Dr STSA

Antibiotics - chemical substances originally produced

by various species of micro-organisms (bacteria, fungi,

actinomycetes) that in high dilution suppress the

growth or cause death of other microorganisms

Objective of Rx- For curative - eradication by lethal

effect,inhibit growth & multiplication,phagocytosis

For preventive

Antimicrobial agents 3

Bacteria

Bacteriostatic• inhibiting the growth or multiplication of bacteria

Bactericidal• lethal effect on mature bacteria /kill the bacteria

Antibacterial spectrum

• list of bacteria which are normally susceptible to

antibacterial action of a particular agent (group or

particular organisms)

Antimicrobial agents 5

Antimicrobial agents 6

Antimicrobial agents 7

C

Classification based on their Mechanism of Actions

1. Drugs that inhibit the synthesis of bacterial cell walls

eg.Penicillins, Cephalosporins, Vancomycin Clotrimazole

2. Agents that act directly on the cell membrane eg‘.Nystatin, Amphotericin

Antimicrobial agents 8

Cont-

3. Drugs inhibiting microbial protein synthesis by their effect on bacterial ribosomes

(A) disrupt the function of 30S or 50S ribosomal subunits to reversibly inhibit

protein synthesis (mainly bacteriostatic)

eg – Chloramphenicol, Tetracyclines, Macrolides,

Clindamycin, Lincomycins

(B) agents that bind irreversibly to 30s ribosomal subunit (mainly

bactericidal)

– Aminoglycosides eg. GentamicinAntimicrobial agents 9

4. Drugs that affect nucleic acid metabolism

eg.Rifampicin,Fluoroquinolones,Griseofulvin Metronidazole

5. The antimetabolites - Drugs affecting the intermediary metabolism which are essential to micro-organisms Sulfonamides Competitive

antagonist of Para-aminosalicylic acid PABA

(PAS) Trimethoprim

inhibit DHFA-reductase enzyme Pyrimethamine

• MOA

-inhibit the bact:cell wall syn by binding to protein,inhibit crosslinking enz ∆ autolysis

Classification of Penicillins

1. Penicillin G - Benzyl penicillins

(a) Penicillin G- Crystalline I.V (Aqueous Pen G as K+ salt and Na+ salt) (2,50000 to 10,00000 units IM, IV)

(b) Penicillin G -Procaine suspension (3,00000 to 6,00000 units IM)

(c) Penicillin G -Benzathine suspension (0.6 to 1.2 mega units IM)

2. Penicillins V (oral) Phenoxymethyl penicillin(250-500mg)

3. Penicillinase-resistant penicillins (Anti-staph) Cloxacillin – orally,IM, IV

Flucloxacillin

Dicloxacillin, Oxacillin

Antimicrobial agents 12

• Methicillin - use as a laboratory tool for identification of

methicillin - resistant - Staphylococcus aureus (MRSA)

(MRSA = resistance to all the penicillinase-resistant penicillins and

cephalosporins) (Vancomycin is a drug of choice in MRSA)

4. Broad spectrum penicillins

Ampicillin

Amoxicillin

5. Antipseudomonal penicillins

Carboxypenicillins - Carbenicillin Indanyl (oral), Ticarcillin

Ureidopenicillins - Piperacillin

6. Penicillin β-lactamase inhibitor combination

Co-amoxiclav (Amoxicillin + clavulanic acid)

Pen GOrganisms Usage Dosage/Route

gram(+)ve cocci (except penicillanase producing )staph -pneumococci -Streptococci

gram (-) cocci - meningococci, gonococci

Infections caused by-non-β-lactamase-producing staphylococci, -pneumococci-Streptococcal pneumo:

-Prophylatic Tx:*

- meningococci, gonococci

Crystalline- IV 30 mg/kg6H (1mg=1667u)Severe inf:50 mg/kg 6H (max 2G)12 H/6HProcaine-IM 25-50 mg/kg 12H/OD(Max 1.2-2.4G)Benzathine –IM25mg/kg OD,3-4wkly

non-β-lactamase-producing anaerobes

non-β-lactamase-producing anaerobes

Organisms Usage Dosage/Route

gram (+) bacilli – C. diphtheriae, B. anthracis, Clostridium, Actinomyces

DiphtheriaInfection due toBacillus anthracisClostridium species-Actinomyces* and other gram-positive rods

C/pen 30-50mg/kg 6H

spirochetes Treponema pallidum (syphilis) and many other spirochetesProphylatic Tx

C/pen “

Pen V

•gram (+)ve cocci (except penicillinase producing staphylococci)* narrow antibacterial spectrum

o minor infections (streptococcal pha-ryngitis)

o prophylaxis of streptococcal infection following rheumatic fever and pneumococcal infection (following splenectomy) fusospirochetel infection (gingivostomatitis)

oral 15 mg/kg 6H (125-250mg) 12.5 mg/kg 12 H

Organisms Usage Dosage/Route

Pen resistent pen

Org Usage Dosage

more effective against penicillinase producing - staphylococci

staphylococcal infections-skin,LRIT

Cloxacillin – orally,IM, IV15 mg/kg 6H25- 50mg/kg 12H,4-6H, Flucloxacillin12.5-25 mg/kg 6H25-50 mg/kg 8H,6H

less effective than pen. G and pen. V against Gram positive bacteria

Some strains of Gram negative bacteria

H. influenzae, E. coli,gonococci, Klebsiella

Aminopenicillins (Ampicillin, Amoxicillin)Org Usage Dosage

gram (-)ve, (+)ve bacteria(H. influenza, E.coli and Proteus mirabilis)

URTI (sinusitis, otitis media, acute exacerbations of chronic bronchitis & epiglottitis) Lower RTI, UTI, Biliary tract Meningitis,

Salmonella infection (Enteric fever) H. pylori

Oral/I.M/I.V 10-25 mg/kg 6H /8H severe -50mg/kg

‴Listeria monocytogen

sensitive against β-lactamase producingstrains of G (+)ve & G (–)vebacteria*.Staph,Gono,H. influenzae, E coli, Klebsiella, Proteus, Bacteroides fragalis, Moraxella catarrhalis

Penicillin - β-lactamase inhibitor combination (Clavulanic acid or Sulbactam)20-25 mg/kg IM,IV 6H

Antimicrobial agents 19

Vancomycin

Antimicrobial agents 20

Red man syndrome

Mechanism of Action• similar to penicillin , bactericidal, inhibit bacterial cell wall synthesis Classification of Cephalosporins I. The first generation cephalosporins Cefalexin Cefadroxil Cefazolin II. The secondgeneration cephalosporins Cefuroxime axetil ,Cefaclor (Oral) Cefuroxime Cefoxitin IV,IM• Cefotetan

III. Third generation Cefixime(oral)

Cefotaxime

Ceftriaxone IV,IM

Ceftazidime

IV. Fourth generation

Cefepime (I.V)

The First Gen:CephaloDrug Theraputic advantage Dosage

Gram- positive cocci (except MRSA)

upper and lower RTI Cefalexin- 7.5mg/kg 6h Cefadroxil 15-25mg/kg 12h Cefazolin

Gram-negative bacteriaEcoli,Kleb,ProteusOral cavity anaerobic cocci

urinary tract infection surgical prophylaxis

some β lactamase producing strains (e.g, Staphylococcus)

skin and soft tissue infections owing to S. aureus and S. pyogens

The second gen:cephaloGram + ve RTI (oral) Cefuroxime axetil 10-

15 mg/kg bdCefaclor 15mg/kg 8h

anaerobes (Bacteroids fragilis)

anaerobic infection -pelvic inflammatory disease,-Intra-abdominal inf,- diabetic foot

Cefuroxime iv25-50 mg/kg 8,12,6 hr

Gram-ve bacteria(< 3rdG) (Neisseria,H.influenzae, Enterobacter Proteus, E.coli, Klebsiella)

G (-)ve bacterial

The third gen:cephaloless active against G + ve DOC for serious

infn (Septicaemia,Pneumonia,Meningitis)

Cefotaxime iv25-50mg/kg-12 h 8 h/6 hCeftriaxone -iv,im25-50mg/kg 12h,8h

more active against G -ve

Oral-Cefixime 5mg/kg od Cefpodoxime ″ bd

much more active enterobacteriaceae &β-lactamase producing strainss/a (H. influenzae & Neisseria)

some - active against P.aerug Ceftaxidime iv,im15-25mg/kg 8h

Enteric feverSevere Lyme’s d/sGonococcal

The forth generation

• Cefepime (I.M ,IV)

25-50 mg/kg 12h

Antimicrobial agents 27

Untoward Effects

1.Hypersensitivity is most common

cross hypersensitivity & resistant < 10%

Caution – Penicillin allergic patient

2. Nephrotoxicity - ↑ with aminoglcosides

3. Renal tubular necrosis (Cephaloridine, Cephalothin)

4. Intolerance to alcohol (disulfiram –like reaction)

28Antimicrobial agents

MACROLIDEAntibacterial Activity Therapeutic Uses Dosage

G +ve (same as Pen G) alternative to penicillins in strep pharyngitis, staph infections, tetanus, syphilis,Bacterial endocarditis ,Rheumatic feverDiphtheria, Pertussis,

ErythromycinOral 10-15mg/kg 6h 25 mg/kg 6h

Chlamydia trachomatis,Mycoplasma, Legionella,

luminal amoebicide

Chlamydial infections, Mycoplasma p’nia,Legionnaires’ diseaseCampylobacter infections Intestinal amoebiasis

Mycobacterium Mycobacterial infection Azithromycin 15mg/kg D17.5mg/kg D2-5

more potent than erythromycinstrept, staph,ChlamydiaMycoplsma and H.pylori

Eradication of H.pylori in peptic ulcer

Chlarithromycin

Untoward Effects- not common• cholestatic hepatitis is common with erythromycin

estolate (esp. in pregnancy)• allergy, GI disturbances, arrhythmia*• reversible hearing lossContraindication• liver disease, pregnancy

Drug Interaction

Erythromycin and clarithromycin inhibit CYP3A4

potentiate the effects of digoxin, theophylline & valproate

LINCOSAMINES (Lincomycin and Clindamycin)

Antibacterial Activity Therapeutic Uses Dosage

Anaerobic bacteria (Bacteroides species, Clostridium)

peritonitis, pelvic inflammation

Lincomycin 10mg/kg 8h oralIM or IV (over 1h)10 -20mg/kg (over 2h)6h

Gram +ve bacteria –more effective(Staph. aureus)

Bony infections - osteomyelitis, sinusitis, periosteitis, periodontitis Aspiration pneumonia, Lung abscess

Clindamycin6mg/kg 6h oralIV over 30min,IM 12h10 -20mg/kg 8h

Gram - ve bacteriaLess effective

Untoward Effects of Lincosamines

• Diarrhoea (superinfection)

• Pseudomembranous colitis due to Clostridium difficile

which produces enterotoxin(Tx –metronidazole)

• Hypersensitivity (rare);

• Granulocytopenia, thrombocytopenia,

• Stevens -Johnson Syndrome

(can occur, but not common)

Antibact Rx Dose& Route

a wide range of G(+)& (-) Salmonella Shigella, V . cholerae H.influenza Bordetella pertussis Brucella, Rickettsia, anaerobic bacteria

Enteric fever Bacterial meningitis H.influenza,N.meningitidis Strep. Pneumoniae Anaerobic infectionsRickettsial infection(typhus fever, Q fever

Brucellosis

IV 1g every 6 hours for 4 weeks in enteric fever Chloramphenicol sodium succinate (1g vial) I.M, I.V

Orally - Chloramphenicol 25mg/kg/D(250 - 500 mg) 6 - 8 hourly

less effect on Staphylococcus

Ophthalmic infection Ear

Eye drop- 2-6 HEar drop- 6H

Untoward Effects

less selective toxicity; may inhibit protein synthesis of

mammalian tissues

1. Haematological toxicity - bone marrow depression

(a) true toxic reaction - dose related, common with prolong therapy

or large dose

- anaemia, leucopenia, thrombocytopenia

(b) Idiosyncratic manifestation - not dose related (occurs in

genetically susceptible patients)

- aplastic anaemia --- can be fatal

2. Grey (gray) syndrome (Gray baby Syndrome)• in premature and newborn infants• due to ineffective conjugation & poor renal excretion with dose above 50 mg/kg/day• dose should be limited to 50 mg/kg/day in full term

infants and 25 mg/kg/day in premature infants

3. Superinfection (oral or vaginal candidiasis) due to alteration of normal microbial flora

4. Haemolysis in G6PD deficient patients (dose-related)

Antimicrobial spectrum Theraputic advantage Dosage

Mainly active against Gram - ve bacteria

(Pseudomonas, Shigella, E.coli, Proteus, H.influ,

Brucella, Klebsiella)active against some

Gram +ve

Mycobacteria (Streptomycin, Amikacin, Netilmicin, Kanamycin)Anaerobic bacteria are

resistant to aminoglycosides

UTI G -ve bacillary infect:GonorrhoeaBowel sterilizationTopical –wounds,burns,dermatitisIntestinal amoebiasisTB

Genta IV,IM 7-8 mg/kg/D1,then 5mg/kg 12H Neonate5-7.5mg/kg/d 24H Streptomycin IM 20-30mg/kg (max:1G)ODAmikacin IV,IM Prem -15mg/kg/D D17.5mg/kg OD Term-15mg/kg/D OD 1 wk to 10yr -15 mg/kgNetilmicin IV,IM 1wk-10yr= 8mg/kg/D1 then 6mg/kgOD ,>10yr = 7 in D1 then 5mg/kg Neonate5 mg/kg/D OD

Unwanted effects1. Ototoxicity• irreversible results from progressive destruction of vestibular or

cochlear sensory cells(a) Vestibular dysfunction (Gentamicin, Streptomycin, Netilmicin)(b) Auditory dysfunction – Kanamycin , Amikacin (potent diuretics potentiate ototoxicity) 2. Nephrotoxicity • due to accumulation of aminoglycosides in the proximal tubular

cells

4. Others• rare - hypersensitive reactions• vague feelings of paraesthesia of the lips or circumoral region• prolong use -- superinfection, diarrhoea, malabsorption

can occur with neomycin

3. Neuromuscular blockade (reversible)due to inhibition of prejunctional release of ACh(Aminoglycosides potentiate d-tubocurarine)

I. First Generation Quinolones• Nalidixic acid II. Second Generation Quinolones• Norfloxacin• CiprofloxacinIII. New fluoroquinolones• Gatifloxacin• Moxifloxacin

• MOA• Bactericidal• Block bact synthesis by inhibiting bact DNA gyrase and

topoisomerase• Antibact spectrum--

E.coli,Salmonella,Shigella,Enterobacter,Campylo-bacter,Neisseria

Pseudomonas(Ciprofloxacin)

Staph( not MRSA)

Strep,Chlamydia,Mycoplasma,Legionella,Mycobact

Clinical Uses of Fluoroquinolones1. Urinary tract infections (Norfloxacin)2. Prostatitis (Norfloxacin, Ciprofloxacin, Ofloxacin)3. Sexually transmitted diseases

(Not for Treponema pallidum )4. Gastrointestinal & abdominal infections

– Traveller’s diarrhoea– Shigellosis (Norfloxacin, Ciprofloxacin, Ofloxacin)– Enteric fever (Ciprofloxacin, Ofloxacin)

5. Bone, Joint & soft tissue infections( osteomyelitis caused by Staph &G-ve rods)

6.Others

M.avium complex (in AIDS)

MDR TB

7. Meningococcal Prophylaxis

• Dosage

Ciprofloxacin- oral= 5-10 mg/kg 12H

IV = 4-7 mg/kg 12 H

Norflox = 10 mg/kg 12H

Prophylaxis

15 mg/kg oral single

Side effects

Generally well tolerated• nausea, abdominal discomfort, diarrhoea, headache,

dizziness, allergy, photosensitivity• cartilaginous erosion in foetus and children (arthropathy)

and tendonitis --- limited used in children age <14 years and pregnancy

• Increse BUSE• Transient ↑ in Liver enzymes,Bilirubin• Disturbance in vision,taste and smell• Risk of haemolysis in G6PD def;

• Drug interaction- Cipro,Ofloxa ,Peflox inhibit the metabolism of Theophylline

• Bacteriostatic• Competitive inhibitor of dihydropteroate

synthase which is responsible for the incorporation of PABA (para-aminobenzoic acid) which is essential for the formation of folic acid (pteroylglutamic acid)

Antibact spectrum Theraputic application

G+ve and –ve except pseudo,proteus

Chlamydia trachomatisToxoplasma

1.Urinary tract infection

2.Other Gram-positive and Gram-negative infections (in penicillin allergic patients)Trachoma & conjunctivitis (Sulfacetamide)Ulcerative colitis -SulfasalazineLocal infections: Dermatitis – Sulfapyridine Burns - Sulfamylon, Silver Sulfadiazine

Pneumocystis carinni Prophylaxis for HIV associated opportunistic infection

Malaria parasites Chloroquine resistant malaria (Pyrexine = Sulfadoxine + Pyrimethamine)

Untoward Effects

1. Renal toxicity• a local reaction with short-acting sulfonamides (high doses)• may precipitate in the urine(obstruction,haematuria)2. Haemopoietic reactions Anaemia-haemolytic/aplastic,granulocytopenia H’lysis in G6PD def: Neonatal jaundice in new-born babies(especially in last trimester—Haemolytic jaundice)

47antimicrobial agents III

3. Allergic reactions --- skin rashes, exfoliative dermatitis, photosensitivity --- more severe with long acting sulfonamides

• Stevens-Johnson Syndrome- mucosal, dermal, genital and occular lesions; joint pain, high fever, oedema, ulcerations of the lips and tongue- erythema multiforme on skin of hands and thighs- severe urethritis and balanitis in males

48antimicrobial agents III

Untoward Effects

• Synergists of Sulfonamides1. Trimethoprim 80mg + Sulfamethoxazole 400 mg

MOA of Cotrimoxazole• Sulfonamides are the competitive antagonist of PABA. They

inhibit the incorporation of paraaminobenzoic acid(PABA) to folic acid.

• Trimethoprim is a dihydrofolic acid reductase inhibitor. It prevents the reduction of dihydrofolate to tetrahydrofolate.

• Inhibition of two consequent steps in the synthesis of DNA and RNA of bacteria when a sulfonamide and trimethoprim are used together.(Sequential Blockade)

• Two bacteriostatic compounds act synergistically and become bactericidal

antimicrobial agents III 51

Antibacterial spectrum Rx uses Dosage

Streptococci, Staphylococci, NeisseriaE. coli, Salmonella, Shigella, Enterobacter Proteus, Klebsiella, Brucella, Chlamydiaexcept Pseudomonas aeruginosaPneumocystis carinii

(1)Urinary tract infections(2) Respiratory tract infections(3) Gonococcal infections (4) Enteric fever (5) Malaria (CQ resistant falciparum malaria)(6) Brucellosis(7) Pneumocystis carinii infection in AIDS Patient

TMP 1.5-3mg/kg 12H IV ,Oral PCP Tx 250mg/m2 stat

150mg/m 2 8H

Prophylaxis for UTI- 5 mg/kg oral PCP- 5mg/kg 3days/wk

Untoward effects- Same as S’.Megaloblastic A with prolonged Rx

Cont - Synergists of S’

2. Pyrimethamine also an inhibitor of DHFA reductase enzyme of malarial parasites and toxoplasmaPyrexine (or)

Fansidar = Sulfadoxine 500 mg + Pyrimethamine 25 mg

Therapeutic Uses --- Malaria, Toxoplasmosis

3. Tetracycline• in combination with sulfonamides produce

synergistic effects because both are bacteriostatic drugs

4. Penicillin:• although bactericidal, it produces a

synergistic effect when used in combination with sulfonamides.

Drug Interactions with Sulfonamides

• warfarin, sulphonylureas, diphenylhydantoin

(1) potentiation of action of other drugs due to competition at plasma protein binding site (drug displacement interaction)

(2) inhibition of metabolism

55antimicrobial agents III

Metronidazole(Nitroimidazole-antiprotozoal)

• MOA - Effect on nucleic acid metabolism

Potent antibacterial ,anaerobes , Bacteroides and Clostridium sp• Theraputic advantage • Anaerobic or mixed intraabdominal infection- Extraluminal amoebiasis - 30-50mg/kg/d oral- Amoebic liver abscess - 7.5to 30mg/kg iv 12H/8H x7-10 days

- Trachomonal vaginitis- Clostridium defficile colitis- Brain abscess

• Side-effects- GI disturbance,metallic taste,peripheral neuropathy,

seizures

Interacting drugs- Alcohol- Warfarin increase anticoagulant effect

(enzyme inhibition)

TETRACYCLINESBroad spectrum bacterostatic

Antimicrobial spectrum Tx - Infections with

Gram+ ve and –ve BacteriaRickettsiae,Mycoplasma,ChlamydiaSpirochetes (Treponema, Leptospira, Borrelia), Vibrio choleraeH.pylori E.histolytica Malaria parasites less effect on Strep, Staph, Pneunococci Not effective against – Pseudomonas,Proteus, Salmonella

Rickettsia Mycoplasma pneumonia Non-specific urethritis Trachoma,Syphilis,STDLeptospirosis, LymesCholera Combination Tx GU/DUAmoebiasisCQ resistant P.f

Dosage

oral –250-500 mg/ 6H( >8yrs) Eye ointment- apply 8H

Anti-TB1st lineIN(A)H

Rifampincin*

PZAEthambutolStreptomycin

10mg/kgoral od

TBM 15 -20mg/kg10-15 mg/kg

20-30mg/kg oral

25mg/kg oral20-30 mg/kg IM

Adverse effectsPeripheral neuro( recommended-B6 20-30mg/D )Hepatotoxicity,Rash

Hepatitis.nephritis,ITP

Hepatitis,Interstitial nephritisRetrobulbar neuritis,yellow-green colour vision defectOtotoxic,Nephrotoxic

2nd lineCapreomycinCycloserineEthionamideAzitho/clarithromycinQuinolones

20mg/kg oral5-10mg/kg oral15mg/kg oral

OtotoxicityCNS toxicityHepatotoxic

Bactericidal drugs

- Penicillins- Cephalosporins-Other --lactam antibiotics- Aminoglycosides- Rifampicin- Fluoroquinolones- Cotrimoxazole- Metronidazole

Bacteriostatic drugs

- Chloramphenicol - Tetracycline - Erythromycin- Clindamycin - Lincomycin - Sulphonamides

Broad-spectrum Antibiotics

- Broad-spectrum penicillins (Aminopenicillins and Antipseudomonal penicillins)

- Coamoxiclav- the second, third and fourth generation Cephalosporins- Tetracyclines- Chloramphenicol- Rifampicin

- Cotrimoxazole

Antipseudomonal Agents

- Carbenicillin, Carbenicillin indanyl- Ticarcillin- Piperacillin- The third generation cephalosporins- The fourth generation cephalosporins- Amikacin, Netilmycin- Fluoroquinolones- Polymyxin - topical application for wounds

Anti-infective agents which can be used for Staphylococcus

- Penicillinase resistant penicillins(Cloxa,Flucloxacillin)- AUGMENTIN (Coamoxiclav) (Amoxicillin + Clavulanic acid)- TIMENTIN (Ticarcillin + Clavulanic acid)- UNASYN (Ampicillin + Sulbactam)- ZOSYN (Piperacillin + Tazobactam)- Some first & second generation Cephalosporins - third & fourth generation Cephalosporins- Erythromycin- Vancomycin- Rifampicin- some fluoroquinolones

Anti-infective agents for anaerobic bacteria

- Metronidazole- Lincomycin, Clindamycin- Chloramphenicol- Fluoroquinolones- the third & fourth generation cephalosporins

Empiric antimicrobial Rx(based on site of Infection)

SOI Pathogens DOC Alternative

Meningitis -Neonate

Ampi+3rd Cepha Ampi(Cotri)+3rd Ce (+Aminogly)

-Child C/Pen +Cefotaxime or Ceftraxone

C.Pen+Chloram

Pneumonia-Neonate Ampi+3rd Cepha

-Younger child C/PenCefotaxime or Ceftraxone

Ampi -sulbactam

-Older child Macrolides Quinolines

SOI Pathogens DOC Alternative

IE acute

Vancomy+Genta Pen-resistant pen+Genta

SBE Pen G+ Genta Vanco+ Genta

Septic arthritis Ceftriaxone Ampi+Sulbactam

Acute OM,Sinusitis Amoxil Amoxil+SulbactCefuroximeTMP-SMZ

Cellulitis Pen-resistant pen VancomycinClindamycin

Peritonitis 3rd cephalo+Metro Carbapenem

Septicemia

(Granulocytopenia)Sepsis d/t UTISepsis d/t GITNeo sepsis Early --

Late -

3rd cephalo+VancoAntipseudo+Amino3rd cepha/ceftazidime3rd cephalo±Genta3rd cephalo +MetroAmpi+GentaAmpi+Genta+Clox/Van3rd Cephalo

STSA

Antiviral drugs1.NucleosideAnalogues*(synthesis of DNA&RNA)

Acyclovir*20mg/kg iv100mgodx 5 dGinclovirCidofovir

HSV1,2VZVCMVEBHHV6Hepa C

Herpes-oral,genital HS-EncephalitisVaricella(immu ↓)CMV retinitis,Pneumonitis

2.AmantadineRimantadine(penetration of cell)

100mg OD200mg OD

Influenza A,BH1N1,H1N2,H1N3

Influenza A-H1N1

3.Foscanet(DNA &RNAsyn:)20mg/kg iv over 30’

CMV,VZVHSV(Aciclovir resist)

CMV retinitis in HIV p/t

4.ImmunomodulatorInterferon α(inhibit the transcription)Plavizumab

Hepatitis B &CHPVCGDRSV

Chronic hepatitis B &C

RSV Bronchiolitis

5.Ribavarin(aerosol-20mg/ml 12-18hrly)(oral5-50mg)

RSV RSV BronchiolitisPn’ia

6.NeuraminidaseInhibitors(release of virus)Zanamivir/Oseltamivir

Influenza A & B Influenza A & B

7.AntiretroviralNRTI-competative inhibit: activated i/c byphosphorylationZidovudine(2mg/kg)Didanosine(ddI )Dideoxycytidine(ddC)Stavudine(d4T)Lamivudine(3TC) Adefovir

HIV

Hepa B

Side effects

A,neutropenia,myopathy

Pancreatitis,Periph neuro,DPeri neuro,pancreatitis,rashPeri neuro,A,LipoatrophyHeadche,N,abdo pain

NNRTI-inhibit viral replication by direct binding to RT Nevaripine120mg/m2 daily oral

HIV

Rash,Steven syn,Hepatitis

Protease Inhibitors-Interfere with post-translational processing of HIV precursor proteinsEg.Ritonavir IndinavirDose-500mg/m2 8H oral

Asymptomatic hyper bili-rubinemia,GI disturbanceSkin,hair changes

Major adverse effects

1. Nephrotoxicity eg. Foscarnet, Amantadine 2. Neurotoxicity - seizures eg. Nucleoside analogues, Amantadine(high dose),INFs 3. E imbalance- hypo K,hypo &hyper Ca eg.Foscarnet 4. Hypo & hypertension eg. INFs5.Bone marrow supression- neutropenia eg. INFs,Aciclovir6.GI disturbance eg.INFs

7. Flu like syndrome- F,fatigue, myalgia• eg. INFs

8. Teratogenic

eg.Aciclovir,Ginciclovir

9.Hepatic steatosis

eg. NRTI

How Does These Drugs Works…

Management in babies born to infected mothers

Scenarios Therapy

- HIV mother on HAART

- HIV mother started on zidovudine at 14-28 weeks gestation

Zidovudine

2mg/kg/dose QIDx 6wks OR

4mg/kg/does BDx6 wks

-HIV mother at delivery with inadequate prophylaxis (<4 weeks)

-Infant born to HIV mother without prophylxis

Single dose Nevirapine

+ Zidovudine

2mg/kg/dose QID 6 weeks

OR4mg/kg/does BD 6 weeks

Antifungal agentsbased on route of administration

1.Systemic

For deep fungal infection(oral/parenteral)

Amphotericin B (I.V) Flucytosine (oral)Imidazoles and Triazoles -Ketoconazole, Itraconazole-Fluconazole

For superficial fungal infections Griseofulvin (Oral)

2.Topical antifungal agents Clotrimazole (CANESTEN)- Miconazole-Econazole-Ketoconazole-Nystatin (MYCOSTATIN)

Miscellaneous MYCODERM

Drug Dose & Preparation

Rx Side effects

Ampho.B(fungistatic/fungicidal)

IV 1.5 mg/kg/dIntrathecalOral 100mg 6hCream,ointmentLocal installation

Local &systemic-Meningitis,Endocarditis due toCryptococcusCoccidioidesHistoplasmaCandida, BlastomycesAspergillus

HypersensitivityNephrotoxicLiver impairmentAnaemia,Hypo-k

Griseofulvin(fungiststic)

5-7mg/kg oralTopical

Broad spectrumMicrosporum,Epidermophyton, Trichophyton (Dermatophytosis) Superficial ringworm infestation (Tineacaptis,Tinea corporis,Tinea pedis)

PhotosensitivityPorphyriaHeadacheHepatitis

ImidazoleKetoconazoleMiconazole(broadspectrum)

5mg/kg oral,cream7.5-15mg/kg iv 8HTopical,vg cream

Supercial & DeepCandidaDermatophytes(Teniasis,Pityriasis versicolar)Seborric dermatitis

N,V,Pruritus,Rash,HepatitisFluid & H2O retensionGynaecomastia

Fluconazole

Itraconazole

Clotrimazole(fungistatic)

(penetrate readily toCSF) 3-6mg/kg oral /iv2-4mg/kg oral

Vaginal tab1%cream,oral

DermatophytosisCandidasisCryptococcusAspergillosis

CandidasisDermatophytosis

Itchiness,burning,Rash

No serious systemic side effect

Nystatin(fungistatic/cidal)

Cream,ointmentVg tabOral

Candidasis(oral thrush,GI,vaginal,Skin)

No systemic side effect

Summary

• Ampho B –drug of choice except candida• Griseofulvin –drug of choice for dermatophytes except aspergillus• Fluconazole ,Miconazole _ for candida/dermatophytes• Nystatin _ for candida

Anti-protozoal drugs

• Antmalarial drugs1. 4 Aminoquinolones CQ2. 8- Aminoquinolones Primaquine3. Arylamino alcohols Quinine, Mefloquine4. Anti-folates Sulphadoxine,Pyrimethamine5. Quinghaosu Artemisin

Blood schizontocidesCQQuinine

Mefloquine

Alleviate symptoms-a/c attackOral 10mg/kg x 3dOral 8.3mg/kg x7-10 dIv 20mg/kgx4h,8.3mg/kg 8H15mg/kg stat,10mg/kg a/f 6-8hr(Prophylaxis- 5mg/kg wkly)

Photosensitivity,n,v,reti-nal damageTinnitus,HglycemiaHypotension(cinchonism)Postural HypotensionCardiac conduct defect

Artesunate

Artemether

Oral 5mg/kg D1,2.5mg/kg D2-D3IV,IM 2mg/kg then 1 mg/kg 6HIM 3.2mg/kg stat 1.6 mg/kg daily

Relatively safe

SporontocidesPyrimethaminePrimaguineProguanil

Prophylaxis

Tissue schizointocides

PyrimethaminePrimaquineProguanil

To prevent parasites becoming established in the Liver25mg tab*0.3mg/kg daily X14 d3.5mg/kg oral

CI –PregnancyH’lysis in G6PDdef,BM˅,alopecia

HypnozoiticidesPrimaquine

To prevent relaspe

GametocidesPrimaquine

0.7mg/kg od

Mgt of Pl.falciparum(Paed:protocol)

• Uncomplicated

1st line-

Artesunate odx3D

Mefloquine od

Alternate:

Artemether/lumefantrine

2nd lineQunine

Clindamycin

• Complicated

1st line

IV Artesunate bdod

2nd line

IV Quinine oral

Doxycycline/Clindamycin

Antihelminthics Drugs Rx advantage Mode of Action Adverse Effects

Mebendazole50-100mg BDx 3D

TrichuriasisEnterobiasisAscariasis

Broad spectrum, inhibit microtubules, glucose absorption immobilization death

Worm migration (rare)

Albendazole 200-400mg single

TrichuriasisEnterebiasisAscariasisHookworm

Pyrantel pamoate10-11mg/kg ODRepeat in D14

TrichuriasisAscariasisEnterobiasis

Depolarization of the neuromuscular (Neuromuscular blocking agent)

Mild abdominal pain

Levamizole3mg/kg

Repeat in 1 wk

AscariasisEnterobiasis

Hookworm

Immunostimulants Paralysis of the muscle of the worm – expelled by peristalsis

Abdominal pain

Ivermectin 0.15-0.4mg/kg

Hookworm, filariasis, strongyloides

Membrane hyperpolarization ; paralysis

Abdominal distension , wheeze, TOC

Thiabendazole 200-400mg OD

Hookworm

• References:- Paed:Protocol (2nd edition)- Nelson Text Book (19th edition)- Basic and Clinical Pharmacology(11th edition)- Basic Medical Science(Easterbrook-3rd edition)