Kerala PG medical entrance rank list published

From http://www.hindu.com/2004/04/09/stories/2004040907040400.htm

The provisional rank list of general candidates and service candidates who have qualified in the entrance test for admission to the various post-graduate medical courses (degree/diploma) for 2004, has been published by the Commissioner for Entrance Examinations.

A press note issued here today said the results of two candidates have been withheld. Two questions in paper 1 and one in paper 2 have been deleted. The marks scored in each paper have been converted as out of 450.

The rank list will be available for reference at the office of the CEE and at the office of the Director of Public Relations. The list will be available for perusal at all the district information centres from April 13 onwards.

Candidates who wish to know their marks and rank in the entrance examination may apply to the CEE on or before May 7 along with a post order for Rs. 100 drawn in his favour, payable at the GPO, Thiruvananthapuram and a self-addressed envelope stamped for Rs. 5.

Bostentan

Question.

218. Bostentan is a:

1. Serotonin uptake injibitor.

2. Endothelin receptor antagonist.

3. Leukotriene modifier.

4. Calciuim sensitizer.

Answer

2. Endothelin receptor antagonist.

Reference

CMDT 2002 Page 450

http://www.pharmacist.com/new_drug/tracleer.cfm

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CMDT, Journals

Discussion

• It is endothelin receptor antagosnist
• Generic name: Bosentan
• Manufacturer: Actelion
• Drug Class:
• PROSTACYCLIN
• Dual endothelin receptor antagonist
• Indications: Treatment of pulmonary arterial hypertension.
• Dosage: Initiate treatment at an oral dosage of 62.5 mg twice daily for 4 weeks and then increase to a maintenance dosage of 125 mg twice daily.
• Evidence of liver damage present in 14% of patients in Bosentan: Randomized Trial of Endothelin Receptor Antagonist Therapy trial, but no evidence suggests agent can cause irreversible liver damage.
• It has been made available to patients at the University of Pittsburgh Medical Center as part of a clinical trial. Bosentan works by blocking the action of a hormone called endothelin. Endothelin exists in higher levels in people with PH is a hormone that is harmful to the lung and pulmonary arteries. The damaged lung and pulmonary arteries create the blood flow resistance that results in hypertension. Bosentan was designed to offset endothelin, lowers the endothelin levels, reversing its effects, resulting in lower artery pressure.
• Tracleer blocks the action of endothelin, a substance made by the body. Endothelin narrows blood vessels and elevates blood pressure. Although endothelin is present in healthy people, high concentrations of the hormone have been found in the plasma and lungs of patients with PAH suggesting it is capable of causing the disease.
• Liver function tests are needed
• Because of its potential to cause birth defects, Tracleer must not be prescribed to pregnant women. Female patients of childbearing potential must therefore take measures to prevent pregnancy, and monthly pregnancy testing will be required.

Explanation

1. Serotonin uptake injibitors are Fluoxetine, Fluvoxamine, Paroxetine.

2. Endothelin receptor antagonist.

3. Leukotriene modifiers are Montelukast and Zafirlukast.

4. Calcium sensitizer is Levosimendan.

Comments

Myocardial stunning refers to the phenomenon of transient myocardial dysfunction after brief periods of coronary ischaemia and reperfusion. During stunning there is less myocardial fibre shortening and myocardial oxygen consumption is near normal, indicating a low efficiency of the contractile apparatus. Depressed responsiveness of the myofilaments to Ca ions is regarded as an important factor in the process of stunning. Levosimendan (Levo) increases the sensitivity of troponin C in a Ca-dependent way.

STRUCTURE AND DYNAMICS OF CARDIAC TROPONIN C

Cardiac Troponin C (cTnC) plays a pivotal role in the function of heart. The heart contraction is induced by a conformational change of cTnC triggered by the binding of calcium ions which are released from the sarcoplasmic reticulum. The conformational change of cTnC allows myosin to interact with actin filaments. Subsequently, the heart contracts as the filaments glide past each other. Knowledge of the three-dimensional structure of cTnC and its induced conformational changes at atomic resolution provide new means for understanding the basic events in the heart contraction. This knowledge is also of applied importance. In a number of cases impaired heart functions can be alleviated by drug molecules designed to make troponin C more prone to a conformational change. These drugs which increase the calcium sensitivity are designated calcium sensitizers. It would be most useful for further development of these pharmaceuticals to be able to demonstrate the drug binding and its consequences to the conformation and dynamics of cTnC.

Considering the fundamental role of cardiac troponin C in the heart function and the possibilities to modulate the function by pharmaceuticals a study of cTnC by methods of structural biology is most interesting and useful. The three-dimensional structure of cTnC should be determined in complex with relevant motifs of TnI. In addition deeper insight into the structure-function relationship should be gained by a molecular dynamics study.

A new calcium sensitizer drug levosimendan was discovered by calcium dependent affinity chromatography on a troponin complex column (Haikala et al., 1992). The screening was based on a hypothesis that calcium sensitizers bind in the hydrophobic patch formed in the regulatory domain of TnC following a calcium induced conformational change (Ovaska and Taskinen, 1991). It was recently shown that the new calcium sensitizer drug levosimendan binds to human cardiac troponin C (Pollesello et al., 1994).

Tips

Newer drugs are being asked with increased frequency these days. Go through the last few pages of Sure Success in PG (big book) by Ram Gopal and also the web site given above

Lignocaine toxicity

Question.

217. Cardiac or central nervous system toxicity may result when standard lidocaine doses are administered to patients with circulatory failure. This may be due to the following reason:

1. Lidocaine concentration are initially higher in relatively well perfused tisseues such as brain and heart.

2. Histamine receptors in brain and heart gets suddenly activated in circulatory failure.

3. There is a sudden out-burst of release of adreneline, noradreneline and dopamine in brain and heart.

4. Lidocaine is converted into a toxic metabolite due to its longer stay in liver.

Answer

1. Lidocaine concentration is initially higher in relatively well perfused tisseues such as brain and heart.

Reference

Harrison 15^th Page 425 and Figure 70.1

Satoskar 17^th Edition Page 384

Goodman Gillman 10^th Edition

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Harrison

Discussion

Lidocaine is a rapidly active drug. In circulatory failure, due to decreased hepatic flow, the metabolism of lidocaine is hampered and this leads to high levels in blood and obviously the high levels affect the well perfused tissues

Explanation

Lidocaine concentration are initially higher in relatively well perfused tisseues such as brain and heart. And this is the reason for Cardiac or Central nervous system toxicity when Standard Lignocaine is given to this patients

Comments

Question for Anaesthetists

Tips

A word about Ester and Amide Local Anaesthetics.

If the Name of the Anaesthetic agent has two times the alphabet “i” it is an amide eg Prilocaine, Lignocaine, Dibucaine.

If the Name of the Anaesthetic agent has the alphabet “i” only once it is an ester eg Cocaine, Tetracaine, Benzocaine.

Gastric Obstruction

Question.

214. Presence of food might be expected to interfere with drug absorption by slowing gastric emptying, or by altering the degree of ionisation of the drug in the stomach. Which of the following statements is not correct example:

1. Absorption of digoxin is delayed by the presence of food.

2. Concurrent food intake may severely reduce the rate of absorption of phenytoin.

3. Presence of food enhances the absorption of hydrochlorthiazide.

4. Anitimalarial drug halofantrine is more extensively absorbed if taken with food.

Answer

3. Presence of food enhances the absorption of hydrochlorthiazide.

Reference

KDT 5^th Edition Pages 372(Phenytoin), 748 (Halofantriene) and 4^th Edition Pages 492(digoxin), 384(Phenytoin), 565(Thiazides),

Halofantriene – Park, Katsung ,Harrison 15^th Edition Table 414-4

Goodman Gilman 9^th Edition Page 957

CMDT 2003 Page 441

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??

Discussion

Presence of Food generally dilutes the drug and retards absorption. Certain drugs form complexes with certain constituents of the food. For example Tetracycline complexes with Calcium and more over food delays Gastric emptying. Thus most drugs are better absorbed if taken in empty stomach. But few drugs which are irritant are better given with food.

Explanation

1. Absorption of digoxin as well as digitoxin is delayed by the presence of food.

2. Concurrent food intake may severely reduce the rate of absorption of phenytoin.

3. Presence of food has no effect on the absorption of hydrochlorthiazide.

4. Anitimalarial drug halofantrine is more extensively absorbed if taken with fatty food (Katsung).

Comments

A question for which one needs knowledge of Pharmacokinetics (often ignored)

Tips

Make a note of drugs that are increased with food (other than Halofantriene)

ICU Infection

Question.

215. In post-operative intensive care unit, five patients developed post-operative wound infection on the same day. The best method to prevent cross infection occurring in other patients in the same ward is to:

1. Give antibiotics to all other patients in the ward.

2. Fumigate the ward.

3. Disinfect the ward with sodium hypo chlorite.

4. Practice proper hand washing.

Answer

4. Practice proper hand washing.

Reference

Katzung 7^th Edition Pg-805,

Nelson Chapter-174

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Nelson

Discussion

Strict attention to hand washing techniques is the most effective measure for preventing the spread of staphylococci from one individual to another

Transmission of S. aureus generally occurs by direct contact or by spread of heavy particles over a distance of 6 ft or less. Spread by fomites is rare. Heavily colonized individuals and perianal carriers are particularly effective disseminators. Neonates are extremely susceptible to staphylococci; the nasopharynx, skin, perineum, and umbilical stump are the most common sites of colonization. Autoinfection is common, and minor infection (e.g., styes, pustules, paronychia) may be the source of disseminations. Handwashing between contacts with patients decreases the spread of staphylococci from patient to patient. Older children and adults are more resistant than the neonate to colonization.

PREVENTION. Staphylococcal infection is transmitted primarily by direct contact. Strict attention to handwashing techniques is the most effective measure for preventing the spread of staphylococci from one individual to another . Use of a detergent containing an iodophor, chlorhexidine, or hexachlorophene is recommended. In hospitals or other institutional settings, all persons with acute staphylococcal infections should be isolated until they have been treated adequately. There should be constant surveillance for nosocomial staphylococcal infections within hospitals. Infectious disease control measures may reduce the spread of infection

Explanation

1. Give antibiotics to all other patients in the ward is not the best method.

2. Fumigate the ward is a far fetched option.

3. Disinfect the ward with sodium hypochlorite – Asking for too much.

4. Practice proper hand washing is the best option.

Comments

A Micro Question from Pharmac / Nelson as well as many surgery books

Tips

Phenytoin Toxicity

Question.

216. Granulocytopenia, gingival hyperplasia and facila hirsutism are all possible side effects of one of the following anticonvulsant drugs.

1. Phenytoin.

2. Valproate.

3. Carbamazepine.

4. Phenobarbitone.

Answer

1. Phenytoin.

Reference

Katzung, 7^th Edition Pages 391

KDT 5^th Edition Page 372 & 4^th Edition Page 385

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All books!!

Discussion

The adverse effects of Phenytoin are

1. Gum Hyperplasia

2. Hirsutism, acne

3. Hypersensiticity reactions – rashes, DLE, Lymphadenopathy, neutropaenia which requires discontinuation of therapy

4. Megaloblastic Anemia due to Decreased Absorbtion and Increased Excretion of Folic Acid

5. Granulocytopaenia and even Pancytopaenia

6. Osteomalacia

7. Hyperglycaemia due to inhibition of Insulin release

8. Foetal Hydantoin Syndrome

a. Hypoplastic Phalanges

b. Cleft Palate

c. Hare Lip

d. Microcephaly

Explanation

1. Phenytoin causes all the fetures given above.

2. Valproate causes Fulminant hepatitis and during pregnancy Neural Tube defects in Off Spring.

3. Carbamazepine produces dose related neurotoxicity and hepatitis, lupus like syndrome, rarely agranulocytosis and aplastic anaemia.

4. Phenobarbitone causes rashes, megaloblastic anaemia and osteomalacia.

Comments

Side effects of the drugs are best read from the Table in Harrison

Tips

Note the 5 H in the adverse effects

н Hyperplasia of Gums,

н Hirsutism,

н Hypersensiticity reactions

н Hyperglycaemia

н Hydantoin Syndrome

pKa of a drug

Question.

213. The extent to which ionisation of a drug takes place is dependent upon pKa of the drug and the pH of the solution in which the drug is dissolved. which of the following statements is not correct.

1.pKa of a drug is the pH at which the drug is 50% ionized.

2.Small changes of pH near the pKa of a weak acidic drug will not affect its degree of ionisation.

3.Knowledge of pKa of a drug is useful in predicting its behaviour in various body fluids.

4.Phenobarbitone with a pKa of 7.2 is largely ionized at acid pH and will be about 40% non-ionised in plasma.

Answer

4.Phenobarbitonewith a pKa of 7.2 is largely ionized at acid pH and will be about 40% non-ionised in plasma.

Reference

KDT 5^th Edition Page 12 Figure 2.3 & 4^th Edition Chapter 2 Pages 11,12 Fig 2.3

Harper 25^th Edition Page 23 Figures 3.6, 3.7

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KDT, Harper

Discussion

pKa of a substance is the pH at which it is 50 % ionized. And small changes of pH near its pKa will not affect the ionization of Acidic as well as Basic Drugs. And of course the knowledge of pKa is needed in predicting the behaviour of various drugs in body fluids. Just because we know the pKa of Aspirin we are able to understand why it is selectively concentrated in the gastric mucosa at concentration much higher than that of the gastric lumen. Because we know the pKa of Phenobarbitone, we are able to Use Forced Alkaline diuresis for its excretion

Explanation

1.pKa of a drug is the pH at which the drug is 50% ionized.

2.Small changes of pH near the pKa of a weak acidic drug will not affect its degree of ionisation.

3.Knowledge of pKa of a drug is useful in predicting its behaviour in various body fluids.

4.Phenobarbitone with a pKa of 7.2 is largely unionized at acid pH and is more ionised in Alkaline pH. Remember Forced Alkaline Diuresis for Phenobarbituric ACID !!!!)

Comments

This question can be solved easily if one knows the basic concepts of Acid, Base and pH

Tips

· As already told, if one has strong correct concepts in Acid Base and Electrolyte Balance, about 5% of Questions can be attended with minimum fuss

· This question carries a chance of being wrongly interpreted and considering Answer 4 as correct. Be careful !!! Phenobarbitone is Phenobarbituic ACID and is not a Basic Drug !!!