UNIT 5

10 MARKS

1.Classify local anaesthetic agents and explain

the MOA? Write the synthesis and uses of
procaine and dibucaine
Local anaesthetics are synthetic drugs, which
produce loss of sensation in particular applied
for clinical purpose via blocking the Na+ e ion
entry inside cell membrane which is required
for generation and conduction of nerve
impulses.
→Clinical & Surgical procedure. can be
performed under regional anaesthesia
(anaesthesia selective for part of The body)
rather than anaesthesia (total body
anaesthesia with the patient rendered
unconscious)
 Ideal properties of Local Anaesthetics’
It must be inert.
It should be non-irritating to the issues.
It must be free from producing allergic
reactions.
It should have sufficient penetrating
properties & provide rapid onset action.
Pharmacological activities must be reversible
and not produce any secondary action /
reaction.
MOA:
Local anesthetics Blocks Vollage-gated Na+
Channels No generation of action potential
- No entry of Na+ ions into the cell- no
depolarization-No gen & conduction of
impulse to CNSlocal anaesthesia
Classification;
1.Benzoic acid derivatives
Ex: Cocaine
USES
It has vasoconstrictive properties so reduces
bleeding and swelling
It is used to anaesthetize the inner lining of
mouth

Hexylcaine,

Uses
Used in oral surgery
Useful for topical anaesthesia
Meprylcaine,

Cyclomethycaine,

Piperocaine

2.Amino benzoic and derivatives

Ex: Benzocaine,
Uses
Uses as a local anaesthetic
Used as dental analgesic
Used in eardrops creams ointments
Butamben,

Uses
Used in the treatment of chronic pain
Used as surface anaesthetic for skin mucous
membrane
Procaine,
Uses
Used as infiltration anaesthesia
Synthesis

Butacaine,

Uses
Surface anaesthesia
Used as dental analgesic
3. Anilide derivatives
Ex: Lignocaine,

Uses
Surface anasthesia
Used for cervical block
Prilocaine,

Etidocaine,
4.Miscellaneous
Ex: Phenacaine,
Uses
Used in skin operative procedures
Used to cause topical numbness
Diperodon,
Dibucaine

Uses
Used as surface anasthesia
Used to numb pain and relative itching
SYNTTHESIS
2.CLASSIFY LOCAL ANASTHETIC AGENTS
WRITE THE SAR OF BENZOIC ACID AND
ANILIDE CLASS OF LOCAL ANESTHETICS
: Structure Activity Relationship
The LA agents structures having three parts
mainly
 Aromatic Ring also known as Lipophilic
ring or substitute Lipophilic ring
 Linker chain either an ester or an amide
or any
  Amine group (Hydrophilic group) that is
secondary or tertiary (Amino alkyl. group)

1 The Aromatic Ring

The aromatic ring or Substituted at different
position mainly adds lipophilicity to the
anaesthetic & enhance penetration power
through biological membrane.
→The aromatic ring & their substituents,
position may increase the lipophilic nature of
the aromatic sing.
→ Substitution on para position of aromatic
ring in ester type of local anaesthetics is the
ability of the molecule to penetrate the nerve
membrane
→ Electron donating substituent shows
increased anaesthetic activity.
→Electron-withdrawing group, the election
cloud around the carbonyl oxygen decreases
the anaesthetic activity decreased.
* Part-II Linker
→The linker may be carbon, oxygen; nitrogen
containing function moieties
→ When the linker having alkyl chain with
increased number of carbon, the lipid
solubility, protein binding. duration of action
& Toxicity increases.
bio steric Replacement of Esters & amides
enhance the activity.
 Part-III Amino alkyl Group
→It is important for making drug water
soluble not necessary to anaesthetic, activity.
→Tertiary amine derivatives are more potent
and less necessary to anaesthetic activity.
→Tertiary amine derivatives are more potent
and less Toxic, Secondary amines may
increases duration of action but causes
irritation but primary amines are Suitable
local anaesthetic as less active & highly toxic
compare to tertiary . & Sec. Order is more
important.

3.CLASSIFY ANTIDIABETIC AGENTS WITH

EX ,WRITE THE SAR AND MECHANISM OF
ACTION OF THIAZOLIDINEDIONES?
diabetic Agents/Hypoglycaemic Agents
Introduction
agents are those, Hypoglycaemic ager which
are used Ito lower the blood sugar and are
used to neat the symptoms of diabetes
mellitus. There are three peptide hormones
secreted by the pancreas which play a major
role in the regulation of metabolism of
carbohydrate lipids & amino acids. These are
insulating alpha and beta glucagon &
somatostatin.
The normal blood glucose level in human's
ranges between 70- 90 m per point.
Hyperglycaemia is characterized by more than
normal concentration of the Hood sugar and
hypoglycaemia develops when the blood
sugar level falls below the normal range.
Diabetes mellitus is the condition arising due
to abnormal metabolism of carbohydrates,
fats and proteins. It is characterized mainly by
an unusually high sur level in the blood
(hyperglycaemia) and the presence of sugar in
the urine
(glucosuria) The large urine volume is due to
the large amounts of glucose and urea in the
urine (osmotic diuresis). Because the
biochemical basis of diabetes is still not clear,
the disease is usually defined by its
symptoms. These include, hyperglycemia,
hyperlipemia. glucosuria, polyuria (loss of
water and salts), polydipsia (increase in
thirst), polyphagia (excessive hunger),
ketonemia (ketone bodies and fatty acids in
the blood), ketonuria (ketone bodies In the
urine), azoturia (increased production and
excretion of ammonia). poor wound healing
and infection. Sometimes, the disease
eventually causes serious
complications like, kidney damage
degeneration, premature atheroscier (heart
disease.
neuro-logical dysfunction a predisposition to
gangrene.

Types of Diabetes:
Linder current clinical terms, diabetes mellitus
can be categorised as under (it) Insulin-
dependent, type 1 (IDDM or juvenile or brittle
or unstable diabetes). Non-insulin dependent
type, type II (NIDDM or adult onset or
maturity onsetdiabetes)
Other types:
Insulin receptor abnormalities
(a) Hormonal etioloy e.g., acromegaly
(b) Pancreatic disease
(c) Genetically related abnormalities
(d) Drug-induced conditions
Another term 'diabetes insipidius is reserved
for the conditions produced by the disorders
of the pituitary gland and the term, diabetes
mellitus is used to describe the actual
diabetes.
(i) Insulin dependent diabetes mellitus
(IDDM)
(ii) (ii) Non-Insulin dependent diabetes
mellitus (NIDDM
(iii) Insulin dependent versus non-insulin
dependent forms of diabetes me
The Hypoglycaemic agents are classified into 2
categories:-
(1)Insulin & Insulin preparations.
(2) Oral Hypoglycaemic agents.

 In Oral Hypoglycaemic agents drugs are

classified as
a. Sulfonyl urea:
Tolbutamide,

Chlorpropamide,
 Glipizide, Glimepiride,
b. Biguanides:
Metformin

c. Thiazolidinediones:
Pioglitazone,

Rosiglitazone
 d. Meglitinides:
Repaglinide,

Nateglinide

c. Glucosidase inhibitors:
Acrabose,
Voglibose

MOA
Thiazolidinediones are selective agonists of
PPARϒ. When activated by a ligand, such as a
thiazolidinedione, PPARϒ binds to the 9-cis
retinoic acid receptor (RXR [retinoid X
receptor]) to form a heterodimer.1This binds
to DNA to regulate the genetic transcription
and translation of a variety of proteins
involved in cellular differentiation and glucose
and lipid metabolism.
SAR
5 MARKS

1.CLASSIFY ANTIDIABETIC AGENTS WITH EX

WRITE THE SYNTHESIS OF TOLBUTAMIDE?
 In Oral Hypoglycemic agents drugs are
classified as
c
Glipizide, Glimepiride,
e. Biguanides:
Metformin

f. Thiazolidinediones:
 Pioglitazone,

Rosiglitazone

g. Meglitinides:
Repaglinide,

Nateglinide
c. Glucosidase inhibitors:
Acrabose,

Voglibose
SYNTHESIS
2.WHAT ARE HYPOGLYCEMIC AGENTS,DISCUSS
ABOUT GLYCOSIDASE INHIBITORS AS
ANTIDIABETIC AGENTS?
Glycosidase inhibitors play a crucial role in
managing diabetes.
 Alpha-Glucosidase Inhibitors (AGIs):
These oral anti-diabetic drugs are commonly
used for type 2 diabetes.
How do they work? By preventing the
digestion of carbohydrates, such as starch and
table sugar, in the small intestine1.
AGIs have a lowering effect on postprandial
blood glucose and insulin levels2.
 Applications of Glycosidase Inhibitors:
Antidiabetic Agents: AGIs like acarbose,
miglitol, and voglibose are widely used in
treating type 2 diabetes. They help regulate
blood sugar levels by delaying carbohydrate
absorption.
Agrochemicals: Glycosidase inhibitors have
potential applications as agrochemicals. For
instance, the validamycin family was
discovered as a treatment for sheath blight
disease in rice plants.
Antivirals: Inhibition of glycosidases can
impact cell–virus recognition processes,
making them relevant in viral infection
management.
Therapeutic Agents for Genetic Disorders:
These inhibitors can alter glycoprotein quality
control, maturation, and transport, affecting
genetic disorders

3.DEFINE THE TERM HYPOGLYCEMIC

AGENTS,GIVE THE STRUCTURE OF ANY 2
SULFONYLUREA DERIVATIVES, OUTLINE THE
SYNTHESIS OF TOLBUTAMIDE?
The term hypoglycaemia refers to the
reduction in blood glucose level below the
normal range
a. Sulfonyl urea:
Tolbutamide,

Chlorpropamide,
4.DISCUSS MEGLITINIDES WITH STRUCTURES AS
ANTI DIABETIC AGENTS?
a. Meglitinides:
Repaglinide,

Nateglinide
Meglitinides are a class of antidiabetic
medications used to manage Type 2
diabetes. These drugs work by stimulating
the pancreas to release insulin in
response to a meal. Specifically, they
close ATP-dependent potassium channels
in functioning pancreatic beta cells,
leading to depolarization of the beta cells.
This depolarization results in the opening
of calcium channels, which leads to an
influx of calcium. The increased
intracellular calcium then induces insulin
secretion .
Two commonly prescribed meglitinides
are:
Repaglinide (Brand Name: Prandin):
This medication has an average rating of
8.2 out of 10 based on user reviews. It
effectively stimulates insulin release and
helps control blood sugar levels
Nateglinide (Brand Name: Starlix):
Although less commonly used,
Nateglinide is another meglitinide that
works similarly to repaglinide.

5.EXPLAIN THE SAR OF AMINO BENZOIC

ACID DERIVATIVES AS LOCAL
ANAESTHETICS?
2 MARKS

1.WRITE A NOTE ON INSULIN AND ITS

DERIVATIVES?
Insulin is a crucial hormone that plays a
pivotal role in regulating blood sugar (glucose)
 levels. Insulin is produced by the beta cells
within the islets of Langerhans in the
pancreas.When blood glucose levels rise (such
as after a meal), these beta cells secrete
insulin into the bloodstream.
Insulin facilitates the absorption of glucose
from the blood into various tissues, including
the liver, fat cells, and skeletal muscle cells.
In these tissues, absorbed glucose undergoes
different metabolic processes:
It can be converted into glycogen via a process
called glycogenesis.
Alternatively, it can be transformed into
triglycerides (fats) through lipogenesis.
In the liver, glucose can be converted into
both glycogen and triglycerides.

2.WRITE THE STRUCTURE AND USES OF

MEGLITINIDE AND CHLORPROPAMIDE?
USES
Meglitinides are short-acting insulin
secretagogues.
They help the pancreas produce and release
insulin, which aids in controlling blood sugar levels

USES
Chlorpropamide is a medication used to treat type
2 diabetes mellitus in adults.
It belongs to a group of medicines called
sulfonylureas and helps control blood sugar levels
in people with diabetes.
This helps to prevent serious complications of
diabetes like kidney damage and blindness

3.WRITE THE STRUCTURE AND USES OF

PIOGLITAZONEAND METFORMIN?
Pioglitazone,

USES
USED TO TREAT TYPE 2 DIABETES MELLITUS
Metformin

USES
USED TO TREAT TYPE 2 DIABETES MELLITUS
4.OUTLINE THE SYNTHESIS OF PROCAINE?
Procaine,

Uses
Used as infiltration anaesthesia
Synthesis

5.OUTLINE THE SYNTHESIS OF BENZOCAINE?

6.WRITE THE STRUCTURE AND MOA OF
NESIRITIDE?