuuli::.ed basal & ho/us insulin replacem enl closes based on blood g/11 co.1·p sellmunitoring res11l1s.
(Ref Kut::.11ng-l31h)
Unit of Insulin : I JU of insulin is the hiologicol equivalent of about 45.5 Jig pure c1ysta!fi11e insulin (1/22 mg exac1/y). Th is
corresponds 10 the amount of insulin required to rec/11c:e the concentration ol blood glucose in a fas ting rahbi1 to 0.0../5 per
cent (../5 mg/ell or 2,5 mmolll ) within.:/ hours.
Strength of insulin : A vial of insulin is a combination q/ insulin horm one and a sterile liquid. culled the diluent. The
concentration of the insulin to the diluenl determines its strength. The "U" value of insulin indicates its strength - 1he number
re/11:c/s 1he numher of'ac/iv e insulin units in each ml of liquid. U-100 will have 100 units per ml, ancl U-40 has ../0 uni1.1·per
ml. Appropriate .syringes are mode jc)r use wilh the respective insulin, marked with th1: correc/ measure for dosage.

Daily insulin secretion : Insulin production by a normal, thin, healthy person is between 18 and 40 unitsldav or uboul O.] tu
0.5 uni1slkg 1?f"body weight per day. About half this amount is secr1:ted in the base,/ stale and about ha/fin r~.1ponse to meals.
Thus, basal secretion is abo111 0. 5 lo I 11ni1s/h; a/ier an oral glucose load insulin secretion rnav increuse to 6 11nits!h. In
nondiabetic:, obese, and insulin-resistant inclivid11ctls, insulin secretion 111uy be incrt'ased /imr/ulcl ~r more. Insulin is secr i!i t'J
into the portal circu/11tion, ancl aho11/ 50% is des!r uvecl hy !hi! liver hefiJ1·1: reaching the .1ys1em ic circulution.
 709 Endocrine Pharmacology
Daily insulin requirement:
• In _type 1 DM patients, the average dose of insulin is usually 0.6 to 0. 7 units/kg per day with a range of 0.2 to I
units/kg per day. ·
• Obese patients generally reG1uire m~r e (2 11111't!-11,·'k g per lay)
J because of·resistance
· ·
ofper,phera/ · ·
tissues to ,nsulm
Dose o(insulin
J. Split dose of intermediate-acting insulin
1
• 2/3" of total daily dose: Before breakfast
1
• 1/3" of total daily dose: Before dinn~r
Morning dose is adjusted according to the afternoon glucose level, and the evening dose is acijusted according to the
fasting glucose level.
Convention~{ therapy presently consists of split-dose injections of mixture of rapid or short-acting and intermediate-
act111g msulms.

2. Mu!tiple daily injection (MDI) therapy: Use long-acting or intermediate-acting insulins with multiple boluses ofrapid-
acttng or short-acting insulin.
Dose: 0.5 unit/kg/day (subcutaneously in 3 divided doses).
Time: Just before meal (B- BLD)
• B - B: Before breakfast
• B - L: Before lunch
• B - D: Before dinner
Current regimen generally uses intermediate- or long-acting insulins with rapid-acting or short-acting insulin.
• Intermediate- or long-acting insulins provide basal or back-ground coverage.
• Rapid-acting or short-acting insulin meet the meal-time requirement.

Q. wiatlare the routes of administration of insulin? (CU-08J)

Ans
Rcfutes of administration of insulin
1. Subcutaneous injection: The standard mode of insulin therapy is subcutaneous (S/C) injection usmg
conventional disposable needles & syringes.
Site: Abdomen, buttock, anterior thigh, dorsal arm .
Abs; pt1on is more~id from the abdominal wall, followed by the arm, buttock and thigh. Rotation of
inswin injection sites has traditionally been advocated to avoid lipohypertrophy and lipoatrophy.
2. Intramuscular or intravenous: In emergency situation (eg, diabetic ketoacidosis).
Inhaled insulin: This is finely powered & aerosolized human insulin & is readily absorbed into the
bloodstream through alveolar walls. It has rapid onset & peak insulin levels (by 30 min) & peak effect (2-
2.5 hrs) & duration of action (6 - 8 hours).

Q. What are the indications of insulin? (DU- I 4J, I !Ju, CU-12J , I0Ju,09/07/06J,05M; RU 17J; SU-07 J)
Q. Write down the absolute the indications of insulin. (CU-l 5JU)
Q( Write down the absolute indications of soluble Insulin. (CU-17 J)
'-A"t1S.
Indications of insulin:
I. Type-I OM (IDDM)
2. Uncontrolled type II OM
3. All diabetic complications:
• Diabetic ketoacidosis
• Diabetic nephropathy
• Diabetic neuropathy
• Diabetic retinopathy
• Hyperglycemic hyperosmolar state . .
4. OM in pregnancy (because insulin is not teratogenic but OHA are teratogenic)
5. Per-operative & post-operati# diabetic patient. L - - -

6. Diabetes with severe infection

~ Pharmacology-91
 BJueprintr,,i Pharmacology 710
7. Diabetic patient after RTA.
8. Hyperkalemia (as insulin increases K influx and thus decreases plasma K level).

Q. Short note: Insulin. (DU-17.1)

Ans. Write in short.fi·om above.

Q. Write the pharmacological basis of using Insulin for type II diabetic patient in perioperative period .
"'.---- (CU-13.Ju)
Ans.
Surgery and diabetes
Surgery, whether performed electively or in an emergency, causes catabolic stress and secretion of counter-
regulatory hormones both in normal and in diabetic subjects. This results in increased glycogenolysis,
gluconeogenesis, lipolysis, proteolysis and insulin resistance. In untreated or poorly controlled diabetes the uptake
of metabolic substrate is significantly reduced , catabolism is increased and ultimately metabolic decompensation
in the fonn of diabetic ketoacidosis may develop in both types of diabetes.
Thus surgery must be carefully planned and managed in the diabetic patient, with particular emphasis on good
metabolic control and avoidance of hypoglycaemia, which is especially dangerous in the unconscious or
semiconscious patient. To achieve this, insulin is used for type II diabetic patient in perioperative period.
(Ref Davidson 's-21''1816-817)

Q. A boy of 20 years has come to you with diabetes mellitus. What drug is suitable for him? (DU-09/08J :
RU-1 OJ)
Ans.
Drug of choice in a 20 years old diabetic boy: This is a case of type-! or juvenile or insulin dependent diabetes
mellitus. In this case there is absolute deficiency of insulin . That's why my drug of choice is insulin .

Q. How will you manage a pregnant lady with postprandial blood glucose level of 13 mmol/L? Justify your
choice of drug. What may be the risk of therapy? (DU-08/07Ju)
Ans.
Drug of choice in a pregnant lady with DM: Oral hypoglycemic agents (e .g. sulfonylureas) are teratogenic.
That's why oral antidiabetic drugs are absolutely contraindicated in pregnancy. So diabetes in pregnancy is
managed by insulin, not by oral hypoglycemic drugs.

Q. What are the adverse effects of insulin? (DU- l 4J, I3J , I2J , CU-14.1 , 12.1, I OJu,09/07 J,06S ; SU-07 J)
Q. Mentioq the complications of insulin therapy. (DU-OSM , SU-03 M) ·
Q. Men tibn the long-term complications of insulin therapy. (SU-13.1)
/
Q:)';fention the cautions of soluble insulin. (CU-OSM)
(
dverse effects I complications of insulin:
/1. Hypoglycemia (most common)
2. Insulin hypersensitivity
,,,3 . Insulin resistance
4. Lipodystrophy: Lipoatrophy & lipohypertrophy
f Insulin edema
6:- Obesity
7. Hypokalemia
8. Alopecia
9. Increased Cancer Risk
(Ref Goodman & Gilman 's-12'\ Katzung-13'1,)

Q. What is the management of insulin induced hypoglycemia? (DU-14.Ju, CU-06M, RU-I OJu)
Q. Write the management of insulin induced hypoglycemic shock. (DU-I SJ)
Q. How will you manage a case of hypoglycemic shock? (DU-13.1 , 12/1 IJ , CU-04J ; RU-13.1)
Q. How will you manage a case of drug induced hypoglycemia? (CU-I 7J)
 711 Endocrine Pharmacology
Ans .
. Ins1'i'lin induced hvpoglycemia / hypoglycemic shock:
'=
Mechanisms of hypoglycemia in a diabetic patient taking insulin: Hypoglycemic reactions are the moS t
common complication of insulin therapy. They may result from-
!. A delay in taking a meal
2. Inadequate carbohydrate consumed
3. Unusual physical exertion
4. A dose of insulin that is too large for immediate needs.

Clinical features of hypoglycemia: Rapid development of hypoglycemia in individuals with intact hypoglycemic
awareness causes signs of autonomic hyperactivity.
1. S~gns of sympathetic hyperactivity: Tachycardia, palpitations, severe sweating, tremulousness
2. Signs of parasympathetic hyperactivity: Nausea, hunger.
r 3. Sudden unconsciousness
4. If untreated, convulsion & coma & ultimately death .

Treatment of Hypoglycemia: All the manifestations of hypoglycemia are relieved by glucose administration.
1. Mild hypoglycemia in a patient who is conscious and able to swallow:
y
Simple sugar or glucose in a liquid form.
y ~extrose tablets, glucose gel, honey, sweet or any sugar containing beverage or food may be
grven.
2. In case of unconscious patient:
• 20-50 mL 50% glucose solution by IV infusion over 2-3 minutes.
• If IV therapy is ,lot available, lnj. Glucagon (1 mg) S/C or IM restores consciousness within 15
minutes.
• If glucagon is not available, small amounts of honey or syrup is given into_the-buccal pouch.
(Ref Katzung-1 Jth)

Q. What }8 insulin resistance? (RU-04M)

Q. Di cJss about insulin resistance and its management. (DU-l 5Ju,07M)
Q. Ho7 Insulin resistance develops? (RU-04M)
Qi hort note: Insulin resistance. (RU-15Ju)
n .
Insulin resistance: Insulin resistance may be due to a decline in number and/or affinity of receptors or to defects
in post-receptor mechanisms. A diabetic patient requiring more than 200 units/day is rare and regarded as insulin
resistant.

Types of insulin resistance:

I. lmmunogenic insulin resi stance
2. Non-immunogenic insulin resistance

A. Immunogenic insulin resistance: In most cases, it is lgE mediated hypersensitivity reaction & Ab is formed
against insulin . So, patient develops insulin resi stance.
Diagnosis: Measuring the insulin specific lgG & IgE antibodies. Skin test is also useful.
Treatment:
• By changing the brand. If the patient has allergic reaction to porcine insulin, human insulin should be
used .
• Antihistamine.
• Glucocorticoid .
B. Non-immunogenic insulin resistance: This is due to a decline in number &/or affinity of receptors or defects
in post-receptor mechanisms.
 Blueprint'''"" Pharmacology 712
Causes:
I. Inappropriate fr>llowing or the prescription
2. Obesity.
3. Hyperinsulinemia.

Treatment:
• Good dieting.
• Use of Sulfonylureas along with insulin (as sulfonylureas increase in sulin re~eptor synthes is)
• Phys ical exercise e.g. walking (it increases insulin sens itivity).
~ (Ref· Goodman & Gilman 's-/2th; Benne/I & Brown-/ hh;

Q. What are the advantages and disadvantages of Insulin over the oral antidiabetic agents? (CU- l 6J, 14J)
Ans.
Advantages of Insulin over the oral antidiabetic agents
l. Rapid onset of action
2. Can be used in pregnancy
3. Can be given in hepatic and renal insufficiency
4. Can be given in diabetic ketoacidosis.

Disadvantages of Insulin over the oral antidiabetic agents

l. Regular monitoring of blood glucose is necessary.
2. Risk of hypoglycemia is more.
3. Risk of hypersensitivity is more.
4. Needs regular injection.
5. Expensive
 713 Endocrine Pharrnacolobry

ri10il~lf4ijhtit•): u,
Q. Classify oral antidiabetic / hypoglycemic agents. (DU- I 2J, CU- I 7M, I 3J, RU-05M/J,04J ; SU-07 J)
Q. Enumerate important oral antidiabetic agents. (DU- ISJ , 14.1)
Q. Name the euglycemic agents. (SU-09Ju; RU-08.l u)
Q. Enumerate the drugs used in type-II diabetes mellitus. (DU-06M)
Q. Name the insulin secretagogues. (DU-I0Ju, RU-I6Ju,I5Ju,10Ju,07J, SU-II,I0.lu)
Q. Name t~e drugs of Insu lin independent DM. (CU -05.1)
Q. W
~ hat/ re the OHAs available in Bangladesh? (CU-04M)
Q. S r note: Insulin secretagogues. (DU-1 SJu)
Ans
OJi,tl antidiabetic / hv o lvcemic aoents OHA :
. Insulin secretagogues: Increase insulin release.
y. Sulfonylureas Ist generation ~ olbutamide
su lfonylureas • Chlorpropamide
1, Tolazamide
2nd t,oeneration /G libenclamide (in USA) or Glyburide (outside USA)
sulfonylureas Glipizide
• Gliclazide
/ ,___ •.,xilimepiride
_;i.
Meglitinides ) ·!-..J \_ ,-y-- - .,.- Repaglinide
3 D-phenylalanine
derivatives
) )_,_-~6l",
---~
~ L-
,,. Nategl inide

B. Biguanides: (insulin se,~~izer, euglycaemic agents) (J)

y Metformin
• Phenformin (not used now a day~)

C. Thiazolidinediones: Insulin sensitizer. Two thiazolidinediones are currently available: { f)

~~ Pioglitazone
Rosiglitazone

D. a-glucosidase Inhibitors: ( 'f~ )

. Acarbose
2. "' Miglitol

E. Synthetic Amylin Analog:

• Pramlintide

F. Incretin-based therapies
t. Iocretin mimetics / Synthetic analog of glucagon-like-polypeptide 1 (GLP-1):
./ .- E;enatide
2. Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors:

(Ref Kat::11ng-I 3th; lippincofl ·s-6th)

' '
<.. ..., ·-
 BlueprintT:\I Phannacoloh')' 714
Q. Define cuglycemics and hypoglycemic with example . (RU-1 2.lu )
A ns.
Euglyccmics: The drugs whi ch reduce (control ) or normali ze bl ood glu cose le ve l without any pot<:ntial
hypoglyce mi c ability arc ca ll ed euglycemi cs anti-di abeti c drugs. Eg, metlormin , pi og litazone.

Hypoglycemic: The drugs that can cause hypog lycemia or have the potenti al ri sk or hypog lycemic in cidence in
addition to their anti-diabeti c pro perty are ca lled hypoglyce mi c dru gs. Eg, in sulin , gli pizid e.
1
_ \ c,~\ , . (Re./ KA tzunr,- JJth ; Davidrnn 's -22nd)
- ' (), ' \t <' <;\.:,, .J'~

Nice to know
• The s11/fony/11reas and biguanides have been available the longest and are the traditional initial treatment choice Ji;r
type 2 diabetes.
• Novel classes of rapidly acting insulin secretagogues, the meglitinides and D-pheny/alanine derivatives, are
alternatives to the short-acting su/fonylurea, to/b u/amide.
• Th e thiazolidinediones, under development since the early I 980s, are ve1y effective agents that reduce insulin
resistance.
• Alpha-glucosidase inhibitors have a relative(v weak antidiabetic effect and significant adverse effects, and they are
used primarily as adjunctive therapy in individuals who cannot achieve their g/ycemic: goals with other medicwions.
(Ref Katzung-/ 2'"175-1- 758)

Sulfonylureas
Q. Write the mechanism of action of sulfonylureas . (DU-05J , CU-13J,09Ju, RU-I 2J, SU-l0Ju,04M)
Q. Explain antidiabetic action of glimepiride / glipizide. (SU- I5Ju, 14J,08Ju)
Q. Explai blood glucose controlling action of glimepiride. (SU-131, I2Ju)
Q. ~p ta· hypoglycemic effects of glipizide / glibenclamide. (CU-0SM;RU-07 J, SU-I 2J,09Ju,07J)
Q. y o does glipizide influence K+ ion channel in pancreatic pcell? (CU-I 4Ju)
A s.
echanism of action of sulfon Iureas/ Ii izide / libenclamide / lime iride:
Sulfonylureas increase insulin release from pancreatic P-cells by blocking ATP-sensitive K+channels:
Sulfo nylureas ---> Block the ATP-sensitive K~channels in pancreati c B-ce ll s ---> Dec reased outward potassi um
efflux ---> Depolarization of the B cell---> opening of vo ltage-gated calcium channels ---> In creased intracel lular
calcium---> Increased secretion of insulin.
(Ref Katzung-1 3th edition)
K+ channel

f:;:l \. 'c · ,,

,/21oses, K·
,: . ( ,, \.' ·-r
/ ucpolarizes)
,. I '
-
J'
·-,\.
ATP

t
Metabolism - +
ca2+ cl1annel
(depolarization
opens)

00
Insulin _-o •

Fig One model of control of insulin release jiwn the pancreatic cell by glucose and by s11/jfJ nylurea drugs.
fl
(Ref Kat::ung- 13th)
2. Reduction of serum glucagon level : Long-term admini stration of sul fo nylureas to type 2 di abetics reduc~s
serum glucagon leve ls, which may contribute to the hypoglyce mic effect of the drugs. The mec hani sm fo r this
 (' - \ C,, ( I _ 1,r~
'/ ~ I
- r"' r ), ) 'r- ( '

715 Endocrine Pharmacology

suppressive effect of sulfonylureas on glucagon levels is unclear but appears to involve indirect inhibition c.Juc
to enhanced release of both insulin and somatostatin, which inhibit A-cell sec retion .
; (RefKatzung-/Jth)

Q. What are the indications of sulfonylureas / glipizide? (CU-09/08Ju,05S; SU-07J)

Ans.
ImHcations of sulfonylureas / glipizide:
I. Type II DM in non-obese persons (In obese persons metformin is used)
2. In c om6111at1on with msulin in some type I & II OM patient (especially in insulin resistant cases as
sr onylureas increase insulin receptor synthesis)

ition the adverse effects of sulfonylureas / glipizide/gliclazide? (DU-06S ; CU-09/08Ju: SU-17 J)

An -.
~ verse effects of sulfonylureas / glipizide / glibenclamide:
l. Hypoglycemia
2. \.. e1 g1f1 ain )
3. IT upset: Nausea, vomiting.
4. Blood: Agranulocytosis, aplastic & hemolytic anemia, cholestatic jaundice.
5. Generalized hypersensitivity reaction.
6. Teratogenicity

Q. Will you recommend sulfonylureas in pregnancy or not? Justify your answer. (DU-06M)
Ans.
Gestational Diabetes Mellitus (GDM) / pregnancy induced DM is usually due to relative deficiency of insulin . So
GDM can be managed by sulfonylureas. But sulfonylureas are teratogenic . That' s why sulfonylureas are
absolutely contraindicated in GDM. So DM in pregnancy is managea by insLflin, not by oral hypoglycemic drugs.

Q. What are the contraindications of sulfonylureas?

Ans.
Contraindications of sulfonylureas:
[/ Type I OM
1.. Pregnancy & lactation
3. Significant renal & hepatic insufficiency
4. In elderly patient especially with cardiac impairment.
(Ref Good111a11 & Gilman 's-1 2rh)

Q. Wh ayfre the drawbacks of sulfonylureas? (DU-07J)

Ans. /
Drawbacks of sulfonylureas
'-' l. To get hypoglycemic effect, 30% of the total ~-cells of pancreas must be functioning.
2. Can only be given to NIDDM .
3. It cannot synthesize new insulins, but can release the stored insulin.
4. Cannot be given to pregnant women because of teratogenicity .
5. Cannot be given when more than 40 IU/da)( of insulin is needed.
6. These drugs are not adequate in diabetic complications.
7. Cannot be given in significant renal & hepatic insufficiency.
8. Secondary failure, ie, failure to maintain a good response to sulfonylurea therapy over the lon g tern1,
remains a disconcerting problem in the management of type 2 di abetes. A progressive decrease in B-cell
mass, reduction in physical activity, decline in lean body mass, or increase in ectopic fat deposition in
chronic type 2 diabetes also may contribute to secondary failure .

Q. A 55 years old obese female diabetic patient suffered from severe MI. she has been receiving 15 mg
Glipizide and her fasting blood sugar was estimated 220 mg/di.
• Design pharmacological management for her.
 Blueprint 1'" Pharmacology 716
• Explain tht' action of drugs ust•d. (SU- I O.lu)
;\ns.
l11 dderly patient espl!cially with cardiac impairment, Glipizidc (sullo nylurcas) is contrainclicalcd . So, we shoui
stop the drug immediately and should chose another, cg, insulin or mctlormin. u

Mechanism of action of meulitinides:

b
Same as sulfonvlureas.
.

Indication of meglitinides: To reduce postprandial glycemic elevations in type II OM.

Adverse effect: Hypoglycemia
Precautions of using meglitinides:
\ I. As repaglinide & nateglinide are metabolized mainly (90%) by the liver, they should be used cautious!
'\ in hepatic insufficiency. y
\ 2. A small proportion is also metabolized by kidney & excreted through it, so they should also be useu
cautiously in renal insufficiency.
(Ref Goodman & Gilman 's-f 2thJ

Biguanides: Metformin
Metformin is taken with or after meals. Its chief use is in the obese patient with Type 2 diabetes either alone or in
combination with a sulfonylurea. It has a mild anorexic effect which helps to reduce weight in the obese.
(Ref Bennett & Brown-ll th/6J5)
Q. ~_yJ-, m how metformin reduces blood glucose level. (DU-l0Ju,06S;CU-07J ,RU-08Ju,06J ,SU-06J)
J,'l.':l"te the anti-diabetic action of metform in. (CU-I 7M. l 6J u, 14Ju, SU-1 5Ju, I4J, IJJ u)
Mechanism of action of biguanicles / metformin: Their blood glucose-lowering action do! s not depend 011
functioning pancreatic B cells. Patients with type 2 diabetes have considerably less fasting hyperglycemia aswell
as lower postpranai~ir hyperglycemia after biguanides; however, hypoglycemia during biguanide therapy is
essentially unknown. These agents are therefore more appropriately termed "euglycemic" agents .
., . \_-\ ry--r--R <:'.'r-.c,.-r-- 6~ ~7':----,
Currently proposed mechanisms of action include- (_~"l"YC<'i<::., h'"'IS.,-.'-- ......, ) '
/r: reduced hepatic and renal gluconeogenesis; 6 \;r c ,~ .., -, --;' · p:-,.--\ <.. t...
Y. slowing of glucose absorption from the gastrointestinal tract, with increased glucose to lactate conversion
by enterocytes;
.J;,.direct stimulation of glycolysis in tissues, with increased glucose removal from blood; and
,A. reduction of plasma glucagon levels.
,-; r
3,....,'-, 1 -,,--_ , _,,...-,:...'-'-' ,'-' '.~ (Ref Katzung-13th)

Q,t:
·
A .
tion the indications of metformin / biguanides. (DU-06S: RU-I 6Ju,06J ,0SM , SU-07J)

ication of bi uanides / metformin:

I. Insulin resistance syndrome : As Metfonnin is an insulin sparing agent & does not increase weight /
pr - ol<eliypogl ycemia, it is used in patients whose hyperglycemia is due to ineffective insulin action i.e.
insulin resistance syndrome.
2. In type-II D ith insulin secretagogues or thiazolidinediones in whom oral monotherapy is inadequate.
3. NfDDM in obes persons.
4. Metformin r ef 1cacious in preventing the new onset of type II OM in middle aged , obese person with
impaired glucose tolerance & fasting hyperglycemia.
(Ref Katzung-13th)
 . . 717 Endocrine Pharmacology
Q. Wluch drugs will be suitable f . . b .. .
. .
Ans. Mett orm1n
or ,ln o csc dmbcttc lady aged 40 yc·1rs?
• · (RU - I JJL1)

~- ~ention the adverse effects of metformin. (DU-I 0Ju,CU-06S;RU-08Ju;SU-07J)

Adverse effects of metformin:

I. GIT upset: Anorexia nausea ·t· bd . .
2_ D . d . . ' ' ' vom, lllg, a Omlllal discomfort diarrhea. They are dose related
ec1elal_se v1tamlll 812 absorption in chronic use leads to meg;loblastic anemia .
3. Meta 1c taste ·

(NB: Phenformin
·
causes lactic acidosz'<·" · 1,
,.,,'hat ,.s why 1.t 1s. not use
. d .now.)
(Ref Katzung- / Jt h)

Q. Mention the contraindications of metformin.

Ans.
Contraindications of metformin:
Y Patient with hepatic & renal insufficiency.
2. Alcoholism
3. Chronic cardio-pulmonary dysfunction, which causes tissue anoxia & increased risk of lactic acidosis.
4. Diabetic ketoacidosis.
(Ref Katzung-13th)
Q. Short note: Metformin. (OU- I 3Ju, I2J)
Ans. Write in short from above.

Q. Enumerate 3 anti-diabetic drugs to be included in essential drug lists of Bangladesh. (CU-07J)

Ans.
3 anti-diabetic drugs that should be included in essential drug list:
I. Insulin
2. Glipizide
3. Metformin

Thiazolidinediones never produce hypoglycemia & hence it is called euglycaemic agents.

/
Q. Explaiy,,hypoglycemic action of pioglitazone. (SU-09/07 Ju,06S/M)
Q. E1 .n blood glucose controlling action of pioglitazone. (SU-l 2Ju)

~ 'itglycemic action of pioglitazone / rosiglitazone: Thiazolidinediones (Tzds) act to decrease insulin

'--resistance by regulating ~enes inv~lved i,~glucose and lipid metabolism and adipocyte differentiation.

Tzds binds with peroxisome proliferator-activated receptor-gamma (PPAR-y) in muscle, fat, and liver.
!
PPAR-y receptors modulate the expression of the genes involved in lipid and glucose metabolism, insulin
signal transduction . ~ - - - -----._

The drug promotes glucose uptake and utilization, especially in adipose tissue.
(Ref Katzung-1 Jth)
Indications of pioglitazone / rosiglitazone:
/ v. Type-II OM (especially i~ ins~li,~ esi_stance case)
;;/ Prevention of type II OM .

Pharmacology-92
BlucprintTi\ l Pharmacology 718
3. Monothcrapy (a long with diet & exercise) in mild degree OM.
J. In co 111 bin ati on wi th bi guanides & sulfonylureas in type II OM.
In !2. lucose int oleran ce patient s.
5. Prevention of rec urrence or OM in hi gh risk Hi spanic women with a hi s!o1y of gestat ional OM .
(Re{ Katzur,g-! 3th & Ti-ipathi- o'1'/270J

1\_(lvcrse effects of pioglitazone

l . Dose related weigh! ga in (average I - 3 kg)
1
Fluid retenti on (w hi ch presents as a mild anemi a & peripheral edema) es pec iall y when used
111
combinat ion with in sulin & sulfonylureas.
~. Hepatotoxicity (especially with rosigl itazone)
4. Teratogenicity
(Ref Katzung-1 Jih)
0o ntraindications of pioglitazone
I. Obes ity
2. Liver di sease (CL O)
3. Hea11 fa ilure
4. Pre ex istin g edema
5. Pregnancy.
(Ref Katzu11g-l J1h;

carbose / Miglitol a-glucosidase inhibitors

Mecha nism of action of acarbose:
Acarbose I mi glitol
l
Com petiti ve inhibition of ' intestinal a-glucosidase '
l
Reduce postprandial digestion & absorption of starch & di saccharides
l
Red uce bl ood glucose level
(Ref Katzung-l 3th)
Adverse effects of acarbose / miglitol:
l . GIT adverse effects: Flatulence, diarrhea, abdominal pain .
2. Reversible hepatic enzyme elevation
(Ref Katzung-13!h)
Co ntraindications of acarbose:
I. Patients with infl am matory bowel disea se (IBS)
2. Any intesti nal co ndi tion that could be worsened by gas & distension
3. Should be used with ca uti ons in pati ents with hepati c & rena l impairment .
(Ref Katzung-l 3th)

Incretin-based thera ies

Q. How does glucose stimulate Insulin release? (CU- l 6J u)
Ans.
How glucose stimulates Insulin release:
Presence of glucose in the gut
l
Glu cose stimulates secretion of gut hormones, or in cretins
l
Jn cret in s (eg, glu cago n-like peptid e (GL P-1 )) stimulates in sulin secret ion in a glucose-dependent manner.
 -:-;-:---:--;:-"""".'-------------·----7:.1:.9~-----------!E~n doc ri nc Ph a rm ;-1co Io gy
Nice to know
In cretin:
• ln c retin s are gut hormon es, which potcntiate g lu cose- indu ced insulin secrctio11.
• Glucagon-like peptide (GLP-1) is an in c ret in ho rm o ne which s timul ate s in s ulin s ccrcl io 11 111 a g! ucu "c -
dependent m a nn e r; thus hypog lyce mi a d oes no t occ ur.
• In addition, GLP-1 s uppresses g luc ago n secretion. d e lays gastric empty in g , reduces appctit l: a1 1d
encourages weight loss .

Drug_s used ~n i~cretin-based therapy: lncret in-based therapies a re m os t useful in o bes e patien t'~ and ca n be.:
used 111 co mb111at1 o n with other ora l a nti-diabetic agents.
1. lncretin mimetics / Synthetic analog of glucagon-like-polypeptide 1 (GLP-1):
• Exenatide
• Liraglutide
2. Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors:
,, / Sitagliptin, 1
VildagliptinJ
• Saxagl i pti n
/

Exenatide
It is a synthetic analog of glucagon-like-polypeptide 1 (GLP-1).
Indication: Adjunctive therapy in perso ns with type 2 diabetes tTeated with m etlorm in or m etformin plu s;
sulfon y lureas who still hav e suboptimal g lycemic co ntrol.
Mechanism of action:
1. Potentiation of g lucose- m e diated insulin secretion. The inc rea sed in sulin sec ret ion is spec ul a ted to be d ue
in part to an increase in beta-ce ll mass .
2. S uppress io n of postprandial g lucago n release
3. Slowed gastric e mptyi ng, and
4. Central loss of ap pet ite .
Route of administration: Exe natid e is injected subc uta neo usly w ithin 60 minutes before a meal.
Adverse effects:
I. Nausea (about 44% of users)
2. Vo mitin g
3. Diarrhea
4. Weight loss ( in some users , presumably because of the na usea and ano rect ic effects.)
5. Necrotizin g a nd hemorrhagic pancreatitis.
(R ef Kat:::u11 g - I 3rh)

Sitagliptin
Q. Write how sitagliptin reduces blood sugar level. (RU-1 SJu)
Q. State the anti-diabetic action of si tagliptin. (SU- I 5Ju. I 3Ju)
An s .
M ech anism of action ofsitagliptin: Sitagliptin is a n inhibitor of di pept id y l peptidase-4 (DPP -4), th e en z v m e tlrn t
'-....,_/c egrades incretin a nd other GLP-1 -like m_o lec ul es. Its 111aJo ~· actio n !s to in ~rease ci rc ul ati n g le ve ls of G LP - \ ::ind
G IP . Th is ultim ate ly decreases postprandial g lucose excurs io ns by 111c reas 1n g g lucose- m ediated in su lin scc re·: 10 11
;nd decreas in g g lucago n level s .
(R<:'_f f.:ur:::1111,\!.·- I 3rl, ;
Nice to know
Route of administration : Ora l.
Dose: I 00 m g ora ll y o nce daily .
Blueprint™ Pharmacology 720
Clinical use: Sitagliptin can be given as monotherapy or combined with rnetformin or T zds.
Adverse effects
1. Nasopharyngitis
2. Upper respiratory infections
3. Headaches
4r. Rarely, severe allergic reactions
(Ref Katzung-1 3th)
 \' C ' \"' \ ' , r' '\ 1

Q. ,E nlist adrenal steroids. (CU- 14.lu)

A,~ .
drenal stero ids / Ad rcnoco rtical hormon es
Layers of adrenal cortex Hormones
1. Zona glomeru losa 1. Mineralocorticoids: I .. -·,,,
- - ;i"
• Aldosteron e ,.. ,... '
• Deox ycorti costerone -.....,_ 1/
\!.- -2. Zona fasciculata 2. Glucocorticoids: ( ~---u2..$_::, Pr__- r,)-- '

• Cortisol '------
• Corticosterone
3. Zona reticularis 3. Sex corticoids:
• Adrenal androgens-
~ Dehydroepiandrosterone
)> Androstenedione
• Estrogen
Glucocorticoi ds
Q. Classify glucocorticoids according to duration of action. (SU-09Ju;RU-10Ju ,06J)
Q. Classify glucocorticoids according to potency. (RU-I 6J , I2Ju,08J)
Q. Enumerate the glucocorticoids. (DU-16Ju)
Q. Classify glucocorticoids based on pharmacokinetic and pharmacodynamic properties. (SU -1 4Ju , 13J)
Q. Name the long acting glucocorticoids. (SU-07J)
Q. Name the glucocorticoids according to route of administration . (SU - I6J)
, (J, List synthetic glucocorticoids. (SU -1 7J)
Ans.
Classification of glucocorticoids:
A . According to duration of actio n:
I
1. Short-to-med ium-acting(< 12 hours) .•/ Hydrocorti sone (Cortisol) \
,•/ Cort1sone
. __ ,
.--~ Prednisone.
{ Prednisol one -~
,. Methylpredni solone
• Me redni so ne
2. Intermediate-acting (12-36 hours) • Tri amcinol one
~ Param ethaso ne
Flu red niso lone
3. Long acting (>36 hours) • Betamethaso ne
,/ Dexamethaso ne
(Rrf f.:ur::1111g-f 3rhJ
B. According to potency:
Anti-lnllammatory activity
(I'otenc'\' relmi ve ru hvclrocorr i.,·011t')
High potency Dexamethasone 30
Betamcth asone '.25-4 0
FIuprecln iso lone IS
 Bh1cprint'r 1\ 1 Pharmaco logy ..
Medium / intl'rmcdiate
potency
Parn111et lwso11l!
---- - - 10
- - -
·- - --

-
-
_7 ria111ci11ol onc
Predniso lonc
5
5 -
--r
Mctlwlpred
.
niso lonc
-
5
-
_..·rvte prcdnisone 5
- -
Low potency Prcdnisone .:1
Hydrocort isone (IJ
Cortisone 0~8
(Ref: 7ri;,atlii-6thl282J
C. According to route of administration :

~
/ VI M 1/e Triamcino lone I

IV, IM ',I Betamethasone I

1/ Dexamethasone I
Hydrocortisone ._ -C . . ,. . 'J (~~
'O"R·~ .r
l Prednisolone - _
• Methylprednisolone
j~ nhaled and nasal sprays (' _• _ Beclomethasone

,~
-_!..• Budesonide
Ciclesonide
.,. Flunisolide
!..,....
!-. Fluticasone
e9-~S-j
\
- • Mometasone
\ Tci.amQ.!1olone
Oral
··'
I~~ Cortisone '
, ~ Dexarn ethasone
• Methylpredniso lone
,,,- Prednisone
.
Topical Betamethasone
I.
~ Hydrocort isoJe

~
,.
•,, Mometasone
Triamcinolone
!,,I ntra-articular • Methylprednisolone
,)
,,... Triamcinolone
(Ref Lippinco/1 's-6'"136 9)

Q. Enumerate some clinically important synthetic glucocorticoids. (CU -08J ; SU -06J)

Q. Name commonly used glucocorticoids. (RU-07J)
Ans. Commonly used glucocorticoids: Hydrocorti so ne, Predni so lone, Betam ethaso ne, Oexarnethasone.
Meth ylpred ni so lone, and Tri amcinolon e.

Q. Classify anti-inflammatory drugs. (RU-09J)

Q. o/tfutare the drugs that affect prostaglandin synthesis'! (SU-I 4J)
Mis.
,__/-A nti-inflammatory drugs/ drugs that affect prostaglandin sy nthesis:

2. 7n
I. Stero id anti-innarnmatory drugs (corticosteroid s)
stero id al anti-innammatory dru gs (NSAIDs)

Q. Describe the mechanism of action of steroids. (CU-I 4Ju)

~ Oescribe the mechanism of action of glucocorticoids. (CU- I OJ)
ft· How does glucocorticoid act at mo lecular level'! (RU-08.J)
 l___ ~ . -\ d ~ i~ C-' . r-.

723 Endocrine Pharmacology

Ans.
Mechanism of action of glucoco rticoids /steroids/ predniso lonc:
Glucocorticoids enter into the cel l & binds with the receptor in the cytoplasm.
- 1-
Conformational change occurs in the receptor
l
The glucoco1ticoid-receptor comp lex is then active ly transpo rted into the nuc leus & it interacts with IJ N/\ &
nuc lear protei~ -- - ·- -- -
l
The complex binds with the glucoco1ticoid response element (GRE) on the gene.
l c.__ _ _ _

After binding, it regulates the transcription by RNA polymerase-II & associated transcription factors.
l
mRNA synthesis

Protein synthesis
- - -i-
New proteins are responsible for glucocortico id action.
(Ref Katzung-13th)
Effects of glucocorticoids:
l . Physio logical effects
2. Pharmacological effects

Q. Describe the effects of glucocorticoids on metabolism. (CU-I !Ju, RU-06J)

Q. En list the im portant pharmacologica l effects of glucocorticoids. (DU- I SJ)
Q. Expl,_;-n !Jriefly the important pharmacological effects of glucocorticoids. (DU-I 3J . I OJ. CU-I 2Ju)
Ans. / /
Eff2
.,cts of glucocorticoids on metabolism
1. On carbohydrate • iG Iuconeogenesis
G\ v_ s:.()S r/ (,\>° cr:3-~"'"'
metabolism • iG lycogenesis
~~
~ ·y'l , •""J"'--l'L
<..
• lGlucose utilization
• iBlood glucose .
2. On protein metabolism In extrahepatic tissue-
• lAmino acid uptake ~-"""v-\-',...... ~ r---,

• lProtein synthesis
• iProtein catabolism
• i Amino acid mobilization form extrahepatic ti ssue into blood .
In liver-
• i Amino acid uptake
• iProtein synthesis
In plasma-
• iP lasma protein
• i Plasma amino acid .
)
D
l
l ., . . ,. . . .\ .l(,__\~r-..
' TI~ ---<"t.· -

3. On fat metabolism • iFatty acid mob ilization from adipose tissue \ ,, '
C \

• iFatty acid utilization for energy

(\
,....r
'\ \-:--.~ ..
• j Ketone body form ation )
' - ~ ,.:_r·, \, ~
• i Plasma fatty acid . ~

(Ref G11vru11-!21l1. Gww11g-2..f.1/JJ

Q. Describe the anti inflammatory effects of glucocorticoids. (DU-I 4.Ju. I 2J, CU -I SJ,07.1 , RU-1 7J.09Ju: SU-
I 6Ju, l 5Ju, I 3Ju)
 1
Bl11q1rinl " l'harmarnlo~y 724
(.). E,pl:1i11 thl' a11li-i11tla111111:1lory cffrrts of corticosteroids . W U- 14.1 ,0lJ.J , CLJ - 11 .lu )
(). 1-:xplain lhl' anli inlbmmalory rok of steroids. (SlJ - 10.1 )
Q. Explain th(· anti intlammator)' dfccts of pr('dnisolonc. (RU-07.Ju ,OGM, SlJ - 14.J , I I .Ju )
Q . Ew l:1i11 anti inflammatory action of dcxamcthasone . (SlJ - 17.J , 12.lu)
Q. L: xplai11 thl' immunosupprcssiw dfccts of corticosteroids with uses exploiting thi s action . ( RU- I SJ)
Q. Explain tlw immunosupprcssivc cffcds of prcdnisolonc. (RU - I I Ju)
i\11 ~.
Anti -inflammatory '-~ i III mII nosuppressive effects of cortieostcroids/nred nisolone: GIucocon ico ids
f- dra111:1tica li)' rl'd uce tile 111anilcstati ons or inllamrn ati on. Thi s is due to th eir profound effec ts on th e conce ntration,
di stributi on, and !'uncti on or periphera l leukocytes and to their suppress ive effects on the infl ammatory cytokincs
and chcrnokincs and 011 other mediators of inflammati on.

Ml'chanism: ,,/'
(. Increased i111lux of neutrophil into 1+r&!1lmc,d-frem bone marrow - dec reased mi gration from bl ood vessel
Decreased neutrophil number in the inflammatory site.
J. Decreased circulator)' lymphocytes, monocytes, eosinophils & basophils due to their mi grati on frorn
the vascul ar bed to lymphoid tissue-~ Decreased number of these ce ll s in the inflammatory si te.
} Inhibit the functions of tissue macrophages and oth er ant igen-present in g cells. As a result.
a) Anti gen presen tation is reduced.
b) Ph agocytosis is reduced.
c) Less production of IL-1 2 and interferon-y, important inducers of THI ce ll activity, and cellu lar
immunit y. a_ ..,,,o' ~\io\bl..
I ' ' -u~,-,.., ,
~r A '('Q.<>'v--. ·r ~ ~<z_ A c',o5Z ·1~\.-._,b,--t--._: l/'---.
4. Inhibition of phospholipase-A2 enzyme: By thi s way- "
a) Glucoco11icoid s inhibit the inflam matory response by reduci ng the prostaglandin , leukotr iene, and
plate let-activatin g facto r synthesis.
b) Red uce COX-2 enzy me in inllamm atory ce ll s.
5. Glu cocorti co id s ca use vasoconstriction and dec rease capillary permeability by reducing histamine
release from basoph il s and mast ce ll s.
6. Comp leme nt ac ti va ti on is unaltered, but its effects are inhibited.
71 Antibody production can be reduced by large closes of steroid s, th ough it is unaffected by moderate
do ages (eg, 20 mg/d of predni sone).
(Rel Kat:ung-l 3th)

Leukocyte
accurnulaU<'.>n

"'Leukocyte
function

Anti~nflammato,y L)'m phocyt.openi.1

Monocytopen la
Mfoct~ monocytopenia
coslnopl}n la

'-"' Comphtment
components level1,,

'-"' Hietamine-me<l latoo

reactions

Fig 1/111 i i11/ l 011111111/or v wtcl i 11111111110.111pJJr c>s., ivc> ro/1: (!/ corf icostt' ro id1 .
 725 Endoc rine Pharmacology
~ plain the perm~ss~Ye role of s_teroi~ls / hydrocortisone. (SU - I 3Ju , I2Ju , 11 J, IOJ)
~: Short note: Pen111ss1Ye effect of corticosteroids. (RU-16J)
1

A\ ,issive action of steroids: Small amounts of glucocorticoids must be present for a number of metabolic
p~r·tions to occur, although the glucocortico ids do not produce the reaction s by themse lves. This effect is called
r,,1c . p . . f~ .
·r permissive action. en111 ss1ve e 1ects rnc lude the requirement for glucocorticoids to be present -
th~1 I. For gIucagon an d catec hoIamrnes
. to exert the1.r ca Iongemc
· · et·t·ects . c.; ' ., 1
2_ For catecholamines to exert their liQol tic effec'fscc----- ') ,,---o ;\~ {fl.> I • ..r;.;

3.
For catecholamines to produce pressor responses and bronchodilation .
--- ~
'.) ~ • :::< --
2-
(Ref Ganong ·s-24th)

Q. Mention the therapeutic principles of glucocorticoids. (RU -13J)

Ans.
Thera peutic prin~i ples of_glucoco rticoids
- \. The dec ision to give glucocorticoids always requires a careful consideration of the relative risks and
benefits in each patient.
2. For any di sease and in any patient, the lowest effective dose should be given for the shortest period of
time.
3. Abrupt cessation of glucocorticoids after prolonged therapy is associated with the risk of adrenal
insufficiency, which may be fatal. So, dose of glucocorticoids should be tapered slowly.
(Ref Goodman & Gilman 's-l 2th)

Q. Mention the cl inical uses of glucocorticoids . (DU-OSM , CU-1 lJ , 1OJ, RU-17J , SU-O6J)
Q. What are the indications of glucocorticoids? (DU-1 SJ, CU-OSM ; RU-14J , SU-1 IJ)
Q. What , re the indications of prednisolone? (C U-OSM , SU -17J)
Q. Outline the immunosuppressive uses of glucocorticoids. (RU-16J )
A~
ndications of glucocorticoids
A. Adrenal uses ort replacement thera py : t , r ,

1. Adrenocorti2i"l insu fficiency :

• Chronic (Addison 's di sease)
• Acute (Addisonian crisis)

2. Adrenocortical hypo & hyper-function :

• Congenital adrenal hyperpl as ia
• Cushing' s synd ro me
• Aldosteronism (primary & secondary)
• For diagnosis of Cushing's syndrome by the "dexamethasone suppression test"
• Iatrogenic adrenocortical insufficiency: Abrupt withdrawal.
(Ref Katzung-13th : Bennett & Brown- 11th)
B. Some Nonadrenal Disorders: 1
Disorder I Examples
Allergic reactions • Angioneurotic edema
• Asthma
• Bee stings
• Contact dermatiti s
• Drug reactions
• Allergic rhinitis
• Serum sickness
• Urticaria

Pharmacology-93
Bluq>rinl "' 1 Ph·umaco lo 11 v 726
'"'· ~

1
Co llagl'll -\'asl'ular disorde rs • Gia nt cell artcriti s
• I,upu s eryth cmatosus
• Mixed co nnect ivc tissul.'. synd romes
• Polymyos iti s
• Polymyalgia rh eumat ic
• Rh eumatoid arthrit is I
1-- •, Tempo ral art er iti s I

E~·c diseases • Acute uveitis

Allergic co njuncti vitis
/• Choro icliti s I
I
• Opt ic neuriti s
Gastrointestinal diseases v• lnnamm atory bowe l disease
' • Non tropical sprue
• Subacute he patic necros is
Hematologic disorders • Acquired hemolytic anemia
• Acute allergic purpura
• Leukemia I
• Autoimmune hemolyt ic anemi a
I ,• Idi opathic thrombocytopenic purpura
• Multiple myeloma
Syste mic inflammation
1n fections
-·• Acute res piratory distress sv11 clro111e (A RDS)
Acute res piratory distress syndrome (ARDS)
I

• Se psis
lntlammatory conditio ns of • Arrhriti s,
bones and joints • Bursitis
•
Neurologie disorders ,. Tenosynov itis
Cerebral edema (forge doses of dexwnethosone arc given to patients
following brain surgerv to minimize cerebral edema in the
postoperative periocU
• Multi ple sc lerosis
Organ transplants
Pu lm onary diseases
•• Prevent ion and treatm ent of rejecti on (immu nosu pp ression)
Asp iration pneum onia
• Bro nchi al asthm a
• Prevention of in font respiratory di stress syndrome
• Sarcoi dos is
Renal disord ers I-,.'' Nephrot ic syndrome
Skin diseases • Atop ic dermatiti s
• Dermatoses
, • Lichen simp lex chron icus (loc ali zed neurodcrm atiti s)
• Mycos is fun go ides
• Pcmphi gus
• Sebo rrheic derm at iti s
• Xerosis
Thyroid diseases
,.• Ma li gnan t exophthalm os
Subac ute th vro iditi s
Misccllaneou s • Hype rcalcemia
• Mountain sickn ess
(Re~/ f.:01::1mK-I 3th)
 727 l~ndocrinc Pharmacology
Q.Wlntt arc the adverse effects of long term use of glucocorticoids? ( DlJ- 15.1 , I JJ,0 8.1 . CU - I J .J . I OJ. RU- 1OJu.
SU-09.l u)
What arc the major adverse effects of glucocorticoids? (SU - I 6Ju)
Q. Write the GIT adverse effects of the synthetic glucocorticoids . (CU-08J)
6: Enum erate t.he ~otential adverse ~ffccts of prolonged on~l corticosteroid ~he,_·apy. (CLJ_-0 7.1) .
Q. What co mphcat1ons m~.Y occur with the long term use ol dexamethasonc ? ((_ LJ- 04 M; SU-1 JJ, 12J,07.I J
Q. Ment io n the adverse eflects o~ prednisolone after chronic use. (CU -OSS)
Q. What arc the consequences ol sudden withdrawal of glucocorticoids? (CU - I 3.1 ,07.1 u:RU-04.J) c r.>- .s,.J
\ ' _bcf•"- -..: L

of
:x;i:;ersc effects lon g term use of glucocorticoids : Two categori es of toxic effec ts res ults fron1 the th crapcufic ,
-:-: or
USl
corticostero id s.
. . , .
I /;T'( \
\./'
/'I I'
· 11,__,\ v( c __. r '-' \·
..,,:,
A. Due to ra pid withdrawa l ot steroid therapy · J

B. Due to continued therapy ,-z, ·- >

c:;\~,--c, , --'-1 . - c ~ -\.=-c c 1 _\.-.<.
A. Due to ra pid / sudden withdrawal of corticosteroid thera py:
) . Flare-up of the underly in g di seases for wh ich steroids were presc ribed
/ 2. _Ac ute ad renal suppress ion
Q,\') - .l_ ~" C ,,.,k.._
3. Other effects: J-...J <'- " )-...,,~.,..; _..,,.
a. Fever, myal gia, arthral gia & malaise
b. Pseudo-tumor ce rebri.

B. Due of continued / lone term use of glucocorticoids: The majo r undesirable effects of glucocorticoids ar...:
th e result of their hormonal action s, whic h lead to the clini ca l picture of iatrogenic Cushing's syndrome.
I. Fluid & electro lyte di sturban ces: ~-
a. Hypoka lemic alkalosi s
b. Edema
c. HTN
2. Metabolic changes:
a. Hypokalem ia wit h glycos uria
b. Iatrogenic Cushing's
syndrome . 0
3 . Increa sed susceptib ility to HaTrlhinning - - - - -1,',
Hlrsutism
infecti on due to suppress ion of ._,,__ _ _ _ _ wtaracts
1 a exopnthatmos
immunity
4. GIT: Peptic ul cer diseases.
5. Myo path y ~ r .\ \
6. Osteoporos is & osteo necros is Peptic utcer - -- 1----1-. \ \-::,,
7. Cataracts Loss of heiQht - - - - ; .
8. CNS & behavioral chan ges: and back pain
from compr ssion
Nervousness, in so mni a, ove rt fractu re
.,,.,.r;r psychos is & changes in mood Hyperglyca emia
t'1 9. Regulation in growt h &
development : Growth retardati on Menstrual - -.,c.___:;;.-1-.,...,,..,,.....,._
dlsturtlance
in children. Decreased skln
1.hlckness
(Ref' Katzung-l 3th; Goodman & May have
Gi/111011 ·s- 12th) exuberan t -+-- - - ,'+--- Wasting and weakness
callus with of proximal th igh
1rae1ures muscles
Ostooporosis

Tendency to_ _ _ _-+P

infections 1 f1--- - - Bruising
with poor wound
healing and little
inltammatoiy
response

Fig. Cushing 's syndro 111e

BlueprintTM Pharmacology 728
Q. Mention the rational management of the adverse effects caused by synthetic glucocorticoids . (CU -O&½
An s.
Management of the adverse effects of corticosteroids:
I. Gradual withdrawal of the corticosteroids
2. T reatment of the developed problems:
a) Treatment of infection by appropriate antibiotics.
b) Treatment of PUD by anti-ulcer drugs.
c) Treatment of HTN by anti-hypertensive drugs.
d) Treatment of fluid & electrolyte imbalances etc.
3. Strict monitoring of the progress of the patient condition including vital signs
4. Prevention of the adverse effects:
a) Using short acting corticosteroids (hydrocortisone, prednisolone, methylprednisolone)
b) Using corticosteroids for the shortest period of time & gradual withdrawal after prolong use.

Q. Mention the contraindications for corticosteroid therapy. (DU-I 2J, RU-l 6J, CU-0SM, SU-11 J)
Q. Mention three important contraindications of glucocorticoid . (DU-08J)
Ans.
&mtraindications of glucocorticoids: Glucocorticoids must be used with great caution in patients with-
! . Peptic ulcer
2. Heart disease or hypertension with heart failure
' ~
3. Certain infectious illnesses such as varicella and tuberculosis
4. Psychoses
5. Diabetes
"
- (

\ ' '
\

~~ \ ( ) ~
I (
(

( \ c· \
6. Osteoporosis (
7. Glaucoma. -y-t '( <~

8. Epilepsy
(Ref Katzung-13th: Bennett & Brown-11th)

What precautions are to be taken during prolonged steroid therapy? (DU-I OJ)
Wh~precautions are to be taken before glucocorticoid use? (CU- l 2J)
· t uss the precautions that should be taken before prescribing steroid hormones . (DU- l 4Ju )
n.
_precautions to be taken during prolonged steroid therapy:
I. Patients receiving glucocorticoids must be monitored carefully fo r the development of-
,,. a. Hyperglycemia
b. Glycosuria
c. Hypertension
d. Fluid retention (weight gain)
e. Hypokalemia (potassium supplement may be necessary)
f. Peptic ulcer
g. Osteoporosis (back pain)
h. Hidden infections.
1. Serious hazard of patient noncompliance.
2. Mild withdrawal symptoms (iatrogenic cortical insufficiency) include conjuncti vitis, rhiniti s, we ight
loss, arthralgia and itchy skin nodules.
3. Patients must always
• cany a card giving details of therapy
• be impressed with the importance of compliance
• know what to do if they develop an intercurrent illness or other severe stress (eg, surgery): double
their next dose and to tell their doctor. If a patient omits a dose th en it should be made up as soon
as possible so that the total daily intake is maintained, because every patient should be taking the
minimum dose necessary to control the di sease.
(Ref Katzung-JJth edition ; Bennett & Brown-I Ith)
 /
729 Endocrine Pharmacology

9ACo · pare gluc~co~icoids

Q. & NSAIDs as anti inflammatory agents. (CU-I 7M, I 4J , I 2Ju ,09/08Ju, SU - I OJu )
w glucocort1co1ds differ from NSAIDs? (SU-l 2J)

r .~parison between glucocorticoids & NSAIDs as anti inflammatory agents :

Inhibit phospholi pase-A 2 enzyme

Inhibited
Present Absent
Absent Present
Absent Present
Absent Present
No Yes
Elevated No change
Occurs No chan e
Causes No change
11. Iatrogenic Cushing syndrome Can occur No
12. H ertension Occurs Does not occur

Q. IVM~ G v1\. \ --S ,---Q-

A1l ennon the principles of withdrawal of corticosteroids.
1 ~~--..1 \ \

·- T '4-fP-'< rv,
Principles of withdrawal of corticosteroids: The longer the duration of therapy the slower ,m\s\ be th
wi thdrawal. ---
1. For use of less than I week (e.g. in severe asthma), although there is some hypothalami c sup press ion,
wi thdrawal can be safe ly accompli shed in a fe w steps.
2. After use fo r 2 weeks, if rapid withdrawa l is desired, a 50% red uction in dose may be made each day .
3. If the patient has been treated for a longer period, reduction in dose is accompani ed by the dual risk of a
flare up of the disease and of iatrogeni c hypoad renalism; then withdrawa l should ~ done very slowly,
e.g. 2.5-5 mg predn iso lone or equi valent at in tervals of 3-7 days.
(Ref Bennett & Brown-I 1th)

drenocortical anta onists

~'roJ.f¼'-t F 1R._
Glucocorticoid antagonist:
Glucocorticoid receptor antagonist: Mife pristone ~sr"'° \,~\~ .t~'-L. ~ °' ~
Adrenal steroid synthesis inhibitors:
c_ of:..
I. Aminoglutethim ide
2. Metyrapone
3. Ketoconazo le
4. Metyrapone
5. Trilostane
6. Abi raterone
(Ref Katzung-1 Jth)

Mineralocorticoid receptor antagonists/ aldosterone antagonist

These drugs compete with aldosterone for its receptor and decrease its effect periph erally.
I. Spirono lactone
2. Epl erenone
3. Drospirenone
 Q. Name the estrogens.
Ans.
Estrouens·
....
Steroidal Natu ra l •Estradi ol
•Estrone
•Estri ol
Synth etic • Ethin yl estradi ol
• Mestranol
• Quin estrol
Non-steroida l Synth etic • Di enestrol
• Diethylstilbestrol
• Benzestrol
• Hexestrol
• Methestrol
• Metha Ilenestri I
• Ch lorotrian ise ne
(Ref Kat::11ng- 13th)

Q. Write the clinical uses of estrogen.

Ans.
Clinical uses of estrogens:
A. Replacement therapy
/ . Primary Hypogonadism : Estrogens have bee n used extensive ly for repl ace ment therapy in estrogen -
defic ient pat ients. (Treatment of primary hypogo11adis111 is 11suully begun at I 1- /3 years of age and
continued until the age of menopause)
2. Postmenopausal hormone replacement therapy (HRT)

B. Pharmacotherapy:
I. In combined OCP along with progesterone
2. In dys functional uterine bleeding (DUB) in combin atio n wit h progesterone .
3. Intractabl e dys men orrhea: Estrogens combin ed with proges tin s ca n be used to suppress ov ulati on in
patients with intractabl e dys menorrh ea.
4. Hirsutism and amenorrhea du e to excess ive sec retion or androge ns by th e ov ary : Estroge ns combined
with progestin s is used to suppress ova ri an fun cti on.
(Ref Kat::w1g- I 3tli: Bi!nne/1 & Brown-! Oth/6-15.6-1 7)

Q. Define HRT? (CU -06M)

Q. What is hormone replacement therapy'! Name the hormone preparation used. Mention th e indications
& / isks . (DU-08Ju )
Q/ Dlscribe the HRT in postmenopausal syndrome . (CU-06M)
~- ort note: HRT. (DU- 13.lu, 12.1 , SU -06M ; RU- ISJ, 13.lu)
/ ll S

Post-meno pausal hormone re placement thera py (HRT ): HRT refe rs to the use or estroge n trea tlll ent in order
to reve rse or prevent probl ems du e to th e loss of ovar ian horm one secreti on afte r th e menopause. ,, hether
rh ysiologica l or induced. The ti ss ues se nsiti ve to estroge n include brain, bone, skin, ca rdi ovascul ar and
geni tourina ry.
 r I
( ~ ( , ... ') ( I (

731 ,, ,. .). ? r -f., A ~ Endo<:rinc l'harn1a<:ology

) ~ 0
iridications of HRT: ' , "/ '
y- To reduce the everyday sy mptom s of estrogen loss : li nt lluslics. slecpl css ncss. lc1l wr •y it lld ckprc :..., io11 ,
vagi nal drvness.
~ .,
To prevent the long-tl'rm ('01nplications associated ·with estrogen deficiency: <):,tco porn li c /"ri1c l urc
and coronary heart disease.
Risks of HRT:
I. End ometrial cancer.
2. Breast cancer.
These di orders may occu r due to estrogen excess.

Preparations used for HRT. There are three types of regimen :

I. Women without a uterus take continuou s estrogen alone.
1
Other wo men require estroge n co mbined with progestogen to prevent endo metri al pro lil'eration.
a. In the commonest, 'sequential' regimen , wo men take estroge n with out brea k, and add a progestogen
from approximately the 14th to 28th clay of each cyc le. The first cou rse i started on th e I st clay ol'
menstruation (if present), and 28-clay cycles of treatmen t follow th ereafter withou t interval.
b. In the 'continuous' regimen , oppropriale on~v.fc>r women who hare heen c1t11enorrheicJ<>r more !hell!
one year. fixed dose co mbinations of estrogen and progestogen are taken with out a break. Continu ous
combination HRT regimens will eventually indu ce amenorrhea in most women, th ereby eliminating
one of the major deterrents to HRT use, withdrawal bleeding.
(Ref· Benne!! & Brmvn- 1 I th)
Q. What are th e adverse effects of estrogen therapy?
Ans.
Adverse effects of estrogen HRT:
A. Common:
I. Postmenopausal uterine bleeding
2. Breast pain (mastalgia)
B. Most serious compl ica tions:
I . Venous thrornboemboli sm
2. Ca endornetriurn
3. Ca breast
C. Others:
I . Nausea
2. Hyper pi gmentation
3. Increased freq uency of 111 igraine headach e
(Re{ flC:'nn ell & Brown - / I rh)

Q. Mention the contraind ica tion s of estrogen therapy.

An s.
Contraindications of estrogen HRT:
I. Patient with estrogen dependent neop lasm ; such as -
a. Ca enclometrium &
b. Ca breast
2. Patie nt with undiagnosed ge nital bleedin g.
3. 1-li story ofthromboemb oli c disorders.
4. Liver di sea~c'> .
5. Relati vely contra in dica ted in heavy smokers
(He/.' f.:ur::1111g- / 3t!I)
 Se lt.:cti, e cstrogL:11 -reccpt <11· modulat ors (SERM ·) arc a new cb1ss or estroge n-n.: l;.rtcd co r~pound s. In _tire pa~t, ,t
m1mber or th ese age nt s had been categori zed as anti es trogc ns, and con equcn tl y, there s so r~1-~ conlu ~1on. Thl:
1

tt:rm SL RM is n()w reserved for compound s that interact al estrogen rece ptors but lr ave Jrflercnt clh:cts
diffen.:nt ti ss w.:s; that is, they di splay se lecti ve agoni srn or antago ni sm accordrn g to_ thc tr ss uc ty~e . For examp0le11
tarnoxif'en is an estroge n antagoni st in breas t ca ncer ti ssue but ca n ca use cndorn elrr al hyperplasia by <1 cting a~~
par1ial ago ni sr in the uterus.
(Rel li/JJJincu11 's -fJth;

Q. Name the selective estrogen-receptor modulators (SERMs).

Ans.
Selective estrogen-receptor modulators (SERMs)
1. Ta111oxifen
2. Toremifene
3. Ral oxifene
4. Clorniphen e is also sometimes desi gnated as a SERM.
(Ref- Lippincou 's -6thJ

Tamoxifen
Tamoxifen, a competitive partial agonist inhibitor of estradiol at the estrogen receptor in breast tiss ue, was the
first se lective estrogen receptor modulator (SERM) to be introduced .
Route of administration: Oral

(Ref Katzung-J3th)
Q. Enumerate the clinical use of Tamoxifen. (CU-I 6Ju)
An s.
Indications/ clinical use of Tamoxifen
I. Palliative treatment of metastatic breast cancer in postmenopausal women .
2. Used as adjuvant therapy following mastectomy or radiation and to reduce the ri sk of breast cancer in
high-risk patients.

Adverse effects:
I . Hot flashes and nausea (most frequent)
2. Menstrual irregularities
3. Vaginal bleeding
4. Hype rplasia and mali gnancies of endometrium.

(Ref Lippinco!I ·s-6th)

Clomiphene
Clomiphene is a partial estrogen agonist. It is an ovul ati on-inducing agent.
Route of administration: Oral
Mechanisms of Action
Clomiphene is a partial agoni st at estrogen receptors. It interferes with the negative feedback of estrogens on
the hypothalamu s.
l
Increases the secretion of gonadotropin -releas in g horm one from hypotha lamus.
l
Increases the secreti on of gonadotropins (FS H & LH) from anterior pituitary
l
Stimulation of ovulation.
 733 Endocrine Pharmacology
Clinical Use: The drug has been used successfull y to treat infertility associated with anovulatory cycles.
Clomiphene is used in the treatment of di sord ers of ov ul ati on in patients who wish to become pregnant

Adverse Effects
I. Hot tlu shes (most common)
2. Headache
3. Constipation
4. Allergic skin reactions
5. Reversi ble hair loss
6. Visual di sturbances
7. Ovarian enlargement

Contraindications & Cautions: Special precautions should be observed in patients with-

/. Enlarged ovaries. (Th ese women are thought to be more sensitive to this drug and should receive sma/1 doses.)
2. Visual symptoms associated with clomiphene therapy .
(Ref Katzung- 13th)

Pharmacology-94
Blu{'print 1 ' 1 Pha rmarnlog~'

Progesterone
Q. Class if~, progt·skrone.
f\ ns.
Pro 0 estcroru.·
~ - - - - - - , - - -- - - - - - - - - -
LNatural I . Pro l.';cstcron e
I S~·nthctic l. orethi nd ro ne
2. L- Norgestrel
3. Hydroxyprogestero ne
4. Medroxyprogesterone
5. Dimethi stero ne
6. Desogestrel
7. L\'nestrenol
rRC'f Katzung-l 3thi

Q. What are the indications and adverse effects of progesterone? (CU -OSJ )
Ans.
Indications of progesterone:
1. In contraception: As combin ed OC P & as progesteron e only pill (POP) / mini pill.
1 As postme nopausal HRT in combi nation with estrogen
3. Second ary amenorrh ea
4. Abnormal uterine bl eeding in patients without underl ying organi c patho logy (fibroid or carci noma).
5. Lutea l-ph ase suppo11 to treat infert ility
6. To decrease estrogen-induced endometrial hyperpl as ia
7. Premature labour
8. Anovul atory dysfun ctional uterine bl eedin g (DUB)
9. Diagnosti c u e:
a. To test fo r estrogen secreti on.
b. To test responsiveness of th e end ornetri um.

Adverse effect of progeste rone:

I. Irregul ar per vagi nal bleedi ng.
2. Headache
3. Mood change
4. Weight ga in
5. Othe r less frequ ently occ urrin g:
• ! HDL
• TLDL
• ! Bone de nsi ty
(!?el Goodman & C,i/111011 '.1- l 21h;

· ,. ·--··
,.·.·.. ·. ·, ., · -.. . : . .
• r - ·, '~ ',
Antt· ro .· terone
. es - . ,:~.-!ii~-···<,·\:-.·· ,;~,,: ·= · ·.,·· ··
- · -·"''· ·, · .,.....
,, • ''!: "', -,l> ,. .._ "- ,; 1 ...

Antiprogcsterone drugs :
I. Mi fe pristone
2. Lik)p ri stone
3. Danazo l

Mifepristone
Mifep ri stonc is a progesterone an tago ni st with parti al agon i t acti vity. Mifcp ri stone also has potent
anti glu cocorti co icl acti vi ty.
Route of administrati on : <)ra l
 735 l<:udo1:riu l: Pharn1a 1.: ol og~

l l ·rh:tnism of ad ion :
'
~ Antipro!!cstcronc action: When ad mini stered in tile ea rl y stage::. 1w11c). 111 1· 1·L'. P11. hii,c Cd
or pre 1
. ll \ C'-

k cidua l breakdown by blockade or ut erin e progc:-;terone recept ors. Th is ka cb tu dctacl11 nc 111 ul tli c
blastocyst. \\'hicil decrL'ases hCG prod ucti on. Milcpristonc also cau : -. c-, ccrvic,1I ::-.u ltc.: 1111 1/.!, \\ liicli
fac ili ta tcs expulsion of the detached blastocyst.

• Mife pristone also binds to glucocortico id and and roge n receptors and exe rts an ti-glucoco rti co id ai id ' 111 ti-
androge nie acti ons. 11
(Rel Guoclnw 11 & C.ii/111u11- I : ' n lit i()/1 I

Indications: .
- \. Termination of early pregnancy: Admini stration of thi s dru g to fe males earl y in pregnanc: rc-...ulh ,_111
most cases (up to 94 %), in abo11ion of the fetus due to the interfe rence with proge ·tero ne and the.: dccl 111L·
in hCG .
2. Mifep ri stone is bei ng in vesti gated as an ora l contraceptive and an emergency con tracepti ve age nt. . .
3. Limited clinical studies suggest that mi fe pristone may be use ful in the treatme nt or e11Jo111etr ios 1_"·
Cushing's synd rome, breast cancer, and poss ibly other neop lasms such as 111enin g,io111a that contain
glucoco11icoid or progestero ne receptors.
(R4 Katzung-l Jth : Lippincutl 's-6 th)

Adverse effects:
I. Vaginal bleeding in fe males
1 Abdominal pain or pelvi c pain
3. Vomitin g
4. Di arrhea
5. Headache.
(Ref Kotzung-13th: Lippincott 's-6 th)

Danazol
Danazo l, an isoxazole deri vati ve of eth isterone with weak progestati onal, androgenic, and glucocortico id
activities, is used to suppress ova rian funct ion. Danazo l inhi bits the midcyc le surge of LH and FSH .

Indications: Danazo l has been em ployed as an inhib itor of gonadal function and has fo und its major use in the
treatment of
l. Endometrios is
2. Fibrocystic di sease of the breast
3. Hematologic or allergic diso rders, includ ing hemophilia, Christmas di sease, idi opathic thrombocytopen ic
purpura, and ang ioneurot ic edema.

Adverse effects
I. Weight gain
2. Edema
3. Decreased breast size
4. Ac ne
5. Oily skin
6. Increased hai r grO\vth
7. Deepenin g of the vo ice
8. Headache
9. Hot flu shes
10. Changes in li bido, and
11 . Mu sc le cramps.
Blueprint 1'"1 Pharmaco log)' 736
Contraindications
l . Hepatic dysf1111ction
2. Pregnancy
3. Breast-feeding.
(Re/ Ku1::.ung- J3tli;

Hormonal contrace tives

,,.ntraceptives: Drugs or devices which are used to prevent unwanted conception arc ca lled contraccrt ivc~.

Qha racteristics of ideal contraceptives: The fol lowing represent the ideal.
fl I. It must be extremely safe as well as highly effective , .
2. Its actio;:r must be quicktn onset and qu,c y an completeZy reversible, even after years of continuous us<;
3. It must not affect tFbido.
(Ref Bennett & Brown-/ Jth;

en · n various methods to prevent conception . (DU-0SS)

A s.
i erent methods of contrace tion in clinical ractice:
A. Spacing or temporary methods:
Methods I I Examples
1. Barrier methods Physical • Condom
• Vaginal diaphragm
• Vaginal sponge
• Cervical cap
Chemical • Foams
• Creams, Jelly, Pastes
• Suppositories
• Soluble films
2. Intra-uterine devices Non-medicated • Lippes loop
(IUDs) Medicated • Copper T
3. Hormonal methods Oral pills • Combined pill- (Estrogen & progesterone)
• Mini pill (Progesterone only pill, POP)
• Sequential pill
• Post-coital pill
• Once-a-month pill
• Male pill
Depot (Slow release) • Injectables
formulations • Subcutaneous implants (eg, Norplant)
• Vaginal rings
4. Post-conceptional • Menstrual regulation (MR)
methods • Menstrual induction (Ml)
5. Miscellaneous Behavioral methods • Sexual abstinence
• Co itus interruptus
• Safe period (Rhythm method)
• Birth control vaccine
Natural methods • Basal body temperature method
• Cervical mucus method
• Sympto-thermic method
• Breast feedin g

B. Terminal or permanent methods (Sterilization):

1. Male sterilization: Vasectomy
 737 Endocrine Pharmat:olo gy
2. Female sterilization : Tuba l li gation or tubcctomy.
111
(Re_/ P(lrk ·s-C"u1111111111ity 11wdicci11e-20 J

Q. E~ n rate the types of hormonal contraceptives wit h composition. (RU- I 6J)

Q. f a9 ~ the hormonal contraceptive regimens. (CU-I I Ju,05M; SU -I 4J, I 3J ,09.l ,07.J)
C ass1fy ora l contraceptive pills. (DU-04S, CU -I3Ju, RU-I I J)
. Name the combined OCPs. (RU-l 2J, CU-I 0Ju)
Q. What are the compositions of OCPs? (CU-05J ; RU-05S)
Q. Enumerate progesterone contraceptive preparations. (CU-05J)
Ans.
Hormonal contraceptive regimens/ oral pills/ OCPs:
Types of OCPs Compositions
1. Combined OCP Estrogen: Ethinyl estradio l (most ly used), 111estranol
Progesterori-e: Levonorgesterol, Norethindrone
2. Minipi lls / Progestin ----.,_
Norgestrel
on ly pills (POP)
3. Post coital or ,. ~ thinyl estradiol: 2.5 mg twice dail y for 5 days
emergency pill Combined pill : 2 tabs as early as poss ib le within 72 hours & th en 2 tabs 12
hours after the first dose.
4. Sequential pills ~/ 151 2 weeks - Ethinyl estradiol
-.r~ ext I week - Norethindrone
5. Male pills Gossy_l22l_

The combination agents are further divided into-

• Monophasic fon11S (constant dosage of both components during the cyc le).
• Biphasic or triphasic forms (dosage of one or both components is changed once or twice during the
cycle).
(R e{ Kut:::ung-l 3th)

e tion the mechanism of action ofOCPs. (DU-I7M , I6J, SU-05M, RU-1 2J, I I.J , CU -I IJ )
ow does combined preparation produce contraception? (RU-16.J)
Ans.
Mechanism of action of oral contraceptive pill:
I. By preventing ov ulation-
Oral combined pill
,l..
tEstroge n & progesterone leve l
,l..
J..G nRH secret ion
,l..
J..FS H & LI-I secretion
,l..

J..FS H secretion J.. u -1sec ret ion

,l.. ,l..
No follicular growth No preovul atory LI I surge
,l..
No ov um fo rmation

.
I __ _ _ _ _ _ _-'lt--+~cr~+ ov ulati on

2. Progesterone makes the end ometrium unfa vorab le fo r i111 pla11tat io11.
J. Progestero ne makes ce rvi ca l mucu s thick & un favo rab l to sperm mi grati on.
 Blufprinl 1 ' 1 l'harmacolog~· 718
4. i\) th L' S(l\));,L' ll & pi'l l:',L' S IL' l'O ll l' c:lll Sl' :1b1llll'lll :1l llllltilit ) or 1·11 11 npi;i 11 tuhc wid llll: I I I . So !h e \ \.'. ll i \.'. l l t

npc lkd l,ut.

'
Q. , t<.'11 arc tlw nu.·chanisms or action of progcskro nc only contraccplivcs / mini pill'!
1\ 11,; ,
1
) r{chanisms of action of progcs lerone only contraceptives / mini pill :
/ I. P1\1Qesterone makes the e11cl o111etriu111 un fav orabk lo r i111 plantati o11 .
') Pwgcstero ne 111,1kcs ce rvica l mucu · thick & unfavorable to sperm mi grnt ion.

yt(a t are th e indications of OCPs? (DU -1 7.1. CU- I IJ, SU- ISJ)
, . Ntrnt arc the non-contraceptive uses of OCPs? (CU -13.Ju)
-........J l S.
Indication s of OCPs:
1. Contracepti on.
' No n-contraceptive uses
a. Encl ometriosis
b. Irregul ar menstruation
c. In ··holy Hajj festi va l"' to prevent menstruat ion.
d. Abnormal menstrual bleedin g
e. Dysfu nctional uterin e bleeding (D UB)
f. Functional ova_rian cyst ·

Q. What are the indications of mini pill? (CU -0S J; RU-04M/S)

Ans.
Indications of progesterone only pill (POP)/ mini Pill / micro Pill :
I. Contraception in lactatin g m
2. Women fo r whonicombined OCPs are contra indi cated because of cardiovascul ar ri sks.
3. Youn g women wi th ri sk fac to rs fo r neop lasia .

Q. Which oral pill could be prescribed to a lactatin g mother and why? Mention its mechanism of action
and adverse effects. (RU- I 4J )
An s.
Progesterone only pill (POP) / mini Pill could be presc ribed to a lactatin g moth er, because it does not suppress
lactation.

Q. Com pare estrogen-progesteron e combined pill & progesterone only pill as contraceptives . (C -
17 ,09JUJ
o uo combin ed oral contraceptives differ from mini pill ? (SU -1 2Ju)
s.
parison of estrogen-progesterone combined pill & proges terone on ly pill as contraceptives:
Traits I Combined pill Progesterone only pill
1. Com position Progesterone + Estro ~en. OnIy progestero ne.
2. Effect on follicular develo pment Has negati ve efl ect. No effect.
3. Efficac y I 00% effective Not I 00% effective
4. Reli ability More Less
5. Causes thromboembolism Yes No
6. Effect on lactation I
Estroge n suppresses It does not supp ress lactation. So
J.actati on lactatin g mother should prefer it.
7. Use iJ}'1actatin g mother Not used. Used.

~ is rationale of usin g combination of estrogen & progestero ne? (SU- 14.1 u)

ion rationale of combination of Eth in y I es tradiol and nor gesterol as cont race >tive. SU-1 7M
An s.
 739 Endocrine Pharmacology
Rationale of using combination of estrogen~~ proacsteronc-
1. Comb in ed OCP is I00% effecti ve. "'
2. It is more reliab le.
3. It has negati ve effect 0 11 follicular deve lopm ent.

1
at are the adverse effects of OCP? (DU- I 7J, CU- I 3J, I I Ju/J, I OJu , RU-05S, SU-07 J,06S)
ention 4 adverse effects of OCP in prolong use. (DU- I 6J)
ns.
Adverse effects of OCPs: The incidence of serious known toxicities associated with the use of th ese dru gs i:-,
low- fa r lower than the risk associated with pregnancy . Minor adverse effects are frequent. but most arc mi Id
and many are transient.
A. Mild adverse effects: V IL ~ ~
I .- Na us ea; mastalgia (breast pain ); breakthrou gh bleeding & edema.
2. Changes in the seru m protein & other effects on endocrin e function.
3. Mild & transient headache
4. Withdrawal bleedin g

B. Moderate adverse effects : Any of the fo llow ing may req uire di sco ntinuance of ora l contrace pti ves: 1" ~tJ?
r-:- Breakthrough bleedin g (must common problem in using progestaliunal agents ulone f nr contraception.)
2. Wei ght gain (c ontrolled by shift ing lo preparations with less progeslin ejf ecr or by clieting)
3. Increased skin pi gmentati on.
4. Acne (exacerbated by agents containing androgen-like progeslins, whereas agents contoining large
amounts of estrogen usually cause marked improvement in acne.)
5. Hirsutisrn
6. Uretera l dilat ion and bacteri uria.
7. Vaginal infect ions
8. Amenorrhea occu rs in some patient s.

Severe adverse effects :

ascu ar Disorders
• Ven ous thro mboernbolic di sease
• Myoca rd ia l infarction
• Cerebrovascu lar diseases: >35 yrs of age
2. Gastrointestinal Diso rders
• ch olestat ic jaundice
• cho lecystitis
• cholangi tis
,.,
) . Depress ion
4. Other
• Alopecia
• erythcrna rnultil'or111 c
• erytherna nodosum
• Ot her skin diso rclers.
(Ref Kut:ung-l 3th edi1 io11)

t arc the contraindications of ora l pills/co mbined OCP'J (C U-l 7M.0 7J, SU-0 51\11 )
An
Qontraindications of oral pills
A. Absolute contraindications include:
I Hi storv ol'thromboe mbol ic venous, arterial or cardi ac di sease .
2: Tr;u1si~nt cerebra I ischern ic artacks without head ac he
3. Li ver di sea es: In fecti ve hepatit is. d1 olestati c jaundice, Du bin-John son and Rotor sy ndromes
 Blueprint n, Pharmacology 740
i\,lig,ra in c.
-t .
5. Carc in uma of th e breast or of the genit al tract, pnst or prese nt
6. Ot l1 cr co ndi ti ons in c_lu din g: SLF. porpliyri a, fo llow in g evac uati on of .-1 hycla ti dilonn mok (un ti l urine ariJ
iJ las rn a gtrnadotror li111 co ncent rat ions arc nonmil ),
7. Undiagnosed vaginal bleed in g.

B. R(•lati ve contraindications or uses with caution , includ e:

I. Fa mily hi story of venous thromboemboli srn , arterial di sease or n known proth ro rn boti c co ndi ti on, c: .g.
fac tor Le iden.
:/. Di abetes rnellitus.
~ Hype11ension (avo id if bl ood press ure exceeds 160/1 00)
¥. Smoking > 40 cigarettes per day .
Age over 35 years (avo id if> 50 yea rs)
fl:. Obes ity (avo id if body mass index exceeds 39 kg/m2)
'f. Lo ng-term imm obility, e.g. du e to leg plaster, confinement to bed
8 Breast feeding (until wea ning or fo r 6 month s after birth).
(Rel Benne// & Brown-If thJ

Q. What factors will you consider before prescribing OCP? (SU- I4J,09J)
Q. How do you select a client for combined OCP? (CU -04M)
Q. What are )Jre' precautions to be taken to advice oral contraceptives? (D U-04M)
Q. Descr· the principles of prescribing OCP to a newly maried woman. (CU -I 5Ju)
Ans.
Sel f n of an ideal client for combined OCP : To se lect a pati ent fo r presc ribing OC P, th orough hi story
sica l examination, and some in vesti gati ons are needed to exclude contrai ndicati ons. ·,
l. Age of the patient is important. If she is more th an 35 yrs of age, she should be presc ribed with caution &
regular checkup is needed.
2. Personal history: In smokers, it is to be prescribed with caution as it is associated with increased
in cidence of thromboemboli sm.
3. Menstrual history is to be tnken to exc lud e preg,~ ncy, und iagnosed uterine diseases etc.
4. Family history of cerebro-vasc ul ar diseases inc luding hypertension, breast ca ncer and hyperl ipidemia
shoul d be exc luded.
5. Medical history rega rd ing throm boembolic episodes, jaun dice, epilepsy, OM , all ergic conditi on.
migra ine should be exc luded.
6. Examination of breast shoul d be done fo r any nodule. Blood press ure and we ight should be noted.
7. Pelvic examination to exc lud e fi bro id or ce rvical pathology is mand atory.
8. Investigation : Vag inal cyto logy if fac il ities are ava il ab le.

From the above menti oned exa mi na ti on to scree n, if it revea ls that the wo man is free from any system ic diseases
and co ntrai ndicati on, she is suitab le ca ndidate for OCP therapy.

Q. Why combined oral pills are not wise to use after 35 yea rs of age? (DU -07J)
Ans.
Y°Rationale of usin g combined OCPs after 35 yea rs of ace: Combined OC Ps has some serious adve rse effects
such as venous thro mboem boli sm. MI, cere brovascu lar di seases, increased chance of breast carci noma etc.
Mo reover the chance of deve lopment of hype11ension, diabetes me llitus, obes ity, heart fa ilure (w hich are relative
contra in dicatio n of OC P) is in creased after 35 years age. So use of OC P should be limited or should use wi th
cauti on & afte r appropri ate advice of a doctor or ed uca ted hea lth personals.
 741 Endocrine Pharmacology
Q. Give 3 important causes of contraceptive therapy failure. (DU-07J)
Ans.
Causes of contraceptive failure:
l. Concomitant use of enzyme inducing drugs (e.g. Rifampicin, Phenytoin)--. Increased concentration of
OCP metabolizing enzymes--. Increased Metabolism of OCP--. Contraceptive failure .
2. Concomitant use of broad spectrum antibiotic --. Decreased normal intestinal flora --. Decreased
enterohepatic circulation--. !Bioavailability of OCP--. Contraception failure.
3. Irregular using of the pills (e.g. missing of pill in one or two consecutive days)

Q. Write short note on: Injectable contraceptives. (CU-06J)

Ans.
Injectable contraceptives:
r. ·))epot medroxyprogesterone acetate (DMP A): IM 150 mg in every 3 months.
Y. Norethisterone enanthate (NET-EN): IM 200 mg 111 every 2 months.
Depot medroxyprogesterone acetate (DMP A): It is a 3-month depot injection of intramuscular progestogen. It
is equal in efficacy to the combined pill and is an alternative.

MIA: It works by inhibiting ovulation, and also renders cervical mucus impenetrable to sperm. After a l 50 mg
dose, ovulation is inhibited for at least 14 weeks.

Side effects:
l. Unpredictable spotting and bleeding, particularly during the first year of use. Spotting and bleeding
decrease with time.
2. Amenorrhea
3. Not desirable for women planning a pregnancy soon after cessation of therapy because ovulation
suppression can sometimes persist for as long as 18 months after the last injection.
4. Reversible reduction in bone density.
5. Changes in plasma lipids with increased risk of atherosclerosis.

Advantage:
I. Long-term DMPA use reduces menstrual blood loss.
2. Decreased risk of endornetrial cancer.
(Ref Katzung- I 3th)

Q. Short note: Postcoital Contraceptives.

Ans.
Postcoital Contraceptives: Pregnancy can be prevented following unprotected coitus by the administration of
estrogen s alone or in combination with progestins ("morning after" contraception). When treatment is begun
within 72 hours, it is effective 99% of the time.

Postcoital Contraceptives
• Conjugated estrogens: IO mg three times daily for 5 days
• Ethinyl estradiol: 2.5 mg twice daily for S days
• Diethylstilbestrol : 50 mg daily for 5 days
• Mifepristone: 600 mg once with misoprostol, 400 mcg once
• L-Norgestrel : 0.75 mg twice daily for I day
• Combined pill: Norgestrel, 0.5 mg, with ethinyl estradiol, 0.05 mg (eg, Emcon) : 2 tabs as early as
possible within 72 hours & then 2 tabs l 2 hours after the first dose .

Adverse effects
I. Nausea or vomiting (relieved by antiemetics)

Pharmacology-95
 mueprint"M Pharmacology 742
2. ~ Other include headac he, di zziness, breast tenderness, and abdominal and leg cramps.
(Ref Katzung- 1JthJ
---
. Short note: Norplant. (DU-05/04.l )
Ans.
Norplant: . . . . . .
It is an im plant of levonorgesterol , a progesterone preparation. Norpl ant 11npl ant consists ot_6 si ali st ic capsules,
non-bio-degradable, 3.5 x 2.4 mm . Each contains 36 mg of levonorgesterol closed at both encfs. ---
--s'fte of insertion : lexor surface of upper left ar~ -::dermaif . . .
Duration of action : Norpl ant 1s e ·ect1 ve fo r s--o-years. Tfie 1mp ant mu st be removed when its effective peri od
has elapsed.
Advantages:
f Extremely effecti ve. .
Y. Low leve ls of hormone have little effect on lipoprotein and carbohydrate metabolism or bl ood pressure.
Disadvantages
/ Surgica l procedure fo r in serti on and remova l of capsules.
/ So me irregular bleeding rather than predi ctable menses.
/ lntracranial hypertension in some women.
(Ref Katzung-1 Jth)

Q. Mention the non-contraceptive health benefits of combined OCPs. (DU-I 7M, CU - l OJu)
Ans.
Contraceptive health benefits of combined OCPs: Contraception
Non-contraceptive health benefits of combined OCPs:
1. Decreased incidence of ovarian & endometri al carcinoma sign ifica ntly:
"• I hey s1gnd1cantly reduce the inc idence within 6 months of use
• The incidence is dec reased 50% after 2 years of use
• The protective effects persists up to 15 yea rs after OC P use is di scontinued
2. Dec rease inc~nce of ovari an cysts & benign fib rocysti c breast di sease
3. OC P has 1m po11ant beneficial effect on rnenstrua 1011:
7 More regul ar menstruation
·y Decreased menstrual bl ood loss & Fe defi ciency anem ia
y. Decreased incidence of dysmenorrhea
4. Decreased incidence of PIO (pelvic in fla mmatory disease)
5. Decreased incidence of ectop ic pregnancies & endometri os is.

Combined OC P preven ts thousand s of deaths, ep isodes of vari ous diseases & cases of hospi ta li zat ion eac h year.
(Ref Goodman & Gi/mcm 's-1 2th)

Andro ens & Anabolic Steroids

Androgens: The and rogens are a gro up of stero ids that have anabolic and/or masc ulinizing effects in both males
and females. ·
Testosterone is the most important and rogen in humans.
• In men. approx imate ly 8 mg of testosterone is produced daily.
• About 95% is produced by th e Leydig ce lls and on ly 5% by th e adrenals.
• Small amount of testosterone is also produced in fe male by th e ovari es and adrena ls and by the periphera l
co nversion of other hormones.
 743 Endocrine Pharmaco logy
Anabn lil' steroid: Anclrof!,cn n::cc ptor ngoni sts used for a,wbolic effects (cg, wci gl11 g;i in , i11crcascd nrn s.clc ,rn, . , s)
an.: ca lled a11;1blllic steroids.

A1ulro!.!t.~11s
Nat nra l
• ·rcstostero nc
• Di hyclrotcstostero11c
• /\11d rostcn cdi one
• Del1 ydrocpi anclrostero11e
Sy nthetic • Testosterone cyp ionate
• Testosterone cna11thate
• Methy Itestosterone
• Fluoxymesterone
• Oxy meth olone
• Oxa ndr ilone
• Nand ro lone d<..:canoatc
(Ref· Katrnny,-l 3th)

Physiologic Effects of Androgens

I. Deve lop ment of seco nd ary sex ual characteristic . in male at puberty .
2. Stimulation and maintenance of sex ual function in men.
3. In crease lea n body ma ss and stimul ate body hair growth and sebum sec retion.
4. Metabolic effects includ e the redu cti on of horm one binding and other carri er prot ei ns and increased liver
sy nthes is or clotting factors, tri glyce ride lipase, a -ant itrypsin, haptoglobin , and sialic acid. They also
1

stimul ate rena l erythropoietin secreti on and decrease HDL level s.

Clinical Uses of Androgens

I. Androgen replacement therapy in hypogo nada l men.
2. Gynecologic Disorders
• To red uce breast engo rge ment during the pos tpartum pe ri od, alo ng with estrogens.
• End ornet ri os is (Danazol)
• J lonn onc rep lace ment therapy in the postmenopa usal period in an atte111pt to elimin ate the
endo metri al bleeding and to en hance li bido.
• Used for chemot herapy of breast tum ors in premenopausal wom en.
3. Use as Protein An abolic Agents: Androgens and anabolic stero ids are used in an attempt to reverse
protein loss afrcr traum a, surgery, or prolon ged immobilizati on and in patients with debilitating di seases.
4. Refractory an emias such as ap lastic anemia . (Now reco111hina11I ery thropoietin is used) .
5. Osteoporosis (now bisphosphonules replaced an irogen usej(,r this pur(Jose .)
6. Use as Growth Stimu lators: These agents have been used to sti111ul ate growth in boys with delayed
puberty. II' th e dru gs are used ca rcl'u ll y, th ese chi ldren wi ll probabl y achieve th eir ex pected ad ult hei ght.
7. Anabo lic Steroid and Androgen Abuse in Sports: Many athktes and th eir coaches believe that
anabo li c stero id s- in doses I0- 200 tim es larger than th e dail y nor111 al producti on- in crease strength and
aggress iveness, thereby imp rovin g competitive perfo rm ance. Suc h effects have been unequ ivoca ll y
demonstra ted onl y in women. Furtherm ore, the adverse effects of these drugs clea rl y make th eir use
inadvi sab le.
8. Aging.
(Ref Ku1::1.111g ~I 3th)

Adverse Effects: The adverse effects are clue large ly to th eir ma sculini zin g ac ti ons an d are most noti ceab le in
women and prepubertal children.
I. In wom en,
Blueprin{l'I\I Pharmacology 744
a. Hirsutism
b. Acne
c. Amenorrhea
d. Clitoral enlargement
e. Deepening of the voice .
f. Endometrial bleeding upon discontinuation
g. Atherosclerotic disease in women.
2. In older males, prostatic hyperplasia, causing urinary retention .
3. Replacement therapy in men may cause acne, sleep apnea, erythrocytosi s, gynecomastia, and
azoosperm ia.
4. Hepatic dysfunction .
5. Alkylated androgens in high doses can produce peliosis hepatica, cholestasis, and hepatic failure . They
lower plasma HDL2 and may increase LDL.
6. Hepatic adenomas and carcinomas.
7. Behavioral effects include psychologic dependence, increased aggressiveness, and psychotic sy mptoms.
(Ref Kalzung-l 3th)

Contraindications & Cautions

1. Pregnant women or women who may become pregnant during the course of therapy .
2. They should be avoided in infants and young children.
3. Carcinoma of the prostate or breast.
4. Patients with renal or cardiac disease predisposed to edema.
(Ref Katzung- l 3th)

Q. Short note: Gynaecomastia.

Ans.
Gynaecomastia: Gynaecomastia is the presence of glandular breast tiss ue in males. N orma l breast deve lopment
in women is estrogen-dependent, while androgens oppose this effect. Gynaecomastia results from an imbalance
between androgen and estrogen activity, which may reflect androgen de ficienc y or estrogen excess .

Causes of gynaecomastia
1. Idiopathic
2. Physiological
3. Drug-induced
a. Cimetidine
b. D igoxin
c . Anti-androgens ( cyproterone acetate, spironolactone)
d. Some exogenous anabolic steroids (diethyl stilbestrol)
4. Hxrogonadism
5. Androgen resistance syndromes
6. Estrogen excess
a. Liver failure (impaired steroid metabolism)
b. Estrogen-secreting tumour (for example, of testis)
c . hCG-sec reting tumour (for example, of testi s or lung)
(Ref Davidso n ·s-2 J''/ 759)
Antiandrogens:
. . Antiandrogens co un ter ma Ie hormona I action
· by 111ter1enng
· c · wit· I1 tI1e synt I1es1·s o1· androgen s· 0 1·
by block111g their receptors.

Steroid Synthesis Inhibitors

• Ketoconazo Ie
Inhibitor of Conversion of Steroid Precursors to
Androgens • Abiraterone
• Finasteride

Androgenic Receptor Inhibitors

• Dutasteride
• Cyproterone
• Cyproterone acetate
• Flutamide
• Bicalutamide
• Nilutamide
• Spironolactone
(Ref Kat::ung-13Lf1)

Indication:
I. Benign prostatic hypertrophy (Finasteride and dutasteride)
2. Prostatic carcinoma (Flutamide)
3. Metastatic carcinoma of the prostate (Bicalutamide and nilutamide)
4. Hirsutism in women (Cyproterone, spironolactone, finasterid e, tlutamide)
5. To decrease excessive sexual drive in men (Cyproterone)
(Ref Kutzung-! 3th)

Q. Enumerate the clinical use of Finasteride. (CU - I 6Ju)

Ans.
Clinical use of Finasteride
I. Beni gn prostatic hyperplasia
2. Hirsutism in women
3. Early male pattern baldness in men
(Ref Kat:wng- I 3th)

Chemical Contraception in Men

Gossypol: Extensive trials of this cottonseed deri vati ve have been conducted in China . This compound destroys
elements of the seminiferous epithelium but does not significa ntly alter the endocrine function of the test is.
In Chin ese studies, large numbers of men were treated wi th 20 mg/d of gossypol for 2 months, followed by a
maintenance dosage of 60 mg/wk . On thi s regimen, 99% of men developed sperm counts below 4 million/ml.
Hypokal emia is the major adverse effect and may lead to transient paralys is. Because of low efficacy and
significa nt tox icity, gossy pol has been abandoned as a candidate male contracepti ve .
(Ref Katzung-13th)
Blm' prin(01 Pim rmal·olog~'

w.tY k., n, a.,;; ,tt] at1~1, am; a, :0am rm 1;;

T(,noid hormones:
/ · 1. Tetra iodothyronine/Thyrnx in e(T.1) _) <V'c\ ,e-.. . o, ( ·" \ \
~- Triiodothyro nine (T.i)
3. Cakito ni;1 - c, -.\'C.\',c~\ c, L-\
- ' ,c, . .
Drugs used in treatment of Hypothyroidism
Q. Mention the thyroid preparations. (RU- I 4Ju)
Ans.
Thyroid preparations: .
A. Synthetic: The synthet ic preparations of the sodiu m sa lts of the natural iso mers of the thyroid hormon es are
~vailable and widely used for thyroid hormone therapy.
I Levothyroxine
2. Liotll'ronine
",:' Lio-trix

B. Animal origin : Desiccated thyroid.

-t~c) (Ref· Katzung-1 Jth)

Levo thyroxine (T 4)
Q. Explain the role of thyroxine in hypothyroidism. (DU-l4Ju , 13Ju)
Q. Why synthetic Levothyroxine is the___e reparation of choice for thyroid replacement? (RU- I 4J u)
Ans.
Synthetic levothyroxine is the preparation of choice for thyroid replacement and suppression therapy
because of its stability, conten~ uni fo~mitt._ low ~ stz. l~ck oi_ all ergeni ~ foreig ~ pr_0ei~, eas1 la~oratory
measurement of serUin levels, a11d long half-li fe (7 days), which permits once-da il ad mini stration. In addit ion, T.1
is conve11ed to T-; intr·acell~arly; thus, administration of Ts produces both hormones. Generic levothyr~
p. ations provide comparable efficacy and are more cost-effective th an branded preparations.
(Ref Katzung-l 3rh)

Liothyronine (T 3)
Q. Liothyronine is not recommended for routine replacement therapy- Explain.
Ans.
Liothyronine is not recommended for routine replacement therapy: Alth ough li othyronine (T:1 ) is three to
four times more potent th an levothyroxine, it is not recommended for routine replacement therapy because of its-
1. Shorter half-li_fe (24 hours), which requires multiple daily doses.
2. Higher cost.
3. Greater diflic ulty of monitoring its adeq uacy of rep lacement by conventi onal laboratory tests .
4. Greater risYof cardi otoxicity.
(Re( Katz11ng-l 3th)
Nice to know
Desiccated thyroid : The use of desiccated thyroid rather than synthet ic preparations is never _justified , since the
disadvantages of protein antigenicity, product instability, variable horm one co nce ntration s, and difficultv in
laboratory monitoring fa r o fweigh tl1e advantage of lower cost. ·
(Ref' Kat21111g-I Jrh)
 747 E,ndocrinc Pharmaco logy

Drugs used in treabnent of hyperthyroidism (thyrotoxicosis)

th
Antithyroid drugs : A large nu111ber of compounds are ca pable or interferin g, directl y or indirectl y, with c
synthes is. release. or action of th yro id hormones.
(Ref Goud111an & Gi/man -12''' edition)
/
I
Q. Eoli antithyroid drugs . (DU-I 3Ju; SU-l 3Ju)
Ao·.
Antithyroid drugs: /

I. Thioamides: They inhibit the thyroid peroxidase-catalyzed reactions and Li Ca rbim azo le
bl oc k iodine organification. In addition, they block couplin g of th e V Methim azo le
iodotyros ines. 'L,." _Proovlthiouracil - 'lf"'-;-Jt,
2. Anion inhibitors: All are monova lent anions & can block uptake of iodide l~ Pe rcl1lorate (CIO.i")
by the gland through competitive inhibition of th e iodid e transpo11 • Pertechnetate (TcOd
mechani sm. , / Thiocyanate (SCN·)
3. Hormone release inhibitor _/' Lithium sa lts
Iodid e
4. Iodotyrosine deiodination inhibitor ,v. Nitrotyrosines
5. Peripheral iodothyronine deiodination inhibitor ( 1''1...\Y) 7 Thiouracil deri vati ve~
• Oral cholecystograph 1c
agents
I/ Amiodarone
31 / 13 11
6. Radioactive iodine (' 1): It is se lect ive ly taken up by the thyro id gland -
emits~ particles - damage thyroid cells - Dec reases th yro id hormone
synthes is. 1 ' '

(Ref Katzung-13th; Goodman & Gi/man-1 2 1, ed1tt0n)

Adjuvant therapy with drugs that have no specific effects on thyro id gland hormonogenes is is useful in
contro tirrg-t:l~e periphera l manifestations of thyrotox icos is. These drugs incl ude-
- 1. mfi ,b,tors of the penphera a eiocl inat ion of th yroxine to the active hormone, trii odothyronine;
) ( ') -blockers: Propranolol , Metopro lol, Ateno lol.
/ Ca 2 ' chann el blockers.
(Ref Goodman & Gilman -1 2'1' edition)
(__ u ~ c.-y--... 11\,Q . . .; I?~"'
- -----
THYROID GLAND

Tran spon I Perox idase I Thy roglobulin

-....---+- ,- - - - + - 1 ' - - + -1 MIT-OIT- T3·T,

Proteolysis

- - - - T4, T3
PERIPHERAL __.,...-- BLOOD
TISSUE S - - - - - - - -
Fig: Biosynthesis of thyroid hormones. The
T,. T3 ~---......_
sites 4 action <Jf various drugs that interfere
i:1:c:~rs. with thyro id hormone biosynthesis are
j corticosteroid&
Amiodarone
shown
( Ref Kotzung-13th)
 - -r·;.j- \) .. --r-. ;
·i V r ~

-...)
r
BlueprintT,\I Pharmacology --- ~r
,/
~

Thioamides
The thi oamides methimazole and propylthiouracil are major drugs for treatment of thyrotoxicosis~ thiinazoit_:
is about ten times more potent than propylthiouracil. - -

Mec~anism of action: The thioamides act by multiple mechanisms. .

, 1. Prevent hormone synthesis by inhibiting the thyroid peroxidase-catalyzed reactions and blockin g iod ine
/4 organification. . .
2. g oc coupling of the iodotyrosines. They do not block uptake of 1od1de by the gland.
/2 . Inhibit the peripheral deiodination ofT4 and T3.

Since the synthesis rather than the release of hormones is affected, the onset of these agents is slow, often
req uiring 3-4 weeks before stores of T4 are depleted .
(Ref Katzung-13/hJ
~c-- -,
Q_ -)- ~ \ \ J -£\er-\- <l\Sc-d.o r, ~ -$f,~·t---
Indications:
I. Hyperthyroidism (thyrotoxicosis)
~ a~,.__\~ -,>-S~\\/ ~ I S ~ b'-"- -rf'/ ~
Pr'--~ t\.., ~~ --t U-<"'F\~~ .)~""Y°&~ l,.._........_
Toxicity: Adverse reactions to the thioamides occur in 3-12% of treated patients. -t\....o:\ t"°D1..,~ 1...,,,,
Nausea and GI distress. --\-o · ~ {._"' :.'J-\..
2. An altered sense of taste or smell (methimazo
3. Most common adverse effect Maculo ular ruritic ras (4---:-6%).
4. Rare adverse effects include an urticaria! rash, vasculit1s, a lupus-like reaction, lymphadenopathy,
hypoprothrombinemia, exfoliative dermatitis, polyserositis, and acute arthralgia.
5. Hepatitis (more common with propylthiouracil) and cholestatic jaundice (more common with
methimazole) can be fatal.
3
6. Most dangerous complication: Agranulocytosis (granulocyte count < 500 cells/mm ). The reaction is
usually rapidly reversible when t e rug 1s 1scontinued.
(Ref Katzung- l 3th)

IODIDES
Prior to the introduction of the thioamides in the 1940s, iodides were the major antithyroid agents; today they are
rarely used as sole therapy.

Mechanism of action: They inhib it organification and hormone release and decrease the size and vascularity of
the hyperplastic gland. -

Clinical Use of Iodide

/ . Preparation for surgical thyroidectomy in hyperthyroid patient
2. Thyrotoxic cns1s (in conjunction with ant1fli yroid drugs and propranolol)
3. to protect the thyroid from radioactive iodine fallout followin a nuclear accident.
4. Strong iodine solution (Lugo l's solution) is widely used and consists of 5% iodine and 10% potass ium
iodiae, which yields a dose of 6.3 mg of iodine per drop. - - -
(Ref Goodman & Gilman-I 211, edition)
Toxicity: Adverse reactions to iodine (iodism) are uncommon and in most cases reversible upon discontinuance.
Theyjnclude-
·1 . Acneiform rash
~ Swollen salivary glands
/J. Mucous membrane ulcerations
-4".'/ Conjunctivitis
Rhinorrhoea
6. Drug fever
r Metallic taste
8. Bleeding di sorders
 749 Endocrine Pharmacology
9. Rarely, anaphylactoid reactions.
(Ref Katzung-13th)

Adrenoceptor-Blocking Agents
Q. Explain the role of propranolol in hyperthyroidism. (SU-I 2Ju) l__ t ' ~ ,) / A.c.~_
Ans.
Role of P-blocker (eg, propranolol) in hyperthyroidism: Beta blockers without intrinsic sympathomimetic
activity (eg, m!_toprolol, propranolol, atenolol) are effective therapeutic adjuncts in the management of
thyrotoxicosis since many of these symptoms mimic those associated with sympathetic stimulation. Propranolol
has been the ~-blocker most widely studied and used in the therapy of thyrotoxicosis. Beta blockers cause clinical
improvement of hyperthyroid symptoms but do not typically alter thyroid honnone levels. Propranolol at doses
greater than 160 mg/d may also reduce T3 levels approximately 20% by inhibiting the peripheral conversion of T4
toT,. O,...,s;:_
-o~"' \ C O-_. - l;l_ ClJoC• ,,- --1 ) .._~ .
G .. Jl CQ....\!\ ' ·- 'L-~· (J<.ef Katzung-/Jth)
- rr--~'~------
<=

G ~ " c: l'"' ,, c
, c,{I P"V'i,'l),"rtJ~
'(~,~
• ® o~~~ea_ ~vv---

1Y- c:A TC:\

@ Qt'~
o.R

® C:0v-f~
~,~ .i>,--~'n~·- C 1'ir·,cc-:.' ,....._ ,c-C."--
'f"l.-- ( ... ·, t,,.'~ ')

©s~~~~,~~

f: (~
. rt" ·. cA

cc.0
'c'' ('Cc \~ ' . \'r,\.-\ ½ ,\-.-,---:,

Pharmacology-96
Blucprin{rM Pharmacology 750

MCQ
Q. Long acting glucocorticoids are- (DU- l 7M) e) May be used to treat excessive menstrual
a) prednisolone bleeding.
b) nudrocortisone a. T, b. T, c. F, d. T, e. T
c) betamethasone
d) dexamethasone Q. Following classes of antidiabetic agents have
e) triamcinolone the ability to reduce Insulin resistance: (CU -
a. F, b. F, c. T, d. T, e. F 14Ju)
a) Alpha-Glucosidase inhibitors
Q. Euglycaemic antidiabetic drugs are- (DU-l 7J) b) Dipeptidyl peptidase- 4 inhibitors.
a. tolbutamide · c) Meglitinides
b. glipizide d) Biguanides
c. metformin e) Thiazolidinediones
d. pioglitzone a. F, b. F, c. F, d. F, e. T
e. insulin
a. F, b. F, c. T, d. T, e. F Q. Absolute indications of insulin are- (DU-13 Ju)
a. type I diabetes mellitus.
Q. Ovulation is induced by- (DU-1 SJu) b. gestational diabetes mellitus.
a. clomifene c. first line therapy in type II diabetic mellitus.
b. mifepristone d. diabetic ketoacidosis.
c. tamoxifen e. hypoglycemic shock.
d. cylofenil a. T, b. T, c. F, d. T, e. F
e. gestrinone
a. T, b. F, c. F, d. F, e. F Q. Drug used in hypothyroidism are- (DU-l 3Ju)
a. levothyroxine.
Q. Insulin- (DU-1 SJu) b. propylthiouracil.
a. _is a polypeptide c. propranolol.
b. may cause antibody production d. liothyronine.
c. causes reduction of protein synthesis e. radioactive iodine.
d. decreases glucose transport into the cell a. T, b. F, c. F, d. T, e. F
e. is preferred in gestational diabetes mellitus
a. T, b. F, c. F, d. F, e. T Q. Insulin enhances- (DU- 13J)
a. glycogenolysis.
Q. Euglycaemic anti-diabetic drugs include- (DU- b. glycogenesis.
141 u) c. glycolysis.
a. chlorpropamide d. gluconeogenesis .
b. glyburide e. potassium transit into the cell.
c. metformin a. F, b. T, c. T, d. F, e. T
d. rosiglitazone
e. insulin Q. Anti-diabetic action of drug involve: (SU-I 3J)
a. F, b. F, c. T, d. T, e. F a. Glipizide release insulin
b. Pioglitazone increases insulin sensitivity
Q. Oral contraceptive preparations: (CU - l 4Ju) c. Metformin promotes glycogenesis
a) Containing estrogen and progesterone are the d. Insulin increases glucose uptake
most effective e. Repaglinide inhibits glucose transporters
b) Containing progesterone only may be a. T, b. T, c. F, d. T, e. F
advantageous after child birth.
c) May lead to iron-deficiency anemia.
Q. Following drugs can cause gynaecomastia-
(SU- l 3J)
d) May lead to hypertension
a. Cimetidine
b. Chlorpromazine
 75) Endocrine Pharmacolo~y
c. Digoxin Q. Glucocorticoids arc used for the treatment of-
d. Ranitidine (DU- 11 Ju)
c. Fluoxetine a. Chronic dermatitis (T)
a. T. b. F, c. T. d. F. e. F b. Asthma (T)
c. Osteoporosis (F)
Q. H) perthyroidism can be treated by- (DU-
1
d. Nephrotic syndrome (T)
I 2Ju) e. Glaucoma (F)
a. Tri-iodothyron ine (F)
b. Iodide (T) Q. Adverse effects of comb ined oral
c. Methimazole (T) contraceptives include- (DU - I IJu)
d. Propylthiouraci l (T) a. Breakthrough bleeding (T)
e. Levothyrox ine (F) b. Increased risk of endometria l cancer (F)
c. Increased risk of ovarian cancer (F)
Q. Short acting insulin preparations are- (DU - d. Nausea (T)
I2Ju) e. Reduced risk of ischemic stroke (F)
a. Insulin glargine (F)
b. Soluble insulin (T) Q. Long-acting glucocorticoids- (DU- I I J)
c. Insulin lispro (F) a. Prednisolone (F)
d. Insulin aspart (F) b. Fludrocortisone (F)
e. NPH insulin (F) c. Betamethasone (T)
d. Dexamethasone (T)
Q. Metformin- (DU-I 2Ju) e. Triamcinolone (T)
a. Causes hypoglycemia.
b. Increases peripheral glucose uptake and Q. Metformin- (DU- I I J)
utilization in target tissues . a. enhances peripheral utilization of glucose (T)
c. Causes weight loss . b. causes hypoglycemia (F)
d. Is contraindicated in renal fai lure. c. increases insulin release from beta ce lls (F)
e. Increases the sensitivity of insulin receptor. d. is contraindicated in renal failure (T)
a. F, b. T, c. T, d. T, e. F e. causes weight loss (T)

Q. Long acting glucocorticoids are- (DU-12Ju) Q. Glucocorticoids- (DU- I OJ)

a. Predn isolone (F) a. inhibit production of lipoprotein (F)
b. Betamethasone (T) b. inhibit phospholipase A2 (T)
C. Fludrocortisone (F) C. have got permissive effect (T)
d. Dexamethasone (T) d. increase circulatory no . of neutrophils (T)
e. Triamcino lone (F) e. increase circulatory no. of T cell s (F)

Q. Side effects of metformin are- (DU- I 2J) Q. Beclomethasone- (DU- I OJu)

a. Weight gai n. (F) a. is an anti-inflammatory dru g (T)
b. Gastrointestinal upset. (T) b. is a natural glucocorticoi,d ( F)
c. Lactic acidosis. (F) c. is given by inhalation (T)
d. Hypoglycemia (F) d. is a bronchod ilator (F)
e. Impaired kidney function . (?) e. inhib its phospholipase A2 enzyme (T)

Q. Insulin- (DU-1 lJu) Q. Regarding aldosterone- (DU-', OJu)

a. Decreases the conversion of amino acid to a. It is a glucocorti co id (F)
glucose. (T) b. It is released from zona glomeru losa (T)
b. Increases gl uconeogenes is (F) c. It ca n cause hyperkalaem ia (F)
c. Increases glucose tran sport into cell s (T) d. Its action can be antagonized by triamterene
d. Induces lipoprotein lipase. (T) (?)
e. Stimulates glycogenes is. (T) e. Its release can be inhibited by losa rtan (T)
 BlueprintTM Pharmacology 752
~Q:-.-:G~l:-:-=ib-e-nc"":'1-am~id~e-~(:i:D~U~-~IO~J::;;.u)_ _ _ _ _....;~--Q~.~M~e~tfi~or-m~i~n--(:"::D~U':-_":"':IO~J~) - - - - - - - - - -
a. is a insulin secretagogue (T) a. is a biguanide preparation (T)
b. blocks ATP dependent K+channel in beta- b. enhances peripheral utilization of glucose (T)
cells (T) c. causes hypoglycemia (F)
c. !nhi?i~s glucose absorption from GIT (F) d. increases insulin release from beta ce lls (F)
d. ts clm,cally useful in treating obese OM (F) e. increase insulin sensiti vi ty (F)
e. does not cause hypoglycemia (F)

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