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Venus Eisha L.

Barte
Medicine 2A

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Drugs against pathogenic microorganisms
without affecting the host cell

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Spectrum of bacterial activity
 Narrow: (Selective, gm + or gm -)
 PCN
 Aminoglycoside
 Macrolides
 Broad: (All)
 Chloramphenicol
 Tetracycline
 Quinolone
Effect on Microorganisms
 Cidal: Kills pathogenic microorganism
 Static: Inhibits growth and multiplication of pathogenic microorganism
 Examples:
 Vermicidal – Kills the intestinal border
 Vermifuge – paralyze the parasite
Source
 From living source - Antibiotics
 Non living source – Chemotherapetic agents (Sulfur, INH, minerals)

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1. Interference with wall synthesis
2. Altering the permeability of the cell membrane
3. Interference with CHON synthesis
4. Interference with nucleic acid and metabolism

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Bacitracin
Cephalosporin – A B lactam antibiotic
Cycloserine
Penicillin – A B lactam antibiotic
Resticetin
Vancomycin – Not an aminoglycoside

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Amphoterecin B – anti fungal
Colistin
Imidazole – anti fungal
Nystatin
Polymyxin

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Aminoglycoside
Chloramphenicol – original
 Bactericidal / static to a few organisms
Lincomycin (Clindamycin) – for anaerobic
microorganisms
Macrolides (Thromycin)
 Original: Erythromycin
 Static, but with max. dose can be cidal
 Latest: Claricid (Expensive cidal drug)
 Claricin: SARS
Tetracycyline - static

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Chloramphenicol
Lincomycin Act on 50s sub unit of bacterial
ribosomes
Macrolides

Aminoglycoside
Act on 30s sub unit of bacterial
Tetracycline ribosomes

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Clofazimine - cidal
Griseofulvin
Metronidazole – cidal, anerobic
Nalidixic acid
Novobiocin
Pyrimethamine
Quinolone – cidal, acts on DNA gyrase enzyme
Rifampin – RNA acting, cidal, anti TB, meningococcemia
prophylactic agent
Sulfonamides – a chemotherapeutic agent
 Sulfamethoxazole + Trimethoprim = Cidal effect
 Sulfadoxine + Pyrimethamine (Fancidar) = For malaria, cidal
Trimethoprim
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Identify the causative organism
Choose the best, the most appropriate drug use
if only when necessary
Consider the nature of illness and health status
of patient
Given an adequate dose so that blood level
shall either be cidal or static
Evaluate the clinical response and maintain
blood level for sometime even after s/sx have
disappeared
Have an adequate knowledge of the drug to
use
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To provide broad coverage (In mixed bacterial
infections)
For initial (Blind) therapy when patient is
seriously ill and results of culture are pending
To provide synergism when organisms are not
eradicated with any single agent
To prevent the emergence of resistance – Multi
drug therapy

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Cidal + Static = Antagonism
 1+1 = 0
 Cidal acts on rapidly multiplying bacteria while
static prevents multiplication
Static + Static = Additive or same
 1+1 = 1
Cidal + Cidal = Synergism
 1+1=3

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Microorganisms produce enzymes that destroy
the active drug
Microorganism develop and altered enzyme
that can still perform its metabolic function but
less affected by the drugs
Microorganism changes their permeability to
the drug
Microorganism develop an altered structural
target for the drug
Microorganism develop and altered pathway
that bypasses the reaction inhibited by the drug

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MIC (Minimum Inhibitory Concentration) –
Lowest concentration of drug that inhibits visible
growth after an overnight concentration
MBC (Minimum bactericidal concentration) –
Lowest concentration of drug that kills at least
99.9% of the original bacterial inoculum
Bacteriostatic – MBC > MIC
Bactericidal – MBC = MIC
PAE (Post antibiotic effect) – Time period after an
exposure to and removal of an antimicrobial agent
during which inhibition of bacterial growth 14
Inhibits Nucleic Acid Synthesis (Quinolone)
Inhibitors of CHON synthesis
(Aminoglycosides)

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Natural Penicillin
Penicillinase resistant
Aminopenicillins
Extended spectrum

Living source of PCN:


 Penicillium notatum arizegenum?

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Penicillin V (Phenoxymethyl Penicillin)
 Narrow spectrum
 Acid stable
 Penicillinase sensitive
 Give PO since
Penicillin G (Benzylpenicillin)
 Narrow spectrum
 Acid labile (Sensitive to HCl)
 Penicillinase sensitive
 Parenteral (IM, IV, intrathecal)
 Vial

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Methcillin (Staphcilin)
 Acid labile with narrow spectrum
Isoxazolyl
 Drugs:
 Cloxacillin (Tegopen)
 Dicloxacillin
 Flucloxacillin – A staphlotoxin, can also be parenteral / capsule
 Oxacillin (Bactocill)
 Narrow spectrum, acid stable, Highly protein bound:
90-97% (High protein bound = Reduced frequent
administration)
Nafcillin (Uripin)
 Penicillinase resistant
 Narrow spectrum, poorly absorbed 88% protein bound
only 18
Drugs
 Ampicillin
 The parent compound
 Less absorbed
 Amoxicillin – q8o, most widely used
 Better penetration even with purulent sputum, can be taken with
food, and also parenteral
 Bacampicillin – a prodrug in the liver
 Epicillin

Has gm + and – activity


Acid stable
Penicillinase sensitive 19
Drugs
 Azlocillin
 Carbenicillin
 Mezlocillin
 Piperacillin – Most expensive
 Ticarcillin

More on gm (–) activity, acid labile,


penicillinase sensitive

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Due to penicilloic acid – antigenic substance
from penicillin, common in expired products
There is a release of Ag-Ab reaction

 Drug Organism

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Type Incidence Ab Time after
PCN
exposure
Immediate 0.02-0.2% IgE 0-30 mins
(Anaphylactic)

Accelerated 1-3% IgE, IgM 30-72hr


(Parenteral)

Delayed IgE, IgM/IgG 5-21 days


(Serum
sickness)
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S CH3

R—C—NH— CH – CH C—CH3
B A

O=C N CH—COOH

D C

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A = Thiazolidine ring
B = B lactam ring
 (B lactamase enzyme, destruction site by
penicillinase, cephalosporins)
C = Site of salt formation
D = Site of penicillinase action
R = Side chain

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Drug Preparation Duration

Benzathine Pen G IM 15-30 days

Crystalline Pen G IM, IV, intrathecal 4 hrs. Order 4h


(K or Na) (for meningitis) RTC

Procaine Pen G IM 24h


(One
administration/day)
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50-70% of cases of early syphilis and later
stages of syphilis
Occurs abruptly after therapy manifested by
fever, headache, myalgia, and malaise and may
last 24 hrs.
Due to release of toxins of T. pallidum
Ask health hx of syphilis

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S

H2N—CH—HC CH2 5 O
2

6 C N C—CH2—O—C
3
O C CH3

COOH

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#1 and #7 I cannot find

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1 = Dihydrothiazine
2 = B lactam
3 = Site of action of Cephalosporins
4 = Site of salt action
5 and 6 = Site of substitution
7 = Aminocephalosporanic acid

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1st generation drugs
 Cefa: LZ
 loridine
 zoline
 Cepha: DLLP
 drine
 lexin
 lothin
 pirin

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2nd generation: AAAMOOOOOU
 Cef:
 aclor
 amandole
 amezole
 minox
 onicid
 oramide
 otetan
 otiam
 oxitine
 uroxime

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3rd generation DIOOOTTTT
 Cef:
 diner
 ixime
 odizime
 operazone
 otaxime
 tazidime
 tibuten
 tizoxime
 triaxone

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Fourth generation
 Drugs
 Cefditoren
 Cefepime
 Cefpirome
 Has more anaerobic activity

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1st gen 2nd gen 3rd gen 4th gen

Gm (+) +++ +++ + +++

Gm (--) + ++ +++ +++

Anaerobes (--) (+)/(--) (+)/(--) ++++

Enterococci (--) (--) (--) (--)

Bbrain (--) (+) +++ +++


distribution [Cefuroxime only]

Dosing q6-8hr q8-12h q6-24h (For q12hr


interval brain abscess)

Elimination Kidney Kidney K / Liver K

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Suspected bacteremia (Most likely the gm --)
especially in debilitated and
immunosuppressed patients. Usually given
with an aminoglycosides
Surgical prophylaxis: Given 2-6hrs before and
12-24hrs after a surgical procedure having
more than 5% risk of infection
Mixed infections especially those including
anaerobes involving chest, abdomen, or pelvis
Penicillinase producing N. gonorrhea
Gm (--) rod bacterial meningitis – 3rd gen is
DOC 34
Monobactam
 Aztreonam (Azactam)
 Active against Gm (--) aerobes only
 No activity against gm (+) organisms and anaerobes
 Ex:
 E. coli
 K. pneumoniae
 H. influenza
 N. meningitides
 N. gonorrhea

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Carbapenens
 Imipenem (Primaxin) – Widest spectrum B lactam
antibiotic
 Cilastatin – Given in combination with imipenem
 A potent selective enzyme inhibitor
 Ensures urinary antibiotic concentration
 Nephroprotective effect

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- Drugs in combination of PCN and B lactamase
inhibitors
- Drugs:
1. Clavulanic acid
From Strep. clavuligerus
2. Sulbactam
1. Semi synthetic copound derived from 6-APA
2. By forming a complex with the B-lactamase, they
render the enzyme inactive so that a B lactam
antibiotic can destroy the organism

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Amoxicillin + Clavulanic acid (Augmentin) =
PO
Ticarcillin + Clavulanic acid (Timentin) = IV
 For gm (--)
Ampicillin + Sulbactam (Uripin) = IV

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THE END
God bless you

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