COTRIMOXAZOLE

MECHANISM:
                    Cotrimoxazole is a combination of sulfamethaoxazole + trimethoprim in a ratio of 5:1 .
Sulfamethaoxazole and trimethoprim separately are bacteriostatic drugs but when combined together they become bacteriocidal .
Cotrimoxazole is a bacteriocidal drug.
Bacteriocidal activity is due to sequential blockade .
Sulfamethoxazole inhibit folate synthase and trimethoprim inhibits
folate reductase.  

PHARMACOKINETICS:

1. Taken orally 
2. Metabolized in liver
3. Excreted in urine 

USE:

1. UTI
2. RTI
3. MRSA
4. Drug of choice for Pneumocystitis jirovecii and nocardiosis .

ADVERSE EFFECTS:

It has adverse effects of both sulphonamides and trimethoprim .

SULPHONAMIDE ADVERSE EFFECTS

1. Aplastic Anemia 
2. Bilirubin displacement from plasma protein leading to Kernicterus
3. Crystalluria
4. Rash 
5. SLE
6. Hemolysis in patients with G-6PD deficiency  

                  mnemonic : ABC RAsH

TRIMETHOPRIM SIDE EFFECTS 

1. Megaloblastic Anemia
2. Leukopenia
3. Pancytopenia
4. Hyperkalemia ( due to amiloride like action , amiloride is a Potassium sparing diuretic ).

SULPHONAMIDE , TRIMETHOPRIM

SULPHONAMIDE:

MECHANISM:

                         Sulphonamide inhibits folate synthase enzyme . Thus bacteria cannot synthesize the folic acid required for its growth . 

This drug does not affect the folic acid level in humans , because humans acquire folic acid directly from food and it's not synthesized.

DRUGS:
Short acting : Sulfisoxazole
Intermediate acting : Sulfadiazine , Sulfamethaoxazole
Long acting : Sulfadoxime
For use in GIT : Sulfasalazine
For topical use : Sulfacetamide, Silver Sulfadiazine

Pharmacokinetics:

1. Taken orally 
2. Metabolized in liver by acetylation
3. Crosses placenta and Blood Brain Barrier
4. Excreted in urine

Use: 

1. Sulfisoxazole used in UTI
2. Sulfadiazine used in nocardiasis 
3. Sulfadiazine + Pyrimethamine used for Toxoplasmosis and as prophylaxis of Pneumocystitis jiroveci
4. Sulfadoxime + Pyrimethamine used in malaria .
5. Sulfasalazine is used in Ulcerative colitis .
6. Sulfacetamide is used for Ocular infections
7. Silver sulfadiazine is used in burns patients .

Adverse Effects:

1. Aplastic Anemia 
2. Bilirubin displacement from plasma protein leading to Kernicterus
3. Crystalluria
4. Rash 
5. SLE
6. Hemolysis in patients with G-6PD deficiency 

                      mnemonic : ABC RAsH


TRIMETHOPRIM:
MECHANISM:
                         These drugs inhibit Folate reductase enzyme , thus inhibiting the synthesis of THFA required for survival of bacteria . 
It is specific for bacterial folate reductase enzyme and has no effects on humans .

PHARMACOKINETICS:

1. Given orally
2. Metabolized in liver
3. Excreted in urine

USE:

1. It is combined with sulphnomides and used widely.
2. Used alone in UTI and Prostitis .

Adverse Effects:

1. Megaloblastic Anemia
2. Leukopenia
3. Pancytopenia
4. Hyperkalemia ( due to amiloride like action , amiloride is a Potassium sparing diuretic ).

                      

AMINOGLYCLOSIDE

Mechanism:

         They bind on 30S ribosome and does the following actions :

1. Inhibition of formation of initiation complex
2. Inhibition of polysome formation 
3. Misreading of mRNA

DRUGS:

1. Streptomycin
2. Gentamicin
3. Tobramycin
4. Amikacin
5. Neomycin

PHARMACOKINETICS:

1. They are given parenterally, topically, orally[but not absorbed by GI tract].
2. They are not metabolized in body.
3. They are excreted unchanged in urine.
4. They do not cross blood brain barrier.

USE:

1. Active against all GRAM -VE organisms
2. Active against GRAM +VE , if used in combination with BETA-LACTAMS or VANCOMYCIN.
3. Streptomycin is used as 1st line drug in TB
   Drug of choice in tularemia and plague
4. Amikacin is 2nd line drug in TB.
5. Neomycin used orally for gut sterilization.Neomycin used topically for skin infections.
6. Spectinomycin used in treating PENICILLINASE-PRODUCING Neisseria gonnorhoea [PPNG].

ADVERSE EFFECTS:

1. OTOTOXICITY:
                 Amikacin, Neomycin causes hearing loss.
                 Gentamicin , Streptomycin causes vestibular toxicity.              Tobramycin causes both.
2. NEPHROTOXICITY:               Neomycin is most Nephrotoxic and not given I.V
                  Gentamycin is most toxic drug given as I.V               Streptomycin is the least toxic.
3. NEURO-MUSCULAR BLOCKADE:
                  These drugs decrease the release of Ach as well as decrease the senstivity of post-synaptic membrane.
   Hence should not be administered in case of Hypocalcemia, Respiratory depression and Neuromuscular blockers .

Fluoroquinolones

MECHANISM:
              Fluroquinolones inhibit DNA GYRASE and TOPOISOMERASE-4. 
Thus inhibiting replication of DNA .

CLASSIFICATION:

1st generation - Norfloxacin, Lomefloxacin
                        ( active against few gram -ve organism )
2nd generation - Ciprofloxacin , Ofloxacin
                        ( active against all gram -ve organism )
3rd generation - Sparfloxacin, Levofloxacin , Gatifloxacin 
               ( active against all gram -ve organism and few gram +ve)
4th generation - Moxifloxacin , Trovafloxacin
                (active against all gram -ve and gram +ve )

Pharmacokinetics :

1. All drugs can be given orally and parenterally . 
2. Metabolized by liver
3. Moxifloxacin and Trovafloxacin excreted in feces 
4. Others are excreted via urine

Uses:

1. Norfloxacin is excreted in urine in large quantities , hence used in UTI
2. Ciprofloxacin and Ofloxacin used in gonorrhoea , pseudomonas , anthrax , meningococcal meningitis , TB 
3. Levofloxacin , Gatifloxacin , Sparfloxacin are active against all gram -ve , few gram +ve and atypical microoraganisms . Hence used in respiratory infections
4. Moxifloxacin amd Trovafloxacin are the broadest spectrum antibiotic.

ADVERSE EFFECTS:

1. GI distress
2. Affect cartilages and hence not used in children below 18 yrs 
3. They cause tendinitis 
4. Photosenstivity
5. Seizures
6. Moxifloxacin and Trovafloxacin causes hepatotoxicity.

PATHOGENESIS OF NEPHROTIC SYNDROME

In a normal kidney glomerulus doesn't let the proteins to get filtered because of the presence of 

1. Tight junctions in the glomerular capillary wall
2. Negative charge of GLOMERULAR BASEMENT MEMBRANE (proteins are also negatively charged)
3. Presence of  PODOCYTES .  

If any one of these components gets damaged , it will lead to Nephrotic syndrome .

NEPHROTIC SYNDROME is a condition characterized by 

1. Proteinuria 
2. Hypoalbuminemia 
3. Generalized edema
4. Hyperlipidemia and Lipiduria

PATHOGENESIS:

• When a damage of glomerular capillary wall or basement membrane or podocytes happen , proteins escape into the glomerular filtrate .
• Thus it leads to proteinuria , primarily albumin is lost hence also called as albuminuria . 
• Albumin level in blood decreases due to loss in urine leading to hypoalbuminemia
• Due to Hypoalbuminemia there is fall in osmotic pressure leading to edema .
• Due to hypoalbuminemia , liver tries to compensate the loss of albumin by increasing it's synthesis, On the process lipid synthesis gets triggered as well leading to HYPERLIPIDEMIA. Albumin is the carrier protein of lipid. Due to hypoalbuminemia there is abnormal lipid transport leading to LIPIDURIA.

PATHOGENESIS OF LIVER CIRRHOSIS

In simple words , 'Liver cirrhosis' means fibrosis of liver and formation of nodules on its surface .

Before we see about the pathogenesis of liver cirrhosis . Let's review about the structure of liver .

Above picture shows that liver gains nutrients from hepatic artery and portal vein , And venous blood is drained by hepatic vein . Bile duct is draining bile from the liver .

This is a simplified diagram showing the course of hepatic artery , portal vein and bile duct inside the liver parenchyma . 
Hepatic artery and portal vein form a sinusoid and drain into the central vein. Central veins will join together to form the hepatic vein . 
In the sinusoid KUFFER CELLS(macrophages) are present.
There is a space between the sinusoids and hepatocytes . It is called as SPACE OF DISSE . It contains STELLATE CELLS. Nutrients from the sinusoids reaches hepatocyte passing through the space of disse .

CAUSATIVE AGENTS:

1. Chronic Alcoholism
2. Hepatitis B & C
3. Hemochromatosis
4. Genetic factor

PATHOGENESIS:

1. Due to the causative agents , hepatocytes gets destroyed
2. Damaged hepatocyte will produce CYTOKINES
3. Cytokines will activate the kuffer cells present in the sinusoids.
4. Activated Kuffer cells will produce GROWTH FACTOR and TNF.
5. GF and TNF will activate the stellate cell . Stellate cell now will convert into a myofibroblast.    
6. Myofibroblast will produce collagen which accumulates in the space of disse
7. Thus space of disse gets thickened due to accumulation of collagen . So transfer of nutrients from the sinusoids to hepatocyte becomes difficult. 
8. This will lead to death of hepatocytes 
9. Some hepatocytes are spared . They will multiple profusely to compensate the lost liver function .
10. This compensatory multiplication leads to the formation of nodules on the liver surface .

CHLOROQUINE

One must be thorough with malarial parasite life cycle to understand about the chloroquine well . So i advice the readers to learn about the life cycle of plasmodium before reading this post.

CHLOROQUINE IS THE DRUG USED WIDELY FOR TREATING MALARIA . BEFORE WE SEE ABOUT THE DRUG IN DETAIL . LET'S REVIEW ABOUT THE DIFFERENT STAGES OF MALARIAL LIFE CYCLE AND THE SCHEMA OF TREATING MALARIA .

IN HUMANS MALARIAL PARASITE UNDERGOES 2 STAGES

1) PRE - ERYTHROCYTIC STAGE ( parasite is inside the liver ) 

2) ERYTHROCYTIC STAGE ( parasite is inside the RBC )

SCHEMA FOR TREATING MALARIA:

1. DRUGS TO TREAT THE ACUTE ATTACK : These drugs kill the plasmodium in the RBC .eg- chloroquine , mefloquine, artemisnin derivatives . 
2. DRUGS FOR RADICAL CURE :  For radical cure , combination of drugs that kill the erythrocytic stage + drugs that kill the exo-erythrocytic(liver) stage is used .
   eg- chloroquine + primaquine
3. DRUGS FOR PROPHYLAXIS : These drugs kill the plasmodium in the exo-erythrocytic(liver) stage.
   eg- primaquine , proguanil 
4. DRUGS FOR PREVENTING TRANSMISSION: These drugs kill the gametes . eg - chloroquine  

                                   CHLOROQUINE

MECHANISM :

                          Chloroquine accumulates in the food vacuole of PLASMODIUM ,  thus it is selective for erythrocytic stage of malaria ( food vacuole in the plasmodium is found only in the erythrocytic stage ). 

Then it inhibitis the conversion of heme to hemozoin .

Heme is toxic to the parasite , thus the parasite in the rbc gets killed.

OTHER ACTIONS of chloroquine:

1. Anti-inflammatory 
2. Anti-histamine
3. Anti-arrythmic
4. Local anesthetic 
5. Active against Giardia lamblia and Entamoeba histolytica

PHARMACOKINETICS :

1. Given orally 
2. Partly metabolized in liver
3. 70% excreted in urine unchanged
   30% excreted in urine as a metabolite .

USE:

1. R - Rheumatoid arthritis
2. E - Extra-intestinal amoebiasis
3. D- Discoid Lupus Erythromatosis
4. L - Lepra reaction
5. I - Infectious mononucleosis
6. P - Photogenic reaction
7. M - Malaria 
8. G - Giardiasis

   RED LIP Mahatma Gandhi is the mnemonic to remember the uses of chloroquine .

ADVERSE EFFECTS:

1. Skin rashes ( Lichenoid eruptions )
2. Peripheral neuropathy
3. Auditory impairment 
4. Blindness due to retinal damage ( bull's eye maculopathy)
5. Porphyria

BULL'S EYE MACULOPATHY

MNEMONIC TO REMEMBER SITE OF ACTION OF PROTEIN SYNTHESIS INHIBITING ANTI-BIOTIC .

MNEMONIC:



                BUY AT 30 AND SELL AT 50

A - AMINOGLYCOSIDE
T - TETRACYCLINES
 
THESE BOTH  BIND ON 30 S RIBOSOME AND INHIBITS PROTEIN SYNTHESIS .

S - STRETOGRAMINS
E - ERYTHROMYCIN
L - LINEZOLID 
L - LINCOSAMIDES

THESE DRUGS BIND ON 50 S RIBOSOME AND INHIBIT PROTEIN SYNTHESIS .

COURTESY: SPARSH MOHAN TEXTBOOK OF PHARMACOLOGY

MACROLIDE

                                  MACROLIDE

MECHANISM : Macrolide attaches to 50 s ribosome and block the translocation of peptide chain containing T RNA from A site to P site .

One must know about the TRANSLATION process happening in the bacterial cell to understand the above mechanism .

DRUGS :

1. Erythromycin
2. Roxithromycin 
3. Clarithromycin
4. Azithromycin
5. Tacrolimus ( it is an immunosuppresant as well )
6. Spiramycin 

PHARMACOKINETICS:

1. All drugs are taken orally except spiramycin .
2. Metabolised in liver
3. These drugs are excreted in bile except Clarithromycin in urine.
4. Do not cross blood brain barrier 
5. Crosses placenta

USES:

MACROLIDES ARE BROAD SPECTRUM ANTIBIOTICS.

They are the drug of choices for the following:

1. C -  Chancroid by Haemophilus ducreyi , Corneybacterium , Campylobacter
2. L - Legionella
3. A - Atypical pneumonia
4. W- Whooping cough by Bordetella pertusis.

Mnemonic to remember the uses is CLAW .

Azithromycin has extended spectrum of uses :

1. H.influenza
2. Nesseria gonnorrhoea
3. Urogenital infection by Chlamydia

Clarithromycin used as prophylaxis and treatment of Mycobacterium avium and H.pylori

Spiramycin is drug of choice for toxoplasmosis in PREGNANCY.

ADVERSE EFFECTS :

1. ERYTHROMYCIN causes diarrhoea due to Motilin Stimulation.
2. Erythromycin causes ACUTE CHOLESTATIC HEPATITIS
3. Erythromycin , Clarithromycin , Roxithromycin causes microsomal enzyme inhibition .
   ALL THESE ADVERSE EFFECTS ARE ABSENT IN AZITHROMYCIN .
   

Vancomycin

                             VANCOMYCIN

Vancomycin comes under a group called as GLYCOPEPTIDES. Other drugs in this group are Teicoplanin , Oritavaricin , Telavancin , Dalbavancin . All glycopeptides inhibit cell wall synthesis in bacteria .

MECHANISM OF ACTION : 

1. They are bacteriocidal antibiotics .
2. They inhibit cell wall synthesis by inhibiting TRANSGLYCOLASE enzyme required for polypeptide chain elongation.

PHARMACOLINETICS:

1. Vancomycin taken as I.V 
2. It is not absorbed when given orally . It is given orally for Pseudomembranous colitis by Clostridium difficile  
3. They are excreted in Urine

USE:

1. MRSA
2. Clostridium jeikium 
3. Penicillin allergic patients as an alternative drug 
4. Pseudomembranous colitis by Clostridium difficile 

ADVERSE EFFECTS:

1. Rapid I.V infusion of vancomycin can lead to RED MAN SYNDROME ( diffuse flushing ) . Because vancomycin releases histamine .
2. Ototoxicity
3. Nephrotoxicity
4. Chills

                                      

ANTI AMOEBIC DRUG - NITROMIDAZOLES

                                    NITROMIDAZOLE

MECHANISM : These drugs gets activated once it enters the microorganism and forms cytotoxic products that damage DNA. Its bio activation happens only in anaerobic micro organisms .  

DRUGS : METRONIDAZOLE , TINIDAZOLE , SATRANIDAZOLE .

PHARMACOKINETICS :

1. These drugs taken orally and I.V
2. Metabolized in liver 
3. Excreted in urine 
4. Tinidazole and Satranidazole is longer acting than metronidazole ( potency and efficacy are same )

USE :

1. Intestinal and extra-intestinal amoebiasis 
2. Trichomoniasis
3. Giardiasis
4. Bacterial Vaginosis
5. Anaerobic bacteria like bacteroides , clostridium 
6. Combination therapy for H.pylori

ADVERSE EFFECTS :

1. Metallic taste
2. Discoloration of urine 
3. Dizziness and Seizure 
4. Disulphiram like action 
5. Nausea 
6. Leukopenia 
7. Abdominal cramps 

TREATMENT OF AMOEBIC DYSENTERY :

METRONIDAZOLE 500 mg 3 times/day 

                      +

DILOXAMIDE FUROATE 500 mg 3 times / day

Diloxamide furoate is a very powerful intestinal amoebicide

Metronidazole is an active extra-intestinal amoebicide , it acts as intestianl amoebicide as well . 

MNEMONICS TO REMEMBER MICROSOMAL ENZYME INDUCERS , ENZYME INHIBITORS , etc .

                                   MNEMONICS 

MENTION SOME ENZYME INDUCERS ????

MENTION SOME ENZYME INHIBITORS ????

MENTION DRUGS METABOLIZED BY MICROSOMAL ENZYMES ????

MENTION DRUGS METABOLIZED BY ACETYLATION ????

These above questions are frequently asked in MBBS viva exam and for PG entrance too . So I gathered some mnemonics to answers these questions easily . I wanted to share this so that it will be helpful for others too . 

ENZYME INDUCERS :

                                GPRS Cell Phone

G - Griseofulvin 

P - Phenytoin

R - Rifampicin 

S - Smoking

Cell - Carbamazepine 

Phone - Phenobarbitone 

ENZYME INHIBITORS :

                           Vitamin K Cannot Cause Enzyme Inhibition 

Vitamin - Valproate 

K - Ketoconazole 

Cannot - Cimetidine 

Cause - Ciprofloxacin 

Enzyme - Erythromycin 

Inhibition - Isoniazid

DRUGS METABOLIZED BY MICROSOMAL ENZYMES :

                     COW PATS

C - Cyclosporin

O - Oral Contraceptive Pills 

W - Warfarin 

P - Phenytoin

A - Acetyl choline esterase inhibitor ( DONEZEPIL )   

T - Theophylline 

S - Statins

DRUGS METABOLIZED BY ACETYLATION :

                              D SHIP

D - Dapsone 

S - Sulphonamide 

H - Hydralazine 

I - Isoniazid 

P - Procainamide 

TREATMENT OF PEPTIC ULCER

          TREATMENT OF PEPTIC ULCER 

Peptic ulcer was one of the most common gastric disease. After introducing drugs like proton pump inhibitors , antacids ,etc number of peptic ulcer cases have gone down drastically . 

Before learning about the drugs for treatment of peptic ulcer one must have a thorough knowledge about the physiology of peptic ulcer formation.

Peptic ulcer occurs due to imbalance between  DEFENSIVE FACTORS AND AGGRAVATING FACTORS

DEFENSIVE FACTORS                   

1. MUCUS                                     
2. BICARBONATE                        
3. MUCOSAL BLOOD FLOW 

AGGRAVATING FACTORS

1. GASTRIC ACID 
2. NSAID'S 
3. CORTICOSTEOIDS
4. HELICOBACTER PYLORI
5. ALCOHOL
6. SMOKING    
   
   Due to the imbalance, patient initially suffers through gastritis ie. inflammation of gastric mucosa due to gastric irritation by aggravating factors (alcohol,NSAID's,etc) .                 

       If this gastritis persists it will lead to peptic ulcer .
       This can be acute or chronic 

Next we will see about gastric acid synthesis and regulation which is very important to understand the mechanism of action of drugs .

Parietal cell is responsible for secretion of gastric acid.
Parietal cell is stimulated by number of factors :

1. When a person thinks about food , gastric acid gets secreted . it is because of stimulation in brain which transmits impulses via vagus nerve which in turn stimulates the M 1 receptor on the Enteric nervous system (ENS) . ENS will secrete Ach which will act on M 3 receptor of gastric mucosa . (REFER ABOVE DIAGRAM)
2. When food reaches the stomach G CELL gets stimulated . G cell produce gastrin , which will act on CCK-B receptor on parietal cell . thus secreting gastric acid .(DIAGRAM)
3. Histamines are released from Entero chromatoffin like cell -2 present in the sub mucosa . Released histamine will act on H2 receptor of parietal cell. ECL -2 secretes histamine throughout the day thus responsible for basal gastric acid secretion .(DIAGRAM)

Thus we saw about the physiology of gastric acid secretion . Next we will move on to the treatment of peptic ulcer .

DRUGS USED IN PEPTIC ULCER 

1. ANTACIDS 
2. PROTON PUMP INHIBITORS
3. H2 RECEPTOR ANTAGONISTS
4. ANTICHOLINERGICS M 1 BLOCKERS
5. DRUGS INCREASING PROTECTIVE FACTORS
6. ULCER PROTECTIVE DRUGS 
7. ULCER HEALING DRUGS 
8. ANTI HELICOBACTER DRUGS  

1)ANTACIDS

MECHANISM OF ACTION : These drugs are weak bases , they neutralize the gastric acid .
                                             
DRUGS: Sodium bicarbonate , Aluminium hydroxide , magnesium hydroxide , MEGALDRATE , Magnesium tricilicate .

PHARMACOKINETICS: 

1. All antacids are taken orally 
2. Only Sodium bicarbonate is absorbed systemically .
3. Sodium bicarbonate is faster acting but has short period of action
4. Other antacids are not absorbed . 
5. Other antacids have slower onset of action but have longer period of action  

USE: 

1. They give prompt pain relief in Peptic ulcer 
2. Treatment for Hypophosphatemia.

ADVERSE EFFECTS:

1. Sodium bicarbonate uses bleching and gastric distention due to the release of CO2
2. Aluminium hydroxide causes constipation 
3. Magnesium hydroxide causes diarrhoea .
   THUS combination of magnesium and aluminium hydroxide is used . It is called as MEGALDRATE .

 2)PROTON PUMP INHIBITORS 

MECHANISM : These drugs by irreversibly inhibiting H+K+ATPase in parietal cells . Thus meal stimulated and basal acid output is decreased .

DRUGS : Omeprazole , Pantoprazole , Lansoprazole , Rabeprazole

PHARMACOKINETICS :

1. These drugs taken orally and I.V
2. These are PRODRUGS.
3. They are converted to active form SULFENAMIDE (not sulphonamide which is an antibiotic. ) in Parietal cells .
4. They are metabolized in liver 
5. They are excreted in Urine

USE :

1. Peptic ulcer 
2. GERD
3. Zollinger-Ellison diesease
4. Lansoprazole is given in pregnancy 

ADVERSE EFFECTS :

1. Decrease Vit-B 12 absorption 
2. Decrease Ca absorption 
3. Decrease iron absorption 
4. Diarrhoea 

3)H2 RECEPTOR ANTAGONIST : 

MECHANISM: These drugs competitively inhibit H2 receptor in parietal cell , thus inhibits gastric acid secretion

Ach and Gastrin also acts partially by releasing histamine . Action of these agents are also decreased partially by these drugs .

DRUGS : Cimetidine , Ranitidine , Famotidine , Roxatidine

PHARMACOKINETICS :

1. Taken orally 
2. Systemic absorption of the drug happens
3. They are excreted unchanged in urine 
4. It crosses placenta 
5. Potency and Longer action ---- Cimetidine < Ranitidine < Famotidine < Roxatidine 

USES:

1. Peptic ulcer diesease
2. Drug of choice for stress induced ulcer 
3. GERD
4. Zollinger-Ellison Syndrome 
5. Prophylaxis of aspiration pneumonia  

ADVERSE EFFECTS :

1. Headache
2. Diarrhoea 
3. Cimetidine has anti-androgenic effect 
4. Cimetidine is an enzyme inducer 

ANTICHOLINERGIC DRUGS:

PIRENZEPINE AND TELENZEPINE are selective M1 blockers .

Thus used in peptic ulcer disease . 

DRUGS INCREASING PROTECTIVE FACTORS :

Prostaglandin E and Prostaglandin I2 play an important role in secretion of protective factors and inhibition of gastric acid secretion .

Thus Prostaglandin analogue can be given in peptic ulcer disease .

Prostaglandin E analogue called Misoprostol is the commoly used drug .

ULCER PROTECTIVE AGENTS :

MECHANISM: These drugs form a coating over the gastric mucosa and thus protect from the exposure of acid .

DRUGS:

1. SUCRALFATE 
2. COLLOIDAL BISMUTH SUBCITRATE

These drugs should not be given with antacids because these drugs are active only in acidic medium . Antacids creates a basic pH in stomach .

ULCER HEALING DRUGS :

CARBENOXOLONE is the drug for healing of ulcer .

ANTI HELICOBACTER PYLORI DRUGS :

Commonly used regimen for treatment of H.pylori is TRIPLE DRUG THERAPY .
TRIPLE DRUG THERAPY is
PROTON PUMP INHIBITOR (Lanoprazole 30mg or pantoprazole 40 mg ) + AMOXICILLIN 1000 mg + CLARYTHROMYCIN 500 mg twice daily for 2 weeks .

HERE ENDS THE TOPIC . IF ANYONE HAS DOUBTS OR HAS EXTRA POINTS TO ADD TO THIS BLOG  PLEASE DO COMMENT. 

PATHOGENESIS OF TUBERCULOSIS

Tuberculosis is an air borne infection !!

1) Once the mycobacteria enters the respiratory tract of a person it reaches the alveoli and is engulfed by the alveolar macrophages

2) Mycobacteria resists killing by macrophages , so macrophage containing bacteria enters the interstitium , now the infected macrophage will produce interleukin - 12 

3) Interleukin -12 will recruit T-Helper -1 cells at that site .

4) T-helper -1 cells after interacting with infected macrophage will start producing INTERFERON-gamma .

5)INTERFERON-gamma  will start recruiting more macrophages at that site . but macrophages cannot kill the bacilli .

6) So macrophages will transform themselves into flattened cells . These flattened macrophages is called as EPITHELIOID CELL .

7)These epithelioid cells will produce TUMOR NECROSING FACTOR (TNF) . TNF will recruit more macrophages to the infected site and convert them to epithelioid cell .

8)These epithelioid cells will form a wall around the affected site . MOTIVE of forming a wall is because these epithelioid cells (macrophages) cannot kill the mycobacteria , so by forming a wall around the site , they can at least prevent the spread of infection to other sites of the lungs and other organs .  

9)Some epithelioid cells will clump together and form a giant cell . this giant cell is called as langhan's giant cell . This giant cell have an characteristic HORSESHOE arrangement of nucleus .

10) Mycobacteria can multiply inside the macrophage and destroy the macrophages . Thus there is an characteristic necrosis seen at the infected site of tuberculosis , this is called as CASEOUS NECROSIS . 

11) Caseous necrosis in the middle surrounded by epithelioid cells and t cells is called as GRANULOMA OF TUBERCULOSIS.





















 We saw about basic pathogenesis of TB. 
 Next i will explain about PRIMARY AND SECONDARY  TUBERCULOSIS.

 PRIMARY TUBERCULOSIS : A PREVIOUSLY UNINFECTED PERSON WHEN GETS INFECTED BY TUBERCULOSIS FOR THE FIRST TIME , IT IS CALLED AS PRIMARY TUBERCULOSIS .

Primary site of granuloma formation is called as GHON'S FOCUS . More often a infected macrophage reaches the hilar lymph node and forms a granuloma there . 

Ghon's focus + Involved hilar lymph node together is called as GHON'S COMPLEX.

1) 70% of times , when a patient get affected by primary TB, he is symptomless (latent TB ) because the infection is well contained by the epithelioid cell . 

2) Only 20% shows some symptoms .

3) Sometimes primary tuberculosis can progress to a fatal condition . This is called as MILIARY TUBERCULOSIS .It is commonly seen in immunodeficient or immune suppressed patients . In miliary tuberculosis there is multiple granuloma formed in the lungs and there is involvement of extra pulmonary sites ( kidneys , brain , bones ) also. 

SECONDARY TUBERCULOSIS: Patients who were affected by primary tuberculosis and remained symptomless for many years because of the bacteria remaining dormant in their lungs .

Later in life Will develop tuberculosis due to reactivation of the dormant bacteria . This is called as SECONDARY TUBERCULOSIS .

In Secondary tuberculosis the symptoms are more severe than the primary Tb . 

Typical brown coloured sputum producing cough is seen in secondary tuberculosis . 

Even secondary tuberculosis can progress to miliary Tb .

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