THE WEST BENGAL UNIVERSITY OF HEALTH SCIENCES M.B.B.S. 2nd PROFESSIONAL EXAMINATION SUBJECT : PHARMACOLOGY 2019 Paper-1 (Regular) Group -A Q1. a) Enumerate the drugs used in treatment of organophosphorus poisoning. Mention the reason of using each drug. State the dosage schedule and duration of treatment of the life saving drug used in the above condition. 34443 ‘Ans. Drugs that are used in organophosphorus poisoning are + (Atropine sulfate + (ii) Cholinesterase reactivators : Oximes like pralidoxime, obidomime etc. + (iii) Others : for supportive and symptomatic treatment (i Atropine : It is highly effective in counteracting the muscarinic symptoms, but higher doses are required to antagonize the central effects. + (iv)It does not reverse peripheral muscular paralysis which is a nicotinic action. All cases of anti-ChE poisoning must be promptly given atropine 2 mg i.v. repeated every 10minutes till dryness of mouth or other signs of atropinization appear. Upto 200 mg may be administered in a day. Continued treatment with maintenance doses may be required for 1-2 weeks. O (b) Cholinesterase reactivators : Oximes are used to restore neuromuscular transmission only in case of organophosphate anti-ChE poisoning. + (i) Pralidoxime : 500 mg/20miintusion, is injected i.v.slowly in a dose of 1-2 g (children 20-40 mg/kg). + (ii) Itcauses more marked reactivation of skeletalmuscle ChE than at autonomic sites and not at allin the CNS as it does not penetrate Blood Brain Barrier. Treatment should be started as early as possible within 24 hours of poisoning before the phosphorylated enzyme has undergone ‘aging’ and become resistant to hydrolysis. + (jli)Doses may be repeated according to need (max. 12g in first 24 hrs, lower doses according to symptoms for 1-2 weeks). The use of oximes in organophosphate poisoning is secondary to that of atropine. MOA: The phosphorylated ChE reacts very slowly or not at all with water. However, if more reactive OH groups in the form of oximes (-OH ) are provided, reactivation occurs more quickly. Pralidoxime (2-PAM) has a quaternary nitrogen atom which attaches to the anionic site of the enzyme which remains unoccupied in the presence of organophosphate inhibitors. Its oxime end reacts with the phosphorus atom attached to the esteratic site. The oxime-phosphonate so formed diffuses leaving the reactivated ChE to act on with acetylcholine. oR Q2. Enumerate the drugs used in treatment of essential hypertension. Mention the drugs preferred in the treatment of hypertension when it is associated with diabetes mellitus with reasons. 44343 Ans. Antihy pertnesive drugs are > 1. Centralsympatholytics-Cionidine, Methyldopa > 2. Bela adrenergic blockers-Propranolol, Metoprolol, atenolol, bisoprolol2 QUEST : A KEY TO UG PHARMACOLOGY > 3. a+ blockers-labetolol, carvedilol > 4. adrenergic blockers-Prazocin, Terazocin, Doxazosin, phenoxybenzamin, phentolamine > 5. ACE inhibitors-captopril, Lisinopril, Enalapril, Ramipril, Perindopril > 6. AT 1 receptors blockers-Losartan, Telmisartan, Candisartan, Valsartan. > 7. Direct renin inhibitor-Aliskiren > 8. Calcium channel blockers-verapamil, Diltiazem, nifedipine, Amlodipine, Nimodipine > 9. Diuretics-thiazides-Hydrochlorothiazide, Chlorthalidone, Indapamide High celing diuretics-Furosemide, Torsamide K+ sparing diuretics-Spironolactone, Amiloride, Triamterin > 10.Vasodilators-Arteriolar, Hydralazine, Minoxidil, Diazoxide, Arterio + venous dilator-Sodium nitroprusside ee wi . i .etes molitus then Angiot zyme inhibitors Fee eeer ee eeecr bockers(AR) are used. These drugs (ACE! inhibit conversion of “angiotensinogen fo angiotensin which is resposible for vasoconstriction and injury to glomerular basement membrane and there by prevent proteinurea and diabetic nephropathy. + Angiotensin receptor blockers (ARBs) block AT1 receptors at nephrones and prevent early proteinurea and hypertension in diabetic subject. Group -B @. Explain why? (any three) 3x3 @2.a) Local anaesthetic is sometimes combined with adrenaline. ‘Ans. Local anaesthetic like lignocaine is combined with adrenaline in some special operative situation where blood supply in that area is high and where operation will take more time than the duration of that local anaesthetics like facial operation, dental extraction etc. + Adrenaline by its alfa 1 agonistic activity produces vasoconstriction. This action reduces local blood flow. So less bleeding occur during surgery and local anaesthetic will not disperse in general circu- lation and will lengthen the anaesthesia @2, b) Nebulised salbutamol is is used in treatment of acute severe bronchial asthma. Ans. Inhalational therapy of salbutamol via nebulisation is preferred in bronchial asthma because of the followings Drugs directly reaches the target organ. Quick onset of action. No or minimum systemic adverse effect. No first pass metabolism-good bioavaitabity. > 5. Very small amount of drug is required compaired to oral route. @2. c) Paracetamol is preferred as antipyretic agent among NSAIDS. ‘Ans. NSAIDs reduce body temperature in fever, but do not cause hypothermia in normothermic individu: als. Fever during infection is produced through the generation of pyrogens including Interleukins, Tumour necrosis factor «, interferons which induce PGE2 production in hypothalamus -> raise its temperature set point. NSAIDs block the action of pyrogens by blocking production of PGE2. The isoform present at this site appears to be COX-2. Paracetamol is a good and promptly acting antipyretic. Paracetamol has negligible antiinflammatory action. It is a poor inhibitor of PG synthesis in periph- eral tissues, but more active on COX in the brain Gastric irritation is insignificant and -mucosal erosion and bleeding occur rare in overdose. It does not affect platelet function and clotting factors. So it can be safely use in haemorthagesic fever like dengue where other NSAIDS can produce haemorrhage. vv aera| | M.B.B.S 2ND PROFESSIONAL EXAMINATION 2019 3 02, 4) Hyoscine Is preferred in treatment of vomiting due to motion sickness. ‘Ans. Hyoscine is an natural alkaloids and an anticholinergic drug used in prophylaxis of vomiting due to motion sickness in journey. + Iti applied as transdermal patch behind pinna before starting a journey. + Itis an anticholinergic drug and stops cholinergic transmission from labyrinthin towards brain which is responsible for positional vertigo during journey. The drug should be given prophylactically (0.2 mg oral), because administration after symptoms have set in is less effective. Oral dose of 0.2 mg Action lasts 4-6 hours. A transdermal preparation (TTS) applied behind the pinna 4 hours before journey has been shown to protect for 3 days. Side effects with low oral doses and transdermal medication are few, but sedation and dry mouth may occur, Group-c @, Write the mechanism of action of (any three) 3x3 3. a) Ramipril in treatment of congestive cardiac failure. ‘Ans, Ramipril is an angiotensin converting enzyme inhibitor which is very much preferred in congestive cardiac failure, + i) It prevent conversion of angiotensin | to angoitensin Il which is a potent vasoconstrictor. vaso- constriction-produced directly as well as by enhancing Adr / NA release from adrenal medulla/ adrenergic nerve endings and by increasing central sympathetic outflow. il) Angiotensin-II acting on chronic basis induces hypertrophy, hyperplasia and increased inter- cellular matrix production in the myocardium and vascular smooth muscle by direct cellular effect involving expression of proto-oncogene, transcription of several growth factors. ¢ i) Indirectly volume overload and increased t.p.r. caused by A-lI contributes to the hypertrophy and remodeling (abnormal redistribution). (@3,b) Acetazolamide in treatment of glaucoma. ‘Ans, Acetazolamide, Carbonic anhydrase enzyme inhibitor-is used orally and it acts by reducing aqueous humour production by limiting generation of bicarbonate ion in the ciliary epithelium. Bicarbonate is an essential component in production of aqueous humour, so loss of bicarbonate hampers aqueous production. It is used to supplement ocular hypotensive drugs for short term indication in emergecy situations and before and after surgery or laser therapy. Dorzolamide (2% eye drop) topically used to inhibit ocular carbonic anhydrase enzyme is a better alternative. it reduces IOT by 20% and used as an adjuvant drug with timolol or PGF2«. 8. c) Sucralfate in treatment of peptic ulcer. ns, tis a basic aluminium salt of sulfated sucrose. Sucralfate has no acid neutralizing action, but delays gastric emptying-its own stay in stomach is prolonged. * Suoralfate polymerizes at pH < 4 by cross linking of molecules, assuming a sticky gel-like consis- tency It preferentially and strong adheres to ulcer base, especially duodenal ulcer; has been seen endoscopically to remain there for about 6 hours. * Itprecipitates surface proteins at ulcer base and acts as a physical barrier preventing acid, pepsin and bile from coming in contact with the ulcer base, Dietary proteins get deposited on this coat, forming another layer. * Augmented gastric mucosal PG synthesis may supplement physical protective action of sucralfate %.d) Warfarin as anticoagulant. Ans. Warfarin is a competitive antagonist of vit-K. Warfarin act by interfering synthesis of vit-k dependent clotting factors Il, VII, IX, X_In the liver. * In warfarin toxicity there is depletion of clotting factors in dose dependent manner as wartarin4 QUEST : A KEY TO UG PHARMACOLOGY inhibit the enzyme vit-k epoxide reductase and interfere with regeneration of active hydro- quinone form of vit-k. + Active hydroquinone form of vit-k act as a co-factor for the enzyme y glutamyl carboxylase that responsible for y carboxylation of factors Il, VII, IX, X which is essential for activation of these factors for coagulation of blood. Q4, Write short notes on any four of the following : Prothrombin Vitamin K (Reduced), Precursor Biologically active] Prothrombin (Carboxylase |’ Oxidative deactivation, (vit pore reductase MAS itamin K (epoxide Group-D 3x4 04. a) Drug tolerance (definition, type with example) Ans. G Definition : Tolerance refers to the requirement of higher dose of a drug to produce a given response. Q Types: > 1) Refractoriness-Loss of therapeutic efficacy of sulfonylureas in type 2 diabetes which is a form of > 2) 3) > 4) > 5) tolerance, is often called ‘refractoriness’ Natural tolerance-The species/individual is inherently less sensitive to the drug, e.g. rabbits are tolerant to atropine and black races are tolerant to mydriatics. Acquired tolerance-This occurs by repeated use of a drug in an individual who was initially responsive. Body is capable of developing tolerance to most drugs but the phenomenon is very easily recognized in the case of CNS depressants e.g-+ Tolerance occurs to analgesic and euphoric action of morphine, but not as much to its constipating and miotic actions. ‘An uninterrupted presence of the drug in the body favours development of tolerance, @.9 nitroglycerine Cross tolerance-It is the development of tolerance to pharmacologically related drugs. €.9- alcoholics are relatively tolerant to barbiturates and general anaesthetics. Closer the two drugs are, more complete is the cross tolerance between them, e.g.—There is partial cross tolerance between morphine and barbiturates but complete cross tolerance between morphine and pethidine. Pharmacokinetic/drug disposition tolerance-the effective concentration of the drug at the site of action is decreased, mostly due to enhancement of drug elimination on chronic us?M.B.B.S 2ND PROFESSIONAL EXAMINATION 20195 mostly by increased metabolism due to induction of hepatic cytochrome enzymes e.g. barbi- turates, carbamazepine, amphetamine. » 8) Pharmacodynamicicellular tolerance-drug action is lessened; cells of the target organ become less responsive, e.g. morphine, barbiturates, nitrates, salbutamol. This may be due to down regulation of receptors or weakening of response effectuation. > 7) Tachyphylaxis-rapid development of tolerance when doses of drug repeated in quick succes- sion result in marked reduction in response. This is usually from neuronal stores at synaptic vacules and seen with indirectly acting drugs, such as ephedrine, tyramine, nicotine. These drugs act via releasing catecholamines in the body, synthesis of which is unable to match the rate of release and stores get depleted. 4. b) Therapeutic drug monitoring (when required, significant for which drugs). Ans, Measurement of plasma drug concentration can give an estimate of the pharmacokinetic variables in that patient and the magnitude of deviation from the’ average patient..so that appropriate adjust- ments in the dosage regimen can be made. Therapeutic drug monitoring (TDM) is particularly useful in the following situations > 1. Drugs with low safety margin -e.g digoxin, anticonvulsants, antiarthythmics, theophylline, aminoglycoside antibiotics, lithium, tricyclic antidepressants. > 2. Ifindividual variations are large- e.g antidepressants, lithium. > 3. Potentially toxic drugs used in the presence of renal failure-aminoglycoside antibiotics, van- comycin. . > 4, Incase of poisoning. > 5. Incase of failure of response without any apparent reason-antimicrobials. > 8. To check patient compliance-psychopharmacological agents. > 7. When the purpose is dose adjustment: In case of drugs which need to act continuously (relatively long-acting drugs), itis prudent to measure the trough steady state blood levels, i.e. just prior to the next dose. Q4. c) Sources of drugs (different sources with example) Ans. Q A. Chemical sources : * 1) inorganic — chemical/mineral-ferrus sulfate salt for anemia, magnesium sulfate for purga- tive, eclamsia treatment, radioisotopes in diagnostics and cacer treatment-) Radioactive lodine (1 ort") for thyroid scan, * ji) organic compounds-chloroquine, all biologics, G B. Plant sources : + ji) alkaloide : nitrogenous compound occuring in nature-atrophine, hyoscine + ii) glycosides : plant product with sugar moiety joined by(-o-) linkage. E.g—digitalis. Q C. Animal sources : insulin from pork or beef, different vaccines and anti-sera like hyperimmunoglobulins antidiphtheritic serum., vitamin B12 from liver extracts. Q D. Microorganism : many antibiotics like penicilin G from penicillium notetum, cephalosporine from cephalosporium species. 4, d) Drug nomenclature (different names with example) Q 1. Chemical name : These name is given according to chemical structures. This is cumbersome and not suitable for use in prescribing. A code name, e.g. Ru-486 (later named mifepristone) may be assigned by the manufacturer for convenience and simplicity before an approved name is coined.acety! salicylic acid is another example of chemical name of commonly used aspirin. Q 2. Non-proprietary/generic/officiaVapproved name : It is the name accepted by a competent scientific body or authority, e.g.the United States Adopted Name (USAN) by the USAN council6 QUEST : A KEY TO UG PHARMACOLOGY Similarly, there is the British Approved name (BAN) of a drug. The nonproprietary names of newer drugs are kept uniform by an agreement to use the Recommended International Nonproprietary Name (riNN) in all member countries of the WHO. + However, many older drugs still have more than one non-proprietary names, @.g. ‘meperidine’ and ‘pethidine’ or ‘lidocaine’ and ‘lignocaine’ for the same drugs. + Until the drug is included in a pharmacopoeia, the nonproprietary name may also be called the approved name. After its appearance in the official publication, it becomes the official name. Aspirin is the universal generic name of acetyl salisylic acid. 0 3, Proprietary (Brand) : Name It is the name assigned by the manufacturer(s) and is his property or trade mark. One drug may have multiple proprietary names, e.g. altol, atcardi, atecor, aten, betacard, fonol, tenolol, tenormin for atenolol from different manufacturers. Similarly disprin, ecosprin is the different brand name of aspirin given by different drug marketing company, Q4. e) Neostigmine (therapeutic use with reasons) ‘Ans. Neostigmine is a lipid-insoluble agents quaternary ammonium compounds produce more marked effect on the skeletal muscles (direct action on muscle endplate cholinoceptors as well), stimulate ‘ganglia, but muscarinic effects are less prominent. They do not penetrate CNS and have no central and ocular effects. O Uses: + 4, Myasthenia gravis : This is an autoimmune disorder affecting about 1 in 10,000 population, due development of antibodies directed to nicotinic receptors (NR) at the muscle endplate , reduction in ‘number of free NM cholinoceptors to 1 /3 of and structural damage to the neuromuscular junction weakness and easy fatigability on repeated activity, with recovery after rest. Neostigmane and as congeners improve Muscle contraction by allowing ACh released from prejunctional endings to accumulate and act on receptors over a larger area, and by directly depolarizing the endplate + 2. Postoperative paralytic ileus/urinary retention : This can be relieved by 05-1 mg s.c provided no organic obstruction is present. This action is due to direct as well as ac secretion from nerve ending. + 3. Postoperative decurarization : Neostigmine 0.5-2.0 mgiv., preceded by atropine to block ‘muscarinic effects, rapidly reverses muscle paralysis induced by competitive neuromuscular blockers. * 5. Cobra bite : Cobra venom has a curare like neurotoxin. Though specific antivenom serum is the primary treatment, neostigmine + atropine prevent respiratory paralysis. + 6. Belladonna poisoning : Though Physostigmine 0.5-2 mg iv. repeatod as required is the specific antidote for poisoning with belladonna or other anticholinergics. It penetrates blood-brain barrier and antagonizes both central and peripheral actions. Howover, physostigmine often itself in- duces hypotension and arrhythmias; is employed only as a last resort. Neostigmine does not block the central effect, but is less risky. * 7. Other drug overdosages : Tricyclic antidepressants.phenothiazines and many antihistaminics have additional anticholinergic property. Overdose symptoms and coma produced by these drugs are Partly antagonized by physostigmine. I! also appears to have a modest nonspecific arousal effect in CNS depression produced by diazepam or general anaesthetics, but is rarely used.M.B.B.S 2ND PROFESSIONAL EXAMINATION 2019 7 2019 Paper-tl (Regular) Group-B 1.a) Enumerate the drug used in treatment of epilepsy. Mention therapeutic uses and adverse effects of pheytoin sodium. 44343, Ans. Presently available antiepileptic drugs are aimed to inhibit the abnormal neuronal discharge rather than to correct the underlying cause. Four main mechanisms of action appear to be important 1, Prolongation of Na+channel inactivation : Phenytoin, Carbamazepine, Valproate, Lamotrigino, Topiramate, Zonisamide, Lacosamide 2, Inhibition of excitatory glutamatergic synapse : Phenobarbitone, Phenytoin, Lamotrigine, Topiramate, Valproate, Levetiracetam, Lacosamide. 3. Facilitation of Gaba mediated Cl- channel opening : Barbiturate Benzodiazepine, Vigabatrin, Valproate Gabapentin Tiagabine 4, Inhibition of '’ type ca2+ current : Ethosuximide. Valproate, Zonisamide Mechanism of action of phenytoin : Phenytoin has a stabilizing effect on neuronal membrane- + (a) Causes delayed recovery of voltage dependent Na channels in its inactive state. This effect causes decreased permeability of Na+ ions of all neuronal membrane. As a result the number of functional channels available to generate action potential is reduced + (b) High frequency discharges are inhibited with litle effect on normal low frequency discharges which allow Na+ channels to recover even when their inactivation is prolonged. + (c) Therapeutic concentrations have no effect on resting membrane potentials: riormal synaptic transmission is not impaired. Phenytoin does not interfere with kindling (cumulative discharge) phenomenon. + (d) It selectively inhibit high frequency firing, + (0) Inhibits the spread of seizure discharge and shortens the duration of after discharge. Therapeutic uses : Phenytoin is a first line antiepileptic drug and indicated in + (i) Generalized tonic-clonic seizure, simple and ycomplex partial seizures. + (ii) Status epilepticus- + (iil) Trigeminal neuralgias. O Adverse drug reactions : after long term use at therapeutic plasma level : (a) Gum hypertrophy-commonest (b) Hirsutism and coarsening of facial features-increased androgen secretion. (c) Hypersensitivity reaction : rashes, DLE, lymphadenopathy, neutropenia, (d) Megaloblastic anemia-due to inhibition of folate absorption. (e) Osteomalacia-due to vit-D deficiency. (0 Hyperglycemia-inhibition of insulin release. (g) Fetal hydantoin syndrome-if used during pregnancy. Itis manifested as hare lip and cleft palate, hypo plastic phalanges etc. It is due to epoxide metabolite formation. Q Dose related adverse effects : At higher doses when plasma concentration exceeding (100-150 umol/) + (i) Ataxia, vertigo, diplopia, nystagmus but no sedation. + (ii) At more higher concentration-marked confusion and intellectual deterioration occurs. + (ili) A paradoxical increase in seizure frequency may occur which is considered a trap to the unwary prescriber.OOO EO EE oe! 8 QUEST : A KEY TO UG PHARMACOLOGY O Others : > (a) Being a barbituric acid analogue thrombophlebitia of the injected vein and if t extravasates tissue necrosis may occur. > (b) Fall in BP and cardiac armhythmias may occur only on 1.V injections which require continu: ‘ous ECG monitoring. Or @2. Enumerate glucocorticoid mention therapeutic uses and adverse effects of glucocorticoids, B48 Ans. O Different glucocorticoids are > (1) Short acting-Hydrocortisone > (2) Intermediate acting-Prednisolone, Methyl prednisolone Triamcinolone (3) Long acting-Dexamethasone, Botamethasone Replacement therap} 1) Acute adrenal insufficiency-Itis an emergency, Hydrocortisone or Dexamethasone are given. 2) Chronic adrenal insufficiency (Addison's disease) Hydrocortisone is given orally > 3) Congenital adrenal hyperplasia (Adreno-genital syndrome) Pharmacotherapy (for nonendocrine diseases) 1. Arthritides : Rheumatoid arthritis, osteoarthritis, sheumatic fever, gout, 2. Collagen diseaes : Systemic lupus erythromatosus, polyarthritis nodosa, nephrotic syn- O Uses: oA y vy vvo drome, dermatomyositis. Severo allergic reactions : Corticoids may be used for short periods in anaphylaxis, angioneuroticedema, urticaria and serum sickness. ‘Autoimmune diseases like Autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura,active chronic hepatitis respond to corticoids Bronchial asthma and other lung diseases : Early institution of inhalational gluccconticeid therapy is now preferred in satatus Asthmalicus. |.V hydrocortisone is given. In aspiration pneumonia, pulmonary oedema due to asphyxia steroid is given Eye diseases : Corticosteroids are used in a large number of inflammatory ocular diseases to prevent blindness. Skin diseases : Topical corticosteroids are widely employed and are highly effective in various skin diseases. Intestinal diseases : Ulcerative colitis, Crohn’s disease, coeliac disease like chronic inflammatory intestinal diseases with remissions and exacerbations. Corticoids are indi- 3. 9 4. . o 2 2 cated during acute exacerbation Cerebral edema due to tumours, tubercular meningitis, neurocysticercosis etc. Malignancies : Steroids are an essential component of combined chemotherapy of acute lymphatic leukaemia, Hodgkin's and other lymphomas, because of their marked lympholytic > 10. action. > 11, Others : Organ transplantation and skin allograft to prevent rejection, thyroid strome, septic shock, to test adrenal-pituitary axis function OQ Adverse effects of glucocorticoids are many, these are mainly on long term therapy : > 1. Cushing's habitus: characteristic appearance with rounded face, narrow mouth, supraciavicu- lar hump, obesity of trunk with relatively thin limbs. > 2. Fragile skin, purple striae-typically on thighs and lower abdomen, easy bruising, telangiectasis, hirsutism. Cutaneous atrophy occurs with topical use also,AURAS AND PROFESSIONAL EXAMINATION pOID re hk ee OOO wud vay w vv > > > @ i ANN, POI, thigh, SSRN S heeter ahs is nongpecitoy tent tabrnowta MAY lar OPpartunitoInfeo- YOOS WH Howe grate pathogens (CANA, at), SE WOU aN SUiRQHOAl MholsionE, eve odorant | HLS shublet Needing a alent perforation of ulders May o0dUh SSE HSA Hovotvang vevtadiae ant other Mat aongy bones, Compression rao: APRS OT VOPRADIRE ANT SOMANAOUS. ‘Raoture of long bones oan ooour & Postarar adoanaular SRIACT MAY develop, ASixeogMA s MAY GeraloN dn suseptible Individuals ater prolonged topical therapy, rower retardation | hy chien 3S Rawta adnoMalAas | Dae palate and other anomalies, SS Agomine Ssedands MAY aol 34. Stegesson of hypothakamoyvtutansadrenal (HPA) avis, i Group~ 8. Exon why? (sry Sve) 3x8 SB a) Ritsmaichs is used once in amonth In treatment of leprosy, ans Skene S adevnstent in leprosy patients al 600 mg dose in supervision once in a month REST SMe and Hered Srags bike dapsone and clofazimine ate given dally, This ls because ARSmpE AY MBNV on Nowy growing Nacteria(sprouter) and mycobacterium leprae ts a slow Sumy Dastang wah mortipieation tine of about 14 days, Thero is almost (9996) killing of nowly grdwig Proadactana an Sngle application and no need for daily application, Moe 2.85, RSMO is & HotOnt hanatic Mierasomal enzyme inducer. Daily application may induce nanate Sug Metaovising enzymes which may cause Metabolism of other antilaprotie drugs GED) locite is used prior fo thyroid surgery. Ass. @.c) ans aad Ans. SS8INS mABInN Lago!’ jostina (Solution of 5% fodine in 10% Potassium lodice) solution ts used prior to yma supe. RS USad PrAapeTaVe preparation of goitre batore thyroidectomy, BS SSNERIY ON fOr TO days just precading surgery. The aim is to makes the ot ®) RE MBKES HSS VASCULAT ANd Aasiar to Operate on (iH) prevent the penpheral conversion of T4 to TS. Dough ssoice itself will lower the thyroid status, it cannot be relied upon to altain euthyroldism uwhicn is done OY Use of carbimazole before starting iodide, Propranolol may be given additionally for rapid control of symptoms. Primaguine is used in treatment of vivax and falciparum malaria. The primary indication of primaquine is for radical cure of vivax malaria: 15 mg (children 0.25 ‘mg Rg) cally for 2 weeks is given with full curative dose of chloroquine (to cover the erythrocytic phase). In this dosage relapse will not occur as the hepatic stage (hypnozoites ) will be eradicated. in falciparum malana there is no exoerythrocytic cycle. In Falciparum malaria a single 45 mg Sose of prmaquine is given to kill the gametes and cut down transmission to mosquito after schizontocides. Trinexyphenidy! is used in treatment of drug induced extrapyramidal disorder. Anticholinergic drugs like trihexyphenidyl is used in drug induced parkinsonism. In drug in- duced parkinsonism there is cholinergic overactivity in nigrostriatal pathway in brain which is40 QUEST : A KEY TO UG PHARMACOLOGY responsible for parkinsonian effects. This drug have higher central : peripheral anticholinergic activity. They act by reducing unbalanced cholinergic activity in the striatum of Parkinson pa- tients. All anticholinergics produce 10-20% improvement in clinical features. Generally tremor ‘are benefited more than rigidity. Hypokinesia is least affected. Sialorrhoea is controlled by peripheral anticholinergic action. The overall efficacy is much lower than levodopa. These anticholinergic drugs are cheap and produces less side effects. Thay can be used in mild cases and when levodopa is contraindicated. They may be combined with levodopa in treatment regimen in an attempt to lower the dose of levodopa. Group-C @3. Write the mechanism of action of (any three) 3x3 Q3..) Penicillin is in the treatment of gram positive infection. ‘Ans. Penicilin is a beta lactum antibiotiotic. All beta-lactam antibiotics interfere with the synthesis of bacterial cell wall, The bacteria synthesizes UDP-N-acetylmuramic acid pentapeptide, called ‘Park pacleotide’ and UDP-N-acety! glucosamine. The peptidoglycan residues are linked together form- ing long strands and UDP is spit off. The final step is cleavage of the terminal D-alanine of the pentide chains by transpeptidases; the energy so released is utilized in establishment of cross linkages between pepide chains of the neighbouring strands. ‘¢ This cross linking provides stability and rigidity to the cell wall. The B-lactam antibiotics inhibit the transpeptidases so that cross linking (which maintains the close Knit structure of the cell wall) does not take place. These enzymes and related proteins constitute the penicilin binding proteins (PBPs) which have been located in the bacterial cell membrane. When susceptible bacteria divide in the presence of a f-lactam antibiotic cell wall deficient forms, are produced. Because the interior of the bacterium is hyperosmotic, the cell wall deficient forms swell and burst -»> bacterial lysis. + Gram 4ve organisms have thick cell wall and penicillin binding protein are very much abundant so highly sensitive to penicillin @3.b) Ciprofloxacin as antibacterial agent. ‘Ans: Ciprofloxacin is a fluoroquinolone group of antibiotic. The FQs inhibit the enzyme bacterial ONA gyrase, which nicks double-stranded DNA, introduces negative supercoils and then reseais the hicked ends. This is necessary to prevent excessive positive supercoiling of the strands when they separate to permit replication. * The DNA gyrase consists of two A and two B subunits: + The A subunit carries out nicking of DNA,whereas B subunit introduces negative supercoils and then A subunit reseals the strands. FOs bind to A subunit with high affinity and interfere with its strand cutting and resealing function. Recent evidence indicates that in gram-positive bacteria the ‘major target of FQ action is a similar enzyme topoisomerase IV which nicks and separates daughter DNA strands after DNA replication. Greater affinity for topoisomerase IV may confer higher potency against gram-positive bacteria. + The bactericidal action probably results from digestion of DNA by exonucleases whose production is signalled bythe damaged DNA. + In place of ONA gyrase or tope isomerase IV, the mammalian cells possess an enzyme topoisomerase Il that also removes positive supercoils which has very low affinity for FQs hence the low toxicity to host cells. Q3,c) Ketamin as anaesthetic agent. ‘Ans. Ketamine hydrochloride is a phencyclidine derivative used to induce dissociative anesthesia. Itis characterised by analgesia, immobility, amnesia with light sleep and feeling of dissociation fromMB.B.S 2ND PROFESSIONAL EXAMINATION 201911 ‘ones own body and the surroundings. The primary site of action is in the cortex and subcortical areas; not in the reticular activating system, Ketamine is used for trauma patients with very unstable, low blood pressure or for elderly patients. Respiration is not depressed, airway reflexes are maintained, muscie tone increases; limb movements occur and eyes may remain open Heart rate, cardiac outbut and BP are elevated due to sympathetic stimulation. ‘* Emergence delirum, hallucinations and involuntary movements occur in upto 50% pati patients during oer eat WV injection is not painful. Children tolerarate the drug better. + Ketamine has been used for operations in head and neck surgery, in in patients who have bleeding, and in asthmatics (relieves bronchospasm), in those who do not want to lose consciousness and for short operations. It is good for repeated usage particularly suitable for bum dressing. It is very useful in patients with hypotension for performing operation. . ss with diazepam, it has found use in angiographies, cardiac catheterization and trauma ‘+ {imay be dangerous for use in hypertensives, in ischaemic heart disease and in patients those with raised intracranial tension as it increases cerebral blood flow. @3.d) Escitalopram as antidepressive agent. Ans : Escitalopram is a selective serotonin reuptake inhibitor. It is the active & (+) enantiomer of ctalopram, effective at naif the dose with similar properties. Side effects are milder and safety is improved. + The SSRIS produces little or no sedation, does not interfere with cognitive and psychomotor function nor produced anticholinergic side effects. They are devoid of a adrenergic blocking action (postural hypotension does not occur) suitable for elderly patients. They have practically no seizure precipitating propensity and do net inhibit cardiac conduction no Q-T prolongation- overdose arrhythmias are not a problem. The SSAI'S selectively inhibit membrane associated serotonin transporter at synaptic cleft. As a result there is increased concentration of serotonin at cleft and that produces antidepression action. Group-D Q4. Write short notes on any four of the followin. ax4 4. a) Pre-anaesthetic medication (name of the drugs used with reasons) Ans : Different drugs are used the night before the day of anaesthesia for different purposes. 1 (1) To relief of anxiety (Benzodiazepine) like + (2) Diazepam (5-10 mg) oral is given. It is a popular drug because it produces tranquility and smoothens induction. There is loss of recall of peri operative events. They counteract CNS toxicity of local anaesthetics.And are being used with fentanyl for a variety of minor surgical and endoscopic procedures. + Lorazepam(2 mg oral /0.05 mg im) is used as alternative to diazepam. + Midazolam is also good amnesic with potent and short lasting benzodiazepine. ‘+ (®) Antinistaminic like promethazine(50 mg im) is @ good sedative antiemetic and anti cholin- ergic drug.tt causes little respiratory depression except in children. * (©) Opioids like morphine(10 mg )/pethidine(75 mg) im + allay anxiety and apprehension of the operation, + produces pre and post operative analgesia, + smoothen induction + reduces the dose of anaesthetic + supplement poor analgesics like thiopentone,halothane or weak anaesthetic(N20). + post operative restlessness is also reduced.12 QUEST : A KEY TO UG PHARMACOLOGY Use of opioids is now mostly restricted to control peri operative pain only because of opioid causes respiratory depression, fallin BP, precipitation of asthma and delayed recovery. Vomiting, consti- pation urinary retention, biliary spasm etc. are also unwanted adverse effects of opioids. ‘+ (d) Anticholinergies like atropine (0.6 mg I.m) oF glycopyrolate(0.2-0.9 mg i.m) are used primarily to reduce salivary and bronchial secretions. This agents are mainly used when irritant anaesthetic like ether is used. Halothane may cause cardiac arrhythmia and bradycardia during anaesthesia, Anticholinergic drugs prevent vagal bradycardia and laryngospasm. Glycopyrolate is a quarternary ammonium compound which does not cross blood brain barrier and has no central effects and preferred over atropine. + (@) H2 BLOCKER /proton pump inhibitor Ranitidine, famotidine or omeprazole are used to decrease gastric acidity which also faclitates gastric emptying so that gastric regurgitation and aspiration pneumonia can be prevented. + (9 Antiemetic like metoclopramide (10 mg im), domperidone or ondansetron(4-8 mg i.v) has been found highly effective in reducing incidence of post operative nausea anc vomiting. 04. b) Insulin resistance (definition, Treatment) 12 (IR) is considered as a pathological condition in which cells fail to respond rormaly to the hormone insulin. Conventionally, when daily requirement of insulin is more than 200 units itis called insulin resistance. When the body produces insulin under conditions of insulin fesistanca, the cells are resistant to the insulin and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level. This often remains undetected and can contribute to the development of type 2 diabetes, obesity or latent autoimmune diabetes of adults Treatment : The primary treatment for insulin resistance is exercise and weight loss. Research shows that a low-carbohydrate diet may help. Both metformin and thiazolidinediones improve insulin resistance, but are approved therapies only for type 2 diabetes, not for insulin resistance. By {growth hormone replacement therapy may be associated with increased insulin Ans : Insulin resistanc contrast, resistance + Metformin has become one of the more commonly prescribed medications for insulin resistance. ‘Some types of polyunsaturated fatty acids (omega-3) may moderate the progression of insulin resistance into type 2 diabetes, however, omega-3 fatty acids appear to have limited ability to se insulin resistance, and they cease to be efficacious once type 2 diabetes is established. rever Q4..c) Tamoxifen (use with reasons) ‘Ans. Tamoxifen potent estrogen antagonist in breast carcinoma cells, blood vessels and at some peripheral sites, but as partial agonist in uterus, bone, liver and pituitary. Inhibition of human breast tancer cell and hot flushes reflect antiestrogenic action while the weak estrogen agonistic action manifests as stimulation of endometrial proliferation lowering of Gn and prolactin levels postmenopausal women as well as improvement in their bone density. O Uses’: } 4. Breast cancer treatment and prevention : Tamoxifen is the standard hormonal treat- ment of breast cancer in both pre- and post menopausal women. Response rate is better in estrogen receptor (+) ve than ER receptor (-) ve women. It has been approved for primary prophylaxis of breast cancer in high risk with ER(+)ve women This is an anti-estrogenic effect. Hot flushes-Reduces FSH and LH level by action pitutary-estrogenic effects. Osteoporos-It prevents osteoporosis in post menopausal women-here acts as a estrogenic agonist. It acts by inhibiting osteoclasts, it prevents osteoporosis. |. Infertilty-Tamoxifen is used to treat infertility in women with anovulatory disorders. May be used as an alternative to clomiphene. Tamoxifen improves fertility in males with infertility vv en vM.B.BS 2ND PROFESSIONAL EXAMINATION 2019 13 by disinhibiting the hypothalamic-pituitary-gonadal axis (HPG axis) via ER antago- nism and thereby increasing the secretion of luteinizing hormone (LH) and_follicle- stimulating hormone (FSH) and increasing testicular testosterone production > 5. Gynecomastia : Tamoxifen is used to prevent or treat gynecomastia by preventing estro- genic action, Q4, d) Aminoglycoside antibiotics (Example with common characteristics) Ans. Example of aminoglycosides are + . A. Systemic use : Streptomycin, Amikacin,Gentamicin, Sisomicin, Kanamycin, Netilmicin, Tobramycin etc. B. Topical use : Neomycin, Framycetin Q Common properties of aminoglycoside antibiotics are > > vvyvvy > 1. All are used as sulfate salts, which are highly water soluble. These solutions are stable for months. 2, They polarized in solution -so are not absorbed orally, distribute only extracellularly; do not penetrate blood brain barrier or CSF. Alll are excreted unchanged in urine by glomerular filtration and not absorbed. Alll are bactericidal and more active at alkaline pH. They act by interferring with bacterial protein synthesis. All are active primarily against aerobic gram negative bacilli and do not inhibit anaerobes. There is only partial cross resistance among them, They have relatively narrow margin of safety. 9. All exhibit ototoxicity and nephrotoxicity. Q4. e) Bezodiazepines (Example, uses) Ans. Examples of benzodiazepine are-Chlordiazepoxide, Diazepam, Flurazepam, Nitrazepam, Alprazolam, Temazepam, Triazolam, Oxazepam, Lorazepam, Alprazolam, Lorazepam, Clonazepam, Clobazam. ete. Uses of benzodiazepines : > 1. As hypnotic-zolpidem, zopiclone are used, > 2. As anxiolytic and for day-time sedation-alprazolam. > 3. As anticonvulsant, especially emergency control of status epilepticus, febrile convulsions, tetanus, etc. > 4, As centrally acting muscle relaxant-diazepam is used. . For preanaesthetic medication, i.v. anaesthesia and conscious sedation-diazepam, midazolam is used. > 6. Before ECT, electrical cardioversion of arrhythmias, cardiac catheterization, endoscopies, in obstetrics and many minor procedures diazepam i.v.is preferred. Alcohol withdrawal in dependent subjects. . Along with analgesics, NSAIDs, spasmolytics, antiulcer and many other drugs. v vv @NTHE WEST BENGAL UNIVERSITY OF HEALTH SCIENCES M.B.B.S. 2nd PROFESSIONAL EXAMINATION SUBJECT : PHARMACOLOGY 2018 Paper-1 (Regular) Group-A Q1.a) Enumerate the drugs used in treatment of bronchial asthma. Mention the routes of administration of drugs used in treatment of acute severe attack of bronchial asthma stating the reasons of using every drug. 34344 Ans. There are various groups of drugs used treatment of bronchial asthma. These are as follows : on . a2 a. . . . Bronchodilators. (a) Bo sympathomimetics : + short acting-salbutamol, Levosalbutamol, Terbutaline + long acting-Bambuterol, Salmeterol, Formeterol, Arformoterol (b) Methylxanthines-Theophylline, Aminophylline,Choline theophylinate, Doxophylline, Acebrophyline (6) Anticholinergics : Ipratropium bromide, Tiotropium Bromide, Aclidinium, Glycopyrrolate Mast cell stabilizers | Sodium cromoglycate, Ketotifen | Leukotriene antagonist : Montelukast, Zafirlukast Corticosteroids A. Systemic : Hydrocortisone, Prednisolone, methyl prednisolone B. Inhalational : beclomethasone, Budesonide, Fluticasone, Flunisolide, Ciclosonide | Biologics: Anti IgE antibody-Omalizumab ‘Acute severe asthma isa lfe threatening condition and should be treated vigorously. In this condition patients are unable to eat or drink properly. ‘The main routes of drug administration in this condition are inhalational and intravenous route so that | the drugs should reach the site of action promplly. | Inhalational routes- drugs used through this route are | (a) £, sympathomimetics like salbutamol, terbutaline, salmeterol, formeterol etc. These drugs are | Used through metered dose inhelars or nebulisation as aerosol and reach in the bronchioles directly without systemic effect. No first pass metabolism occur. Very small amount of drug is required and quick onset of action. (b) Anticholinergios like ipratropium or tritopium bromibe is used. Theses drugs are also given through | metered dose inhelars or nebulisation. They reach the target bronchioles directly and due to their anticholinergic effect dilates bronchioles, decreases production of mucous and helps in muco- ciliary clearance. (6) Inhalational steroids : Beclomethasone, Budesonide, Fluticasone, Flunisolide, Ciclosonide etc are used via metered dose inhelar or nebulisation. These drugs do not dilates the bronchioles but they increases the effectiveness of 2; sympathomimetics also releaves mucosal edema, prevent hyper-reactiveness of bronchioles, prevent inflammation of bronchioles, pre . , prevent fi degranulation and antigen-antibody reactions. " ther mast ok 14M.B.B.S 2ND PROFESSIONAL EXAMINATION 2018 15 I" the condition of patient does not improve then intravenous drug therapy should be instituted. * 9 _[nlection Aminophyiline 250-500 mg in 5% dextrose is to be infused slowly. Alternatively injection Theophylline 100 mg slow 1.V is to be given. These group of drugs will reach the lungs 100% bioavailability promptly and will dilate the bronchioles by relaxing bronchial smooth mascies. * 1 (navenous steroids ke injection Hydrocortisone 200 mg thrice daily is to bo given, This drug wilfeach the lungs through systemic circulation when smaller bronchioles are pluggea by mucous and inhalational steroids are unable to reach at that site of action, These injectable steroids act in {he same way as of inhalational steroids with systemic adverse effects on repeated administration LV route is 100% bioavailability These drug therapy will be concomitant with oxygen inhalation to maintain the O2 level in blood (Q1.b) Discuss biotranstormation of drugs. State chemical reactions with ‘examples which ure involved in drug biotransformation. Give examples of active drug generated by biotranstormation in ‘human body. 34344 Ans. Biotranstormations are chemical alteration of the drug in our body to make lipid soluble drugs (non- Streptomycin, amikacin are little biotransformed and excreted as such. The aim of biotransformation is to protect body from ingested toxins Fhe primary site of biotransformation is liver, others are kidneys, intestine, lungs, plasma. Biotransformation may lead to the following three pattern : > 1. Inactivation of active drugs-most common type e.g-phenobarbitone to hydroxyphenobarbitone, Propanolol to 4 hydroxypropanolol * 2, Aotive drugs to active metabolites-codeine to morphine, diazepam to oxazepam, amitryptline to nortryptiline etc. ® 3. Inactive drugs (prodrug) to active drugs-levodopa —> dopamine, prednisone —> prednisolone, Enalapril > enalaprilat OQ Chemical reactions involved in biotranstormations : The Chemical reactions involved in biotransformations are classified into : BIOTRANSFORMATION Non Synthetic reaction PHASE-1 Synthetic reaction PHASE-2 Oxidation) (Reduction) (hydrolysis) (@clazation] Conjugation 9 Q _Phase-1 reaction : a functional group is generated and the metabolites may be acive or inactive and may be polar or nonpolar. G__Phase-2 reactions : an endogenous radical is conjugated with the drugs. Metabolites are mostly inactive and polar compounds.if the metabolites in phase-1 reaction is nonpolar compound then itis attached with a endogenous compounds such as glucoronic acid, sulfuric acid, acetic acid,amino acid. After conjugation these compounds became polar and excreted in urine. (deeyclazation)16 a a2. QUEST : A KEY TO UG PHARMACOLOGY Active drugs that are generated by biotransformation examples are : [ye Thactive drugs Aotive drugs 1 Levodopa Dopamine 2 prednisone Prednisolone 3 Enalapril Enalapritat 4 Acyclovir Acyclovirtriphosphate 5 Sulfasalazine 5 aminosalicylic acid 6 Bacampcillin Ampicillin 7 Proguanil Cycloguanil 8 Dipivefrine Epinephrine Group-B Explain why(any three) Q2. a) Tamsulosin is used in benign hypertrophy of prostate. Ans. “Tamsulosin is a relatively uroselective a1/A/a1D blockers. “The affintyof tamsulosin to ccta:a1b affinity of tamsulosin is 1:7 to 1: 38 subtype are predominant in bladder base and prostate. a” are found in blood vessels and CNS. $5, Tamsulosin does not cause significant change of BP and hear rate, No increase in adverse cardiovascular events Postural hypotension is less frequent. Itrelaxes smooth muscles of bladder neck, decongestion of enlarged prostate and helps in voiding. 2. b) Telmisartan is used in hypertension. Ans. 2.0) Ans. Telmisartan is a angiotensin receptor (AT1) blocker. Angiotensin are peptides present in our blood and are potent vasoconstrictor. telmisartan is 10,000 times more selective in blocking AT1 receptors than AT2. itis used orally in a dose of 20-80 mg daily. ‘The drug is well tolerated and minimun adverse effects. “Therapeutic doses causes fallin BP in hypertensive patients without change in heart rate and cardiac reflexes. No significant change in plasma lipid profile and carbohydrate tolerance. They are also used to prevent cardiac remodelling, They are also used to prevent hypertensive cardiomyopathy, diabetic nephropathy. Hypotension may occur but rarely. Cough and angioedema is not a problem with telmisartan, ‘Thiazide diuretics may be prescribed in diabetes insipidus. Thiazides paradoxically exert anti diuretic effects in DI. Hydrochlorthiazides 25-50 mg TDS or equivalent dose of a longer acting acting agents may be used for this purposes. It convenient and reduces polyuria to some extent. aesM.B.B.S 2ND PROFESSIONAL EXAMINATION 2018 17 The exact mechanism of action is not known. It is effective both renal and pitutary origin DI. -Thiazides induces a state of sustained electrolyte depletion and extracellular fluid volume depletion, so glomerular filtrate is more completely reabsorbed in proximal tubules. ~ Because of reduced salt reabsorption in cortical diluting segment a smaller volume of less dilute urine reach Na+ is presented in collecting duct-this same may pass out. - Thiazides reduces GFR and thus smaller filtrate, 2. d) Ondansetron is drug of choice in chemotherapy induced emesis. Ans. | Ans. | a3, Ondansetron is a SHT3 receptor blocker. It is used during or before chemotherapy to prevent emesis becaue of the fact that : Vorniting occur due to stimulation of vomiting centre situated in the medulla oblongata which receives afferents from CTZ (chemoreceptor Tigger Zone) and NTS (nucleus Tractus solitarius). ‘The CTZ receives afferent impulses from GIT and directly stimulated by blood borne chemicals,drugs, mediators, hormones and toxins etc as CTZ is outside the Blood Brain Barrier(BBB). During chemotherapy large number of calls are destroyed and releases huge amount of mediators mainly SHT3 that stimulate gut receptors and these impulses via vagus afferent reaches to NTS and CTZ. CTZ also directly stimulated by these released mediators and toxins. Ondansetron blocks emetogenic impulses to the CTZ and NTS-both in central relay as well as at the peripheri. So input to the vomiting centre is blocked and no emesis. ) Vitamin K is used in warfarin toxicity. Vitamin k is a fat soluble vitamin. Itis used in warfarin toxicity to prevent bleeding. The mechanism by which it acts is as follows : Warfarin is a competitive antagonist of vit-K. Warfarin act by interfering synthesis of vit-k dependent clotting factors I, Vil, IX, X In the liver. In warfarin toxicity there is depletion of clotting factors in dose dependent manner as warfarin inhibits the enzyme vit-k epoxide reductase and interferes with regeneration of active hydroquinone form of vit-k. Active hydroquinone form of vit-k act as a co-actor for the enzyme y glutamyl carboxylase that is responsible for y carboxylation of factors Il, Vil, IX, X-essential for activation of these factors for coagulation of blood. So Vik is used to prevent warfarin induced toxicity. Group-¢ Write mechanism of action of (any three) Q3. a) Pyrodostigmine in myasthenia gravis Ans. Pyrostigmine is a reversible anticholiesterase, protects acetylcholine from hydrolysis at neuromuscular junction. It produces cholinergic effect in vivo and potentiates Ach both in vivo and vitro. myasthenia Gravis is an autoimmune disorder due to development of autoantibodies directed to nicotinic receptors at the muscle end plate —> reduction of free Nm receptors and structural damage of the neuromuscular junction —> weakness and easy fatigability on repeated activity with recovery after rest. Anticholiesterase compounds like Pyrodostigmine prevents degradation of Acetyl choline at motor18 QUEST: A KEY TO UG PHARMACOLOGY ‘and plate where concentration of Ach is raised at many fold which act on Nm receptors for a prolonged periods, though the number of Nm receptors are less. By this way there is improvernent of muscle power, + Moreover, pyridostigmine is a longer acting drug than neostigmine, so frequent dosing is not required + Anticholiesterases like neostigmine or pyridostigmine do not affect release of aceyl choline or it has no direct action on Nm receptors. 03. b) Adrenaline in epistaxis. ‘Ans. Adrenaline is a prototype sympathomimetic drug. It is naturally secreted from adrenal medulla and act on at, a2, 61, B2 receptors. + Epistaxis is bleeding from nasal mucous membrane. To stop bleeding we have to constrict the supplying blood vessels in that area of nose(Little's area) + Adrenaline 1:10,000 dilution socked in cotton applied locally effectively control the bleeding from Little's area. Adrenaline mainly acts on vasoconstrictor «1 receptors as well as extrajunctional «2 receptors thereby potent vasoconstriction occur and bleeding stops. Q3..c) Fruesemide in treatment of acute left ventricular failure. Ans. Intravenous administration of furosemide is used in acute left ventricular failure. V furosemide causes increased synthesis and release of vasodilatory prostaglandin —> increases renal blood flow —> diuresis, + It also causes venodilatation thereby preload is also reduced. This result in shift of blood from pulmonary to systemic circuit > decreased left ventricular filing pressure. + Subsequently, decreased in blood volume and venous return is responsible for the improvement, Q3. 4) Nitrates in angina. ‘Ans. Organic nitrates are rapidly denitrated enzymatically in the smooth muscle cell to release the reactive {ree radical nitric oxide(NO) which activates cytosolic guanyl cyclase —> increase CGMP —> causes dephosphorylation of myosin lite chain kinase —> interfere with activation of myosin — fails to interact with actin to cause contraction —> relaxation occur. 4 (1) Pre load reduction : Veins express greater amount of enzymes and generate No from Glyceryl Trinitrates (GTN) —> venodilatation —> capacitance vessels are dilated —> pulling of blood in inferior vena cava —> decreased venous retum to heart —> reduction of pre load —> less wall tension of ventricular muscles —> less 02 demand — relief from angina. + (2) Afterload reduction : ritrates dilate arterioles to some extent. Dilatation of arteries cause less impedance to ventrile for ejection of blood —> decreased after load —> decrease work by ventricular muscles’ less 02 demand’ relief from angina. ‘+ @) Redistribution of coronary blood flow : nitrates dilates angiographycally visible larger coronary 4 arteries and there is favorable redistribution of blood flow to ischemic region. In ischemic region there is already ischemia induced vasodilatation of small vessels and dilatation of large coronary arteries by nitrates causes increase flow of blood in sub-endocardial ischemic zones while in non ischemic zones small blood vessels do not dilates as they maintain their tones. + The relaxant effect of larger coronary arteties is the principal action by counteracting coronary spasm in Varient angina. In stable angina reduced work done by myocardium is the principal action though increased blood supply to ischemic region may contribute. Thus Exercise tolerance in angina patients may improve,M.B.B.S 2ND PROFESSIONAL EXAMINATION 2018 19 Group-D 4. Write short notes on any four of the followings 4x3 @4. a) First pass effect (definition, significance, example) Ans. Definition : Refers to metabolism of a drug during its passage from the eite of absorption into the systemic circulation. Significance : First pass metabolism affects bioavailability. Orally administered drugs are mostly metabolised in liver and to some extent in gut wall and fungs. Drugs with high first pase metabolism oral route are avoided. Highly lipid soluble drugs are given through sublingual route. Lidocaine, Hydrocortisone, Testosterone are given through parenteral route to avoid first pass metabolism. Propanolol, verapamil, salbutamol, morphine etc. are given in sufficient high doses in oral route to compensate the first pass metabolism. 4. b) Physiological antagonism (with example) Ans. Two drugs act on different receptors or different mechanisms but have opposite effect on the same Physiological function and /or pharmacological effect in opposite direction. So that action of one drug will be neutralised by applying other drug. * Examples are : insulin and glucagon on blood sugar level is the example of physiological or functional antagonism. + Histamine and adrenaline on bronchial smooth muscles. Q4. c) Low moleclar weight heparin Ans. Heparin with molecular weight between 3000-7000 are called low molecular weight heparin(LMWH). LMWH is preferred over conventional heparin in treatment and prophylaxis of blood clotting. + Pharmacodynamic effect : LMWHS have a different coagulation profile, selectively inhibit factor Xa with little effect on Ila, They act by inducing conformationall change in AT Ill and thrombin. LMWHs have smaller effect on coagulation profile, Little effect on antiplatelet action, thrombocytopenia is very rare. So, there is less chance of spontaneous bleeding. Pharmacokinetic advantages : > 1) better subcutaneous bicavallabity 90% compaired to unfractionated heparin(30%). Variability in response is minimized. > 2) Longer and more consistent monoexponential t1/2.Once daily subcutaneous injection is sufficient. > 3) Since aPTT and clotting time is not prolonged-laboratory monitoring is not required. G Indications : {i) prophylaxis and treatment of Deep venous thrombosis. + (ii) Pulmonary embolism. + (ili)Unstable angina (iv) Iv) to maintain patency of canula or shunt in patients taking ILV therapy.