Pharm Drugs Sulfonamides through Antimicrobials

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created 6 years ago by stefan_mcfarland
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1. Mechanism of action 2. Therapeutic uses 3. Adverse/Toxic effects 4. Drug interactions
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1

Sulfonamide Drugs

Dapsone
Para-aminosalicylic acid
PABA
Sulfacetamide

2

Sulfonamide mechanism

Inhibit folic acid synthesis

3

Sulfonamide therapeutic uses

UTIs, OM, bronchitis, GI (entero-bacteria, salmonella, shigella infections), pneumocystic carinii, malaria, MRSA.

4

Sulfonamide adverse/toxic effects

Crystaluria secondary to poor solubility of the drug, high pKa; allergies - fever and skin rashes; hemolytic anemia; kernicterus - brain damage in newborns secondary to free bilirubin (due to competition on albumin)

5

Sulfonamide drug interactions

interaction with warfarin due to competition on albumin

6

Sulfonamide mechanism of resistance

Increased production of PABA, production of a dihydropteroic acid synthetase that binds PABA more tightly and sulfonamide less tightly, altered permeability of cell to sulfonamides, increased concentration of dihydropteroic acid synthetase.

7

Dapsone

SULFONAMIDE (not formally but same mech of action) - 1. inhibits folic acid synthesis; 2. used for leprosy and immunocompromised patients; 3. crystaluria, allergies, hemolytic anemia, kernicterus; 4. interactions with warfarin

8

Para-aminosalicylic acid

SULFONAMIDE (not formally but same mech of action) -1. inhibits folic acid synthesis; 2. used for tuberculosis; 3. crystaluria, allergies, hemolytic anemia, kernicterus; 4. interactions with warfarin

9

PABA

SULFONAMIDE - 1. inhibits folic acid synthesis; 2. same as sulfonamides; 3. crystaluria, allergies, hemolytic anemia, kernicterus; 4. warfarin

10

Sulfacetamide

SULFONAMIDE - 1. inhibits folic acid synthesis; 2. eye infections; 3. crystaluria, allergies, hemolytic anemia, kernicterus; 4. warfarin

11

Penicillins and Cephalosporins

Cycloserine
bacitracin
Penicillin
cephalosporin
vancomycin
augmentin

12

Penicillins and cephalosporins mech of action

Inhibit bacterial cell wall synthesis. described by step in cell wall synthesis that is interrupted.

13

Stage I

interrupts precursor formation, competitive inhibitor of an enzyme.

14

Stage II

Transport of precursors across cytoplasmic membrane and synthesis of an alternating copolymer on cell surface. INHIBITS TRANSPORT OF PRECURORS ACROSS CELL MEMBRANE.

15

Stage III

Inhibition of cross linking of polymers on cell surface that create the cell wall - bactericidal.

16

cycloserine

P & C - 1. Stage I; 2. Second line for TB; 3. CNS Toxicity. 4. None

17

Bacitracin

P & C - 1. Stage II; 2. External use only (too toxic to absorb well); 3. None. 4. None.

18

PENICILLIN, Pen G, V, Oxacillin, Cloxacillin, Nafcillin, Ampicillin, Amoxicillin, Carbenicillin

P & C - 1. Stage III; 2. All but amp/amox narrow range - strep, staph, gram +, neisseria gram -, syphillis; 3. CNS toxicity; 4. Probenecid adminstered concurrently with penicillin will cause competitive inhibition of penicillin excretion in the renal tubule, clavulanic acid inhibits penicillinase.

19

Cephalosporin, cefalosporin

P & C - 1. Stage III; 2. 1st gen - Gram + staph and strep, 2nd -4th gen - A G+ and A G-, 3rd gen crosses blood/brain barrier; 3. None; 4. None

20

Vancomycin

P & C - 1.Stage III; 2. Gram +, narrow spectrum parental; 3. None; 4. None

21

Augmentin

P & C - 1. Stage III, Penicillin plus clavulanic acid (inhibitor of penicillinase) provides a synergistic effect; 2. Same as PCN; 3. Same as PCN; 4. Same as PCN.

22

Beta Lactam Agents

Synthetic. Used exclusively in hospitals due to high cost. Similar mechanism to PCN.
Aztreonam (Azactam)
Imipenem (Primaxin)

23

aztreonam

Beta-Lactam. - 1.Similar to PCN, resistant to penicillinase; 2. narrow spectrum, parenteral. 3. None. 4. None.

24

Imipenem

Beta-Lactam - 1. Similar to PCN, resistant to penicillinase; 2. Broad spectrum, parenteral; 3. None; 4. None.

25

Clavulanic acid

Beta-Lactamase Blocker. 1. administered orally or parenterally with a PCN. 2. Beta Lactamase blocker. 3. None. 4. None

26

Cephalexin (Keflex)

Cephalosporin 1st Gen. Given orally.

27

Ceflacor (Ceclor)

Cephalosporin 2nd Gen. Give orally or parenteral.

28

Ceftriaxone (Rocephin)

Cephalosporin 3rd Gen. Crosses Blood-brain barrier. Give parenteral.

29

Antimicrobial Drug Types

Bacterial Protein Synthesis Inhibitors
Fluoroquinolones
Antimycobacterial Drugs

30

Protein Synthesis Inhibitors Mechanism

Selective toxicity - act by binding to the bacterial ribosome and there inhibiting protein synthesis

31

Protein Synthesis Inhibitors Classes

Aminoglycosides
Tetracyclines
Chloramphenicol
Clindamycin
Macrolides

32

Aminoglycosides (Gentamycin)

PSI. 1. Misincorporation of aa. G+ and - Aerobes only. Bactericidal. Resistance in G- from modifying enzymes.. 2. Immunocompromised Pts need rapid control of life threatening infection; must be given IV; synergistic with Beta-Lactam; post antibiotic effect. 3. Renal tox, ototoxicity, neuromuscular paralysis. 4. Synergistic with Beta-Lactam drugs to decrease dose and increase spectrum.

33

Marolides (Erythromycin/ E-mycin)

PSI. 1. Inhibits peptide bond formation. Narrow spectrum G+. Resistance from altered ribosome. Bacteriastatic. 2. Drug of choice for corynebacteria (diptheria), mycoplasma, chlamydia. 3. Cholestatic hepatitis, epigastric distress. 4. Inhibit hepatic metabolism of other drugs (oral anticoagulants). Can affect bioavailability of Digoxin.

34

Tetracycline (Tetracycline HCl, Doxycycline HCl)

PSI. 1. Inhibits peptide bond (tRNA binding). Broad spectrum. Bacteriastatic. Resistance from decreased accumulation due to efflux pumps. 2. Drug of choice for Rickettsia, Mycoplasma, Chlamydia, Vibrio, Borrelia (Lyme) Infecitons. Has activity against some protozoan and mycobacteria infections. 3. Superinfections from elimination of normal flora. Inhibits bone formation. GI, renal, and hepatic toxicity.Photosensitivty (esp. Doxycycline). 4. Use with metronidazole for H. pylori; chelator complexes with multivalent and inactivated antacids - milk (Ca) and antacids prevent absorption; may affect action of oral anticoagulant due to Vit K decrease (flora).

35

Clindamycin (Cleocin)

PSI. 1. Inhibits peptide bond. Extended spectrum G+ and ANaerobic G-. Resistance from altered ribosome. 2. Anaerobic infections. Not useful for aerobic G-. Alternate for S. aureus in Pt. allergic to Beta Lactam drugs. Alternate for prophylaxis of baterial endocarditis. 3. Pseudomembranous collitis superinfection of C. diff. 4. None.

36

Chloramphenicol (Chloromycetin)

PSI. 1. Inhibits peptide bond. Broad spectrum. Resistance in G- from drug modifying enzymes. 2. Alternate for severe infections (meningitis) in Beta-lactam allergic Pts. 3. Bone marrow toxicities. Inhibits mitochondria protein synthesis. Gray baby syndrome. 4. Inhibits metabolism of other drugs.

37

Fluoroquinolones (Ciproflaxacin)

1. Inhibits type II topoisomerase and disrupts DNA synthesis. Extended spectrum. Gram + and - aerobes. 2. Mycoplasma, Chlamydia, Mycobacteria. 3. Cartilage degeneration in young (not used if < 17). GABA inhibitor, may cause seizures. 4. Inhibits metabolism of other drugs. Absorption impaired by multivalent cations (antacids, Ca).

38

Antimycobacterial Drugs

Isoniazid
Rifampin
Pyrazinamide

39

Isoniazid

1. Prodrug activated by baterial enzyme.Inhibits mycotic acid synthesis (cell wall). Bactericidal. 2. Mycobacterial infections. 3. Peripheral neuritis (Vit B6 cofactors - eliminated by giving pyriodoxine). 4. Inhibits metabolism of other drugs.

40

Rifampin (Rifadin)

1. Inhibits bacterial RNA polymerase. 2. Mycobacterial infections; N. meningitidis. 3. Hepatic toxicity. 4. Increases metabolism of other drugs (anticoagulants, oral contraceptives)

41

Pyrazinamide

1. Inhibits mycotic acid synthesis - diff mechanism than Isoniazid (cell wall). 2. Mycobacterial infections. 3. Liver toxicity. Hyperuricemia. 4. None.


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