Pharmacology
• Antimicrobials
Lecture No.-01 Dr Ankit Kumar (MD, DM)
1 Classification
2 Cell wall inhibitors
3 Cell membrane inhibitors
• Antimicrobials
CLASSIFICATION T/+ of Infection
natural source (Bacteria obtained) → 4- Antibiotics
Antimicrobial
synthetic
AntimicrobialsClassification
PEPTIDOGLYCAN
β ② Cell wall:
1. Cell wall inhibitors ↳ ② Cell Memb: STEROL
2. Cell membrane inhibitors ③
4 5
DNA Proteins Folic acid
synthesis
3. DNA/Nucleic acid inhibitors
4. Protein synthesis inhibitors
BACTERIA
5. Folic acid inhibitors
Cell wall
PEPTIDOGLYCAN
synthesis
inhibitors
• Beta lactams (penicillin, cephalosporin, carbapenem, monobactam)
B
group: PCCM MOA: inhibit Transpeptidase enzyme
B • Bacitracin ✓
C • Cycloserine
inhibit Transglycosylase
④
• Getting: Glycopeptides (Vancomycin, teicoplanin) : MOA:
group
F • FAMOUS: Fosfomycin ✓
① All above DRUGS are BACTERCIDAL → except CYCLOSERINE
(IDAD STATIC
② All DRUGS are NOT effective in ATYPICAL BACTERIA QQ.
LACK Cell
◦ MYCOPLASMA
wall
◦ CHLAMYDIA
◦ RICKETTSIA
• Bacitracin
obtained from BACILLUS SUBTILIS
MOA: inhibit
kills Gram ⊕ cocci → STAPH- , STREPTOCOCCI
Bactrophenol
only Topical CREAMS
* dephosphorylase
Never i/v → Highly Nephrotoxic
MOA: inhibit
• Cycloserine I MDR-TB,
* Alanine Racemase/
SE: CNS → Psychosis Ligase
Depression (↑ suicides)
/ MOA: inhibit
Kills Gram ⊖ Bacteria, Enterococcus
ENOLPYRUVATE
• Fosfomycin T + UTI → DOSE: 39ms Per oral
Transferase.
single dose
Beta Lactams group
p 1. Penicillin MOA: Inhibit Trans peptidase enzyme.
C 2. Cephalosporins All are Bactericidal
C 3. Carbapenems
M 4. Monobactam
STRUCTURE
Common Different
BETA LACTAM
① Penicillins
RING.
C SIDE ② Cephalosporin
C
Ring ③ CARBepenem
1 BLR
* MONO BACTAM > No side Ring
€
1 S PECTRUM of Activity
inhibit Transpeptidase ② Sle: HYPERSENSITIVITY
-
Penicillin = cephalosporin ⇐ Carpaper
0 Cell wall synthesis CROSS Allergy: on
Q: If a pt is Allergic to Penicillin: would you cephalosporin or
Carbapenem.
Ans: NO → CROSS Allergy
Monobactam can be given: NO CROSS Allergy
♀
Penicillin's group
- CILLIN
• Penicillin G → #BENZYL P1 /CRYSTALLINE Pr
(FUNGUS)
HISTORY: Only natural penicillin
Notatum (Alexander flemming)
1ˢᵗ obtained: Penicillium
Penicillium Crysogenum (chain & florey)
Commercial synth:
USES
DOC
PNG
S YPHILLIS
Neurosyphillis
changed now
Meningococcal meningitis *
A CTINO MY COSIS
R AT BITE FEVER. (SUDOKU fever)
T ETANUS
Player : PASTURELLA multiocida
G AS Gangrene (MYO NECROSIS
A nthrax
Y AINS
L EPTOSPIROSIS
E very species STAPHYLOCCUS & STREPTOCCUS if sensitive /now days: Resistance)
Meningoccal Meningitis (Neisseria meningitidis
ing. CEFTRIAXONE > > Pn G-
TI DOC
CLOSE contact: Prophylaxis to eliminate NASAL Carriers
* DOC ORAL CIPROFLOXACIN.
CEFTRIAXONE
* Pregnancy & children: ing.
Penicillin HYPERSENSITIVITY.
Hypersensitivity
→ CAUSE All types of HS
Type I: Immediate → Allergy (RASHES, urticaria)
↳ Anaphylaxis.
Type 2: Hemolyte Anemia [Coombs test ⊕].
→ incidence: 2- 41.
Type}: serum sickness
↳ Type 4. : Delayed type
→ CROSS Allergy
carbapenems.
Don't give Cephalosporin
Monobactam [AZTREONAM] is safe.
> Erythromycin
DOC Penicillin Allergy
Azithromycin (MACROLIDES)
overcome
NEIN Synthetic Penicillins
→ 4 DRAWBACKS
Penicillin G
Drawback of Penicillin G New synthetic penicillin
Acid labile 1 Acid stable penicillin
Short acting ② Long acting penicillin ✓
Narrow spectrum 3 Extended spectrum penicillin
Acquired resistance ④ a) Penicillinase resistance penicillin
b) Beta lactamase inhibitors
1
Pn G: Acid labile Acid stable penicillin : not degraded by HQ
ORAL
ORAL Png: degraded by HQ
in stomach. V V: Penicillin V > if Phenoxy Methyl Pr
O Oxacillin
BA
Poor ORAL D Dicloxacillin → KI FLU CLOXACILLIN.
* Png → injections only
C Cloxacillin
A Ampicillin
A Amoxicillin
Best ORAL Amoxicillin
BA
*
* tood does not reduce Absorption of Amoxicillin
2
Pn G: Short acting Long acting penicillin
RAPIDLY excreted through kidney
into URINE
1. Penicillin G + Probenecid inhibit OATP in
IM depot injection
by OATP Transporter 2. Procaine Penicillin
REPOSITORY injection)
(Organic Anion Transport protein)
3. Benzathine Penicillin
. Never in
Procaine → neurotoxic
Benzathine Pr Benzathine → cardio toxic
Pn →
♀ longest
Png + Probenead
Q Aqueous Pr
Procaine- Pn
Longest (the ≈ 1 month)
Benzathine Pn
① • Prophylaxis of Rheumatic fever
DOC.
✗ 6 months.
1. 2 million IU I/m once a month
DOSE:
→ All STAGES of syphilly
• Syphilis
② DOC
except: Neurosyphilles (give Aqueous Pn)
Syphilis > TREPONEMA Pallidum.
• Primary syphilis (CHANCRE: genital ulcer) Benzathine Pn
• Secondary syphilis
• Early latent syphilis </yr) 2. 4 million IU i/m once.
[one injection only]
2.4 ✗ 3
• Late latent syphilis (> 1 year) Benzathine Pn
• Tertiary syphilis
2. 4 million 20 i/m once a week ✗ 7. 2
• Cardiovascular syphilis ,
for. 3 weeks
• Neurosyphilis AQUEOUS Pn (Png or Procaine Pn)
• Syphilis with penicillin allergy Doxycycline >> Erythromycin
• Syphilis in pregnancy
Penicillin Densensitization
c-PenicillinAllergy
Penicillin Hypersensitivity in syphilly
99
66
¥5 JARISCH HER ✗ HEIMER Reaction
Pn
Blood •a ◦
tell Immune
-y O compla
Antigens YYY Antibody-
syphils
depostrgan
Type 3 HS
JarischHerxheimer
Reaction
④
PnG: Narrow spectrum Extended spectrum penicillin
not effective in Enterobacteraceae effective Against Enterobacterance
*
E Coli, Pseudomonas,
Klebsiella, etc
(Gram ⊖ family)
Amino - Pn Carboxy - Pn Ureido -Pn
A2 CT MAP
Ampicillin Carbenicillin Mezlocillin
Amoxicillin Ticarcillin Azlocillin
Q
Piperacillin
1. E coli
2. Pseudomonas ✓
3. Klebsiella ✓
CT, MAP
Q: Pn is effective in Psuedommas
= injections
MAP.
Q: Pn is effective in Klebsiella
Q Pn can be orally → A²
♀ All are effective in Salmonella and Shigella!
Ampicillin ORAL & ing. Amoxicillin
DOC Streptococcus Pneumoniae
DOC LISTERA meningitis
→ ENT infection
DOC Enteroccocal fecates → Community Acquired pneumonia
More effective in Salmonella (typhoid)
More effective in H. influenzae < Vs
Shigella
DOC
CEFTRIAXONE
* Better oral Abs
* Less oral Abs
Bile → Less Risk of
* Less excretion in
Diarrhea.
* Excreted in Bile (maximum) → High RISK of
Diarrhea
# EBV infection → ↑ Allergic Rashes
Ampicillin
• Bile
Hampe bact-4 f Dianhee
kill intestine
[Clostridium difficile].
good bacture.
Q BAC-Ampicillin → Better oral absorption
→ Prodrug of Ampiceller
PIVA-Ampicillin
Acquired resistance a) Penicillinase resistance penicillin
in BACTERIA
4
b) Beta lactamase inhibitors
Q
1. Resistance in Staphylococcus > Streptococcal, Neisseria Gonorrhea
CAUSE: Penicillinase enzyme production > Degrade Png
OVERCOME Resistance: Penicillinase Resistant Penicillins
2. Resistance in Enterobacteriaceae (E.coli, klebsiella, Psuedomonas etc)
extended spectrum) Degrades Extended Spectrum Pn.
CAUSE: ESBL enzyme
Beta Lactamase is 3rd Gen Cephalosporins
Combining extended spectrum Pn + Beta Lactamase ⊖
OVERCOME resistance:
or
inhibit ESBL enzyme
3rd Gen cephalosporins
1. Resistance in Staphylococcus
> Streptococcal, Neisseria Gonorrhea
→ Degrades Png
Penicillinase sroducing STAPH. AUREUS
It Penicillinase Resistant Penicillins
Sle
◦ clotting factor: Bleeding.
CLOXACILLIN oral
✓
Hepatotoxic
✓ ✗ ACILLIN oral
Neutropenia
✓ NAFICILLIN ing.
Hepatotoxic
✓ DICLOXACILL.in oral
Interstitial nephritis
✗ Methicillin ing.
no Longer used.
1. Resistancein Staphylococcus> Streptococcal,NeisseriaGonorrhe
Penicillinaseresistancepenicillin
Cloxacillin
STAPH. AUREUS
Oxacillin Penicillinase enzyme production
Resistant
Naficillin
1- Penicillinase Resistant Pn
Dicloxacillin [CONDM]
Methicillin
Another. Resistance
MRSA (Methicillin Resistant Staph aureus)
MRSA (MRSE)
Resistance: mutation in Trans peptidase enzyme
Protein)
(Ms: PBP-2A: Penicillin Binding
encoded by MEC-2A gene
All Penicillin
MRSA is Resistant to ALL Beta Lactams
in Cephalosporin
" Carbaperon
" Monobaction
except: 5ᵗʰ Gen
cephalosporins) Resistant
Tft MRSA
ORAL DRUGS To sical CREAMS.
i V DRUGS (SERIOUS
infection) QQ
(skin, softtissue)
DOC VANCOMYCIN (TEICOPLANIND • Clindamycin Mupirocin (21)
• Cotrimoxazole
FUSIDIC Acid
◦ FQ
URSA: LINE ZOLID
◦ Rifampicin
◦ Linezolid
LRSA: STREPTOGRAMIN
DOC MRSA → VANCOMYCIN
SRSA: DAPTOMYCIN
TIGECYCLIN DOC VRSA → Linezolid (in India)
LEFAMULIN ↳ DAPTOMYM (in US A)
CEFTAROLINE/CEFTABIPROL (5ᵗʰ Gen Cephalosporin)
2. Resistancein Enterobacteriaceae(E.coli, klebsiella,Pseudomonase
* ESBL producing Enterobacteriaceae → Degrades extended spectrum Pn
[Gram ⊖]
&
3rd Gen cephalosporin
¥ Beta Lactamase inhibitor: combined with
inhibit ESBL
Penicillin /3rd Gen cephalosporins Beta lactamase inhibitors
Amoxicilllin Q Clavulanic acid
Sulbactam
Ticarcillin
Tf of ESBL producing
enterobacterance
Ampicillin Sulbactam
Cefoperazone
But DOC IS
Piperacillin Q Tazobactam
CARBEPENERS
Ceftolozane
ESBL producing Enterobacteriaceae Metallo-betalactamase→producing
Resistant to ESBL
NDM-1
enzyme
CRAB
♀ SULBACTAM (alone) → kill Acinetobacter baumanii
Above drugs NEW BETA LACTMASE INHIBITOR CRKP
Carbanemens
STORY
Gram negative infection: Community Acquired infection
E. Cole UTI/Dianhee
Typhoid DOC 3ʳᵈ Gen Cephalosporin
Meningococci Extended spectrum Pn.
Gonococci
H-influenzae
• ESBL enzyme: HOSPITAL Acquired infection
Resistant Bacteria
(Nosocomial)
- Acinetobacter
= Pseudomonas * DOC : CARBAPENEMS
Burkonderia. * Beta Lactamase 0 Combined I
Proteus.
Serratia A 4ᵗʰ Gen cephalosporins
Abobacter
8 CARBEPEMEMASE → DEGRADES CARBA perems
Another
enzyme
Also
Metallo beta Lactamase)
# New Beta Lactamase inhibitor 1 CARB PERMS.
°C
inhibit
② COLISTIN CDRUG OF LAST Resort
TIGECY Clue
BLOCK Metallo beta Lactamase
NEW
Beta lactamase inhibitors Combined with:
Avibactam Ceftazidime
Q I carbaperon Resistant
Vaborbactam → Meropenem
carbapenems infection
Relebactam imipnem Q
Beta lactam antibiotics Beta lactamase inhibitors
Amoxicillin Clavulanic acid
Ticarcillin
Ampicillin Sulbactam Inhibit ESBL
Cefoperazone
Piperacillin Tazobactam
Ceftolozane
Ceftazidime Avibactam
→ inhibit Metallo beta
Meropenem Vaborbactam Lactamase enzyme.
Imipenem/Cilastatin Relebactam
I Carbaperers Resistant
infection.
Summary
Gram ⊖ infection
3rd Gen cephalosporin > extended
DOC Community Acquired infection
* spectrum
penicillin
→ • ESBL DOC Canbapenems. > combined [
DOC Hospital Acquired infection
*
Beta Lactamase
New: Metallo betatactamase DOC COLISTIN
(Degrade Carbapemens)
Cephalosporins
Generation Spectrum Use Drugs
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Thank you
