Meerut Institute of Engineering & Technology, Meerut

Second Sessional Exam. Odd Semester (Session: 2020-21)

(December – 2020)

Programme: Bachelor of Pharmacy Semester: V

Course: Pharmacology-II Course Code: BP 503T
Max. Marks 30 Time: 2.00 Hrs
Section A

Q.1 Attempt any FOUR parts from the following: (4X 2 = 8)

a. Enlist Endocrine Glands.

Endocrine Glands are listed below:-

1. Pineal Gland
2. Hypothalamus Gland
3. Pituitary (anterior and posterior lobes) Gland
4. Thymus Gland
5. Thyroid Gland
6. Parathyroid Gland
7. Adrenal (cortex and medulla) Gland
8. Pancreas Gland
9. Gonads: Ovary (Female); Testis (Male)

b. Illustrate role of Propylthyouracil in Thyroid treatment.

Propylthiouracil, anti-thyroid drug inhibits thyroid peroxidise-catalyzed

reactions, blocks iodine organification, oxidation and iodination (step 2)
and de-iodination is peripheral conversion of T4 to T3 (step 6) involved in
synthesis and secretion of Thyroid hormones respectively.

C. Sketch uses of corticosteroids.

1. Replacement therapy with physiological doses of cortisol in primary or

secondary adrenal insufficiency is intended to simulate the normal daily
secretion of cortisol.

2. Short term, high dose suppressive glucocorticoid therapy is indicated

for anti-inflammatory effect in the treatment of medical emergencies like
necrotising vasculitis, status asthmaticus, inflammatory bowel disease
and anaphylactic shock.

3. In Organ transplant patients and those with autoimmune disorders

(Rheumatoid arthritis) corticosteroids are used for their
immunosuppressive effects.

D. Report anti-platelete mechanism of Aspirin.

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 Low doses (typically 75 to 81 mg/day) of aspirin are sufficient to
irreversibly acetylate serine 530 of cyclooxygenase (COX)-1. This effect
inhibits platelet generation of thromboxane A2, resulting in an
antithrombotic effect.

e. Draw rationale behind regulation of plasma glucose level by insulin,

somatostatin and Glucagon.

Regulation of blood glucose is largely done through the endocrine

hormones (insulin, somatostatin and Glucagon) of the pancreas, a
beautiful balance of hormones achieved through a negative feedback
loop. Insulin (formed in pancreatic beta cells) lowers blood glucose levels,
whereas glucagon (from pancreatic alpha cells) elevates blood glucose
levels. Somatostatin is formed in the delta cells of the pancreas and acts
as the “pancreatic policeman,” balancing insulin and glucagon. It helps
the pancreas alternate in turning on or turning off each opposing
hormone.

f. Report Rheumatoid arthritis with suitable examples.

Rheumatoid Arthiritis is a chronic, inflammatory and systemic

autoimmune disease. The primary symptoms of Rheumatoid Arthiritis
include pain, swelling and destruction of cartilage and bone as a result
of which permanent disability occurs. Symptoms of Rheumatoid
Arthiritis include:

1. Morning stiffness that last for at least 1 hr.

2. Joint pain with warmth, swelling, tenderness and stiffness of the joint
after resting

3. Low-grade fever.4. Inflammation of small blood vessels cancause

small nodules under the skin, but they are generally painless.

Section B

Q.2 Attempt any FOUR parts from the following: (4 X 3 =12)

a. Analyze Pharmacology of 5HT3 antagonists with examples.

5HT3 antagonists: Their efficacy relates to the blockade of 5-HT3 receptors

(subtype of serotonin receptor), which are located in high density in the area
postrema and nucleus tractus solitarius and on vagal afferent nerve endings
in the gut. 5HT3 antagonists are routinely used as anti-emetics
postoperatively and during chemotherapy. No schedule is better than a

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single dose daily given before chemotherapy. Their side effects are headache,
constipation, diarrhoea and asthenia (abnormal physical weakness or lack
of energy).
Azasetron hydrochloride is given in a usual dose of 10 mg once daily by
mouth or intravenously.
Granisetron: it is more effective than other 5-HT3 antagonists in preventing
delayed nausea and vomiting that occur more than 24 h after the first dose
of chemotherapy. Its main effect is to reduce the activity of the vagus nerve
which activates the vomiting centre in the medulla oblongata. It does not
have much effect on vomiting due to motion sickness.
Ondansetron (Zofran), a 5-hydroxytryptamine3 receptor agonist, is a potent
antiemetic originally used for treatment of chemotherapy-induced nausea
and vomiting. Ondansetron is given orally or intravenously, 4–8 mg up to
every 8 hours. It is better tolerated by patients than promethazine, with no
dystonic or extrapyramidal side effects. The weight based dose for
intravenous ondansetron should not exceed 16 mg due to cardiac safety
concern. Its adverse reactions are headache, fever, fatal arrhythmia and
bowel dysfunction. It prolongs the QT interval which indicates potentially
fatal arrhythmia.
Dolasetron: An antinauseant and antiemetic used in chemotherapy and
postoperatively.
Ramosetron (Ibset) is also indicated for a treatment of diarrhea-
predominant irritable bowel syndrome in male and women.
Tropisetron has been used experimentally as an analgesic in cases of
fibromyalgia.
Alosetron: A 5-HT3 antagonist used to treat diarrhea-predominant irritable
bowel syndrome (IBS).
c. Debate insulin preparations in diabetes.

Types of insulin: A person can take different types of insulin based on how
long they need the effects of the supplementary hormone to last.

There are three main groups of insulin: Fast-acting, Intermediate-acting and

Long-acting insulin.

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Fast-acting insulin: It is absorbed quickly from your fat tissue
(subcutaneous) into the bloodstream. It is used to control the blood sugar
during meals and snacks and to correct high blood sugars.

In contrast, insulin analogs have a more predictable duration of action.

Insulin analogs are replacing human insulin. The rapid acting insulin
analogs work more quickly, and the long acting insulin analogs last longer
and have a more even, “peakless” effect.

Rapid Acting Insulin Analogs (Insulin Aspart, insulin Lyspro, Insulin

Glulisine) They have an onset of action of 5 to 15 minutes, peak effect in 1
to 2 hours and duration of action that lasts 4-6 hours. With all doses, large
and small, the onset of action and the time to peak effect is similar, The
duration of insulin action is, however, affected by the dose – so a few units
may last 4 hours or less, while 25 or 30 units may last 5 to 6 hours. As a
general rule, assume that these insulins have duration of action of 4 hours.

Regular Human Insulin which has an onset of action of 1/2 hour to 1 hour,
peak effect in 2 to 4 hours, and duration of action of 6 to 8 hours. The larger
the dose of regular, the faster the onset of action but the longer the time to
peak effect and the longer the duration of the effect.
Intermediate-acting insulin: It is absorbed more slowly, and lasts longer. It
is used to control the blood sugar overnight, while fasting and between
meals
Includes:

NPH Human Insulin which has an onset of insulin effect of 1 to 2 hours, a

peak effect of 4 to 6 hours, and duration of action of more than 12 hours.
Very small doses will have an earlier peak effect and shorter duration of
action, while higher doses will have a longer time to peak effect and
prolonged duration.
Pre-Mixed Insulin which is NPH pre-mixed with either regular human
insulin or a rapid-acting insulin analog. The insulin action profile is a
combination of the short and intermediate acting insulins.
Long-acting insulin: It is absorbed slowly, has a minimal peak effect, and a
stable plateau effect that lasts most of the day. It is used to control the
blood sugar overnight, while fasting and between meals Includes:
Long acting insulin analogs (Insulin Glargine, Insulin Detemir) which
have an onset of insulin effect in 1 1/2-2 hours. The insulin effect plateaus
over the next few hours and is followed by a relatively flat duration of action
that lasts 12-24 hours for insulin detemir and 24 hours for insulin glargine.
Table: Insulin Action

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 Type of
Onset Peak Duration Appearance
Insulin

Fast-acting

Regular ½-1 2-4 hr. 6-8 hr. clear

hr.

Lyspro/ <15 1-2 hr. 4-6 hr. clear

Aspart/ min.
Glulisine

Intermediate-acting

NPH 1-2 hr. 6-10 hr. 12+ hr. cloudy

Long-acting

Detemir 1 hr. Flat, Max 12-24 hr. clear

effect in 5
hrs.

Glargine 1.5 hr. Flat, Max 24 hr. clear

effect in 5
hrs.
c. Categorize Histamine receptor blockers with examples on the basis of
their therapeutic uses.

I. H1 Receptor Antagonists

a. 1st generation H1 Receptor Antagonists: are used as Sedative/sleep

aid, Antiemetic: prophylactic for motion sickness (promethazine), anti-
vertigo (meclizine), local anesthetic: (diphenhydramine) and anti-
tussive (diphenhydramine). They are used as adjunctive in
anaphylaxis and other cases where histamine release can occur (H2
antagonist and epinephrine must also be used in anaphylaxis),
treatment of allergy (allergic rhinitis, allergic dermatoses, contact
dermatitis) and to prevent motion sickness (meclizine, cyclizine).
b. 2nd generation H1 Receptor Antagonists: They are non-sedating and
used in the treatment of allergy.

CETIRIZINE (Zyrtec), FEXOFENADINE (Allegra), LORATADINE

(Claritin), DESLORATADINE (Clarinex), LORATADINE (Claritin Hives
Relief), AZELASTIN (Intranasal Spray)
I. H2 Receptor Antagonists: They prevent H2 receptor mediated acid, fluid
and pepsin secretion and are used in treatment of peptic ulcer.
Example: Ranitidine, Cimetidine

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II. H3 Receptor Antagonists (potential new drugs being developed): They
prevent H3 receptor mediated pain and itching.

Example: Thioperamide, iodophenpropit ,. clobenpropit

c. Examine pharmacological actions, uses and side effects of Aspirin.

Aspirin is 1- Acetylsalicylic acid. Aspirin can be thought of as a traditional

Non-steroidal anti-inflammatory drug (NSAID), but it exhibits anti-
inflammatory activity at relatively high doses that are rarely used. It has
gained much more usage at lower doses for the prevention of cardiovascular
events such as stroke and myocardial infarction.

Mechanism of action: It is often differentiated from other NSAIDs, since it is

an irreversible inhibitor of cyclooxygenase activity.

Aspirin pharmacological effects and respective mechanisms of action vary

with dose:

 Low doses (typically 75 to 81 mg/day) are sufficient to irreversibly

acetylate serine 530 of cyclooxygenase (COX)-1. This effect inhibits
platelet generation of thromboxane A2, resulting in an antithrombotic
effect.
 Intermediate doses (650 mg to 4 g/day) inhibit cyclooxygenase (COX)-1
and COX-2, blocking prostaglandin (PG) production and have
analgesic and antipyretic effects.
 High doses (between 4 and 8 g/day) are effective as anti-inflammatory
agents in rheumatic disorders; the mechanism(s) of action at these high
doses may include both PG-dependent (particularly COX-2 dependent
PGE2) and independent effects.

Side-effects: However, the usefulness of aspirin at these high doses is

limited by toxicity, including tinnitus, hearing loss and gastric ulcer
(intolerance).

d. Differentiate between PGI2 and PGE2 prostaglandins with

examples.
Prostacyclin (PGI2) inhibits platelet aggregation and promotes
vasodilation. Example: Eporostenol PGE2 and PGI2 cause an increase
in blood flow, but do not cause edema in inflammation.
Prostaglandins cause smooth muscle relaxation and induce
erythropoiesis by stimulating the renal release of erythropoietin. PGE2
increases the rate of longitudinal contraction in the gut and decrease
transit time. PGE2 causes contraction of uterine smooth muscle in
pregnant women but it causes relaxation of non-pregnant uterus.
PGE2 and PGI2 act on parietal cell in stomach wall to inhibit acid and
pepsinogen secretion therefore their analogues are used in treatment

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 of ulcer. PGE2 & PGI2 are potent vasodilator of vascular Smooth
muscle.
f. Analyze role of Allopurinol in treatment of Gout.

Gout is metabolic disease in which plasma urate concentration get

increased (hyperuricaemia i.e. more than 1-4 mg/dl in blood).
Allopurinol, hypoxanthine analogue was synthesized a purine
antimetabolite. It has substrate as well as inhibitor of xanthine oxidase,
the enzyme responsible for uric acid synthesis. Xanthine oxidase is the
key enzyme in purine degradation. Purines originate from food and the
degradation of nucleic acids and nucleotides. Xanthine oxidase converts
hypoxanthine to xanthine, and xanthine to uric acid, respectively. Uric
acid is product of purine metabolism at low pH (acidic) has low water
solubility in man. When urate level increases it gets precipitates and
deposits in joints, kidney and cutaneous tissue which is called as tophy.

Section C

Q.3 Attempt any TWO parts from the following: (2 X 5=10)

a. Appraise classification of hormones secreted from anterior lobe of

Pituitary gland with their physiological actions.

Pituitary Gland: endocrine gland that is attached to the hypothalamus

of the lower forebrain. The pituitary gland is attached to the
hypothalamus of the lower forebrain. The body’s master gland; located at
the base of the brain (Bone Sella Turcica) and attached to the
hypothalamus via a stalk called the pituitary stalk. Hormones produced
(or secreted) by the gland include:
a. Anterior pituitary: The following hormones are produced by the
anterior pituitary and released in response to hormone signals from the
hypothalamus.
 Growth hormone stimulates growth factors.
 Adrenocorticotropic hormone (ACTH) simulates adrenal glands to
secrete glucocorticoids such as cortisol.
 Thyroid-stimulating hormone stimulates thyroid gland to secrete
thyroid hormones.
 Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
stimulates production of gametes and sex steroid hormones.
 Prolactin stimulates mammary gland growth and milk production.

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b. Categorize autacoids with their physiological actions.

The word autacoid comes from the Greek "autos (self)" and "acos"
(healing/remedy; i.e., drug). Autacoids are substances released from the
cells in response to various stimuli and elicit normal physiological responses
locally. Autocoids are endogenous organic molecules with potent
pharmacologic effects that are not part of traditional immune or autonomic
groups. They act like local hormones, have a brief duration, and act near
their site of synthesis.

Classification: Numerous substances belong to this group.

1. Amine derived: Histamine, Serotonin (Tryptophan)

2. Peptide derived: Angiotensin, Bradykinin
3. Lipid derived: Prostaglandins, Leukotrienes, Interleukins, Platelet
Activating Factor

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 Fig.: Autacoids, their physiological and pharmacological actions

C. Justify physiological effects of Angiotensin.

Angiotensin is a peptide hormone that causes vasoconstriction and an

increase in blood pressure. It is part of the renin–angiotensin system, which
regulates blood pressure. Angiotensin also stimulates the release of
aldosterone from the adrenal cortex to promote sodium retention by the
kidneys.

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 Fig. 3: Renin Angiotensin Aldosteron System

The system can be activated when there is a loss of blood volume or a

drop in blood pressure (such as in hemorrhage or dehydration). This loss of
pressure is interpreted by baroreceptors in the carotid sinus. It can also be
activated by a decrease in the filtrate sodium chloride (NaCl) concentration
or a decreased filtrate flow rate that will stimulate the macula densa to
signal the juxtaglomerular cells to release renin.

1. If the perfusion of the juxtaglomerular apparatus in the kidney's macula

densa decreases, then the juxtaglomerular cells (granular cells,
modified pericytes in the glomerular capillary) release
the enzyme renin.
2. Renin cleaves a decapeptide from angiotensinogen, a globular protein.
The decapeptide is known as angiotensin I.
3. Angiotensin I is then converted to an octapeptide, angiotensin
II by angiotensin-converting enzyme (ACE), which is thought to be
found mainly in endothelial cells of the capillaries throughout the
body, within the lungs and the epithelial cells of the kidneys.

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4. Angiotensin II is the major bioactive product of the renin–angiotensin
system, binding to receptors on intraglomerular mesangial cells,
causing these cells to contract along with the blood vessels
surrounding them and causing the release of aldosterone from
the zona glomerulosa in the adrenal cortex. It acts as
an endocrine, autocrine/paracrine, and intracrine hormone.

Angiotensin II has a variety of effects on the body:

 Throughout the body, angiotensin II is a

potent vasoconstrictor of arterioles.
 In the kidneys, angiotensin II constricts glomerular arterioles, having a
greater effect on efferent arterioles than afferent. As with most other
capillary beds in the body, the constriction of afferent arterioles increases
the arteriolar resistance, raising systemic arterial blood pressure and
decreasing the blood flow. However, the kidneys must continue to filter
enough blood despite this drop in blood flow, necessitating mechanisms
to keep glomerular blood pressure up. To do this, angiotensin II
constricts efferent arterioles, which forces blood to build up in the
glomerulus, increasing glomerular pressure. The glomerular filtration
rate (GFR) is thus maintained, and blood filtration can continue despite
lowered overall kidney blood flow. Because the filtration fraction, which
is the ratio of the glomerular filtration rate (GFR) to the renal plasma flow
(RPF), has increased, there is less plasma fluid in the downstream
peritubular capillaries. This in turn leads to a decreased hydrostatic
pressure and increased oncotic pressure (due to unfiltered plasma
proteins) in the peritubular capillaries. The effect of decreased
hydrostatic pressure and increased oncotic pressure in the peritubular
capillaries will facilitate increased reabsorption of tubular fluid.
 Angiotensin II decreases medullary blood flow through the vasa recta.
This decreases the washout of NaCl and urea in the kidney medullary
space. Thus, higher concentrations of NaCl and urea in the medulla
facilitate increased absorption of tubular fluid. Furthermore, increased

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 reabsorption of fluid into the medulla will increase passive reabsorption
of sodium along the thick ascending limb of the Loop of Henle.
 Angiotensin II stimulates Na+/H+ exchangers located on the apical
membranes (faces the tubular lumen) of cells in the proximal tubule and
thick ascending limb of the loop of Henle in addition to Na+ channels in
the collecting ducts. This will ultimately lead to increased sodium
reabsorption.
 Angiotensin II stimulates the hypertrophy of renal tubule cells, leading to
further sodium reabsorption.
 In the adrenal cortex, angiotensin II acts to cause the release
of aldosterone. Aldosterone acts on the tubules (e.g., the distal
convoluted tubules and the cortical collecting ducts) in the kidneys,
causing them to reabsorb more sodium and water from the urine. This
increases blood volume and, therefore, increases blood pressure. In
exchange for the reabsorbing of sodium to blood, potassium is secreted
into the tubules, becomes part of urine and is excreted.
 Angiotensin II causes the release of anti-diuretic hormone (ADH), also
called vasopressin –ADH is made in the hypothalamus and released from
the posterior pituitary gland. As its name suggests, it also exhibits vaso-
constrictive properties, but its main course of action is to stimulate
reabsorption of water in the kidneys. ADH also acts on the central
nervous system to increase an individual's appetite for salt, and to
stimulate the sensation of thirst.
These effects directly act together to increase blood pressure and are
opposed by atrial natriuretic peptide (ANP).

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