medicine - antibiotics

1. Antibacterials:
Penicillins & Cephalosporins

2. Antibacterials
• Antibacterials /antimicrobial drugs - Substances that
inhibit the growth or kill bacteria or other microorganisms
• Bacteriostatic = Inhibits growth of bacteria
• Bactericidal = Kills bacteria

3. Antibacterials
• Mechanism of Action:
1. Inhibition of cell wall synthesis - Bactericidal
2. Alteration in membrane permeability - ‘Cidal’ or
‘Static’
3. Inhibition protein synthesis - ‘Cidal’ or ‘Static’
4. Inhibition of bacterial RNA & DNA - Inhibits
synthesis of RNA & DNA
5. Interferes with metabolism in the cell - ‘Static’

4. Antibacterials
• Drugs -
1. Penetrate bacterial cell wall in sufficient
concentrations
2. Affinity to the binding sites on the bacterial cell:
- Time drug remains at binding sites = effect
- Time controlled by pharmacokinetics

5. Effects of concentrated drug dosing

6. Antibacterials
Penicillins
• From mold genus “Penicillium notatum”- ‘miracle drug’
from WWII – 1941.
• A beta-lactum structure (beta-lactum ring) interferes with
bacterial cell wall synthesis by inhibiting the bacterial
enzyme – “ transpeptidases” necessary for cell division &
synthesis.

7. • Bacteria synthesis cell wall using UDP-N-
acetylmuramic acid pentapeptide -“ Park
nucleotide” and UDP-N-acetyl glucosamine.
• Final step is the cleavage of the terminal D-alanine
by transpeptidase ; the energy so released is used
for establishing cross linkage between the peptide
chain.

9. • Gram positive bacteria cell wall is entirely made
of peptidoglycan. In gram negative bacteria it
consist of alternating layer of lipo protein and
peptidoglycan. So higher susceptibility of the
gram – positive bacteria to penicillin.
• Blood , pus and tissue fluid don’t interfere with
action of B- lactams.

10. Classification- Pencillin
• Natural Penicillin
purified from mould.
High sensitive to beta lactamase
2 types - Penicillin G ( iv ) , Penicillin V ( oral )
Narrow spectrum of coverage only.
Good gram +coverage, strept
pneumoniae(resistance icreasing), fair gram –
(N.gonorrhoeae,N.meningitidis), good anaerobic.

11. Extended spectrum penicillin
• Semi synthetic penicillin active against some gram
negative organism.
• 1. Amino- penicillin
Amino group is added to side chain to increase
spectrum against gram negative organism- E.coli
and H.influenzae.
None are resistant to beta lactamase.
Ampicillin , Amoxycillin

12. Ampicillin
• Active against all organism sensitive to penicillin
G.
• Wide spread use lead to resistance.
• Still active for H.influenzae, E coli, pneumococci ,
meningiococci , gonococci.
• Less active against other G+ cocci ,pseudomonas ,
klebseilla , proteus , bacteroids.
• s/e : diarrhoea: altered gut flora due to incomplete
absorption.
• Sulbactum is added to increase spectrum.

13. Amoxicillin
• Oral absorption better.
• Less incidence of diarrhoea.
• Spectrum same as of ampicillin.
• Clavulanic acid is added to to amoxcillin so re-
establish activity against beta lactumase producing
staph aureus , H. Influenzae , Klebsiella,
salmonella , shigella ,bact .fragilis and
branhamella. S/e is hepatic injury with
combination.

14. • Staph aureus and Strept pneumoniae gain
resistance through mechanism other than Beta-
lactamase production, rendering the above
combinations of little value for beta lactum
resistant strain.

15. Anti Staphylococcal penicillin
(penicillinase resistant penicillin)
• Members are resistant to Beta lactamase due to
side chain- semisynthetic.
• But cant penetrate g-ve bacteria outer membrane .
• Only effect in gram + bacteria
• Only indicated in penicillinase producing staph
except MRSA.
• Cloxacillin / dicloxacillin / naficillin / methicillin.

16. Methicillin
• “methicillin only used in labs due to a/c drug
induced interstitial nephritis”.

17. Cloxacillin
• Isoxazolyl side chain present
• Less active against penicillin sensitive organism
so should not be used as substitute.
• So combination Ampiclox.
• No action against MRSA.

18. Anti Pseudomonal penicillin
• Effective against pseudomonas
• Sensitive to beta lactamase so spectrum is
increased by adding beta lactamase inhibitor
• Carboxypenicillin ( Carbenicillin, Ticarcillin).
• Ureidopenicillin ( Piperacillin).

19. Carboxypenicillin
• Carbenicillin – active against pseudomonas and
proteus, enterobacter.
neither penicillinase resistant /acid resistant.
s/e: bleeding due to impaired platelet function,
each gram contain 5.3 mEq Na, increases liver
enzyme.
Ticarcillin : more potent than carbenicillin, cover
E.coli , Serratia , bacteroides.

20. Ureidopenicillin
• Piperacillin – 8 times more antipseudomonal than
carbenicillin.
good activity against klebsiella and used in
neutropenic and immunocomproised patients with
severe Gram negative infections and burns.
dose 100-150 mg/kg/day in 3 dd
adding Tazobactum increases spectrum against
beta lactamase producing organism but not against
pseudomonas , which gain resistance by
decreasing permeability of piperacllin.

22. Antibacterials
Cephalosporins
• From a fungus Cephalosperium acremonium
- Gram (+) & gram (-)
- Resistant to beta - lactamase
- Bactericidal - action similar to PCN’s
- 4 groups (generations) - each effective against a broader
spectrum of bacteria
- about 10% of people allergic to PCN also to allergic to
cephalosporins
- Action - inhibits bacterial cell wall synthesis
- IM & IV - onset = almost immediate

23. Antibacterials
Cephalosporins
• 1st Generation Cephalosporins - cefadroxil
(Duricef) & cephalexin (Keflex) - PO; Cefazolin
(Ancef) & cephalothin (Keflin) - IM
- Gram (+), & gram (-)
- Esp. used for skin/skin structure infections
- Keflin used for resp, GI, GU, bone, & joint
infections

24. Antibacterials
Cephalosporins
• 2nd Generation Cephalosporins - cefaclor (ceclor) -
PO, cefoxitin (Mefoxin), cefuroxime (Zinacef),
cefotetan (Cefotan) - IM & IV
- Gram (+), slightly boarder gram (-) effect than 1st
generation
- for harder to treat infections

25. Antibacterials
Cephalosporins
• 3rd Generation Cephalosporins - cefotaxime
(Claforan), ceftazidime (Fortaz), ceftriaxone
(Rocephin), cefixime (Suprax) - IM or IV
- More effective against gram (-), less effective against
gram (+)
- for harder yet to treat infections
• 4th Generation Cephalosporins - cefepime
(Maxipime) - IV or IM
- Resistant to most beta-lactamase bacteria
- greater gram (+) coverage than 3rd generation

26. Ch. 26 - Antibacterials
Macrolides, Lincosamides, Vancomycin
• All differ in structure, but similar spectrums of antibiotic
effectiveness to PCN
• Used as PCN substitutes, esp. w/ people allergic to PCN
• Erythromycin frequently prescribed if hypersensitive to
PCN
• Macrolides - Erythromycin, Azithromycin (Zithromaz),
Clarithromycin (Biaxin) - PO/IV, Dirithromycin (Dynabac) -
PO - Broad spectrum of activity
- Low to mod dose = bacteriostatic
- high doses = bactericidal
SE = GI disturbances, Allergic rxns = Hepatotoxicity

27. Antibacterials
Lincosamides
• Clindamycin (Cleosin), Lincomycin (Lincorex)
- PO, IM, IV
- Inhibit bacterial protein synthesis
- ‘Static’ & ‘cidal’ actions depending on drug
dosage
- effective against most gram (+), no gram (-)
- Clindamycin more effective than lincomycin

28. Antibacterials
Vancomycin
• Glycopeptide bactericidal antibiotic - IV
- Use: Drug resistant Staph A., cardiac surgery -
prophylaxis for clients w/ PCN allergies
- SE = Ototoxicity - damage to auditory branch of
8th cranial nerve permanent hearing loss or loss
of balance & Nephrotoxicity
- Serum Vanco levels drawn to minimize toxic
effects

29. Antibacterials
Tetracyclines
• Tetracycline, Doxycycline (Vivbamycin), Minocycline
(Minocin)
- Broad spectrum - Gram (+) & gram (-) bacteria
- Bacteriostatic
- Wide safety margin, but many side effects
- Primarily used for skin/skin structure infections
- Also used to treat Helicobacter pylori (H. pylori) -
bacterium in stomach that can cause peptic ulcers
- Tetracycline mostly

30. Antibacterials
Tetracyclines
• Considerations
- SE = Photosensitivity - sunburn rxn
- Should not be given to children < 8 yrs or to
women in last trimester of pregnancy -
Irreversibly discolors permanent teeth
- Tetracycline during 1st trimester of pregnancy
can cause birth defects
- Take on an empty stomach - antacids & dairy
products prevent absorption of the drug

31. Antibacterials
Aminoglycosides
• Amikacin (Amikin), Gentamicin (Garamycin),
Tobramycin (Nebcin), Netilmicin (Netromycin)
- Inhibits bacterial protein synthesis, ‘cidal’
- Gram (-) & some gram (+)
- Used to treat serious infections
- Cannot be absorbed from GI tract, cannot cross into CSF
- To ensure a desired bld level - IV use
- Narrow therapeutic range - Peak & Trough levels drawn
- SE = Ototoxicity, Nephrotoxicity

32. Antibacterials
Fluoroquinolones (Quinolones)
• Ciproflaxacin (Cipro), Levofloxacin (Levaquin),
Ofloxacin (Floxin), Norfloxacin (Noroxin) - IV or PO
- Interferes w/ synthesis of bacterial DNA
- Bactericidal
- Broad spectrum - gram (-) & gram (+)
- Rx - UTI’s, lower resp. infections, bone & joint
infections, GI, skin
- Wide safety margin
- CI - Children < 14 yrs

33. Chapter 27
Sulfonamides
• One of the oldest - broad spectrum - gram - & gram +
• First group of drugs used against bacteria
• Bacteriostatic - inhibits bacterial synthesis of folic acid,
essential for bacterial growth
• Alt. for people allergic to PCN
• Use - UTI’s, ear infections, newborn eye prophylaxis
- Not effective against viruses or fungi
• PO, sol’n & ointment for ophthalmic use & cream
- Silver sulfadiazine (Silvadene) - for burns

34. Antibacterials
Sulfonamides
• Special consideration - Drink fluids to prevent
crystalluria (d/t poor water solubility) & hematuria
• SE -
- allergic response - skin rash & itching
- Anaphylaxis not common
- Bld disorders w/ prolonged use & high doses
- GI disturbances
- Photosensitivity

35. Chapter 28
Antitubercular, Antifungal
Peptides, & Metronidazole
• Inhibit or kill organisms that case diseases
• Tuberculosis (TB) -
- Caused by the acid-fast Bacillus Mycobacterium
tuberculosis - frequently referred to as the tubercle bacillus
- One of the major health problems in the world & kills more
people than any other infectious disease
- About 11/2 billion people have TB & don’t know it
- TB in US until 1980’s & AIDS d/t compromised
immune system

36. Antiinfective Agents
Tuberculosis
• Transmitted by droplets dispersed in the air through
coughing & sneezing inhaled into alveoli (air sacs) of
lungs spread to other organs via blood & lymphatic
system
- Strong system = phagocytes stop multiplication of
tubercle bacilli
- Compromised system = tubercle bacilli spread

37. Antiinfective Agents
Tuberculosis
• Drugs: Isoniazid (INH) - 1952, Rifampin
- Prophylactic therapy for persons close to TB, HIV +, a
+ TB skin test, young children in contact w/ active TB,
- Family members on Isoniazid 6 months to 1 yr
- Spectrum = Myobacterium tuberculosis, ‘cidal’
- Combo of Isoniazid & Rifampin = No bacterial resistance
& less Rx time = more effective
- SE = ‘flu-like’ symptoms, neurotoxicity, hepatotoxicity,
Monitor drug therapy carefully

38. Antiinfective Agents
Antifungals (Antimycotics)
• Topical - skin/mucus membranes (athletes foot)
• Systemic - lung, CNS (pulmonary conditions, meningitis)
• Fungi - Candida (yeast) - normal flora of mouth, skin,
intestine, vagina
• Candidiasis = opportunistic infection - body’s defense
mechanism impaired allowing overgrowth of fungus
• Drugs - antibiotics, contraceptives & immunosuppressives
may alter body’s defense mechanisms
- mild = vaginal yeast infection, severe = systemic infect.

39. Antiinfective Agents
Polyenes
• Amphotericin B (Fungizone), Mystatin (Mycostatin)
• Broad spectrum antifungal activity
• Fungizone = IV administration
SE = Flushing, chills, N & V, dec. BP
Considered highly toxic - nephrotoxicity & electrolyte
imbalance poss
• Nystatin = orally or topically for candidal infections
Swish & swallow to allow contact w/ mucus membranes

40. Antiinfective
Antifungal
• Metronidazole (Flagyl) - treatment of various
disorders associated w/ organisms of GI tract - PO
and IV
• SE = GI discomfort, Headache, depression (not
common)
• Also used to treat H. pylori associated w/ peptic
ulcers

41. Math Problems
A dose of 200 mcg is ordered. The strength available is 0.3 mg. in 1.5 mL.
Convert mg to mcg. 1 mg = 1000 mcg
0.3 mg = 300mcg
200 mcg X 1.5 ml. = X ml
300 mcg
2 X 1.5 = 3 = X = 1 ml
3 3
To give 200 mcg you must administer 1 ml.

42. A dosage of 0.7 g. has been ordered. Available is a strength of
1000 mg. in 1.5 mL.
Convert g. to mg.
0.7 g = 700 mg
700 mg. X 1.5 mL = X mL
1000 mg.
7 X 1.5 mL = 10.5 = X
10 10
10.5 divided by 10 = 1.05
Round up to 1.1. So administer 1.1 mL.