How to Use This Book a sof questions are asked in the professional examinations of different universities. This, aeexis alvided in many sections to solve these questions. Several sections are given in tabular Poms or quick evision atthe last hour. Tis chapter describes’ what to writein different questions?” and most importantly how to use this book?” ‘SECTION 1 — IMPORTANT DRUG CLASSIFICATION What is expected from a student? This is usually a part of a long question and therefore important drug classifications have been given at the end of theory for a quick revision just before the exam. SECTION 2—EXPLAIN WHY TYPE QUESTIONS. several type: What is expected from a student? The question is self-explanatory and the student need to explain the reasons for the given statement. If the reasons are given in pointwise manner, it seems more appropriate and can fetch you more marks with the same content. Flow charts or simple diagrams also help in getting better marks. How to use this book? The section of ‘expain why” questions in every chapter details the answers of the given Questions. These have been answered in points with several flow charts and diagrams to facilitate understanding, The student can reproduce the answers as such in the examinations. — ‘SECTION 3— RATIONALE QUESTIONS vn Is expected from a student? one of questions, mostly the rationale of using a drug (or group of drugs) in a particular enston \s asked. This is the alternate way of asking the “explain why” question, e.9. t cue rationale of using tropicamide in fundocscopy. howe, explain why tropicamide is used in fundoscopy? Nowtousethis book? sey ; dineatusenne is dedicated to this type of questions. This section explains the reasons for the nana of@ particular drug (or group or combination) in that particular condition, These have st it can red in points with several flow charts and diagrams to facilitate understanding. The /eproduce the answers as such in the examinations.- — Le SECTION 4—SHORT NOTES ‘What is expected froma student? Mosty this type of question i asked about a drug of rug 9TOUP.€9- Q. Write a short note on cardioselective beta blockers: or Write a short note on metoprolol. Foe ral be ble te brlefy describe the salient points retest, cy asuaten, rr ead cce mechanism of action uses, averse eletsand anyother ‘special feature ike Interactions, etc) of the given drug. How tose this Book? aor inte book given ina tabular orm with se genera RTS oe to Jepot te drug, mechanism of action, uses and 20ers effects. The section also mentions grown of nc pont about «rug tobe writen cet, Tne for quick Separately he spec Prep examination Pease Do Not row the ae in We cxaminaion The revision befor make Separate headings rather than making 21able: patho seweral short notes can be answered fom one column 0 Use This Book nd aripiprazole. é ses | | hotics, clozapine olanzapine risperidone a ips rt note om each ofthese drugs and specific points in scion St [Pharmacokinetics] Wechanlam of H 3 3 U ai ii au t eee gb 7 é F & PP HELE : ale 3imped Parmactogy:ANatong A for EEE 1, write ashor note on Cosapine. - tial (Common point. Imraan gras with weak receptor blocking pote Prorecotineti: rae conor poi. Mechanism of ton xc minor effect by blocking D, receptors (Common point Schizophrenia (Common porn 2 spice! antipsychotics are schzophrena (Common porn highly effective at controling negative symptoms of averse eect: Maynor syodrme (Common pots) wogre san yperipere = in resetnce «Eyam symptoms ess hequentthantypial antépychotcs) (Common point) 1 SSatee Common pa 1 Saxon (Common port) 1 Coxapme cass esti Spec paints about clzopine) Sfrmuloeros © yperatvation tee Write a shor note on Olanzapine. re imroduction: Newer antipsychotic rugs with weak D, receptor blocking potential (Common point Pharmacokinetics: Iris effectwe orally (Common point (Mechanism of action: Major actions SH, antagonistic minor effect by blocking D, receptors (Common point). Uses: ena (Common point * Atypical antipsychotics are highly effective at controlling negative symptoms of Schizophrenia (Common point) 1 Mania (Specific point bout olanzapine) * Bipolar sisorder (Specific point about olanzapine). Adverse effects: ‘+ Upodystrophy syndrome (Common points) ~ Weight gain = Hyperglycemia re How ta Use This Book — Hyperlipidemia Insulin resistance + Extrapyramidal symptoms [less frequent than typical antiosychotic) (Common points) 1 setzures (Common ports 1 Sedation (Common points Write a short note on Risperidone, Introduction: Newer antipsychotic drugs with weak D, receptor blocking potential (Camman point Pharmacokinetics: eis effective orally (Common point, Risperidone i also available as long acting injectable (LAD preparation (Specific point about risperidone). [Mechanism of action: [Major action is HT, antagonistic minor effect by blocking D, receptors (Common point, Uses: + Schizophrenia (Common point) + Atypical antipsychotics are highly effective at controling negative symptoms of ‘schizophrenia (Common point. it can be used for un-cooperative patients because is avallable as LAI preparation (Specific point about risperidone), Adverse effects: * Lipodystrophy syndrome (Common points) = Weight gain ~ Hyperalyeemia ~ Hyperlipidemia = Insulin resistance + Extrapyramidal symptoms (les frequent than typical antipsychotics) (Common points) + Seizures (Common points) +. Sedation (Common points) Write a short note on Aripiprazole, Introduction: "Newer antipsychotic drugs with weak D, receptor blocking potential (Common point) Pharmacokinetics: {tis effective orally (Common point. Aripiprazole is very long-acting antipsychotic drug (Specific point about arpirazole). ‘Mechanism of action: Ablorazl scaled dopamine serotonin stable (Speci points bout arporazl + D, partial agonist + SHT, partial agonist + SH. agonists, Uses: * Schizophrenia (Common point) * Atypical antipsychotics are highly effective at controlling negative symptoms of Schizophrenia (Common point)eter shoud be abe to an Te sade emp of cial condition drug isused fused) JTRS eetrap teins second ne orarely ued fr not used inthat subtype offical conaoon. 5. Jot te answer by giving £950". Le ae sn fst me. what the advantage of this drug over ether drugs used In that conciton ihe arog isnot frst line, why other drug is ist line means whe is the limitation ofthe ven drug as compared to other crags Means the stucent shouldbe abe to compare the given drug with other options available forthe sane aatcison and explain the reasons forthe use of particular drug ina given clinical condition How to use this book? “This section inthe book s given in tabular form. Please Do Not Draw the Tablein the examination. IRimentions the therapeute status ofthe given drug in that particular condition with other drugs Usedin that condition, The final column compares the salient features of the different drugs used in ter particular concen. Agatone table can be used to answer therapeutic stan of mary ‘drug infact all enportant drugs used in that particular condition) ‘Therapeutic status | Other drugs used for same condition Relative comparison with other ‘drugs. eee maemo a rome” [ecccmesee|* Saas a leet iene [2 Beta-biockers |» DOC for prophy- | blockers: {Propanolol) in axis of angna. |" Ranolazine Sore. Seana | ateo > Nitrates: Nivoalyerine andisos0r- de dntrato are given sublingual, for acute atack of angina. Thess fre vory fast acting rugs and are ‘sefuln both types of angina: cas ‘al and variant. Nitrates can also be given for ‘prophylaxis of angina by oral oF ‘wanaderma ule Major intations are low oral bio= availablity (veto high frst 9955 ‘metabolgm) and development of |_tlranc on ong ter ue Cont ow to Use Thi Book cone i ‘awe ot net 5 Propanolol in| Containdiated | rman angina ealcism chan: | Third tne drugs for] Sal ickere fn prophann of ane Shana poctore| gina ator ne ba ockers ERanciazine 19 Sng peters | phylens a second ee ort tine rugs. forsame | Other drugs used aes ‘condition “These an also cause hypotansion | ‘ren can be We trestaning i at aking sider or erecta Spstuncton \ + Beta blockers: These are fete ‘igre ophylane chrome an | na. Thre ae he only drugs that Gan decroase mortality n weer | hear disease, However tee ae | 280s cet vasospasm and ets | Blockers may aggravate coronary \avoconstclon oy ntororing wh | | emaciated vasoaiaton Ut, {ine of blockers include risk of bradyeardia, hypotension. pte | ‘cause they can Slay the recovery | from hypoatycemia ttazom ana long-acting | HPs tke amioapine can be used for prochyiane of acca! ae well ‘25 varant angina. However, these {0 not decrease mortaity whereas | Short-acting OHPs ike nifedipine | | Seige ncease meaty se torenex tacnyearaat Ranolarna Ris 9 naw drag ta | acts by blocking a Na" channel {carrying funny current. |) and | metabole modulation (aril fty {20 oxidation inher is ust | “Ate nde | ="Aavantage of ranolazine assings macs 1p Aid Yor Exams Sec ceaemucien cin = these question, prmmncmna te t omic Mos tyewreat Seppe con. cots een eda ese arin a aaa irre ntactof angina pectoris Other drugs used for angina ot en ona womens ois mes oe eee ome Donec ering arp ard oe pam sofa Sicues Mitacein somali aetna ee tar tolerance on long-term use. These can also cause hypotension which can Seren enengmce nec th ane pe oem pce ere Me et nas as ncaa tents ts pina one one erecta cri ina cr eres mere era ae ea ee heed Recor meena ki em eree oe euostes av aapinars ea earn eee omen ere eee aeons See eee are agent es Scrat cee prer ence cn ce aero hen pea Sie eer teen me ante Cera bes sara oees ener Sees eo te wa et ee ae vee daet Saree Rear et acm linda stir cnet ion im caroeyerd Se ile Sate hoarse Fare ae as rae eth enti Sane heh acetal eee ae ae ene abeaky clean pr oe area eae agree Silaererad erent aeeeaer 2. ote rape sats brs baces manga pecs, fee eee gf cae wep cen gn, howe hte ae cae ound oe Cher ed a ost aes 1 SS scl ao Set cer etn gf propyl rican Tee ae theo than deen mati nscsorc eee ke en inva angi tt oe voope saca nea e areca \eocnsticon by wersing wit feed nea era aN include risk of bradycardia, hypotension, ‘precipitation of asthma and CHF. These should Deawidein den ont ce Rec Tes shou 3. ow to Use This Book Nitroglycerine and Hrosorbide dinitrate ate given sublingually for acute attack of angina These are very fast-acting drugs and are useful in both types oF angina elec and variant. Nitrates can also be given for prophylaxis of snains by otal oe waren) Foute. Major limitations ae lw orl bioavaiabity hue to hgh fet ass metaboncen oe evelopment of tolerance on long-term use. Theve ean also cause hypotension which eee be life-threatening in patient raking sidenafil for erectile dystunceom, Calum channel blockers ike verapamil ditiazer and long-acting Ons ike amlodipine «an be used for prophylaxis of classical as well as variant angina However these ae nee decrease mortality whereas short acting OHPs ike nifedipine can actually inesemse sory ue to reflex tachycardia. RRanolazine sa new drug that acts by blocking a Na” channel (carying funny currents) and ‘metabolic modulation (partial fatty acid oxidation inhibitor It suseful only for poston fof angina. Advantage of ranolazine as compared to other ant anginal daisy that hag ‘no effect on BP (most other ant-anginal drugs can cause hypotension) and heart rte aed ‘an be safely used with drugs for erectile dysfunction lke sldenafl, Majer bentation Fisk for development of OT prolongation in ECG leading to torsades de pontes ‘Write therapeutic status of calclum channel blockers in angina pectoris. ‘Ans. Calcium channel blockers ae third line drugs for prophylaws ef angina afer nitrates and coon Cine ted or asia pcos nde ote 1 Sta oct 1 Rone Calm chant lohan ka raps az andong acing HPs ke smione Cine ed orpropyics of can wes ara sgn Sento ee crease orally whern Shoractng OHDste nledpne ooacann ee Guerorehertecyeasie Beta lockers a stn dso propnanisof enc angina Treat ny gs thtcandecrense marty nichemic hear eee Mower nese tenons Invafant angina ast auc ovtorus and etniocesrey sega ee visoonscton by inrtering wth Br tedted voce Unie eB oe, nde so tadyeathypotron peptone dC Tes soe avoiedindabetpatensonease they cn dota eee tos ea Niroplycerine an sosorbide dinitrate ae ger savigual i ak at angina These are very fseacng ug and are etlinbamuene er cnees een 2nd vain Rte Can abo be en fr pops of ong Oy al arson ‘cute Major itatons re ow ol Bonvaany luc otighiat pore sy devsopmentattkrance onions tam are Texeeansociec toten ae belie treatning na patent king seat rect operon Ranolacins aw cute arb) Bocas canl anos curen\and Imetabolc modulation gut ty sasonataninnonon Kaeo aren fangs vantage of anounne compu cher onan ears nolo hint ater antag dag cancane yore) sncea a Can be safety ued wih args for ele duncion Meas Maree en ‘kt delopment of prongatonm cleadagte onsee eaeEE simpnea Praracotorawenne AE ranotasine in 2008 bg rermvans of angina pectors 25 Cot wen terpeaitt Tews of" rata leaemieinel a ‘hres ea orange 1 ec loka ina funny caret) and = Cot cane ear acsbytackng aN" channel AY u anew rag at tion inhibitor) ttis useful only for prophylaxis, en ara 2S Stat dg at gna Acvortage of ranclacine Sos cn couse hypotension) and hear rate and Seeman en most a 3 on Oke dena. Major tiation is an be safety use wen 09> gtion in ECG leading to torsades de pointes Fe eapar sr anon acing DH elope =m saa Horse at can be wes fs proper anot-actng OMPs he nfedipine canactualyinerease moray ences "wecccmeona Seer gy rophvnsolcoicaga Teeth ny de cher dee However these are contig tac can decrease ovwlijue to vasospasm and beta-blockers may aggravate coronary madre variation intatons of Bloc i sion, precipitation of asthma and CHF. These should are acy hyten, A Sere teertcan ty ean cy rene em esr, aoe a eds aiteate are ger sublingual for acute tad Mr ta rgnandre stain bo ype of ongne ssa a ee a or prophyon of angina by or of Worsderma ae ee acaraapury deta igh passerby ahd oe eee ase Thee conto cae hypotension WHEN an Cr rica ain teal for eectiedhSurcon SECTION 6—DRUG TREATMENT cond or third line drug to since: in vena angina 2 What is expected from a student? The student is expected to write the: + Therapeutic objectives for the management ofthe given clinical conditions + Thedrugs used to obtain the above objectives + Dose ofthe major drugs (Firs line drugs) forthe above conditions. How touse this book? Tis section describes the therapeutic objectives forthe given clinical condition along with drugs and doses used for obtaining the same. This also given in the tabula form. Please 00 Not Draw the Tie inthe examination, How to Use This Book example _— varondiien | Trerepewtc objective | Grup weabment | Tagermen, (+ Temclined 1 Hygena img |= Seed ‘moses, | eeure ‘tone 9 ‘a day onocan Seer 2. Emaar Sig ral once nba deed a |. Atlxine Sma ort + ‘Aretves to ont * + Formodarata (1) + (2) fay cough wh | ACE canoes ‘This table can be used for answering the different questions on drug treatment of hypetension. a. ans. a2. ‘Ans. Write drug treatment of hypertension. Hypertension is increase in blood pressure beyond 140/90 mm Hg, ‘Therapeutic objective: ‘Objective is to control the blood pressure to prevent the complications of hypertension. Drug treatment: Salt restricted diet and dally exercise must be advised to all patients Mild hypertension: Hydrochlorthiazide 25 mg oral once a day is prescribed lfe long. Moderate hypertension: Hydrochlorthiazide 25 mg oral once a day along with enalapril S mg oral once a day are ‘given lifelong, Alternatives to enalapril are ramipal lisinopril etc. Those developing dry ‘ough with ACE inhibitors can be prescribed ARBs ike losartan telmisartan, etc. Severe hypertension: + Hydrochlorthiazide 25 mg ora along with enalapril 5 mg oral and amlodipine S mg oral once a day are prescribed life long, Alternatives to enalapril are ramipril lisinopril etc. ‘Those developing dry cough with ACE inhibitors can be prescribed ARGS like losartan, telmisartan ete ‘+ Regular monitoring of blood pressure and adjustment of dose of the drug as required should be done in all cases. Write drug treatment of mid hypertension. Hypertension is increase in blood pressure beyond 140/90 mm Hg. ‘Therapeutic objective: ‘Objective is to control the blood pressure to prevent the complications of hypertension.psed oa patient nae tong fori hypertension Meee osaanarktur co are omor tsnop et. gered ARB ke esata, Ps ngusmert of ose ote casein rope En iantitos <| ‘rose deve 9 pressure rete Regs 2 sear pu be one a cae moderate hypertension food pressure beyond 140/90." HS. rte drag trestment of a ana. Hypertension 8 eH Trerapestic object Serene to contra the blond pressure aa ily exercise must be advised to all patients. i prevent the complications of hypertension + Sates a peated by hydrochlrthianide 25 mg oral once day along | scene ns ge ersten Rae et nbepares a Sore re i bearers and adjustment of dose ofthe drug as required (04, Write drug treatment of severe hypertension. ‘Ans. Hypertension 'sncrease in blood pressure beyond 140/90 mm Ha, ‘Therapeutic objective: ‘objective ta contol the blood pressure to prevent the complications of hypertension, rug treatment: + Salt-estricted at and dally exercise must be advised to all patients + Severe hypertension is treated by hydrochlortiazide 25 mg ora along with enalapril mg ora and amlodipine 5 mg oral once a day prescribed life long. Alternatives to enalapril are ramipril, sinopri ete Those developing dry cough with ACE inhibitors can be prescribed ARES like losartan, telmisartan, etc * Regular monitoring of blood pressure and adjustment of dose ofthe drug as required should be done in all cases 4. General Pharmacology 2. Autonomic Nervous System 3, Autacoids 4, Cardiovascular System 5. Diuretics 6. Endocrinology 7. Central Nervous System 8. Peripheral Nervous System 8. Hematology 10. Respiratory System 11. Gastrointestinal Test 12. Anti-microbial Agents 13, Anti-cancer Drugs 14. Immunomodulators and Miscellaneous Contents SSS 28 146 162 208 26 298 309 335 401 4161 General Pharmacology i i drug is given to a person, it will have harmacology is the science dealing with drugs. When a E tome vefecton the patient (pharmacodynamics) and the patient’s body will have some effect on the drug (pharmacokinetics). These are two major branches of pharmacology. Routes of drug administration ao | Local f x 4 Topical [intra-articular |[" intrathecal (skin and ‘mucous membranes) These may be divided into local and systemic routes. Local routes include topical application on skin and mucous membranes as well as routes like intra-articular (e.g. hydrocortisone) and intrathecal (e.g. amphotericin B). Systemic routes include oral, transdermal, inhalational, nasal, sublingual, rectal and other parenteral routes (intravenous, intramuscular, intradermal and subcutaneous). * Oral route is safer and economical but several drugs are not effective by this route because of high first pass metabolism in liver and intestinal wall (nitrates, lignocaine, propanolol, pethidine etc), * Sublingual route avoids first pass metabolism, can be used in emergencies and also after getting the desired action, rest of the drug can be spitted. Drugs like nitroglycerine, isosorbide dinitrate, clonidine and nifedipine can be given by this route. * Transdermal route is used only for drugs which are highly lipid soluble and can be absorbed through intact skin. Nitroglycerine, nicotine, fentanyl and hyoscine are given through transdermal patch. * Drugs given by nasal route are nafarelin (GnRH agonist) and desmopressin.pe controtied ike. infusion, sehchate cr de (3 ipratropium inhalational hr satu mice ‘Drazepam is given perrectally for T tanatavonel outa the route Dy a ry hs route ie nitrous o ‘Tre arugs aN agents Srvo anennaaone a sone extent cad frst BH + Real oe rot anaesthetic ao tn meas © ree PHARMACOKINETICS 5 vector tvoshandostt nebo aka rns the effect f body on nS sorption, Distribution, Metabolism 2 (hed ADM study 25 dels 1. Absorption 1 can cross the biological membranes. fa ren on ecto ny i se ord vent each te SSrpeerslostme insect memes eaeecone tthe ona orem: = is water soluble. eee kp soluble whereas ionized form When Medium is Same, Drugs Gan Gross the Membrane rom ti statement we can find hat acdc drugs can cross the membranes in acidic medtum I eae medium tor hs acdc us must be manly inthe se ee eae em, Opposite i so true for basc drugs. AS gastric pHs aide, Hae ee oocyte be absorbed fom the stomach, because these vl be rao esau orn here. Thus asprin is moreikey tobe absorbed inthe stomach thon morphine or sropine (bei 495). Bioavailability + esthe fraction of administered drug that reaches the systemic culation inunchanged frm. + When we give acrug oly sts absorbed into portal circulation and reaches iver. Here ‘ome ofthe drug may be metabolized (frst pass metabolism or pre-systemic metabolism) dnd rest of the drug reaches the systemic circulation. Thus absorption and frst pass ‘metabolism ate two anportant determinants of bioavailability + Bioaalaity by ix. routes 100%. Iecan be calcutta by comparing the AUC (area under plasma concentration ime curve fri ‘outeandfor that particular router can alo be calculated by comparing the excretion in urine Biosauivalence ‘Many diferent pharmaceutical companies can manufacture same compound (with same dose as well a5 dosage form) eg. phenytoin is available as tab. Dilantin as well as Tab. Eptoin. If the ‘iferencein the broavailailty ofthese two preparations (same drugs, same dose, sare dos39° forms) i less than 20%, these are known to be bloequivalert. As the term implies, these a7 Dologcaly equal will produce similar plasma concentrations. General Pharmacology 2. Distribution ‘ter a drug enters the blood, It may be distributed to various tissues. It determined by a hypothetical parameter, volume of distribution (V).Ifmore amount of rug enters the tissues, hasmore vohime of distribution and vie-a-versa itepencls on several etoratike ip’ soltaity and plasma protein binding Lipid soluble drugs are more likely to cross the blood veseel wall and thus have more volume of distribution. fa drug ishighly bound to plasma proteins. twill behave like a large molecule and thus more chances of staying in plasma and lass will go wo issues resulting inless Further, itis the ree form {which snot bound to plasma proteins) which is responsible for action as well as metabolism ofa EE = =a [rk di 2 : — om | {| #2? | vg : i; seule somali maak Illa, “di Liep TE oot ee 3 id: * “ERP | EE Sm) Ee TELE gt : | § af os : a i a2 — sd Lp ae er ee & Say neem enHelping Ald for Exams Sit amen an rn eo 2 LAIN WHY TYPE QUESTIONS _ ga Gant epost rector 1. Explain why urinary pH should be changed in certain drug poisoning? ‘Ans Incase of poisonings, the aim of treatment is to cause as early an excretion of the poison from the body 3s possible. The excretion of the drug depends on the pH of the urine, The drugs are present in the lipid soluble form in the same medium whereas in the opposite imedium the drugs are ionized and become water soluble (or lipid insoluble), ‘Thus, in case of poisoning by an acidic drug (like barbiturate) the excretion of the drug 4 + eaogen ene: Zan be enhanced by making the urine basic. THs Téads to the drug becoming ionized and i Se ae tiire sf edaonoavern ga Similar, ease of baste drug polsoning (ike amphetamine) the urine s made acidic with +3 3 3 the administration of ammonium chlonde. Bur 5 33 ht ai 3 e. 2 is. "2 32522 . (02. Explain wy sepirn having pita alte of 2.5 primarily absorbed frm small intestine 2: although pH of intestine ts between 6 and 8? +t #6 ‘Ans Major factors affecting the absorption of a drug are: zg 38 + Lipid solubility aboGk + Surface area ofthe ste of absorption + Time for which drug stays in an area fase on Henderson-Hasselbach equation acidic drugs are lipid solblein acidic medium ts and base drug ar lipid soluble in alaline medium. Therefore, aspirin (acidic drag) should +33 bat bbe absorbed mainly in stomach (pH is acidic). However, even aspirin is absorbed more in” ee 2 ‘cPROTEN COUPLED. * Aspirin stays for very short period in stomach because of rapid gastric emptying Therefore, inspite of being lipid soluble, most of the molecules pass to intestine + Intestine has large surface area and the drug stays here for long periods. Therefore, aspirin can be absorbed for prolonged periods in the intestine. Explain why bioavailability of tetracyclines decreases when taken with milk? Bioavailability isthe fraction of administered drug that reaches the systemic circulation in the unchanged form. The bioavallablty of tetracyclines decreases when taken with milk aver YU: ‘owe PATS as. Ans «+ Adrenecbeta recepimpos Prarmacoloy : Ae}ping Ai fF exams because the milk contains and thereby retard i a including milk retards th orm a complex with tetacjcting, 3 which may form 2 com nes multiple cations wut Also the presence of any food materi, eaerpaeption of most of the STUTE stun at epee fr deposton and. damage 0th ning th calc s 80 e5POn “Te affinity of er acy ‘bones and teeth sno certain drugs isin excess ofthe total blogg volume of distributio (04, Explain ryt apparent volume and not an actual volume tthe volume ho a ccs opp ae ec te pasate ey geese sedate on Dose administered iv Plasma concentration (C,) Cis jasma concentration willbe lesser,On this seaeconcentted inthe 005 vats matric erences es ee enue ofthe dun fads oe Tm ‘hanthelr parenteral dose of some drugsis several foldshigher' 5. Explain why oral dose! Festpass 100 + 100% absorption No frst pass rmetabotem 100 p00 lw.adminisration systemic /~ availability te ‘Ans When a drug is administered orally, the main factors affecting its bio-2¥a ability jon and fist pass metabolism. ite earth Only at fraction can produce action which is absorbed Iemear fraction which snot absorbed, willbe excreted infaeces and is Wt «+ Fist pass metabolism: When any drug is administered by the oral Wee ae through the gut and reaches the portal circulation. In the Net ara calls, it may undergo “first pass metabolism’. Therefore, the effect" iso AN Not absorbed, so excreted Ans. ‘Ans eral Pharmacology reaching the system crcultion may be les than the tt ingested However. the same amount of dag i administered by the parenteral rout, the dn ‘escapes the metabolism in the intestinal wall as well as eee the liver. So, a greater faction of the total drug reaches the systemic culation. Hence, the dose ofthe drug required by ‘the parenteral route may be les than the oral route. tanta amount ofthe drug Explain why onset of action of a drug is faster via nasal route? ‘The onset of action ofa drug is faster via nasal route because ofthe following reasons: +The rich network ofthe blood vessels in the nasal mucosa i responsible forthe faster absorption ofthe drug + Thedrug administered by the nasal route avoids the first pass metabolism Explain why a new born is more susceptible to many drugs? [Anew born is more susceptible to many drugs because: + Ithas reduced capacity to excrete the drugs from kidney + Theres ess metabolism in liver due to less drug metabolizing enzymes Both these factors increase the concentration ofthe drugin the plasma, High concentration Increases the risk of adverse effect ofthese drugs in the new born, Explain why partial agonist antagonizes the action of full agonist? ‘Two important terms related to the receptors are affinity and intrinsic activity (A). * Affinity isthe ability of a drug to bind to the receptor. a drug has no affinity, twill ‘not bind to the receptor. So all drugs acting via receptors (agonist, antagonist, inverse agonist and partial agonist) possess some affinity forthe receptors. + After binding to the receptor, the ability to activate the receptor is called its intrinsic activity. varies from -1 through zeroto +1. Partial agonists activate the receptor submasimally VA between Oand +1).So,inthe absence ‘of an agonist it produces a sub>-maximal action onthe receptor.Onthe other hand, because ithas occupied the receptor it prevents any other molecule including an agonist) to attach withthe receptor and produce action, When the agonistisnot able to bind tothe receptor, itcan not produce its maximal action. Thus, in the presence ofa partial agonist, the action ‘of a full agonist is antagonized, Sales +S] 3" Agonist soneFeces asan affinity for ayant FPO dicates thatthe drug 1 fors0me OF aemodialysis ser ume or son tate org in a ssue reduces ts plasma “rine estan oF resent in plasma only. Hence, even Temoves substances Ped completely from the body, S, isarag cont Pe etayemovedby Memos vse s terminated if mInaten Cause ofthe phenomenon of iy ing barbiturate be Ise p mt re has very Nh A its anaesthetic action. However. it gts ng high lid content tke muses Fe ‘scion of thiorento” Seana er sconce aii cle size 1. cepain why part On test 1g form important because determines the rate of eof a drug n So the particle size and increas Ther MM gofthe tablets reduces the P se fo Saran ofc TRemMrPCE eth he gastrin] mes Soe nin gor forthe proper sintegratin, dissolution “frag in slid form is important in Loading dose =V, x Target plasma concentration 4 | Manterane doe = CLx Target plosma concentration __ se _____seznowa:suomtnores Q1. Write a short note on Biotransformation or Metabolism. Ans. Biovansformation metabolism) means chemicalaltration ofa druginthebody 1 nein, to render the lpisoluble (non-polar) compounds water soluble (polar) s0 25° acl ‘their excretion through the kidneys, a. Pharmacology “The primary site for drug metabolism sliver. Other minor sites for blotransformation ate ce erntestine, lungs and plasma The drugs afte its botransformation can have ether ofthe fllowing consequences: er Most of the drugs are inactivated by metabolism (2.9, paracetamol. lignocaine) oc drugs may be activated fom the inactive compounds (known a3 Prodrugs ike Sopamine from levodopa c. Foudrugemay givese toactive metabolites from the active compound (eg. diazepam Seatoic reactions may be cassfied into phase | (non-synthetio and phase Wynter areas Function of phase | reactions isto atech a functional group to the drug coals whereas phase li reactions serve to attach a conjugate to the drug molecule. Feurohage|reacton, drug may be water soluble oF lipid soluble whereas after phase To erions all drugs become water soluble (lipid insoluble). Phase! reactions include aigation, reduction, hydrolysis, cylization and decyclzation etc. whereas phase I reactions atc glucuronidation, acetylation, methylation, sulfation and glycine conjugation etc rrctatom may occut withthe help of microsomal (presentin smooth endoplasmicreticulur) aaron microsomal enzymes. Microsomal enzymes (monooxygenase, cytochrome P4S0and Siaccronytransferase) may beinduced or inhibited by other drugs whereas nen-microsomal aecmes are not subjected to these interactions. The drugs which are metabolized by srRctosomal enzyme is known as substrate and the chemical Increasing or decreasing aie cmber of enzymes is known as inducer or inhibitor respectively. Enzyme inducers Gnd inhibitors alter the metabolism of other drugs and thus increase (with inhibitor) or Gecreae (ith inducer) their effect. Therefore dose of such drugs (which are metabolized ‘by microsomal enzymes) should be increased when administered along with microsomal enzyme inducers. Example of enzyme inducers include rifampicin, phenobarbitone etc. ‘whereas enzyme inhibitors include ketoconazole, cimetidine etc Write short note on Essential drugs or Essential medicines. “The World Health Organization (WHO) has defined Essential Medicines/Drugs as "those that satisfy the priority health care needs of the population. They are selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost effectiveness. Essential medicines are intended to be avallabie within the context of functioning health systems at ll times and in adequate amounts in appropriate dosage forms, with assured ual and adequate norman, and at a price the invidunt community can ‘The eriteria for the selection of an essential medicine are as follows: |. Adequate data on its efficacy and safety should be available from clinical studies. 1, It should be availabe ina form in which quality, including bioavailability, and stability fn storage can be assured. Its choice should depend upon pattern of prevalent diseases; availability of facilities and tained persone franca reroures gente ‘demographic and environmental ctors. Iv, In case of two or more similar medicines, choice should be made on the basis of their felt efcacy safety quay, rice and vai (Cost-benefitratio should bea majorpr ——_—S samme: avsomaneeme ‘implied ive pormacsne POPE w: crace may 8 ear ane 07098 ji nds Fixed ratio combination produc, ines should Be 300 se faa seamen rea ene Ysa medicine be saith action, eI ions ay slat medicines based 0” tationg Towed an emonasaed to select essen med iy oy the WHO Expert Comite in py Me acm py Peo cremains spe ess ea tN aang c cette Sree enone mae ete sree or “pecs “ion. Drugs having short half ives "pe tt atone ae adr eto achieve the steady state plasma concentration, Ittakes 4to 5 halfives fora drug to reach its steady state, Iasmaconcentration ofa substance tohalfsoyy Tar ife is less and vice-versa. tis a seconday ie om wo primary parameters volume dstributonang 0.693x¥, fa ck vows Rest order kinetics, its half ie is constant. This (re bor ornsvass aon tot earns en ge ona hen Saag el rises reaches a steady state and when infusion is tePPe the pla eves ae aug pias 5% none hae, 50 aan et lies 8755 (50 + 25 +1235) in tree half ves and so on. The sane A rising plasma concentration also i.e. with constant Lv. infusion, in one half life cancnntration is half of steady state and in two haf lives, itis 75% and so on- Significance of halflife a. Tells about the time to achieve steady state plasma concentration oa b. Knowing the half-life helps a prescriber to: decide whether or not to initiate Les ie) ‘with aloading dose. Drugs with very long half life when given for acute condition: tobe given in loading dose e.g. amiodarone sat «Tels about the time for which therapeutic action ofthe drug slikely to be Pr 4. Alteration in halflife s expected in diseases affecting the liver and kidney UN General Pharmacology “ame eo Pa ves) Fig. 12: Plasma concentration time curve in ft order Kneis when drug adinstation is stopped at ‘steady state concentration Q4, Write short note on Plateau principal. ‘Ans. When fixed doses of a drug are administered at regular intervals, some remnant of the previous dose will be present in the body. This continues with every dose until the rate ‘of elimination balances the rate of administration of the drug. At this point the average concentration of the drug (known as steady state plasma concentration) remains constant inspite of repeated administration of the drug. Ths principle is called as plateau principle of drug administration. “+ fa drug is administered at fxed dosing rates: ‘+ Steady state plasma concentration achieved depends on the dosing rate + Time to reach steady state plasma concentration depends upon halflife (4-5 halflives) “+ The variation between peak and trough concentration depends upon frequency of dosing (On constant iv infusion, after one half-life the mean concentration is 50% of the plateau (steady-state) concentration, after two half-lives itis 75%, ater three half-lives fis 87.5%, and after four half-lives itis 93.75%. The steady state is reached in 4-5 halflives, ‘The fluctuations in plasma concentration between peaks and troughs are minimal esnd tor Exams vas. does not Produce adverse tor agonistic action I can inane compounds that cause tary bladder and reversa, ting than neostigmying nye ment 282 eniaon of myashenicandchOiericci, ng ent ese to Tere rive for thetreatment of Alzheimer, gre ond aT atin not COMMON Wed Becae Seer oe ates ralation par Sree eT pincaesorganophosphates(malthion parathion reverie snd propo span od atone (rear preferred veo increased adverse effects, Jin glaucoma buts AOE A et edes and are Important eto ther potent ry ae used seul + Ecothophate 1 other drugsin ts cae Joisoning are pin-point pupil nett endo rg ocean te enegpnopneshae andar tenn + opine dr of ore and diacetmonoxime canbe used to regenerate ACHE + nye eactiators tke prolidon contra-indicated in carbamate poisoning, The siteon Jnorganophosphate poisoning Bute is occupied by carbamates whereas itis free ee a chy epee er arog cara Son. | [4% : cement salivation, lacrimation, sensor ey Simao thre mo place | Eee | SP EES oa] enzyme a ——— + Diacetyimonoximecan cross blood brain barrier (@88) and regenerate ACE In brain wherest ralidosime cannot cross BBB. Glaucoma {tls characterized by progressive damage to optic nerve usually associated with raised intraocul Leyes 2 ies Ha). Rise in intraocular venston Is either due to excessive production or dit oles drainage of aqueous humor. So, the drugs used for glaucoma act by elther {he atcretion bet Hocker, 22 agonists ond carbonic anhydrase inhibitor) or by wereasing ‘stow nites, dpretine and prostaglandin analogues) of aqueous humor ‘Autonomic Nervous System ous drugs usefulin primary open angle glaucoma (POAG) are 1 Prestoglandin analog: PF, ncreares ueotcea otf Latanoprost binatoprost iidurmprenton ac PGFs dovvatives usehlin glaucoma These oe now the drag of Tholce or FONG. Bimatoprostcaures growth of eyelashes at an adverse fect which Ednbe tized for rentment of hypotrichoss, 2 beta Blockers These ave among the frst line drugs fr POAG. Ciliary processes contain beta2 fesodlatory) ane sipha-2 waroconsticion receptors Wherever vavodiaton tccurs amount of blood reaching in the cary body increases resulting n exceaswe SScretionof aqueous humor Therefore, betabiocke’sand alpha agonsts coh decrease the $crelon of aqueour Timolol, betaxoio,levobetaxolel, evobunolo, carteolel and ‘etipranclol have been approved for use in glaucorma Lerobunolels longest ating Sineeoe betxoll i cardoseloctive (therefore les efheacious bur sofe in asthatied bets bocke 3 Alpha-Agonists Dipivefrine (prodrug of adrenaline) and adrenaline act by increasing ‘tabecult outflow whereas apracionidine and brimoniaine act by eareasiigaccous Secretion. Apracionidine can cause id retraction whereas brimonidine is associated ‘nth anterior uvelts. 4 Carbonic antryase inhibitors: Acetazolamide (ra) brinzolamide and dorzolamide {Goth topeal act by decressing the secretion of aucovs humor 5 Mioties:Pilocarpine (directly acting cholinommimetic) ane physostigmine (indirect {ting chollnomimeti) increase aqueous outow by causing Mesa: Plocorpine hort ‘cting therefore requires frequent daly dosing, For dlosed-angle glaucoma, definitive veatment is surgery. The only drugs used to control intra-ocular tension preceeding surgery are cholinomimetics (miotics), acetazolamide and ‘osmotic diuretics (e.g. mannitol). The onset of other agents is too slow in this situation, ANTICHOLINERGIC DRUGS Tse drugs act by Blocking muscaink o pict receptors Orgs Locking Nyrecpron we ‘led neuromusctlr blocking agents and those blocking Nae cokes oon beso ‘opine obtainedtrom Arop beladond) and seopeamine -hyoncee) reenact thatactas now selectve atagonst ata muscarinic reese ‘Actions of Antimuscarinic Agents 1 NS: Atropine Is CNS stimulant whereas scopolamine causes CNS depress fatchof scopolamine applied behind the pina) bused for presenter lean ee conser ee os cotta ans Remit ech bere berpne ad pen 3 VS: Aopine causes tachycardia by inibting ceptor by nhibkingM, receptors kisusllnretmentf br rhythms he AV block and agitate induced raya meinwentmentof brady ee