Dr. Rajendra Nath Professor

Slides:



Advertisements
Similar presentations
Gentamicin – principles of use and monitoring September 2013 Dr Robert Jackson.
Advertisements

All the following are antibiotics used for gram –ve bacteria.
Training for junior doctors and pharmacists
Younas Masih RN, Post RN BSc.N (Lecturer ) New Life College Of Nursing Karachi 11/7/20141Antimicrobial medications.
Anti-tuberculous drugs. Mycobacteria Slow-growing bacillusDormant forms in macrophages.
PHL 424 Antimicrobials 9 th Lecture By Abdelkader Ashour, Ph.D. Phone:
AMINOGLYCOSIDES Streptomycin* Gentamicin* Tobramycin* Amikacin Kanamycin Neomycin(topical) * most commonly used Antibacterial Spectrum Bactericidal ( exclusive.
PENICILLIN G PRESENT BY: ADEL T. AL-OHALI. Introduction: Penicillin G is one of the natural penicillins. it discover at 1929 and did not use until 1941.
CHEMOTHERAPY ANTIBIOTICS Chemical substances produced by microorganisms and have the capacity to inhibit or destroy other organisms. ANTIBIOTICS Chemical.
PHL 424 Antimicrobials 6 th Lecture By Abdelkader Ashour, Ph.D. Phone:
Antibiotics By Dr. Humodi A. Saeed Associate Prof. of Medical Microbiology College of Medical Lab. Science Sudan University of Science and Technology E.
Aminoglycosides Mark Johnson, Pharm.D., BCPS
Antibiotics Biotechnology II. Univ S. Carolina Antibiotics Disrupt Cell Wall Synthesis, Protein Synthesis, Nucleic Acid Synthesis and Metabolism.
Drugs acting on bacterial protein biosynthesis
Non-pharmacologic Elevate the affected area to facilitate gravity drainage of edema and inflammatory substances – Patients with edema may benefit from.
Antibacterial Inhibitors of Cell Wall Synthesis –Very high therapeutic index Low toxicity with high effectiveness β- lactam Drugs –Inhibit peptidoglycan.
Dr. Saba Abdi 1.  Selective toxicity with minimal side effects to host  Easy to tolerate without a complex drug regimen  Bactericidal rather than bacteriostatic.
Chapter 37 Aminoglycosides
1 Inhibitors of Protein Synthesis Bacterial cells are 50% protein by dry weight –Inhibition of protein synthesis leads to cessation of growth or cell death.
Chapter 40 Aminoglycosides and Polymyxins Department of pharmacology Liu xiaokang( 刘小康) 2010,3.
AMINOGLYCOSIDES The different members of this group share many properties in common. The different members of this group share many properties in common.
Aminoglycosides All aminoglycosides are produced by soil actinomycetes. Obtained from the species of – Streptomyces (suffix mycin) – and Micromonospora.
1 PROTEIN SYNTHESIS INHIBITORS. 2 These antibiotics exert their actions by targeting the bacterial ribosome which has components that differ structurally.
PHL 424 Antimicrobials 5 th Lecture By Abdelkader Ashour, Ph.D. Phone:
Chemotherapy of Tuberculosis By Prof. Azza El-Medany.
Chapter 4 Pharmacokinetics Copyright © 2011 Delmar, Cengage Learning.
CLINICAL PHARMACOLOGY OF ANTIBACTERIAL AGENTS. Actions of antibacterial drugs on bacterial cells.
Urinary Antiseptics. Organisms  Escherichia coli  Proteus  Pseudomonas species  streptococci  Klebsiella  Enterococcus  Staphylococcus epidermidis.
CHLORAMPHENICOL First broad spectrum antibiotic. First broad spectrum antibiotic. Originally isolated in Originally isolated in Now produced.
PHARMACOKINETICS Part 3.
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. Chapter 86 Aminoglycosides: Bactericidal Inhibitors of Protein Synthesis.
2. Antibiotics - Aminoglycosides Pharmacognosy IV PHG 423 Dr/ Abdulaziz Saeedan Pharmacy College 1.
Antimicrobial drugs. Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity (that is, they have the ability.
4 th Lecture By Abdelkader Ashour, Ph.D. Phone: DENS 521 Clinical Dental Therapeutics.
TDM Therapeutic Drug Monitoring
Antibiotics Affecting Protein Synthesis Medications for Infection.
1 Lecture 6 Medicinal Chemistry 1 (PC 509) Prof. Dr/ Ghaneya Sayed Hassan
Treatment Of Respiratory Tract infections. Prof. Azza ELMedany Department of Pharmacology Ext
Principles of Drug Action
INHIBITOR of BACTERIAL PROTEIN SYNTHESIS. BACTERIAL PROTEIN SYNTHESIS The selectivity for bacterial protein synthesis is caused by differences in the.
Topical Antibiotics.
Lecture: 6 MACROLIDES. Among the many antibiotics isolated from the actinomycetes is the group of chemically related compounds called the macrolides.
PRINCIPLES OF ANTIBIOTIC THERAPY
Among the many antibiotics isolated from that genus, several are compounds closely related in structure to streptomycin. Six of them kanamycin, neomycin,
PROTEIN SYNTHESIS INHIBITORS THEY WORK BY TARGETING BACTERIAL RIBOSOMES AMINOGLYCOSIDES MACROLIDES TETRACYCLINES SPECTINOMYCIN.
Aminoglycosides Antibiotics Dr. yasodha krishna janapati Associate Professor Dept. of Pharmaceutical Chemistry, College of Health Sciences (CHS), Ayder Campus, Mekelle University, Mekelle, ETHIOPIA Introduction: Aminoglycos
DNA gyrase inhibitors Quinolones
Antibiotics By Alaina Darby.
PHL 424 Antimicrobials 2nd Lecture By Abdelkader Ashour, Ph.D. Phone:
Protein Synthesis Inhibitors
AMINOGLYCOSIDES.
The aminoglycoside antibiotics
Protein Synthesis Inhibitors
Miscellaneous Antibiotics
4. Antibiotics - Polymyxins (Polypeptides)
Aminoglycosides.
By :Lecturer Nabeel Ahmed Al anbagi
Inhibitors of Protein Synthesis
Vancomycin Vancomycin has become increasingly important in the treatment of life-threatening infections. MRSA infections. Methicillin-resistant Staphylococcus.
CHEMOTHERAPY ANTIBIOTICS Chemical substances produced by microorganisms and have the capacity to inhibit or destroy other organisms . CHEMOTHERAPEUTIC.
Course Coordinator Jamaluddin Shaikh, Ph.D.
Aminoglycosides.
Course Coordinator Jamaluddin Shaikh, Ph.D.
Drug Resistance Bacteria are considered resistant to an antibiotic if the maximal level of that antibiotic that can be tolerated by the host does not halt.
Course Coordinator Jamaluddin Shaikh, Ph.D.
Gentamicin – principles of use and monitoring
Antibacterial Agents: Protein Synthesis Inhibitor Antibiotics
Chapter 38 Aminoglycosides
2- Tetracyclines Classification
Principles of Antimicrobial Therapy
Presentation transcript:

Dr. Rajendra Nath Professor Aminoglycosides Dr. Rajendra Nath Professor

Aminoglycosides It includes Gentamicin ,Tobramycin , Amikacin, Netilmicin , Kanamycin ,Paromomycin, Streptomycin (systemic) & Neomycin, Framycetin ( topical) ( Paromomycin- It is used orally for intestinal amebiasis and in the management of hepatic coma. ) Primarily used to Tt inf.s caused by aerobic G- ve bact. & Streptomycin is an important agent for the Tt of Tuberculosis.

Aminoglycosides In contrast to most inhibitors of microbial protein synth. which are bacteriostatic the Amgl.s are bactericidal . Mutations affecting proteins in bact. ribosomes can confer marked resist. to their action

Aminoglycosides These agents contain amino-sugars linked to an aminocyclitol ring by glycosidic bonds . -They are polycations - There polarity is responsb. in part for pharmacokinetic property shared by all memb.s of the gp. e.g.- none is abs. adequately after oral administration. - Inadequate conc.s are found in CSF.

Aminoglycosides All are excreted rapidly by normal kidney. Amgl.s are widely used but their toxicity limits their usefulness ( esp. nephrotoxicity & ototoxicity ). History : -They are natural prod.s or semisynth.

Aminoglycosides derivatives of compd.s produced by variety of soil Actinomycetes . Streptomycin first isolated from Streptomyces griseus. Gentamicin & Netilmicin are broad spect. antb.s derived from sp. of the Actinomycetes - Micromonospora .

Aminoglycosides The difference in spelling : -micin ,antb.s originate from Genus- Micromonospora -mycin, antb.s originate from Genus- Streptomyces -semisynth. derivatives e.g. Netilmicin also end with suffix “micin” -Tobramycin is one of several components of an Amgl. complex that is produced by S. tenebrarius. It is ≡ Gentamicin . - Amikacin a derivative of Kanamycin

Aminoglycosides & Netilmicin a derivative of Sisomicin are semisynth. product . Chemistry : Amgl.s consists of two or more amino sugars joined in glycoside linkage to a hexose nucleus . This hexose or aminocyclitol is either streptidine

Aminoglycosides ( found in Streptomycin ) or 2-deoxy streptamine (found in all other Amgl.s) -Amgl. family is distinguished by the aminosugar attached to the aminocyclitinol . Mech. of action : Amgl. antb.s are rapidly bactericidal

Aminoglycosides It is conc. dependent. The higher the conc. the greater is the rate at which bact.s are killed (Conc. Dependent Killing ) -The post antibiotic effect i.e. residual bactericidal action persist after the serum conc. falls below the MIC (minimum inhibitory concentration) also a

Aminoglycosides a characteristic of Amgl.s ( accounts for once daily dosing regimen of Amgl. antb.s ). Amgl.s diffuse through aq. channels formed by Porin protein in the outer membrane of G-ve bact. to the periplasmic space.

Aminoglycosides -Transport of Amgl. across cytoplasmic ( inner) memb. depends on electron transport . This phase of transport has been termed as energy dep. phase I ( EDP I) . {It can be blocked by divalent cations e.g. Ca++ & Mg ++ ions ( rate limiting ) , hyperosmolarity , low pH and & anaerobic conditions }

Aminoglycosides (thus the AM action of Amgl. is reduced markedly in the anaerobic environment of an abscess & in hyperosmolar acidic urine) . Once inside the cell it binds to polysomes & interfere with protein synthesis by causing misreading &

Aminoglycosides premature termination of mRNA transl. → aberrant protein prod. & insertion into the cell membrane → altered permeability & ↑ further transport of Amgl. This is termed as energy dep. phase II (EDPII ) which is ≈ disruption of cell membrane by aberrant protein.

Aminoglycosides This progressive disruption of the cell envelop , as well as other vital processes may help in explaining the lethal action of Amgl.s . (The primary intracellular site of action of the aminoglycoside is 30 S ribosomal subunit )

Aminoglycosides

Aminoglycosides Spectrum of Amgl.s : -AM activity of Gentamicin ,Tobramycin, Kanamycin , Netilmicin & Amikacin is directed primarily against aerobic G- ve bacilli .

Aminoglycosides - Kanamycin & Streptomycin has limited spectrum compared with other Amgl.s ( not used in inf. caused by Serratia or P. aeruginosa ). Amgl.s has little effect against anaerobic micro-organisms.

Aminoglycosides or facultative bacteria under anaerobic conditions . Action against most G +ve bact. is limited & they should not be used as single agents to treat them (G- ve cocci are also not sensitive ) e.g. in comb. with Penicil. & Vancomy.

Aminoglycosides The Amgl. Gentamicin & Streptomycin are tested extensively , they produce synergistic bactericidal effect in vitro against Enterococci , Streptococci & Staphylococci. the aerobic G- ve bacilli vary in their susceptibility to the Aminoglycosides

Aminoglycosides Tobramycin & Gentamicin exhibit similar activity against most G-ve bacilli . Tobramycin > active against P. aeruginosa & some proteus spec. (Amikacin & in some instances Netilmicin retain their act. against Gentamicin resistant strains because they are a poor substrate for many of the Amgl. inactivating enzymes.)

Aminoglycosides Absorption ,Distribution ,Dosing & Elimination of the Amgl. : -Amgl. are highly polar cations & hence poorly abs. from GIT . -The drugs are not inactivated in the intestine & are eliminated in the feces

Aminoglycosides (Long term oral or rectal administration of Amgl.s may result in accumulation up to toxic concentration in pts with renal impairment .) . -Installation of these drugs into body cavities with serosal surfaces also may result in rapid absorption &unexpected toxicity ( recurrent muscular blockade ).

Aminoglycosides -Similarly topical application for long periods ( in large wounds , cut ulcers & burns ) causes toxicity . -All are absorb rapidly from I.M. site of inj.s .( Peak conc. reaches after 30-90 min.s )

Aminoglycosides Distribution : -Polar nature so not penetrate into most cells , CNS & eye . -They do not bind to pl. albumin (except Streptomycin) -Conc. of Amgl.s in secretions & tissues are also low.

Aminoglycosides High conc.s are found only in the renal cortex , endolymph & perilymph of the inner ear (& likely contribute to nephrotoxicity & ototoxicity respectively) . Bile represents only minor route of elimination.

Aminoglycosides inflam. ↑ the penetration of Amgl. in the peritoneal & pericardial fluids . - Conc. of Amgl.s in CSF with parenteral administ. usually are sub- therapeutic ( Concentration in CSF is< 10% of plasma & ↑ to 25% in meningitis and intrathecal & intraventricular administration of Amgl.s and can achieve therapeutic levels) .

Aminoglycosides -Administ. in women in late pregnancy may result in accumulation of drug in fetal plasma & amniotic fluid & can cause hearing loss (e.g. Streptomycin & Tobramycin ). So they are used with caution during pregnancy & only for strong clinical indication.

Aminoglycosides Dosing : Current procedure is to give total daily dose as a single injection ( It is associated with less toxicity & as effective as multiple doses )

Aminoglycosides -Once daily dosing also cost less & administered more easily .so it is better to give single daily dose. ( exception is use in pregnancy , neonates & pediatric infection & combination low dose therapy in endocarditis )

Aminoglycosides Once daily dose should be avoided in pt with Creatinine clearance< 20 -25 ml/min because accumulation can occur so less frequent dosing ( 48hrly ) is more appropriate .

Aminoglycosides Creatinine Cl. % of max. Freq. of daily dose dosing 100 100 75 75 every 24 hr 50 50 25 25 20 80 10 60 every 48 hr < 10 40

Aminoglycosides -The maximum daily dose for -Amikacin ,Kanamycin & Streptomycin -15mg/kg, -Gentamicin & Tobramycin is -5.5mg/kg -Netilmicin -6.5 mg/kg (Monitoring will be done in multiple daily dosing where renal function test are compromised or impaired .)

Aminoglycosides Elimination : eliminated almost entirely by glomer. filtrate.( renal cl. of Amgl. is ⅔ of creatinine cl. ). Amgl.s can be remove from the body by either hemodialysis or peritoneal dialysis .

Aminoglycosides S/E – All Amgl.s have the potential to prod. reversible or irreversible vestibular /cochlear & renal toxicity. These side effects complicate the use of these compounds .

Aminoglycosides Ototoxicity - - Vestibular & auditory dysfunction is because of accumulation of drug in perilymph & endolymph . - The t ½ is 5-6 times high in otic fluid than in plasma . (Ototoxicity has been linked to mutation in the mitochondrial ribosome RNA gene -genetic predisposition. ) .

Aminoglycosides It is largely irreversible ( more resistant in Cochlear changes & results from prolong destruction of vestibular or cochlear sensory cells . - Repeated course of Amgl. can probably resulting in the loss of nerve cells which leads to deafness & ataxia.

Aminoglycosides (Drug e.g. Ethacrynic acid & Furosemide potentiates the ototoxic effect of Amgl.s if given simultaneously ). More in pts having preexisting auditory impairment . ( Streptomycin & Gentamicin predominantly produces vestibular toxicity whereas Amikacin ,Kanamycin & Neomycin affects auditory function ,Tobramycin affects both equally ).

Aminoglycosides Cochlear Toxicity- First symptom is tinnitus & if drug is not discontinued then impairment of auditory function occurs after a few days .

Aminoglycosides Vestibular toxicity- headache in 1-2 days → nausea ,vomiting & diff. in equilibrium ( if persists for 1-2 wks)→ vertigo in upright position , diff in standing & sitting ( +ve Romberg test). Rarely spontaneous Nystagmus & Chronic labrynthitis leads to ataxia in in walking .

Aminoglycosides Nephrotoxicity : -Mild renal impairment. – if Amgl.s are given for more than several days & is reversible -Late effect- mild proteinuria & appearance of hyaline & granular cost in microscopic examination of urine → ↓↓ GFR .

Aminoglycosides - Severe acute tub. necrosis may occur rarely ( mild ↑ in creatinine cl.) . - The impairment in renal functions is almost always revers. (because the prox. renal tubular cells have the capacity to regenerate ). Neomycin is highly nephrotoxic & not given systemically .

Aminoglycosides Streptomycin does not conc. in renal cortex so least nephrotoxic. AmphotericinB , Vancomycin, ACEIs, Cisplatin & cyclosporin may pot. Amgl induced nephrotoxicity.

Aminoglycosides Neuromuscular blockade : Order of decreasing potency for this is Neomycin > Kanamycin > Amikacin > Gentamicin & Tobramycin ( especially after intra pleural or intra peritoneal instillation in high doses .) - Pts of myasthenia gravis are more susceptible to Amgl.s for this effect.

Aminoglycosides -It is due to ↓ in prejunc. release of Ach & also due to ↓ in post synaptic sensitivity to transmitter. (Tt. is – IV Ca- gluconate / IV Neostigmine ) Others – -Streptomycin can cause optic nerve damage . -H/S react.s are rare – skin rash, eosinophilia , fever , blood dyscrasia

Aminoglycosides angiodema , exfoliative dermatitis & stomatitis. 1.) Streptomycin : Used for the Tt of certain unusual inf. gen. in comb with other AM agents. it is less active than other memb.s against aerobic G -ve rods .

Aminoglycosides Given deep I.M. / I.V. & I.M may be painful at the site of injection. ( dose – 10-15mg/kg/day) Uses : 1. Bact. endocarditis ( Streptomycin + Penicillin produces synergistic & bactericidal effect) 2.Tularemia -DOC ( Gentamicin, Fluroquinolones & Tetracyclines are also given)

Aminoglycosides 3. Plague – effective in all forms –(2gm I.M./ day in 2div.doses x7-10 days≡ Gentamicin & Tetracyclines) 4. Tuberculosis – always used in combination with at least one or two other drugs. (dose- with normal renal function is 15 mg/kg/day OD. X 2-3 months or 2-3 times a week. .)

Aminoglycosides 2.) Gentamicin (& other Amgl.s ): (dose- 2mg/kg , ⅓ given 8 hourly or single daily dose -5-7 mg/ kg ) Uses : - UTI – not indicated in uncomplicated inf. - Pneumonia – in comb. with β- lactum - Meningitis – with G- ve org. (resistant to β- lactum e.g.- Pseudomonas , Acinobacter .)

Aminoglycosides Bact. endocarditis - synergistic effect with Penicillin or Vancomycin. Sepsis : febrile patient with granulocytopenia. & infection with P. aeruginosa Topical use – Gentamicin absorb slowly when applied topically (but more rapidly when applied as cream) .

Aminoglycosides 3. )Tobramycin ≡ Gentamicin ( also as ophthalmic oint. & soln.) > effective in inf. with P. aeruginosa 4.) Amikacin : broadest spectrum (because resistant to many Amgl. inactivating enzymes ).

Aminoglycosides -Specific role in hospital acquired infection ( dose- 10 mg/kg/day ) DOC in serious nosocomial G -ve infection of hospitals. Not effective against most G-ve anaerobic bacteria.

Aminoglycosides Active against M. tuberculosis including Streptomycin resist. cases & atypical mycobacteria in AIDS pts . 5.) Netilmicin : Latest ≡ Gentamicin - not metabolize by Amgl.s inactivating enzymes like Amikacin.

Aminoglycosides UTI – in complicated infection ( Dose – 1.5-2 mg / kg 12 hrly . ) - Useful in Tt . of aerobic G- ve bacilli inf. & inf. with Enterobacteriaceae. 6.) Neomycin: Broad spectrum antibiotic (G- ve - highly sensitive species are – E.coli , Enterobacter , Klebsiella , Pneumococci , Proteus vulgaris , G+ve - S.aureus & M. tuberculosis –acid fast rods)

Aminoglycosides Uses : - Topical- skin & mucous memb. Infect. (Neomycin sulfate- burns , wounds ,ulcers & infective dermatosis) . -Oral with Erythromycin ( for bowel prepr.) or Polymixin (40 mg Neomycin + 2 lack Unit of Polymixin for irrigation of bladder) -In hepatic encephalopathy (4-10 gm orally if renal functions are normal )

Aminoglycosides S/E – Hypersensitivity react . in topical use, It kills the ammonia producing org.s in the large gut, but now Lactulose is preferred . S/E – Hypersensitivity react . in topical use, renal impairment & nerve deafness oral – intestinal malabsorption. & superinfection

Aminoglycosides 7.) Kanamycin : most toxic & spectrum of activity is limited (Dose – 1.5 mg/kg /day ) - almost obsolete . (only in India – in resistant Tuberculosis with comb. of other drugs ) -prophylactic use -in hepatic encephalopathy ( 6 gm /day ) .

Aminoglycosides Framycetin: ≡ Neomycin- It is also very toxic so used only for topical purpose ( as ointment ) – Skin inf. , otitis externa , furunculosis , burns & scalds & also as eye drops .

Aminoglycosides Spectinomycin (produced by Streptomyces spectabilis ) : It is Aminocyclitol related to aminoglycosides , which is used as single dose treatment for – -Penicillinase producing Neisseria gonorrhoea ( PPNG ). -For gonorrhoea in Penicillin allergic patients

MCQs 1.Tick the drug belonging to antibiotics- Aminoglycosides: a) Erythromycin b) Gentamicin c) Vancomycin d) Polymyxin . 2. Aminoglycosides are effective against: a) Gram positive microorganisms, anaerobic microorganisms, spirochetes b) Broad- spectrum, except Pseudomonas aeruginosa c) Gram negative microorganisms, anaerobic microorganisms d) Broad- spectrum, except anaerobic microorganisms and viruses 3. Aminoglycosides have the following unwanted effects: a) Pancytopenia b) Hepatotoxicity c) Ototoxicity, nephrotoxicity d) Irritation of gastrointestinal mucosa

4. The most important mechanism of bacterial resistance to an Aminoglycoside antibiotic is : (a) Plasmid mediated acquisition of aminoglycoside conjugating enzyme (b) Mutational acquisition of aminoglycoside hydrolyzing enzyme (c) Mutation reducing affinity of ribosomal protein for the antibiotic (d) Mutational loss of porin channels 5. Which toxic effect of aminoglycoside antibiotics is most irreversible in nature ? (a) Vestibular damage (b) Hearing loss (c) Neuromuscular blockade (d) Kidney damage 6.Select the antibiotic whose dose must be reduced in patients with renal insufficiency : (a) Ampicillin ( b) Chloramphenicol (c) Tobramycin (d) Erythromycin

7. The aminoglycoside antibiotic which is distinguished by its resistance to bacterial aminoglycoside inactivating enzymes is : (a) Kanamycin (b) Sisomicin (c) Amikacin (d) Tobramycin 8. An aminoglycoside antibiotic should not be used concurrently with the following drug : (a) Ampicillin (b) Vancomycin (c) Ciprofloxacin (d) Rifampin 9. The aminoglycoside that can be used in amoebiasis is : (a) Paromomycin (b) Framycetin (c) Amikacin ( ( d) Netilmicin 10. Streptomycin sulfate is not absorbed orally because it is : (a) Degraded by gastrointestinal enzymes (b) Destroyed by gastric acid (c) Highly ionized at a wide range of pH values (d) Insoluble in water

(a) They are primarily active against gram negative bacilli 11. Aminoglycoside antibiotics have the following common property : (a) They are primarily active against gram negative bacilli (b) They are more active in acidic medium (c) They readily enter cells and are distributed in total body water (d) They are nearly completely metabolized in Liver 12. Which aminoglycoside antibiotic causes more hearing loss than vestibular disturbance as toxic effect ? (a) Streptomycin (b) Gentamicin (c) Kanamycin (d) Sisomicin

13. Single dose of Aminoglycoside administration is more preferable than 8 hourly dose because of: a) Post antibiotic effect b) Increase perfusion of renal cortex c) MIC d) Time dependent killing

Answer Key 1-a ,2-d, 3-c, 4-a, 5-b , 6-c , 7-c, 8-b, 9-a , 10-c, 11-a, 12-c, 13-a

Bibliography 1.Goodman & Gilman’s ,The Pharmacological Basis of Therapeutics (12th Edition). 2. Principles of Pharmacology by H. L. Sharma & K K Sharma ( Latest Edition) 3. A complete Textbook of Medical Pharmacology by S. K. Srivastava ( Latest Edition ) 4. Essentials of Medical Pharmacology by K. D. Tripathi (7th edition)