Diuretic | Medicinal Chemistry | Aqsa Murtaza

 

PHARMA BY AQSA MURTAZA (PharmD)

Aim to help Pharmacy Students. We cover a wide range of topics, from Medicinal Chemistry, Pharmacology, and Drug Interactions to Medication Management and Disease State Management.



Medicinal Chemistry

DIURETICS

Site of action of each Diuretic
It acts on the nephron.


There are four sites in the nephron where it can act:
1. Site I - Proximal Convoluted Tubule (PCT)
2. Site II - Ascending Loop Of Henle
3. Site III - Distal Convoluted Tubule (DCT)
4. Site IV - Collecting Duct

Drugs acting on PCT inhibit carbonic anhydrase
1. Acetazolamide
2. Methazolamide

Drugs acting on ascending loop of henle inhibit the co-transport system
1. Furosemide
2. Ethacrynic Acid

Drugs acting on DCT inhibit Na+/Cl- cotransporter
1. Chlorothiazide
2. Hydrochlorothiazide

Drugs acting on the collecting duct inhibit Na+ reabsorption and K+ excretion
1. Spironolactone
2. Triamterene



Acetazolamide

• Acetazolamide act on site I - PCT.
• Drugs acting on site I are 5-membered ring compounds derived from
thiadiazole.
• They are carbonic anhydrous inhibitors.

Indication
• Epilepsy
• Glaucoma
• Mountain sickness

ADR
• Nephrotoxicity
• Renal stone formation
• Skin toxicity

Mechanism of action
• Acetazolamide inhibits Na+ reabsorption by inhibiting the
carbonic anhydrous enzyme.

Contraindication
• Hypersensitivity of sulphonamide

Drug interaction
Folic acid and Phenytoin Acetazolamide cause toxicity
by increasing activity.

SAR
• The sulfonamide group (-SO2NH2) is essential for the carbonic anhydrase inhibitory activity of acetazolamide.
• Sulfmoyl nitrogen atom must be unsubstituted.
• Substitution of the methyl group (-CH3) on one of the ring nitrogen atoms retains carbonic anhydrous activity and this compound is now known as Methazolamide.



Acetazolamide Structure

Furosemide


• Furosemide act on site II - Ascending Loop of Henle.
• They inhibit the Co transport system.
• It is known as a high ceiling diuretic.

Indication
• Hypertension
• Edema

Contraindication
• Hypersensitivity
• Gout
• Pregnancy


Mechanism of action
• Furosemide inhibit Na+ reabsorption by
inhibiting the cotransport system.

ADR
• Otoxicity
• Nausea
• Vomiting

Drug Interaction
• Cephalosporin Nephrotoxicity
• Aminoglycosides Ototoxicity

SAR
• Substituent at the 1-position must be acidic, the carboxyl group (-COOH) provides the maximum diuretic activity.
• The sulfonamide group (-SO2NH2) is essential for the diuretic action of furosemide.
• Chlorine at 4-position gives maximum diuretic effect and it can only be replaced with Br-, CF3, or NO2.


Furosemide Structure

Chlorothiazide 

• Act on site III - DCT
• Inhibit Na+/Cl- cotransporter
• It is a thiazide diuretic.

Indication
• Edema
• Hepatitis edema
• Hypertension

Contraindication
• Renal impairement
• Hypersensitivity

ADR
• Electrolyte imbalance
• Photosensitivity
• Calcium accumulation

SAR
• 3rd and 4th position saturation increases the diuretic effects up to 10 times more than unsaturation of this position will have.
• Electron withdrawing group at the 6th position increases the diuretic activity of the drug.
• Small alkyl group like CH3 can be substituted at 2nd position.
• The sulfamoyl group at the 7th position is essential for its activity.


Chlorothiazide Structure



Triamterene


• Act on collecting duct
• It is a potassium-sparing diuretic.
• Na+ channel inhibitors

Indication
• Hypertension
• Edema

Contraindication
• Liver impairment

Mechanism Of Action
• Triamterene inhibits the epithelial sodium channels (ENaC) that normally promote sodium uptake and potassium secretion.

ADR
• Hyperkalemia
• Vomiting
• Nausea

SAR
• Primary amine can only be replaced with a small alkyl group like CH3.
• Para-substitution of phenyl ring with OH group increases activity.


Triamterene Structure


Interaction
• Potassium supplements
• Indomethcin with Triamterene causes nephrotoxicity.


Thank you
Dr. Aqsa Murtaza 


Comments

Post a Comment

Popular posts from this blog

Anti-Fungal | Lecture | Dr. Aqsa Murtaza

Image
ANTI-FUNGAL DRUGS The disease caused by fungus is called mycoses. It can cause infection either on the skin, subcutaneous or systemic. The fungal cell membrane contains ergosterol.  Drug for Subcutaneous and Systemic Mycotic Infection  1. Amphotericin B Naturally occurring polyene anti-fungal produced by Streptomyces Nodosus. Drug of choice for the treatment of several life-threatening mycoses. Depending on the organism and drug concentration, it is either fungicidal or fungistatic. Mechanism Of Action Amphotericin  B binds to the ergosterol of fungus cells. There it forms pores, which disrupts membrane function, allowing electrolytes and small molecules to leak from the cell, resulting in cell death. Adverse Effect  Fever and chills Hypotension   Thrombophlebitis Renal insufficiency 2. Antimetabolite Antifungal Flucytosine (5-FC) is a pyrimidine anti-metabolite often used with other antimetabolite agents. It is fungi static. Mechanism Of Action 5-FC e...
Read more

Hormone Part 2 | Medicinal Chemistry | Aqsa Murtaza

Image
  PHARMA BY AQSA MURTAZA (PharmD) Aim to help Pharmacy Students. We cover a wide range of topics, from Medicinal Chemistry, Pharmacology, and Drug Inte ractions to Medication Management and Disease State Management. CORTISOL PROPERTIES Antiinflammatory hormone White crystalline powder Water insoluble and soluble in organic solvents Rapidly absorbed from GIT Can cross the placenta barrier Synthesized in Zona fasciculate and Zona reticularis cells INDICATION Allergy Immunosuppressants ADR Osteoporosis SAR Flouride ion in place of the hydroxyl group with methyl increases its activity. Activity decreases if the hydroxyl group is replaced with chlorine or bromine group. Unsaturation in ring A lead to an increase in the activity of the drug. Substitution of the hydroxy group in ring B leads to a decrease in the activity of the drug. Structure of Cortisol GLUCAGON Contain 29 amino acids Synthesized in Pancrease A large dose of it leads to the intestine relaxation Have ionotropic effects o...
Read more

Antineoplastic Drugs | Medicinal Chemistry | Dr. Aqsa Murtaza

Image
  PHARMA BY AQSA MURTAZA (PharmD) Aim to help Pharmacy Students. We cover a wide range of topics, from Medicinal Chemistry, Pharmacology, and Drug Interactions to Medication Management and Disease State Management. MEDICINAL CHEMISTRY “Medicinal Chemistry is the science that deals with the discovery and design of new therapeutic chemicals and their development into useful medicines.” ANTINEOPLASTIC DRUGS 5-Fluorouracil INDICATION  Head and neck cancer Breast cancer Liver cancer Lung cancer PROPERTIES White crystalline powder Odorless Insoluble in chloroform Slightly soluble in alcohol Pyrimidine analog Contraindicated in Pregnancy and lactation IV and topical route of administration CBC and Renal/Hepatic function must be monitored MECHANISM OF ACTION 5- Fluorouracil inhibit the biosynthesis of DNA by interfering with the conversion of deoxyuridylic acid → thymidylic acid thus ↓se the thymidine level in the cell. Produce effect in the S-Phase of the cell cycle. Interact with Ci...
Read more