Q BANK (MED-CHEM)

Structure, MOA, uses of warfarin Warfarin is a type of anticoagulant known as a Vitamin K antagonist.  Here’s how it works: Inhibition of Vitamin K : Warfarin inhibits the production of reduced from of Vitamin K by blocking the action of an enzyme called Vitamin K oxide reductase .  Impact on Clotting Factors : The reduced form of Vitamin K, Vitamin KH2, is a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin . Without sufficient active Vitamin K1, these clotting factors have decreased clotting ability . Resulting Anticoagulant Effect : By inhibiting the reactivation of Vitamin K , Warfarin decreases the synthesis of these clotting factors in the liver, thereby reducing the blood’s ability to clot. USES of WARFARIN - Venous Thromboembolism  Treatment of Myocardial infraction  Ischemic Attacks  Pulmonary embolism 

Anticoagulants, often referred to as blood thinners, are a family of medications that prevent your blood from clotting too easily. They work by breaking down existing clots or preventing new clots from forming.  Here are some reasons why they are important: Prevent Life-Threatening Conditions : Anticoagulants can help prevent life-threatening conditions like strokes, heart attacks, and pulmonary embolisms, all of which can occur due to blood clots. Treat Existing Clots : Anticoagulants are used to treat individuals who already have a blood clot, such as a clot in the veins of the leg (a deep vein thrombosis, or DVT), or in the arteries of the lung (a pulmonary embolus, or PE). Prevent Clot Formation : They are also used to prevent a blood clot in someone who is at high risk of getting one. Manage Health Conditions : Anticoagulants can protect individuals who have a condition or disease that could cause them to have any of the above clot-related events. Some of these conditions include

ANTICOAGULANTS Anticoagulants, also known as blood thinners, are medications that prevent or reduce blood clots. They do this by interfering with the coagulation cascade, which is the series of chemical reactions that leads to blood clot formation. Example: Heparin, Warfarin  USES Stroke: This happens when a blood clot restricts the blood flow to the brain. Transient Ischemic Attacks (TIA): Also known as mini strokes, these have similar symptoms to a stroke, but the effects typically last less than 24 hours. Heart Attacks: A blood clot can block a blood vessel that supplies blood to the heart. Deep Vein Thrombosis (DVT): This is when a blood clot forms in a deep vein, usually in the legs. Pulmonary Embolism: This is when a blood clot blocks a blood vessel around the lungs. Atrial Fibrillation: This is a heart condition that increases the risk of clots. Hip or Knee Replacement Surgery: These surgeries increase the risk of blood clots. Ischemic Stroke: This type of stroke is caused

 Procainamide  MOA & USES-

  K +  sparing Diuretic MOA of K + sparing Diuretic Aldosterone Receptor Blocker ¯ ¯ Expression of Lumen Na channel → ¯ Transport of Na to the Collecting tubule cell ¯ Expression Na/ K ATPase pump → ¯ Transport of Na to Blood ( ¯ K to the urine) ¯ ­ Na and Water in the urine Uses – Spironolactone is used to treat Hypertension and Heart failure Amiloride used to treat high blood pressure and Heart failure with combination with loop diuretics Thiazide diuretics  MOA of Thiazide diuretics  USES  Hypertension  Oedema  Heart Failure 

  Example of oral hypoglycemic agent is-  Metformin  Structure  MOA  Uses  Prediabetes: Metformin may prevent or delay the onset of diabetes in people with high blood sugar levels Gestational diabetes Polycystic ovary syndrome (PCOS)

Example of biguanide is-  Metformin  Structure  MOA  Uses  Prediabetes: Metformin may prevent or delay the onset of diabetes in people with high blood sugar levels Gestational diabetes Polycystic ovary syndrome (PCOS)

Example of 1st Gen Sulfonylurea is Chlorpropamide and Tolbutamide  General MOA  (1) They act on the so-called  ‘sulfonylurea receptors’ (SUR1)  on the pancreatic β cell membrane.  (2) This action causes  depolarization  by reducing the  conductance of ATP-sensitive K+ channels .  (Raised ATP production followed by raised Glucose also reduces the conductance of ATP sensitive K+ Channels) (3) This process enhances  Ca2+ influx  (Followed by the stimulation of Voltage sensitive Ca++ Channel)   and degranulation (followed by calcium dependent translocation), which  increases the rate of insulin secretion . Chlorpropamide Structure  Tolbutamide Structure  GENERAL USES OF SULFONYLUREAS  To treat high blood sugar levels caused by type 2 diabetes mellitus To prevent or delay the complications of diabetes, such as heart disease, kidney disease, nerve damage, and eye problems To test the function of the pancreas in diagnosing diabetes or other conditions

Different Insulin Preparations  Short Acting  Regular : Rapid acting with 0.5 - 1 hour Duration of Action Lispro : Rapid Acting with 6 - 8 hrs DOA. Insulin Zinc : Insulin Suspension having 6 - 8 DOA  Intermediate Acting Isophane (NPH) : Also Called protamine Hagedorn (NPH) insulin, 18 -24 hrs DOA. Long Acting: Protamine Zinc: DOA in upto 36 hrs Insulin detemir: DOA upto 24 hrs  Insulin degludec: DOA upto 24 hrs  MOA of Insulin  Insulin is a hormone produced by the pancreas that plays a crucial role in regulating blood glucose levels.  Here’s how it works: Glucose Absorption:  When carbohydrates are consumed, body breaks them down into glucose, a simple sugar that serves as a vital energy source.  (a) Insulin attaches to insulin receptors of the target cell. (b) Activates a  cascade of signaling leading to the formation of certain protein called GLUT4 which is a glucose transporter protein,   (c) GLUT4 is then  translocated to the Plasma membrane  and Transport glucose into the cell.

Classification of Anti-diabetic Agents Sulphonylureas :   first-generation drugs -  tolbutamide  and chlorpropamide , and  second-generation drugs like,  glipizide ,  Biguanides : The most common example is  metformin Meglitinides :  Examples include  repaglinide Thiazolidinediones :   Examples include  rosiglitazone Alpha-glucosidase inhibitors : E xamples include  acarbose. Dipeptidyl peptidase-4 (DPP-4) inhibitors :  An example is  sitagliptin. Glucagon-like peptide (GLP-1) analogues :  An example is  exenatide. Insulin : A hormone that regulates blood glucose by stimulating its uptake into cells and inhibiting its production by the liver. Short Acting : Regular, Lispro, Insulin zinc Intermediate Acting: Isophane (NPH) Longer Acting : Protamine zinc  Example of 2nd Generation sulfonylurea Antidiabetic Agent is Glipizide .  Structure  MOA  It is a class of Sulfonylurea drugs  (1) They act on the so-called  ‘sulfonylurea receptors’ (SUR1)  on the pancreatic β cell membrane.  (2) This

Metformin  Structure  MOA  Uses  Prediabetes: Metformin may prevent or delay the onset of diabetes in people with high blood sugar levels Gestational diabetes Polycystic ovary syndrome (PCOS) Tolbutamide   Structure  MOA  It is a class of Sulfonylurea drugs  (1) They act on the so-called  ‘sulfonylurea receptors’ (SUR1)  on the pancreatic β cell membrane.  (2) This action causes  depolarization  by reducing the  conductance of ATP-sensitive K+ channels .  (Raised ATP production followed by raised Glucose also reduces the conductance of ATP sensitive K+ Channels) (3) This process enhances  Ca2+ influx  (Followed by the stimulation of Voltage sensitive Ca++ Channel)   and degranulation (followed by calcium dependent translocation), which  increases the rate of insulin secretion . Uses  To treat high blood sugar levels caused by type 2 diabetes mellitus To prevent or delay the complications of diabetes, such as heart disease, kidney disease, nerve damage, and eye problems To test the func

Definition of Oral hypoglycemic drugs Oral hypoglycemic agents are drugs that lower blood glucose levels by-  stimulating insulin secretion ,  enhancing insulin action, or  delaying carbohydrate absorption.  They are used to treat type 2 diabetes mellitus , a condition characterized by insulin resistance and relative insulin deficiency.  Oral hypoglycemic agents are also called oral antidiabetic drugs or oral antihyperglycemic agents. Examples of Oral Hypoglycemic drugs  Sulphonylureas :   first-generation drugs - tolbutamide and chlorpropamide , and  second-generation drugs like, glipizide ,  Biguanides : The most common example is metformin Meglitinides :  Examples include repaglinide Thiazolidinediones :   Examples include rosiglitazone Alpha-glucosidase inhibitors : E xamples include acarbose. Dipeptidyl peptidase-4 (DPP-4) inhibitors : An example is sitagliptin. Glucagon-like peptide (GLP-1) analogues : An example is exenatide.

Definition of Local Anesthetics  Local anaesthetics are the agents which upon topical application or local injection causes reversible loss of pain sensation in a restricted area of the body. -         Acts by blocking both sensory and motor nerve conduction system, without loss of Consciousness.

Structure, MOA, USES of lignocaine and benzocaine 

Classification of Local Anesthetics  General MOA of LAs  Local Anaesthetic Crosses the biological membrane, and gets ionised. Ionised form of LA can bind with the LA receptor located at the intracellular part Binding of LA to its receptor stabilizes the channel in the inactivated state, inactivated gate closes, No Na + ion can flow inside Prevention of Depolarization of at the time of Action potential generation. No Action potential Generated → Loss of Sensation 

Procaine  Mode of Action:   Local Anaesthetic Crosses the biological membrane, and gets ionised Ionised form of LA can bind with the LA receptor located at the intracellular part Binding of LA to its receptor stabilizes the channel in the inactivated state, inactivated gate closes, No Na + ion can flow inside. Prevention of Depolarization of at the time of Action potential generation. No Action potential Generated → Loss of Sensation 

SAR of LAs  Aryl Group (lipophilic portion) – *        The aryl group is the most important functional group for the lipophilicity of LA. Aryl group helps the LA to cross the cell membrane. *        Substitution of aryl group alters the potency. -         Substitution of EDG (methoxy, Amino) enhances potency   -         Substitution of EWG (carbonyl, halogen) decreases potency. *        Substitution that enhances the formation of Zwitterion increases the potency. Bridge/intermediate linker – (Ester/amide/thioester/thioamide) *        The intermediate bridge can be C, O, N or S. *        Isosteres of these atoms can alter the potency. For example Esters are less potent than Amides. *        These modifications can also alter the Duration of Action (DOA) For example, Amides are more resistant to metabolic hydrolysis than Esters. *        Increasing chain length will increase potency but, will also increase TOXICITY.   Hydrophilic Portion (Aminoalkyl group) –

General Structural Features of LAs  Aryl Group (lipophilic portion) – *        The aryl group is the most important functional group for the lipophilicity of LA. Aryl group helps the LA to cross the cell membrane. Bridge/intermediate linker – (Ester/amide/thioester/thioamide) *        The intermediate bridge can be C, O, N or S. It helps to connect the lipophilic and hydrophilic Parts.  Hydrophilic Portion (Aminoalkyl group) – *        Aminoalkyl group is not necessary for LA action but is important for the formation of water-soluble salts.

Antithyroid Agents Antithyroid agents are a class of drugs that act as hormone inhibitors on thyroid hormones . They are primarily used to treat conditions like hyperthyroidism , where the thyroid gland produces more thyroid hormones than the body needs, and Graves’ disease, an immune system disorder that results in the overproduction of thyroid hormones. Examples: Methimazole  (Brand name: Tapazole) Propylthiouracil  (PTU) CLASSIFICATION  Uses Hyperthyroidism : Antithyroid agents are used to treat hyperthyroidism, a condition where the thyroid gland produces more thyroid hormones than the body needs. Thyroid Cancer : Some antithyroid agents are used along with surgery and radioactive iodine therapy to treat certain types of thyroid cancer. 

Propylthiouracil STRUCTURE   MECHANISM OF ACTION  It binds with Thyroid peroxidase and inhibits the conversion of iodide to iodine. Thioglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3). It also blocks the incorporation of iodine with the thioglobuline for that reason, it can not be converted to T3 and T4.  USES  Treatment of overactive thyroid (Hyperthyroidism) 

Levothyroxine  Levothyroxine is a synthetically prepared levo-isomer of thyroxine (T4), a tetra-iodinated tyrosine derivative. It acts as a replacement in deficiency syndromes such as hypothyroidism . Structure:  Mode of Action: Levothyroxine works by mimicking the body’s thyroid production of T4.  Levothyroxine enters cells and binds to thyroid hormone receptors (TRs) .  These receptors are located in the nucleus of cells and are responsible for regulating gene expression.  When levothyroxine binds to TRs, This binding activates the transcription of genes, which leads to the production of proteins that are involved in a variety of cellular processes. For example,  Increased utilization of Carbohydrates  Increased Protein catabolism  increased Heat production  Uses  Levothyroxine is primarily used to treat hypothyroidism.  Levothyroxine injection is used in adults to treat myxedema coma.

ANTICANCER ANTIBIOTICS  Anticancer antibiotics are a class of drugs used in cancer treatment. They are produced by various species of microorganisms and are capable of killing or slowing the growth of cancer cells Examples: Doxorubicin  Structure of Doxorubicin  Mode of Action:  Affects DNA synthesis and Replication by inserting into DNA strands, or by producing superoxide that causes DNA breakage in DNA strands preventing the growth of tumor and cancerous cells.  Uses: Treatment of Solid tumors  breast cancer, lung Cancer 

  Folate Antagonist:  (Methotrexate) Structure of Methotrexate: MOA:  Inhibition of Dihydrofolate Reductase (DHFR) :   The majority of antifolates work by  inhibiting  DHFR ,  an enzyme that reduces dihydrofolate to tetrahydrofolate. Tetrahydrofolate is a necessary component in the synthesis of nucleotide precursors , so when DHFR is inhibited, it leads to a deficiency in the nucleotide precursors, thus inhibiting DNA synthesis.

ANTIMETABOLITES  Antimetabolites are a type of chemotherapy drug that work by interfering with the DNA replication process in cancer cells. They mimic the structure of essential molecules that cancer cells need to replicate their genetic information and prevent them from creating the enzymes they need to divide.  These compounds are known as Antimetabolites because they inhibits the metabolic conversion of certain Chemicals (i.e. Folic Acid) to compounds which are essential for synthesis of DNA (Replication). 

ALKYLATING AGENT  Introduction  Alkylating agents are named because they can add an alkyl group to a molecule. Alkylating agents can add alkyl groups to molecules in a variety of ways. One common way is through a process called nucleophilic substitution . In nucleophilic substitution, an alkylating agent reacts with a molecule that has a nucleophilic atom, such as a nitrogen atom or an oxygen atom. The nucleophilic atom attacks the alkylating agent, and the alkyl group is transferred to the molecule. Definition: An alkylating agent is a substance that causes replacement of hydrogen by an alkyl group especially in a biologically important molecule; specifically : one with mutagenic activity that inhibits cell division and growth and is used to treat some cancers. Mode of Action of Alkylating Agents:  Alkylating agents are a type of anticancer drugs that work by damaging the DNA of cancer cells and preventing them from replicating .  They have a chemical structure that contains a b

Classification of anti cancer agents with example Antineoplastic agents are drugs used to treat cancer by killing or stopping the growth of cancer cells.  They can be classified into different types based on their mechanism of action, such as : ALKYLATING AGENTs  Nitrogen Mustards : Chlorambucil   Ethylenimine: Thiotepa    Alkyl sulfonate : Busulfan    Nitrosoureas: Carmustine   Triazine : Dacarbazine   Methyl Hydrazine : Procarbazine    ANTIMETABOLITEs Folate Antagonist : Methotrexate  Purine Antagonist: 6-Mercaptopurine   Pyrimidine Antagonist : 5-Fluorouracil  PLATINUM Co-ODRINATION COMPOUNDs  Example : Carboplatin   ANTICANCER ANTIBIOTICs (Anthracycline)  Example: Doxorubicin & Daunorubicin 

Structure, moa, uses of cimetidine Structure of Cimetidine Mode of Action Cimetidine Binds with the H2 Receptor (located at gastric parietal cells) competitively and blocks the binding of Histamine to the H2 receptor and decreases the release of Gastric acid (from Proton pump)  by decreasing the conversion of cyclic AMP from ATP inside the Gastric Parietal Cell.  Uses Heartburn Stomach and Duodenal ulcer    GERD

Structure, moa, uses of diphenhydramine hydrochloride STRUCTURE OF DIPHENHYDRAMINE  MECHANISM OF ACTION  Diphenhydramine is an H1 Receptor antagonist which blocks the H1 Receptor and prevent the binding of endogenous molecule Histamine with the receptor thereby preventing the Physiological Actions produced by Histamine i.e. Allergic Reactions.  USES Allergic reaction, Motion sickness Insomnia, Cough, Nausea

Synthesis of Cimetidine

  Synthesis of Promethazine