Mechanism of action of sucralfate

 https://youtu.be/-uMkwAfSb-I

Loop diuretics increase calcium excretion and thiazides diuretics decrease calcium excretion

FUNCTION OF Na+ K+ 2Cl- channel

👉  Na K 2Cl channel at the thick ascending limb of loop of Henle is responsible for transport of  Na+, K+ and 2Cl- from intra-luminal to intra-cellular part of the loop of Henle.

👉K+ diffuses back into the lumen and Na+ is transported across the basolateral membrane to the ecf.

👉 Back diffusion of K+ into lumen creates a positive potential difference between the luminal (positive side) and basolateral (negativeside) membranes. 

👉 Positive potential difference drives reabsorption of Ca2+ and Mg2+  into the tubular capillaries.

MECHANISM OF INCREASED Ca+ EXCRETION BY LOOP DIURETICS

👉 Loop diuretics inhibit Na K 2Cl channel at the thick ascending limb of loop of henle.

👉  Reabsorption of Na K 2Cl does not occur

👉No development of positive potential difference.

👉No reabsorption of Ca2+

👉Increased excretion of Ca+

FUNCTION OF Na Cl SYMPORTER AT DISTAL TUBULE

👉 Reabsorption of only Na Cl. Therefore, unlike loop of Henle, there is no role of K+ back diffusion and therefore no question of positive potential difference.

👉 No potential difference driven Ca2+ reabsorption 

MECHANISM OF DECREASED Ca2+ EXCRETION BY THIAZIDE DIURETICS

👉  Inhibition of Na Cl symporter

👉 Decreased Na in tubular epithelial cells

👉 Compensatory increased functioning of Na+ Ca2+ exchanger at the basolateral membrane  to maintain  intracellular Na+.

👉 Decreased intracellular Ca in the epithelial cells.

👉 Increased reabsorption of Ca+ from luminal to intracellular side

👉Decreased Ca+ excretion in urine

Penicillinase resistant penicillin (methicillin), MRSA and Ceftaroline

 

Ø In gram positive bacteria, peptidoglycan residues cross link to form cell wall.

Ø Cross linking occurs by transpeptidation of glycine with D-alanine of two adjacent peptidoglycan residues.

Ø Beta lactam antibiotics inhibit the enzyme transpeptidase that cross links peptidoglycan residues.

Ø Penicillinase (beta lactamase) producing gram positive bacteria destroy beta lactam ring and become resistant to beta lactam antibiotics.

Ø Penicillinase resistant penicillin (methicillin) are not destroyed by penicillinase producing bacteria. So, such bacteria are sensitive to methicillin and known as Methicillin Sensitive Staph aureus (MSSA).

Ø Methicillin Resistant Staph aureus (MRSA) produce altered transpeptidase (PBP2a). PBP2a do not bind with beta lactam antibiotics and therefore MRSA is resistant to all beta lactam antibiotics.

Ø Therefore, non-beta lactam antibiotics like sulfonamides, tetracyclines, clindamycin, vancomycin, linezolid etc are used in the treatment of MRSA. Vancomycin and linezolid have proven efficacy in treatment of MRSA.

Ø Vancomycin was discovered in the 1950s but seldom used in therapeutics because of adverse effects.

Ø When MRSA were reported in 1960s, vancomycin rapidly became popular for treatment of MRSA. No beta lactam was effective against MRSA at that time.

Ø Only after many years of research, the first beta lactam antibiotic with clinically significant anti-MRSA activity was approved in 2010. The name of the beta lactam antibiotic effective against MRSA is ceftaroline.

Are we adequately treating amoebiasis: the forgotten role of diloxanide furoate

 

Coming soon

Reye’s syndrome with aspirin: one man's meat is another man's poison

Aspirin is a drug with multiple uses. At low dose, it is used as an anti platelet. It has analgesic, anti-pyretic and anti-inflammatory actions in a wide dose range. However, aspirin is not the drug choice for fever in any age group. Paracetamol is considered safer. In children, it is more true because aspirin has been found to be associated with Reye’s syndrome when used as antipyretic in children suffering from chickenpox, influenza and other viral illness. In such illness, aspirin may cause hepatic mitochondrial damage. There is inhibition of fatty acid metabolism and increase in serum ammonia levels. Hyperammonemia may induce diffuse cerebral edema and raised intracranial pressure. The child presents with profuse vomiting, stupor which may rapidly progress to coma, cardio respiratory failure and death.