mbbs broad spectrum amas, macrolides and misc. amas class i

8/12/2019 MBBS Broad spectrum AMAs, Macrolides and Misc. AMAs Class I

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1. Broad spectrum AMAs

2. Macrolides

3. Misc. AMAs

Class I

Dr.U.P.RathnakarMD.DIH.PGDHM

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Protein synthesis inhibitors

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1. Broad spectrum AMAsTetracyclines

Chloramphenicol

2. Macrolides

3. Misc. AMAs

Clindamycin,

Streptogramins,

Linezolid

Vancomycin{Cell wall[-]}

Topical agents [Varied MOA]

Mupirocin

Fusidic acid

Polymyxin B, Colistin, Bacitracin, Tyrothricin

Aminogycosides


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BACTERIAL PROTEIN SYNTHESIS INHIBITORS

BROAD SPECTRUM MODERATE SPECTRUM NARROW

SPECTRUM

TETRACYCLINES MACROLIDES KETOLIDES LINCOSAMIDES

CHLORAMPHENICOL STREPTOGRAMINS

LINEZOLID

Topically used [Varied MOA]

1. Mupirocin

2. Fusidic acid

3. Polymyxin B, Colistin, Bacitracin, Tyrothricin

Cell wall synthesis inhibtor

Vancomycin

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18

Ch

AG

Protein synthesis in microorganisms

Exit PeptidylAcceptor
http://localhost/var/www/apps/conversion/tmp/scratch_2/Protein%20synthesis%20and%20inhibitors%20of%20synthesis.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_2/Protein%20synthesis%20and%20inhibitors%20of%20synthesis.wmv


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18-A

Protein synthesis in microorganisms

Step 1, the charged tRNA unit carrying amino acid 6

binds to the acceptor site {TC}

Step 2 (transpeptidation), Peptidyl tRNA at the

donor site, with amino acids binds the growing

amino acid chain to amino acid 6. {CHLO}

Step 3, Uncharged tRNA left at the donor site is

released

Step 4 (translocation), new 6-amino acid chain

with its tRNA shifts to the peptidyl site {E & C}

AG
http://localhost/var/www/apps/conversion/tmp/scratch_2/Protein%20synthesis%20and%20inhibitors%20of%20synthesis.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_2/Protein%20synthesis%20and%20inhibitors%20of%20synthesis.wmv


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Tetracyclines

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TetracyclineOxytetracycline

Demeclocycline

DoxycyclineMinocycline

Tablets,capsules, ointments, in ject ions


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Tetracyclines

MOA

7

Bind to 30S ribosomes &

prevent attachment t-RNA to A site

Peptide chain fails to grow.

The tetracyclines bacteriostatic;

TC


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Tetracyclines

Resistance

14

Not transported inside

Efflux mechanism Binding site for tRNA protected Inactivation enzymes

Cross resistance among other TCs Minocycline may be unaffected by cross

resistance

Partial cross resistance with chloramphenicol


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SpectrumTetracyclines[G+ve, G-ve, Aerobic, Leprae, anaerobic, ricketssiae, spirochetes, protozoa]

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G-ve bacilli- BrucellaV.CholeraY.Pestis

Spirochetes B.BurgdoferiB.recurentis

Mycoplasma pneumoniae

ChlamydiaCalymm granulomatisH.ducreyi

Ricketsia ricketsii

E.Histolytica

Propioni bacterium acne

Pseudomonas, proteus, Klebsiella, salmonella were never sensitive


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12

2. First choice

G-ve bacilli- BrucellaV.CholeraY.Pestis

Spirochetes B.BurgdoferiB.recurentis

Mycoplasma pneumoniae

ChlamydiaCalymm granulomatisH.ducreyi

Ricketsia ricketsii

BrucellosisCholeraPlague

Typhus, rocky mountain spotted fever, Qfever

Atypical pneumonia

Lymes diseaseRelapsing fever

Non sp.urethritisGranuloma inguinaleChancroid

Tetracyclines - Uses

1. Empirical therapy


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Tetracycline (T)

Oxytetracycline(O)

Demeclocycline Doxycycline (D)

Minocycline(M)

Source Fungus[O]

Synthetic[T]

Fungus Semisynthetic

Absorption-GIT Moderate Moderate Complete, food

does not interfere

Excretion Renal Renal Dox-FaecesMino-Bile and renal

Plasma half life 6-10h 10-18h 18-24h

Suprainfection High Moderate Least

Phototoxicity Low Highest HighDose 250-500 mg QID 300mg BD 200100mg OD

Toxicity

Renal

Hepatic

SuprainfectionBone & teeth

Less

tooth

discoloration[O]

Diabetes

insipidus

[Dox]-less renal

toxicity

[M]-Vestibular

toxicity

Tetracyclines


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10

Tetracycline (T)

Oxytetracycline(O)

Demeclocycline Doxycycline (D)

Minocycline(M)

Source Fungus[O]

Synthetic[T]

Fungus Semisynthetic

Absorption-GIT Moderate Moderate Complete, food

does not interfere

Excretion Renal Renal Dox-FaecesMino-Bile and renal

Plasma half life 6-10h 10-18h 18-24h

Suprainfection High Moderate Least

Phototoxicity Low Highest HighDose 250-500 mg QID 300mg BD 200100mg OD

Toxicity

Renal

Hepatic

SuprainfectionBone & teeth

Less

tooth

discoloration[O]

Diabetes

insipidus

[Dox]-less renal

toxicity

[M]-Vestibular

toxicity

Tetracyclines


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9

Tetracyclines

ADEs Irritation: GIT, i.m. sites, i.v. [phlebitis]

Hepatotoxic- Jaundice[accumulate in liver], hepaticnecrosis in pregnacy

Kidney: Nephrotoxic [existing disease] except Doxy.Date expired-Fanconi syndrome

Phototoxicity

Teeth & Bones-[Pregnancy, lactation & children]

Metabolism: catabolic effect

Diabetes insipidus-Demeclocycline Vestibular toxicity-Mino

Superinfection: Doxy & Mino less likely

Hypersesitivity

Intra cranial tension- infants


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Glycyclines

Tigecycline

Tigecycline, derivative of minocycline, Structurally similar to the tetracyclines

Expanded broad-spectrum activity

MRSA, multidrug-resistant Streptococcus pneumoniae,

VRE, lactamase producing gram-negative bacteria, manyanaerobic organisms.

Not active against Proteus, and Pseudomonas species.

30- to 60-minute intravenous infusion every 12 hours Use- Serious community acquired pneumonia.

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TC-Administration

Oral-preferred form

Not in pregnancy, lactation & children

Caution-hepatic & renal insufficiency Strict adherence to expiry date

Do not mix with other agents

Not intrathecally

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Chloramphenicol

MOA

18

Bind to 50S ribosomes &

Prevents chain elongation

Peptide chain fails to grow.

C


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Chloramphenicol[Mechanism of Action]

Chloramphenicol inhibits protein synthesis

Prevents binding of peptide chain to new t-RNA

Chain elongation inhibited

Bacteriostatic [Cidal-H. influenzae, Neisseriameningitidis,and S. pneumoniae]

Broad spectrum

Can inhibit mitochondrial protein synthesis inmammalian cells

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Chloramphenicol[ADEs]

Dose related bone marrow suppression-reversible

Aplastic anemia-Idiosyncratic-fatal

Gray baby syndrome-overdose in neonates,

especially if premature [vomiting, refusal to

suck, irregular and rapid respiration, abdominal

distention, periods of cyanosis, and passage ofloose, green stools ]

Hypersensitivity

GIT 5


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Chloramphenicol[DIs]

Enzyme inhibitor[DIs] oralantidiabetics, warfarin, phenytoin.

Rifampicin & phenobarbitone enhancemetabolism of chloramphenicol

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Chloramphenicol[Precautions]

Never when others are available Do not repeat

Less than 2 weeks,

Daily


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Chloramphenicol[Uses]

Chloramphenicol is an occasion al alternat ive to

more standard therapy for

1. Meningococcal, H influenzae, or pneumococcal

infections of the CNS;

2. Anaerobic or mixed infections in the CNS, eg, brain

abscess;

3. Alternative to tetracyclines in rickettsial infections,

especially in pregnant women, in whom tetracycline is

contraindicated.

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Chloramphenicol[Uses]

When other antimicrobial drugs that are equallyeffective and potentially less toxic are available, they

should be used instead of chloramphenicol

Top ical ly in eye-no t in sk in

1

mbbs broad spectrum amas, macrolides and misc. amas class i

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