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Emergency Drugs and Antibiotics Guide
- 2. Antibiotics, Analgesics and Emergency Drugs Abhishek Roy II MDS
- 3. Contents Antibiotics Introduction Classification Choice of agent Drug factors Individual antibiotics Analgesics Pain Classification Opiods Non opiods Emergency drugs Injectable Non injectable Conclusion References
- 4. Antibiotics
- 5. Introduction Antibiotics are substances produced by microorganisms which selectively suppress the growth of or kill other microorganisms at very low concentrations They are naturally occurring products that are used in the therapeutic management of infections The discovery of Penicillin in 1928 by Sir Alexander Flemming led to the development of this field although it was not until 1942 that Ernst Chain, Howard Florey and Edward Abraham were successful in producing Penicillin G
- 6. Classification Chemical Structure Mechanism of action Spectrum of Activity Type of Action Source
- 7. Chemical Structure Class Drugs Sulfonamides Sulfadiazine, Sulfones (Dapsone, Paraaminosalicylic Acid) Quinolones Ciprofloxacin, Norfloxacin Β – Lactums Penicillins, Cephalosporins, Monobactams, Carbapenems Tetracyclins Oxytetracycline, Doxycycline Nitrobenzene derivative Chloramphenicol Aminoglycosides Streptomycin, Gentamycin, Amikacin
- 8. Chemical Structure (contd.) Class Drugs Macrolides Erythromycin, Clarithromycin Lincosamides Clindamycin Glycopeptides Vancomycin Nitroimidazoles Metronidazole Azole derivatives Clotrimazole, Ketoconazole Others Rifampicin, Ethambutol
- 11. Choice of an antibiotic agent Age Renal and Hepatic Function Local Factors Drug allergy Impaired host defence Pregnancy
- 12. Drug factors Spectrum of activity Type of activity Sensitivity of organism Relative toxicity Pharmacokinetic profile Route of administration
- 13. Sulfonamides
- 14. Sulfonamides Primarily bacteriostatic Rapid emergence of resistance has caused limited utility in current scenario Common use in present times combination with trimethoprim - Cotrimoxazole
- 15. Sulfonamides Short Acting (4-8 hours) – Sulfadiazine – 0.5 – 2gm TID oral Intermediate Acting (8-12 hours) – Sulfamethoxazole – 0.5 – 1 gm BD for 2 days Long Acting ( approx. 7 days) – Sulfadoxine – serious cutaneous reactions Special Purpose – Sulfacetamide sodium, Silver Sulfadiazene – 1% cream topically
- 16. Mechanism of Action Structural analogues of Para-aminobenzoic acid (PABA) Bacteria that utilize Folic Acid for metabolic functions are affected by this class of drug Competitvely inhibit union of PABA with pteridine Bacterial Folate synthesis cascade stopped
- 17. Cause for Resistance Resistant mutants either Produce increased amounts of PABA Folate synthase enzyme has low affinity for sulphonamides Adopt an alternative pathway for folate metabolism
- 18. Pharmacokinetics Primary pathway for metabolism is acetylation by non microsomal acetyl transferase, primarily in liver. They are excreted mainly by the kidney through glomerular filtration. Both renal tubular secretion and reabsorption also occur.
- 19. Adverse effects Nausea Vomitting Epigastric pain Hypersensitivity reactions Crystalluria – precipitation in urine
- 20. Quinolones
- 21. Early use Primarily active against gram negative bacteria First drug – Nalidixic acid It had low potency, limited spectrum and high frequency of bacterial resistance
- 22. Fluoroquinolones Advancement by the fluorination of the quinolone structure Advantages Affects gram +ve cocci and anaerobes Longer metabolic stability (t1/2)
- 23. Classification of Fluoroquinolones Norfloxacin, Ofloxacin, Ciprofloxacin • First Generation Levofloxacin, Gatifloxacin, Moxifloxacin • Second Generation
- 24. Mechanism of Action Inhibit enzyme Bacterial DNA Gyrase •DNA Gyrase cuts and joins double stranded DNA FQs bind to the A subunit of DNA thereby affecting its ability to cut and reseal strand •DNA Gyrase - •A Subunit cuts and reseals DNA •B Subunit introduces negative supercoils Recent studies indicate site of action in Gram +ve is Topoisomerase IV •Topoisomerase IV cuts and separates daughter DNA strands after DNA replication
- 25. Features of Fluoroquinolones Rapid bactericidal activity and high potency Long post antibiotic effect on Enterobacteria and Staph. Species Low frequency of mutational resistance Intestinal flora not affected Active against many β lactam and aminoglycoside resistant bacteria
- 26. Ciprofloxacin (prototype) MIC – < 0.1 μg/ml Rapidly absorbed orally High tissue penetrability Excreted through urine Higher urinary concentration than plasma E.Coli, Enterobacter, H.Influenzae Highly susceptible Staph. Aureus, Legionella, Brucella Moderately susceptible Strep. Pyogenes, Strep. Faecalis, Mycoplasma Less susceptible Clostridia, anaerobic cocci Resistant
- 27. Indications Typhoid – Drug of choice – 500-750 mg BD for 10 days orally 200 mg IV 12 hourly at start then oral Chancroid – 500 mg BD oral for 3 days alternative to ceftriaxone / erythromycin Multi drug resistant tuberculosis – combination chemotherapy 1000 mg OD has been more effective than 500 mg BD Gram negative septicaemias – combination with 3rd gen cephalosporin or aminoglycoside Prophylaxis Conjunctivitis
- 29. Adverse effects GIT – nausea vomiting anorexia CNS – dizziness headache anxiety insomnia Hypersensitivity – rash, pruriritis, urticaria
- 31. Penicillins
- 32. Classification
- 33. Mechanism of action All β-Lactams interfere with synthesis of bacterial cell wall Inhibit the transpeptidases so that cross linkage does not occur Act on UDP-N- acetylmuramic acid pentapeptide and UDP-N- acetyl glucosamine Cell wall deficient forms of bacteria are formed Interior of bacterium is hyperosmotic – these forms swell and burst – bacterial lysis
- 34. Penicillin G Narrow spectrum – gram +ve bacteria, Streptococci, Clostridia Ineffective in bacteria having Penicillinase, as β lactam chain is opened and penicillin is inactivated It is acid labile and destroyed by gastric acid Very rapid renal excretion – Plasma t1/2 is 30 mins Dosage – 0.5 – 5 MU IM/IV 12 hourly
- 35. Uses Streptococcal infections – Pharyngitis, otitis media, scarlet fever Meningococcal infections – Meningitis Syphilis Diphtheria Tetanus Prophylactic use – Rheumatic fever, bacterial endocarditis
- 36. Adverse effects Local irritancy – Pain at IM site, nausea on oral injestion, thrombophlebitis of injected vein Direct toxicity – CNS toxicity manifests as mental confusion, muscular twitchings, convulsions Hypersensitivity – rash, itching, urticaria, fever Jarisch – Herxheimer reaction – injection in a syphilitic patient(particularly secondary syphilis) produces shivering, fever, exacerbation of lesions
- 37. Dosage of semi synthetic penicillins Penicillin V – 125-250 mg tab oral Amoxicillin – 0.25 – 1gm TID oral; 250-500 mg capsule oral Piperacillin – 100-150mg/kg/day in 3 divided doses Clavulanic acid – amoxicillin(250/500mg) + 125mg oral TID Tazobactum – Piperacillin(4gm) + 0.5gm IM
- 38. Cephalosporins
- 40. Uses Alternative to penicillins in sensitive patients Respiratory, urinary and soft tissue infections caused by gram –ve organisms like Klebsiella, Enterobacter, Serratia Penicillinase producing organisms Septicaemias of gram –ve organisms Surgical prophylaxis Meningitis Gonorrhoea
- 41. Adverse effects Pain after IM injection Thrombophlebitis of infected vein Diarrhoea Hypersensitivity reactions Nephrotoxicity – highest with cephaloridine hence withdrawn
- 42. Dosage of Cephalosporins Cefotaxime – 1-2gm IM/IV 8-12 hourly Ceftriaxone – 0.25,0.5,1.0 gm per vial IM/IV Cefixime – 100-200 mg tab/cap BD Cefpirome – 1-2gm IM 12 hourly
- 43. Tetracyclines
- 44. Types Tetracycline Oxytetracycline Demeclocycline Doxycycline Minocycline
- 45. Mechanism of action Primarily bacteriostatic Inhibit protein synthesis by binding to 30S ribosomes Attachment of aminoacyl-t-RNA to mRNA-ribosome complex is hindered Peptide chain fails to grow
- 46. Antimicrobial spectrum Cocci – most gram +ve and –ve microorganisms although many have developed resistance like Strep. pyogenes, Staph. aureus, enterococci Most gram +ve bacilli – Clostridia, Listeria, Corynebacteria Sensitive gram –ve bacilli – Helicobacter pylori, Brucella Spirochetes – T. pallidum Rickettsiae and chlamydiae Mycoplasma and actinomyces
- 48. Uses 1st choice drugs – Venereal diseases Atypical pneumonia Cholera Brucellosis 2nd choice drugs – Penicillin for tetanus, anthrax Ceftriaxone or amoxicillin for gonorrhoea Penicillins for leptospirosis Other situations – UTI Amoebiasis
- 50. Precautions Tetracyclines should not be used in pregnancy, lactation and in children Avoided in patients on diuretics as there is increase in blood urea Used cautiously in patients with renal or hepatic insufficiency Tetracyclines should not be used with penicillins as the latter gets inactivated
- 51. Chloramphenicol
- 52. Mechanism of action Inhibits bacterial protein synthesis Attaches to 50S ribosomes Hinders access of aminoacyl-tRNA to acceptor site for amino acid incorporation Prevents formation of peptide bonds At high doses inhibits mammalian protein synthesis especially bone marrow cells
- 53. Chloramphenicol Primarily bacteriostatic Bactericidal at high doses Broad spectrum ability and inexpensive Indiscriminate use led to development of resistant strains Rapidly and completely absorbed after oral ingestion Freely permeates blood-brain barrier and placental barrier Forms conjugate with glucuronic acid in liver and excreted through urine Plasma t1/2 = 3-5 hours in adults
- 54. Adverse effects Bone marrow depression – aplastic anaemia, thrombocytopenia, pancytopenia Hypersensitivity reactions – rashes, fever, atrophic glossitis Gray baby syndrome – high doses (approx. 100mg/kg) given to neonates Baby stopped feeding, became hypotonic and hypothermic, abdomen distended, respiration irregular Ashen gray cyanosis followed by CVS collapse and death Occurs due to inability of newborn to metabolize and excrete the drug, due to which electron transport is blocked in liver, myocardium and skeletal muscles
- 55. Uses Enteric fever – 0.5 gm 6 hourly for adults 50 mg/kg/day for children Pyogenic meningitis – 50-75 mg/kg/day as a 2nd line drug after cephalosporin and vancomycin Anaerobic infections – in addition to clindamycin or metronidazole Intraocular infections – endophthalmitis Oral – 250-500 mg capsule 6th hourly
- 56. Aminoglycosides
- 57. Classification Systemic •Streptomycin •Gentamycin •Amikacin •Kanamycin Topical •Neomycin •Framycetin
- 58. Mechanism of action Bactericidal Transport through the bacterial cell wall and cytoplasmic membrane through porin channels Binding to 30S, 50S or 30S-50S interface of ribosomes resulting in inhibition of protein synthesis
- 59. Properties Used as sulphate salts which are highly water soluble Do not penetrate the brain or CSF Excreted unchanged in urine by glomerular filtration More active in alkaline pH Exhibit ototoxicity and nephrotoxicity
- 61. Precautions Contraindicated in pregnancy – risk of fetal ototoxicity Not to be used in conjunction with ototoxic(minocycline) or nephrotoxic (vancomycin, cyclosporine) drugs Cautious use in patients past middle age with kidney damage Cautious use of muscle relaxants in patients receiving aminoglycoside therapy
- 62. Streptomycin First aminoglycoside but least potent Highly ionized Absorbed rapidly in IM Mostly present extracellularly Excreted unchanged in urine through glomerular filtration Half life = 2-4 hours Accumulation occurs in patients with renal insufficiency and half life is prolonged
- 63. Uses Streptomycin - Tuberculosis – 1gm IM OD or BD weekly for 30-60 days Subacute bacterial endocarditis – 1gm IM BD 7-10 days (gentamycin used now) Gentamycin – 3-5mg/kg/day IM either single dose or divided TID Respiratory infections in critically ill patients – AIDS, Resuscitation wards, Corticosteroid therapy, ICUs Burns, UTI, pneumonia Meningitis – along with cephalosporins Osteomyelitis – gentamycin polymethyl methacrylate chains are used – small beads impregnated with 7.5mg and threaded over surgical wire put in cavity after removal of sequestra and left for 10 days
- 64. Macrolides
- 65. Erythromycin Bacteriostatic at low conc. but bactericidal at high conc. Acts by inhibiting protein synthesis by binding to 50S ribosome Nonionised form penetrates the bacterial cell wall and it is preferred at high pH so this drug works better in alkaline medium Antimicrobial spectrum is narrow – mostly gram +ve and few gram –ve Acid labile hence given as enteric coated tablets Can cross serous membranes and placenta but not blood-brain barrier Plasma t1/2 is 1.5 hours Dose is 250-500 mg oral tablets 6 hourly (max. 4gm/day) for adults and 30-60 mg/kg/day for children. Treatment persists for 7 days.
- 66. Uses • Streptococcal pharyngitis, tonsillitis, mastoiditis • Diphtheria Alternative to Penicillin • Atypical pneumonia • Whooping cough • Chancroid – 2gm/day for 7 days First choice drug • Campylobacter enteritis • Chlamydia infection of urogenital tract Second choice drug
- 67. Newer Macrolides Roxithromycin Clarithromycin Azithromycin Overcome limitations of erythromycin – Narrow spectrum Gastric intolerance Low oral bioavailability Poor tissue penetration Short half life
- 70. Analgesics
- 71. Pain Pain" is defined by IASP(International association for the study of pain): "an unpleasant sensory and emotional experience arising from actual or potential tissue damage or described in terms of such damage” Analgesia: Absence of pain in response to stimulation which would normally be painful (e.g. using drugs) Analgesic - A drug that selectively relieves pain by acting on CNS or on peripheral pain mechanisms without significantly altering consciousness
- 72. Classification Opiods • Phenanthrene derivatives • Morphine • Codiene • Benzoisoquinoline derivatives • Papverine • Noscapine Non-opiods • Non selective COX inhibitors • Aspirine • Ketorolac • Diclofenac • Naproxen • Selective COX 2 inhibitors • Nimesulide • Celecoxib
- 73. Opiods
- 74. Morphine Morphine is the most important alkalloid of opium Many new opioids have been synthesized but none of them are superior to morphine as an analgesic It is the prototype of this group
- 75. Mechanism of action Opioids exert their major effects by interacting with opioid receptors in the CNS Opioids activate 7- transmembrane GPCRs located pre-synaptically and post- synaptically along pain transmission pathways High densities of opioid receptors known as mu, delta and kappa are found in the dorsal horn of the spinal cord and higher CNS centers Most currently used opioid analgesics act mainly at mu opioid receptors. Morphine acts at kappa receptors in lamina 1 and 11 of the Substantia Gelatinosa of the spinal cord and decreases the release of substance p, which modulates pain perception in the spinal cord
- 76. Mechanism of action (contd.) Opioids causes hyper polarization of nerve cells , inhibition of nerve firing and presynaptic inhibition of transmitter release. Cellular effects of these drugs involve enhancement of neuronal potassium efflux (hyperpolarizes neurons and makes them less likely to respond to a pain stimulus) and inhibition of calcium influx (decreases neurotransmitter release from neurons located along the pain transmission pathway) Opioids relieve pain both by raising the pain threshold at the spinal cord level and more importantly by altering the brains perception of pain
- 78. Pharmacokinetics Absorption of morphine from GIT is slow and incomplete Quick effect is produced on subcutaneous injection It is partly bound to plasma proteins It is metabolized by conjugation with glucuronic acid It is almost completely excreted in urine within 24 hours Bioavailability is 20 to 40 per cent Given subcutaneously , onset of action is in 15 – 20 min, peak effect in 1hrs Plasma t1/2 = 2-3 hours
- 79. Pharmacological actions Analgesia Respiratory depression Cough suppression Vagal stimulation (bradycardia) Sedation & hypnosis Hypothermia Itching Physical & psychological dependence Euphoria Histamine release Hypotension
- 80. Adverse effects nausea vomiting dizziness mental clouding respiratory depression constipation dysphoria urinary retention allergic reactions
- 81. Precautions Bronchial asthma Respiratory insufficiency – emphysema, pulmonary fibrosis Head injury – retains CO2 and raises intracranial pressure Hypotensive states and hypovolaemia Elderly males – urinary retention Hypothyroidism, liver and renal disease patients are more sensitive to morphine
- 82. Uses Analgesic – traumatic, visceral, postoperative, burn, cancer patients Preanesthetic medication Relief of anxiety – myocardial infarction, internal bleeding Acute left ventricular failure (cardiac asthma) Cough – mainly codeine Diarrhoea – constipatory action of codeine used to check diarrhoea and increase consistency of stools in colostomy Dosage – 10mg/ml IV; 10,30,60,100mg continuos release tab, 30-100 mg BD
- 83. Non opiods
- 85. Classification Non selective COX inhibitors Salicylates – aspirin Propionic acid derivatives – Ibuprofen, Naproxen Aryl acetic acid derivatives – Diclofenac Pyrrolo-pyrrole derivative – Ketorolac Preferential COX2 inhibitors Nimesulide Nabumetone Selective COX2 inhibitors Celecoxib Parecoxib
- 87. Adverse effects GIT – gastric irritation, erosions,peptic ulcerations Renal – sodium and water retention, chronic renal failure CNS – headache, behavioural disturbances Haematological – bleeding, thrombocytopenia, haemolytic anaemia Others – asthma exacerbation, pruritis
- 89. Aspirin Analgesic dose – 0.3 – 1.5gm / day Antiinfalmmatory dose – 3-6 gm/day Absorbed from stomach and small intestine Rapidly deacetylated to salicylic acid in liver, gut and plasma Freely crosses placenta but slowly enters brain Excreted by glomerular filtration and tubular secretion Plasma t1/2 = 3-5 hours 8-12 hours in antiinflammatory doses upto 30 hours during poisoning
- 90. Precautions Peptic ulcer - contraindicated Chronic liver disease – cautious use Diabetics – cautious use Stopped 1 week before elective surgery During pregnancy causes low birth weight babies, delayed labour, greater postpartum blood loss Avoided by breast feeding mothers
- 91. Uses of Aspirin Analgesic – headache, backache, myalgia Antipyretic – paracetamol preferred more as safer Acute Rheumatic Fever – 75-100mg/kg/day produces symptomatic relief in 1- 3 days followed by maintenance dose of 50mg/kg/day for 2-3 weeks Rheumatoid arthritis – 3-5gm/day Postmyocardial infarction and poststroke patients – 60-100mg/day
- 93. Diclofenac sodium Similar efficacy to naproxen Inhibits PG synthesis and is somewhat COX2 selective Well absorbed orally and almost completely protein bound Metabolized and excreted both in bile and urine Plasma t1/2 is 2 hour Most extensively used NSAID Dose – 50 mg TDS oral, 75 mg IM
- 94. Ketorolac Post operative pain management equals that of morphine Rapidly absorbed orally and IM Highly plasma protein bound and 2/3rd excreted unchanged in urine Plasma t1/2 is 5-7 hours Dose – 10 mg oral, 30 mg in 1 ml ampoule
- 95. Emergency Drugs
- 96. Classification Injectable drugs •Primary •Epinephrine •Antihistamine •Narcotic antagonist •Anticonvulsant •Secondary •Analgesic •Vasopressor •Corticosteroid •Antihypoglycemic •Drugs for advanced cardiac life support •Sodium bicarbonate •Lidocaine •Atropine Non Injectable drugs •Oxygen •Vasodilating agents •Respiratory stimulant •Antihypoglycemic agent •Bronchodilating agent
- 97. Injectable drugs
- 98. Epinephrine Properties - it has got rapid onset of action, potent action as a bronchial smooth muscle dilator, anti-histaminic properties and vasopressor properties Side effects-tendency to predispose the heart to arrhythmias and relatively short duration of action. Indication –cardiac arrest, anaphylaxis or an acute asthmatic attack Precaution- it should not be used in treatment of shock because it can decrease the venous return with increased ischemia and it can also precipitate ventricular fibrillation it should be used with caution in pregnancy as it decreases the placental blood flow and may induce pre-mature labor
- 99. Epinephrine The rationale for the use of epinephrine for cardiac arrest is the beta- stimulation of the myocardium Availability-For parenteral administration supplied in 1:1000 concentration each ml will contain 1mg of agent Administration- it can be administrated by I.V or Intra cardiac route. Dental personnel may give it into the frenulum under the tongue. Dose is 0.32-0.5mg of solution Subcutaneously or Intramuscularly
- 100. Antihistamine Drugs of choice- Chlorpheniramine, diphenhydramine, pheniramine malate Indication-It is usually used in delayed allergic reaction in which onset of symptoms is more than 1 hour after administration of allergens Precaution-It is contraindicated in management of acute asthmatic episode, as thickening of bronchial secretion results from the drug drying action Availability-Chlorpheniramine(10 mg/ml I.V),Diphenhydramine(10 mg/ml) and pheniramine maleate(amp 1-2ml I.M)
- 101. Anticonvulsant Drug of choice-Diazepam and alternative drug is Barbiturate Action - Diazepam or Barbiturate will terminate seizure activity without pronounced depression of respiratory and cardiovascular system Side effects-Respiratory depression Availabitity and doses - Valium 5mg /ml Administration-It should be administrated I.V or I.M
- 102. Narcotic Antagonist Drug of choice – Naloxone Indication - It is pure opioid antagonist and it is the drug of choice for opioid induced apnea Action - More than one administration may be needed because of its short duration of action Administration-It is given I.V but can be given subcutaneously or I.M Dose-0.4mg/dl
- 103. Analgesic Drug of choice - Morphine sulphate or Mepiridine Indication - Acute myocardial infarction, congestive heart failure, intense prolonged pain and anxiety Side effects - CNS and Respiratory depression Precaution-It is contra-indicated in head injuries and multiple trauma. It is also used with care in patient with compromised respiration Availability-Morphine sulphate 10mg/ml and Mepiridine 50mg/ml
- 104. Vasopressor Drug of choice – methoxamine and phenylephrine Action – adrenergic agonist - It produces mild increase in blood pressure due to peripheral vasoconstriction Indication – acute adrenal insufficiency, drug overdose, hypotension and allergic reaction Precaution – used in caution with hyperthyroidism, bradycardia, partial heart block, myocardial disease and atherosclerosis Dose – methoxamine 10mg/ml , phenylephrine 10 mg/ ml IV or IM
- 105. Corticosteroid and Antihypoglycemic Corticosteroid – Drug of choice – hydrocortisone sodium succinate Indication – allergic reaction ,anaphylaxis and adrenal crisis Action – slow onset of action Antihypoglycemic - Drug of choice – 50% dextrose solution indication – to manage hypoglycemic episodes Administration - IV or IM
- 106. Sodium Bicarbonate It is effective in management of metabolic acidosis It elevates the pH of blood by combining with hydrogen in blood Dose – 300-500ml of 5% sodium bicarbonate IV
- 107. ATROPINE SULPHATE It is a parasympathetic drug that decrease vagal tone Indication – sinus bradycardia accompanied symptomatic hypotension Precaution – not indicated in patient with MI
- 108. Non injectable drugs
- 109. Oxygen Most important drug in emergency Patient with chronic obstructive pulmonary disease should be given with caution because apnoea may result
- 110. Vasodilator Drug of choice – nitroglycerine or amyl nitrate Indication – to manage acute anginal attack and MI Contraindication – not given in hypotensive patient Action – taken sublingually, it acts in 1-2 minutes Availability – Tab nitroglycerine - 0.1,0.3,0.6 mg Nitroglycerine spray – 0.4mg Amyl nitrate vaporous – 0.3ml
- 111. Respiratory Stimulant Aromatic ammonia spirit – used to treat syncope Action – irritating the membrane of upper respiratory tract resulting in stimulation of respiration and blood pressure Contraindication – used with caution in asthma as it may precipitate asthma Availability – silver-grey vaporole- 0.3ml
- 112. Antihypoglycemic agents Oral glucose or any available liquid carbohydrate is used to manage oral hypoglycemia in concious and semiconcious diabetic patients
- 113. Bronchodilating agents Drug of choice – metaproterenol or epinephrine, isoproterenol Indication – management of bronchoconstriction and allergic reaction Contraindication – tachyarrhythmia Dose – 1 or 2 inhalations every hour
- 114. Conclusion Antibiotics, analgesics and emergency drugs form a core therapeutic division of pharmacological management of patients It is essential to understand the mechanism of the various drugs and their usage and dosage
- 115. References Essentials of Medical Pharmacology – K.D. Tripathi – 6th Edition Online sources