SYNTHETIC DRUGS 1

SULPHA DRUGS (SULPHONAMIDES)

In 1932 , Prontosil,ie, 4-sulphonamide 24 - diamino benzene a dye intermediate was suggested to have antibacterial
property . Prontosil breaks dwn in the tissues to sulphanilamide and suggested that antibacterial property is resided in
this part of the molecule.
In 1937 sulphapyredene which was the structural analogue of sulphanilamide proved tremendous success in curing
pneumonia was first discovered. Many structural modification of sulphanilamide were then prepared which have been
extensively used against many common bacterial infections.
CLASSIFICATION OF SULPHONAMIDES :-
Sulphonamides may be classified broadly on the basis of their site of action as
Suplhonamide for general infections:-These are invariably employed against the streptococcal, meningococcal ,
gonococcal,and pneumococcal infections . Examples : Sulfanilamide, sulphapyredene, sulpha thiazole,sulfadiazine etc.
Sulpphonamides for urenary infections:- Examples:- Sulfacetamide,sulfafurazole etc
Sulphonamides for intestenal infection :- Examples:- Sulfaguanidene, pthalyl sulfathiazole etc
Sulphonamide for local infections:- Examples:- sulfacetamide sodium,Mafenide etc
MODE OF ACTION OF SULPHONAMIDES :- Sulphanomides are bacteriostatic in nature.However in large doses they
may also act as bactericidal. Sulphanomide sensitive microorganism require p-aminobenzoic acid(PABA),for
the synthesis of folic acid,which is essential for the synthesis of DNA and RNA and there for for the growth and
multiplication of bacteria. Sulphanomides can compete with PABA and prevent the utilization of PABA and
thereby the synthesis of bacterial DNA and RNA,thus the sulphanomides have selective effect on the sensitive bacteria.
ANTI BACTERIALS
ANTIBIOTICS:- Antibitics are medication used to treat bacterial infections either by killing bacteria (bactericidal)
or by inhibiting the growth of susceptible bacteria (bactereostatic) . Examples : Sulpha drugs, Penicillines,
Ciphalosporin, Tetracyclin etc
PENICILLINS:- Penicillins are first introduced in 1940 Alexander Fleming . These are bactericidal and inhibit cell wall
synthesis in bacteria, kill a wide variety of them. The basic structure in penicillin contains lactum ring and are called
lactum eg: Penicilline-G , Amoxycilline , Ampicilline etc
MECHANISM OF ACTION
Penicillins enter the bacteria via the cell wall. Inside the cell, they bind to penicillin-binding protein. Once bound,
normal cell wall synthesis is disrupted. As a result: bacteria cells die from cell lysis
USES:- For the Prevention and treatment of infections caused by susceptible bacteria, such as: gram-positive
bacteria -Streptococcus, Enterococcus, Staphylococcus species


Antipyretics , Analgesics and Anti-inflammatory agents 2
Anti inflammatory agents are drugs used to diminish or reduce inflammations and pain arising from it. Non narcotic
analgesic differ from narcotic analgesic in the way that they do not depress the CNS(central nervous system) and are
divoid of addiction liability
General mode of action:-
Prostaglandins play an important role in radiating pain , fever and inflammation . Antipyretics , Analgesics and Anti-
inflammatory effects of drugs are due to inhibition of synthesis and release of prostaglandins. Release of prostaglandin
is reduced by stablilsing the cell membrane and the synthesis is reduced by blocking the enzyme prostaglandin
synthetase.

Antiinflamatory action:- These drug stabilize cell membranes so that the cells become less permeable thus
decreasing the formation of edema, Irritating substances are inhibited from affecting nerve endings and prostaglandin
synthesis is blocked.
Examples and uses of antipyretics , analgesics and anti-inflammatory agents:-
Asprin:- Used as antipyretic, Antirheumatic and antithrombolytic agent
Paracetamol (Aceteminophen):- Used as antipyretic and mild analgesic
Analgin(Novalgin):- Used to relieve mild to moderate pain
Mefenamic acid:- Used in the relief of head ache, tooth ache, muscular pain and stomach pain
Ibuprofen:- Used to relief muscular pain, tooth ache and joint pain.
Diclofenac:- Used in the treatment of rheumatoid arthritis,spondylitis and acute musculoskeletal disorders.
Antihistamines
- Histamine is a biological amine widely distributed in the body tissues especially in the mast calls.It is synthesized in the
body from histidine by decarboxylation.When present in the cell it is inert, but when released it produces a number of
biological actions such as allergic manifestations,oedema,bronchiole constriction and gastric acid secretion.
Drug which antagonize the effect of histamine are called antihistamines. There are two groups of antihistamines H
1

receptor antagonists and H
2
receptor antogonists.When not specified the term antihistamine refer to H
1
receptor
antagonists
Mechanism of action.:-
i. H
1
blockers:- They competitively inhibit the interaction of histamines with H1 receptors. Blockade of these
receptors significantly reduces the secretion of acids and pepsin outputs from the target tissues
ii. Mast cell stabilizers:- Act by stabilizing the cell membrane of mast cell so that the release of histamine is
blocked.
Examples and uses of antihistamines:-
i. Pheniramines:- Used in the treatment of allergic dermatitis, rhinitis and food allergy
ii. Clorpheniramine:- Used in the treatment of allergic dermatitis, rhinitis and Urticaria
iii. Diphenhydramine:- Used in the treatment of all kinds of allergies , cough and cold.
iv. Doxylamine:- Used as an anti emetic to arrest nausea and vomiting concerned with pregnancy and traveling.
H
2
receptor blockers:- As stated earlier histamines activate two types of receptor H
1
and H
2
receptors. The activation of
H
2
receptors leads to increased gastric acid secretion, increased contraction of the isolated atria and inhibition of
isolated uterus. These effects are blocked by H
2
receptor antagonists
Examples and uses of histamines H
2
receptor blockers:-
i. Famotidine :- Used in the treatment of gastric and duodenal ulcer and in the treatment of hyper acidity and
reflex usophagitis.
ii. Cimetidine:- Used in the treatment of gastric and duodenal ulcer and in the treatment of hyper acidity.
iii. Ranitidine:- Used in the treatment of gastric ulcer and reflex eusophagitis

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Expectorants and antitussives:- Expectorants are drugs employed to aid in the relief of congestions in the
lower respiratory tract below the epiglottis, in the trachea, bronchi or lungs and therefore they are helpful in the
treatment of cough
Expectoration may be caused by :-
i. Enhancing bronchial secretion
ii. Making secretion less viscous
iii. Suppressing cough
Anti tussives are agents that normally depress the area in the CNS which usually controls the cough reflex
Examples and uses of expectorants and antitussives:-
i. Guaifensin:- It is used as an expectorant
ii. Terpinhydrates:- used as an expectorant in bronchitis
iii. Benzonatate:- It is used as antitussives
iv. Levopropoxyphene:- It is used as antitussives and cough suppressant
MUSCLE RELAXANT :- Drugs which blocks the transmission of nerve impulses at the neuromuscular junction and
thereby producing relaxation of the skeletal muscles are known as skeletal muscle relaxants. They are also known as
neuromuscular blocking agents.
The skeletal muscles may be relaxed by two different groups of drugs, namely : first, by those exerting an action on the
CNS and used mainly for the relief of painful muscle spasms in neuromuscular or musculoskeletal disorders; Secondly,
those affecting neuro muscular transmission that are employed as adjuncts in anaestesia inorder to modify the muscle
relaxation ability.
Examples and uses :-
1) Pancuronium- Used in anaesthesia in surgeries 2) Mephenesin- Used in the relief of muscular spasms
3) Galamine triethiodide- Used in the treatment of muscular rigidity. 4) Methocarbamol- Used in the treatement
of muscular spasm
ANTIMALARIAL DRUGS:- Malaria is a disease caused by plasmodium parasites which are spreaded by a female mosquito
from a malaria patient to a normal person. More than one million people die of malaria and most of these people
belong to the third world countries . Antimalarials are chemotherapeutic agents which are used for the prevention and
treatment of malaria . Some of the alkaloids extracted from cinchona bark like quinidine , cinchonine, are found to be
effective . Soon after II world war a large number of compounds were synthesized and tested for antimalarial actions
which leads to the discovery of antimalarials such as Chloroquine,Proguanil,Camoquine etc
ANTISYCOTICS (Tranquilizers):- Antisycortics are primarily employed for the treatment of symptoms in mental
diseases,their overall influence being to free the mind from passion or disturbance and thus calm the mind ,ie they
cause sedation without indusing sleep.
Tranquilers are drugs essentially used in the management and treatment of sycosis and neurosis.They specifically
exerts their action on the lower brain area to produce emotional calmness and relaxation without appreciable
hypnosis,sedation,euphoria or minor impairement. They are used to control the effects of stress and feeling of
discomfort, tension and disforia in patients with neurosis and mild depressive statesExamples : Chlorpromazine ,
Chlozapine , Diazepam
Antiulcer drugs: upper GI tract drugs:
The most common problem associated with the stomach is the secretion of excess acid. the stomach is well protected
with the mucosal cells from the acid and proteinase pepsin.
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When there is a damage of the mucosal layer erosion can occur in the gastric mucosa leading to a gastric ulcer. When
this acid enters the duodenum it can cause duodenal ulcer. In some cases there can be further
erosion and the fluid can leak into the peritoneal cavity leading to life threatening peritonitis. When the acid enter the
oesophagus a burning sensation is felt and this is commonly termed as a heart burn and is treated with an antacid.

Antacids:
Mechanism of action: are weak bases which readily combine with the HCl and neutralize it. They also raise the pH of the
stomach and over a pH of 4 pepsin is inactive. There are usually basic compounds of Al, Na, Ca, Mg and K. normally
used are AlOH and MgCO3 in combination. These are mixed in a correct
proportion to nullify the effect of Al causing constipation and mg acting as a laxative. E.g. hydrotalcite.

Peptic Ulcer:
There are three receptors in the stomach that needs to be stimulated for the production of acid they are H2 histamine
receptor, muscarinic cholinergic receptors and gastrin receptors. Gastric ulcers are mainly due to a defect in mucus
production whereas duodenal ulcers are due to excessive acid production. The use of colloidal bismuth in combination of
two antibacterials for the treatment of gastric ulcer due to the cause of a bacteria is known as triple therapy.

Example:-
H2 receptor antagonist cimetidine, nizatidine, ranitidine ; Proton pump inhibitor omeprazole
Antacids Aluminium Hydroxide, Magnesium Hydroxide .; Bismuth compounds
Sucralfate ; Antibiotics necessary for the treatment against H. Pyroli

ANTI EMETIC:-
Drugs used to treat Nausea and vomiting:
To treat vomiting suppositories are convenient whereas in the case of nausea the cause is determined and is prevented
then being cured. When nausea and vomiting is due to the psychogenic factors involving the cortical center of the brain
the use of benzodiazepine is useful as a sedative.

Antimuscarinic drugs:
The only antimuscarinic drug used to treat against emetics is hyoscine and is used in the treatment of motion sickness. It
is available in various forms and is an effective way of treatment. It has a long lasting effect.

Metoclopramide and domperidone:
They reduce the stimulation of the CTZ (Chemoreceptor trigger zone) and as a result prevent nausea and vomiting, they
also inc the rate of gastric emptying and dec the sensitivity of the receptors in the pharynx and upper gut to noxious
stimuli.

CANCER & CHAEMOTHERAPY
Cancer is the uncontrolled growth of cells coupled with malignant behavior: invasion and metastasis. Cancer is thought to
be caused by the interaction between genetic susceptibility and environmental toxins.
In the broad sense, most chemotherapeutic drugs work by impairing mitosis (cell division), effectively targeting fast-
dividing cells. As these drugs cause damage to cells, they are termed cytotoxic. Some drugs cause cells to
undergo apoptosis (so-called "self-programmed cell death").
Scientists have yet to identify specific features of malignant and immune cells that would make them uniquely
targetable. This means that other fast-dividing cells, such as those responsible for hair growth and for replacement of
the intestinal epithelium (lining), are also often affected. However, some drugs have a better side effect profile than others,
enabling doctors to adjust treatment regimens to the advantage of patients in certain situations.
As chemotherapy affects cell division, tumors with high growth fractions are more sensitive to chemotherapy, as a larger
proportion of the targeted cells are undergoing cell division at any time. Malignancies with slower growth rates, such as
indolent lymphomas, tend to respond to chemotherapy much more modestly.
Drugs affect "younger" tumors (i.e., more differentiated) more effectively, because mechanisms regulating cell growth are
usually still preserved. With succeeding generations of tumor cells, differentiation is typically lost, growth becomes less
regulated, and tumors become less responsive to most chemotherapeutic agents. Near the center of some solid tumors,
cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumors is the
fact that the chemotherapeutic agent often does not reach the core of the tumor. Solutions to this problem
include radiation therapy and surgery.