ANTIMICROBIAL AGENTS Dra. Teoxon Prepared by: Ernie G.

Bautista II Definition of terms  Chemotherapy – drugs that treat diseases  Antimicrobial drugs – interfere the growth of microbes within a host  Antibiotic – substance produced by a microbe that in small amount inhibits another microbe.  Selective toxicity – drugs that kills harmful microbes WITHOUT damaging the host o Toxic to a specific bacteria History  1928 – Alexander Fleming discovered penicillin o Penicillum – from FUNGI  1940 – Howard Florey & Ernst chain able to produce enough penicillin in 1940 to experiment with its effects on mice. CELL WALL synthesis Penicillins Monobactams Cephalosporins Vancomycin Carbapenems Chlorampenicol Aminoglycosides Macrolides Tetracyclines Fluroquinolones Rifampicin/ Rifampin Sulfonamides Timethoprim Pyrimethamine

INHIBIT CELL WALL SYNTHESIS/ (4) B-Lactam antibiotic
1. PENICILLINS  Originated from fungi, can kill spirochetes o Penicillin G – acid labile (easily destroyed by acid); do not give orally; given systemically/ IV o Penicillin V – acid stable; given orally o Methiallin o Nafcillin resistance to B-lactamase o Oxacillin o Cloxacillin o Ampicillin broad spectrum; either systemic o Amoxicillin or orally; for gm (+/-) o Carbenicillin o TIcarcillin antippseudomonans o Piperacillin (Pseudomonas auerrginosa)  Pen G & Pen V = are narrow spectrum MODE OF ACTIONS st  1 step – binds to penicillin-binding CHON (PBPs)  2nd step – inhibits activity of transpeptidase o Enzyme cross linking of peptidoglycan chains o LYSIS o Only for those with (+) cell wall rd  3 step – activate autolysin MECHANISM OF RESISTANCE  Penicillinases (B-lactamase) breaks lactam ring structure (ie. Staphylococcus)  Structural change PBPs  Change in porin structure ADVERSE EFFECTS  Hypersensitivity (5-7 %) – most common AE  GI distress – diarrhea; epigastric pain  Jarisch-Herxheimer reactions o Patient with syphilis then treated with penicillin suffer this reaction o A transient Hypertension (secondary)  Interstitial nephritis (caused by methicillin)  Maculopapular rash (caused by ampicillin) o Elevated lesion at least <5 mm with erymathous border  “TIGDAS”

2. CEPHALOSPORINS 1 Gen (CEPH) Cephalothin Cephalpirin Cephradine Cephalexin Cefazolin Cefadroxil
st

2 Gen (CEF) Cefamandole Cefuroxime Cefonicid Cefaclor Cefonitin Cefotefan Cefprozil Ceforanide Cefmetazole

nd

3 Gen (CEFT) Ceftzoxime Ceftriazone Ceftazidime Ceftibuten Ceftaxime Cefixime Cefpodoxime Cefoperazone Cefdinir

rd

4th Gen Cefepime 1 generation cephalosporin  Effective in gm (+) cocci; some gm (-) bacilli  NOT MRSA (Methyl Resistance Staphylococcus Aureus)  Doesn’t enter CNS, can’t cross BBB  Ex: gm (-) kleibsiella  Not for meningitis 2nd generation  For gm (-) anerobes  Doesn’t enter CNS 3rd generation  Gm +/- cocci ; (-) rods  Enter CNS (traverse BBB) – except Cefoperazone  (+) meningitis & meningococcemia 4th generation  Broad spectrum (only LAST option; expensive)  Prescribe if patient become resistant  Resistant to most B-lactamases  Use for any type of bacteria ADVERSE EFFECTS  Hypersensitivity (2%)  IV injections – can cause phlebitis (must SLOW IV push)  If IM – there is PAIN 3. Carbapenems 4. Monobactams *CEFTRIAZOME – DOC for Gonorrhea; painful (IM)
st

PROTEIN synthesis

NUCLEIC ACID FOLIC ACID

IMIPENEM & MEROPENEM  MOA: same as penicillin  Drug resistance: resistance to B-lactamase  Coverage: gm (+) cocci; gm (-) rods; anaerobes AZTREONAM (Azactam)  MOA: monobactam inhibitor of transpeptidation  DR: resistance to B-lactamase  Coverage: gm (-) rods VANCOMYCIN  MOA: acts at early stage of cell wall synthesis binding at the D-ala pentapeptide to sterically hinder the transglycosylation reactions involved in elongation of peptidoglycan chains  Coverage: MRSA gm (+) cocci o ex. Enterococci; o anaerobe clostridium difficile (back up drug)  ? when taken with clindamycin, give metronidazole  DR: o Vancomycin resistance staph. aureus (MRSA) o Vancomycin resistance enterococcus (VRE)  Adverse effect o Ototoxicity – CN8 damage o Hypotension o Diffuse hyperemia (red man syndrome)

AE: discoloration of teeth (not recommended for fetus or <6 years & pregnant women

o

BELOW the diaphragm is METRONIDAZOLE

AMINOGLYCOSIDES  MOA: interfere with initiation codon functions  Block association with 50s ribosomal unit (STATIC) & misreading of code (CIDAL)  “Bacteriostatic & Bacteriocidal”  Insertion of A.A. at 30s ribosome  Examples: “MYCIN/ MICIN”
o o o o o o o o Streptomycin, neomycin, kanamycin, *amikacin, gentamycin, tobramycin, *sisomicin, netilmicin

FOLIC ACID SYNTHESIS

 

More active at ALKALINE pH AE: otoxic & nephrotoxic (must request for audiometry)

CHLORAMPHENICOL  MOA: inhibit the attachment of AA to the nascent/ inhibit acitivity of peptidyl transferase  50s binder  AE: “gray baby” syndrome – pale/ bluish skin (NOT given to neonates) MACROLIDES  MOA: Inhibit translocatiob of peptidyl TRNA (static)/ prevent binding of aa to nascent peptide  Examples: “-THROMYCIN” o Erythromycin o Clarithromycin o Azithromycin o Roxithromycin  DOC if allergic to penicillin  Affects 50s, for bacterias underdeveloped cell wall  Causes discomfort (esp. erythromycin)  CLINDAMYCIN o 1st known drug to cause pseudomembranous colitis/ uses 50s o Affects protein synthesis o Uses in infection ABOVE diagphram

FLUOROQUINOLONES  Inhibit DNA synthesis  “Floxacin & Nalidixic acid (UTI)”  “typhoid fever”  broad-spectrum antibacterial agents with bactericidal activity  treatment of community-acquired pneumonia and intra-abdominal infections.

ANTITUBERCULAR DRUGS (RIPES) – all can cause HEPATITIS  RIFAMPICIN – Red o MOA: Inhibits DNA – dependent RNA polymerase/ inhibits nuclear acid synthesis o MOR: Change in enzymes o AE:  proteinuria  hepatitis  flu-like syndrome  induction of P450  thrombocytopenia  development of red orange metabolites (2 – urine orange) ISONIAZID (INH) o MOA: Inhibits mycolic acid synthesis (AFB) o MOR:  increase level of resistance –

PROTEIN SYNTHESIS INHIBITOR TETRACYCLINS  Inhibit protein synthesis  Block attachment of aminoglycyl to the nascent peptide chain  Affects 30s  Bacteriostatic  Examples: “-CLINE” o Doxycycline; Minocycline; Demeclocycline  Coverage: Susceptible gm (+) & (-)  DOC: Rickettsiae, Chlamydia, Mycoplasma pneumonia (no cell wall or weak cell wall)

 o AE:

deleterious in katG - gene encodes catalase needed for INH baioactivation low level resistance deletions of INH gene

 Hepatitis  Neuritis (supplement with vit. B6)  Hemolysis  In G6PD def., SLE in slow acylators o Don’t give INH alone to prevent resistance PYRAZINAMIDE (PZA) o MOA: unknown, metablolically activated by bacteria starins lacking the bioactivating enzyme are resistant o AE:  Polyarthralgia (multiple joint pain)  Myalgia  Hepatitis  Rash  Hyperurecemia ETHAMBUTOL – Eye o MOA: inhibits synthesis of arabinogalactan (cell wall component) of mycobacterium o AE: dose dependent retrobulbar neuritis; visual acuity & red-green discrimination STREPTOMYCIN o Given if the pt. develop resistance to anti tb drugs/ noncompliance o MOA: protein synthesis inhibition o Class of aminoglycoside  ototoxic! o Administered IM o AE: deafness; vestibular dysfuntion, nephrotoxicity