Semister - V Medicinal Chemistry All Units.
UNIT-3 :- Anti-Arrhythmic Drugs
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Introduction
Cardiac arrhythmias remain a major source of morbidity and mortality in developed countries. Cardiac arrhythmia is a disturbance in the conduction of impulse through the myocardial tissue. These cardiac arrhythmias may be caused from disorders in pacemaker function of the sinoatrial node thereby resulting into tachycardia, bradycardia, cardiac arrest, atrial flutter, atrial fibrillation and ventricular fibrillation. Hence, the antiarrhythmic agents are also termed as ‘antidysrhythmic drugs’ or ‘antifibrillatory drugs’.
Antiarrythmic drugs (AADs) may be defined as the “drugs that are capable of reverting any irregular cardiac rhythm or rate to normal”.
UNIT-4 :- Drugs acting on Endocrine system
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Endocrine system
UNIT-5 :- Antidiabetic agents
ANTIDIABETIC AGENTS
Agents which are used in the treatment of diabetes are called as antidiabetic agents. They used to lower the blood sugar level in patients suffering from hyperglycaemia. These are also called as anti-hyperglycaemic agents. Diabetes mellitus: It is a chronic metabolic disorder which is characterized by
hyperglycaemia (increased blood sugar level). The common symptoms are polydipsia (excess thirst), polyphagia (excess hunger), and polyurea (excess urination).
Type-1 (IDDM) Type-2 (NIDDM)
Insulin dependent diabetes mellitus
Juvenile onset diabetes mellitus
Occurs in children
Non-insulin dependent diabetes mellitus
Adult onset diabetes mellitus
Occurs in adults
Pancreatic β-cells are destroyed
No insulin secretion
Less insulin secretion or insulin resistance
(cells don’t respond to insulin)
Treatment: insulin injection Treatment: oral hypoglycaemic agents
The chemical knowledge of isolated compounds gave a way for many synthetic substances. Hundreds and thousands of new organic chemicals are prepared annually throughout the world and many of them are entered into pharmacological screens to determine whether they have useful biological activity or not. This process of random screening has been considered the identification of new inefficent, but it has resulted in the identification of new 'lead compound' whose structure has been optimized to produce clinical agents.
The modern drug research owes its rationality to the German Physician and
imn1tmologist, Paul Ehlrich, who coined intellectual tools of Medicinal science, such as
receptor for drugs. The antibacterial agent Prontosil laid the foundation of the concept
of biochemical metabolites and stearic analogues. This enabled the Medicinal chemists
to 'drug design'.
The drug design was based on modification of the structure of a "lead" compound. The lead compound was suffering from some therapeutically undesirable side effect. The efficiency of it's increased recently by high-throughput screening (HTPS) system utilizing cell line culture systems with enzyme linked immune system assay (ELISA) and receptor molecules derived from gene cloning.
The techniques of molecular graphics and computational chemistry have provided novel chemical structure that have led to new drugs with potent medicinal activates.
Medicinal chemistry covers the following stages:
- In the first stage new active substance or drugs are identified and prepared from natural sources, organic chemical reactions or biotechnological processes. They are known as lead molecules.
- The second stage is optimization of lead molecule to improve potency, selectivity and to reduce toxicity.
- The next stage involves optimization of synthetic route for bulk production and modification of pharmacokinetic and pharmaceutical properties of active substance to render it clinically useful.
Drug is a chemical molecule. All chemicals other than food would affect living process. If the affect helps the body it is a medicine and if it causes a harmful effect on the body then it is a poison. Drugs are defined as "a medical a~ent used for diagnosis, prevention, treatment of symptoms and cure of disease". All the drugs have the potential for producing more than one response. The desired pharmacological response of the drug can only be achieved if it is present at the site of action in appropriate concentration for sufficiently long time. This appropriate concentration is governed by the following factors.
During the last 20 years, our understanding of cardiac electrophysiology and fundamental
arrhythmia mechanisms has increased significantly, resulting in the identification of new
potential targets for mechanism-based antiarrhythmic therapy. However, antiarrhythmic drug development has remained slow, despite much effort given our limited understanding of what
role various ionic currents play in arrhythmogenesis and how they are modified by arrhythmias. Multichannel blockade, atrial selectivity, and the reduction of the risk of adverse events have all constituted the main theme of modern atrial fibrillation (AF) drug development. The increasing appreciation of ventricular arrhythmias as a marker of underlying heart disease and, therefore, a potential drug target, led to the development of multiple new antiarrhythmic drugs in the late 1970’s and early 1980’s. Most currently available AADs have been derived from naturally available compounds (e.g., quinidine adapted from a compound from the bark of the cinchona tree) or were originally developed for other purposes (e.g., amiodarone and sotalol were initially developed for the treatment of angina). The multiple electrophysiological effects of each of these compounds make mechanism-based therapy difficult.
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