Pharmacology Review Sheets: Antibiotics, p.

1
Sulfonamides
Common Properties
- Structure: Substitutions on ring activity
- P-aminobenzoic acid (PABA) analog
- Competitively inhibits pteroic acid synthetase
- Absolutely specifically toxic
- Bacteriostatic
- Needs time to take effect (effects arent immediate)
- Resistance
PABA concentration
- uptake of sulfonamides
- affinity of pteroic acid synthetase for enzyme
- Spectrum: UTIs, nocardiosis, chlamydial infections
- Distribution
Gets into CNS (even without inflammation)
- Doesnt penetrate prostate well because its acidic
- Metabolism and Excretion
- Parent or acetylated derivative excreted in the urine
- Adverse effects
- Drug Allergy: Stevens-Johnsons syndrome (necrotizing loss of skin)
Crystaluria (esp. with older sulfonamides)
- Kernicterus: yellowing of fingernails and sclera, possible neurological symptoms
- DONT give to women in 3rd trimester, nursing mothers, neonates
- G6PDH Deficiency: Hemolytic anemia
- Displacement of drugs (oral antibiotics, methotrexate) from albumin
Cotrimoxazole (Bactrim ): Sulfamethoxazole + trimethoprim (working synergistically)
- Synergism: Trimethoprim inhibits dihydrofolate reductase; relatively selectively toxic (bacterial affinity allows selection)
- In general, Cotrimoxazole (Bactrim) has Potency, Spectrum, Resistance
- Used for UTIs, Respiratory/ear infections due to H. influenzae, S. pneumoniae, PCP, Toxoplasmosis, Malaria
- Problems: Crystaluria, megaloblastic anemia in those with folate deficiency, contraindicated in pregnant mothers b/c of possible induction of folate deficiency
Pharmacokinetics
Drug Name
Triple sulfa
(sulfadiazine
sulfamerazine
sulfamethazine)
Sulfisoxazole
Sulfamethoxazole
Sulfacetamide
Silver sulfadiazine
Sulfasalazine

Use/Spectrum

Admin/Absorption Distribution
Rapid absorption

Most commonly used single

sulfa
Use in combo with trimethoprim
(cotrimoxazole)
Topical (ophthalmologic use)
ONLY
Topical use only
Prophylaxis of burn patients
Ulcerative colitis
Split by intestinal flora
Crohns disease
Salicylate is anti-inflammatory

Metabolism/Excretion

Adverse Effects
risk of crystaluria

Highest urine solubility

Urine solubility < than
sulfisoxazole

Males: sterility

Sulfadoxine

Toxoplasmosis

Rapid absorption

LONG t1/2 (9 days)

Allergic reactions (dermatitis)

Pharmacology Review Sheets: Antibiotics, p.2

-lactams: Penicillins
Common Properties
- 6-aminopenicillanic acid; alkyl group off of chain at position 6 determines drug susceptibility to penicillinase or acid hydrolysis
- Bacteriocidal; binding to penicillin-binding proteins, interfering with transpeptidation (cross-linking) step in cell wall synthesis
- Resistance:
Chromosomally/plasmid-encoded -lactamase
Protection: changing side chain at C6, or adding a -lactamase inhibitor (sulbactam, clavulanic acid, tazobactam)
- Immunity for organisms lacking a cell wall (mycoplasma, fungi, protozoans, viruses)
- penetrability (channels allowing entry modified)
- binding to PBPs
- Distribution: By circulation
- Does NOT distribute well to prostate, eye, CSF; entry to CSF facilitated by meningitis
- Crosses the placenta (non-teratogenic), enters breast milk
- Metabolism: Very little; Excretion: Primarily renal (organic acid secretory system); probenecid interferes with excretion
- Adverse effects: Hypersensitivity: Anaphylaxis, rashes; Allergy to one may result in cross-allergy to other drugs in that class!!; diarrhea
- Synergistic with aminoglycosides; but DONT mix them because they inactivate each other chemically!
Benzylpenicillins
Pharmacokinetics
Drug Name
Penicillin G
Penicillin V

Use/Spectrum
S. pneumoniae, S. aureus, S. epidermidis, S. viridans, N. gonorrhoeae, N. meningitidis, Clostridia spp., Bacteroides oralis, T. pallidum
S. pneumoniae, S. aureus, S. epidermidis, S. viridans, N. gonorrhoeae, N. meningitidis, Clostridia spp., Bacteroides oralis, T. pallidum

Admin/Absorption
Parental admin (im, iv)
Oral admin

Adverse effects
Seizures!!

Anti-staphylococcal: For penicillinase-producing Staphylococcus aureus. Includes methicillin (prototypeno longer used), dicloxacillin, cloxacillin, oxacillin, nafcillin
- MRSA is resistant to all except vancomycin (and maybe not even that now)!!

- Nafcillin enters bile; excreted by biliary route

Extended-spectrum penicillins
Pharmacokinetics
Drug Name
Ampicillin
Urasyn (ampicillin
+ sulbactam)
Amoxicillin
Augmentin
(amoxicillin plus
clavulanic acid)

Use/Spectrum
Proteus mirabilis, Listeria monocytogenes, H. influenzae (alternate)
S. aureus + anaerobes

Admin/Absorption
Oral
IV ONLY

Distribution
Enters bile
Enters bile

B. burgdorferi, P. mirabilis, L. monocytogenes, H. influenzae (alternate)

H. influenzae, Moraxella catarrhalis (seen in nursing homes)

Oral
Oral, IV

Enters bile
Enters bile

Adverse Effects
Maculopapular rashes, esp. those on allopurinol, or w/ mono.

Antipseudomonal penicillins
Pharmacokinetics
Drug Name
Carbenicillin

Use/Spectrum
Indole + Proteus sp., Enterobacter (excluding Klebsiella)

Admin/Absorption
Oral (indanyl form) & Parental

Ticarcillin

P. aeruginosa, Enterobacter (including Klebsiella)

Parental (im, iv)

Timentin
(ticarcillin plus
clavulanic acid)
Piperacillin
Zosyn
(piperacillin +
tazobactam)

P. aeruginosa, Enterobacter (including Klebsiella)

Parental (im, iv)

P. aeruginosa (most potent), Klebsiella spp., Serratia marcescens

P. aeruginosa (as effective as ticarcillin); Zosyn has extended spectrum

Parental (im, iv)

Parental (im, iv)

Distribution

Adverse Effects
platelet aggregation
platelet aggregation, hypokalemia due to K+ excretion

Enters the bile

Azlocillin
Mezlocillin

P. aeruginosa (but less active than piperacillin for other Gm negs)

Similar to ticarcillin, more active vs. Klebsiella

Parental (im, iv)

Parental (im, iv)

Pharmacology Review Sheets: Antibiotics, p.3

-lactams: Cephalosporins
Common Properties
- 7-aminocephalosporanic acid; alkyl group off of chain at position 7 determines drug susceptibility to penicillinase or acid hydrolysis
- Substitutions at position 2 determine pharmacokinetics
- Action: Inhibit the transpeptidation (cross-linking) step of cell wall synthesis (same as penicillins)
- Resistance: plasmid-encoded/chromosomal cephalosporinase
- Cefuroxime, cefoxitin, 3rd/4th gen. cephalosporins are most resistant to cephalosporinases
- Absorption: Longest t1/2: ceftriaxone (followed by cefonicid, cefotetan)
- Distribution: In general, distributes well into pleural, pericardial and synovial fluid
- Cefazolin, cefamandole, ceftizoxime penetrate bone well
- Cefepime gets into the prostate
- Metabolism: Ester groups at C3 can be hydrolyzed
- Excretion: All by kidney, except ceftriaxone (biliary excretion)
- Adverse Effects
- Allergy: If patients are allergic to penicillins, cephalosporins are ABSOLUTELY contraindicated!!
- Diarrhea
- Ceftriaxone: Biliary sludge and pseudolithiasis
- Cefamandole, cefoperazone, cefotetan: possess methylthiotetrazole side chain on C3
- Disulfuram effect (Antabuse) alcohol-containing substances contraindicated
- Hypothrombinemia due to interference in Vit K-dependent carboxylation involved in clotting cascade
1st generation: Narrow spectrum, Used for Gm +
Pharmacokinetics
Drug Name
Cefazolin
Cefadroxil
Cephalexin

Use/Spectrum
Gm+ cocci (enterococci resistant); used in implant surgery
Gm+ cocci (enterococci resistant)
Gm+ cocci (enterococci resistant)

Admininistration
Parental (im, iv)
Oral
Oral

Distribution
Penetrates bone well

2nd generation: Extended-spectrum

Pharmacokinetics
Drug Name
Cefaclor
Cefuroxime
Cefuroxime acetil
Cefoxitin

Use/Spectrum
Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp.
Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp.
Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp.
Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp., Bacteroides fragilis

Admininistration
Oral
Parental (im, iv)
Oral
Parental (im, iv)

Distribution

3rd generation: Good vs. Gm , but worse than 1st generation vs. Gm +
Pharmacokinetics
Drug Name
Ceftriaxone
Cefixime
Cefotaxime
Ceftizoxime
Ceftazidine
Cefoperazone

Use/Spectrum
Drug of choice for N. gonorrhoeae, N. meningitidis; H. influenzae, S. typhi, P. aeruginosa
P. aeruginosa, H. influenzae
P. aeruginosa, H. influenzae
P. aeruginosa, H. influenzae
P. aeruginosa (enhanced activity vs. other 3rd generation cephalosporins)
P. aeruginosa (enhanced activity vs. other 3rd generation cephalosporins)

Admininistration
Parental (im, iv)
Oral
Parental (im, iv)
Parental (im, iv)
Parental (im, iv)
Parental (im, iv)

Distribution

Penetrates bone well

4th generation: Good vs. Gm + and Gm (except MRSA of course)

Pharmacokinetics

Drug Name
Cefepime

Use/Spectrum
Good vs. Gm+ and Gm
Broad-spectrum, but not really a drug of choice for any specific organism

Admininistration
Parental (im, iv)

Distribution
Penetrates prostate

Pharmacology Review Sheets: Antibiotics, p.4

-lactams: Carbapenems (Imipenem/cilastatin; Meropenem)
Common Properties
- Lack an amine group at position 6, but are intrinsically resistant to penicillinase
- Broadest spectrum antibiotic; used to Rx fevers of unknown origin; NOT effective vs. MRSA
- Resistance to carbapenems by P. aeruginosa is rapid
- Imipenem can be broken down by host dehydropeptidase I; the metabolite produced is toxic. Cilastatin is a dehydropeptidase I inhibitor, protecting imipenem.
- Meropenem is NOT affected by dehydropeptidase I.
Ph arm a co ki ne ti c s
Drug Name
Imipenem/cilastatin
Meropenem

Use/Spectrum
Serratia marsescens, Enterobacter, Acinetobacter, P. aeruginosa, Gm+/Gm- anerobes
Serratia marsescens, Enterobacter, Acinetobacter, P. aeruginosa, Gm+/Gm- anerobes

Admin/Absorption
Parental (im, iv)
Parental (im, iv)

-lactams: Monobactams (Aztreonam is the only one)

Properties of Aztreonam
- Stable to penicillinase
- Works for enterobacteriacea, P. aeruginosa
- Lacks activity vs. Gm+ organisms, anaerobes.
Penicillin substitutes: Vancomycin
- Drug of last resort (prudent use is key!!!)
- Inhibits transglycoslase step of cell wall synthesis (-lactams inhibit the transpeptidase step)
Pharmacokinetics
Drug Name

Use/Spectrum

Resistance

Admin/Absorption Distribution

Vancomycin

MRSA, MRSE,
penicillin-resistant enterococci,
pts w/allergy to penicillins.
C. difficile (after metronidazole
fails), prophylaxis for surgical
procedures with high rates of
infections by MRSA/MRSE

Transposon containing 9 genes; IV for systemic inf., Widely distributed,

sensor protein activates cascade Oral for antibiotic- but NOT to bile or
of genes, changing a peptide
induced colitis
CSF
bond to an ester bond so
vancomycin cant bind to it.

Metabolism/Excretion

Metabolism: Not well delineated

Excretion: Renal; t1/2 in renal
failure

Adverse Effects
Shock from rapid infusion
Ototoxicity from high serum levels
Nephrotoxicity (esp. if given with other
nephrotoxic drugs)

Penicillin substitutes: Streptogramins

Pharmacokinetics
Drug Name

Use/Spectrum

Resistance

Quinupristin/
Dalfopristin

Vancomycin-resistant strains

Not well known

Admin/Absorption Distribution
Admin: IV
Not well known
Abs: Not well known

Metabolism/Excretion

Not well known

Adverse Effects

Work like macrolides, but effectiveness questionable

Other toxicities not well known

Penicillin substitutes: Chloramphenicol

- Propanediol segment binds to 50S subunit (different binding site than clindamycin)
- Resistance by plasmid-encoded acetyl-CoA transferase, penetrance, affiinity
- Broad-spectrum; bacteriostatic/bacteriocidal, depending on organism
Pharmacokinetics
Drug Name
Chloramphenicol

Use/Spectrum
Brain abscesses due to anaerobes; H. influenzae; non-resistant
strains of S. typhi, alternative for Rickettsial infections

Admin/Absorption
Admin: Oral, topical
for eye
Abs: Complete with

Distribution
Excellent throughout
body; penetrates CSF
even without infl.;

Metabolism/Excretion
Metabolism: Extensive, with
glucuronidation; metabolite
formed by oxidative dechlor.

Adverse Effects
Hemolytic anemia in G6PDH deficiency; dose-related
reversible anemia, leukopenia, thrombocytopenia;
Dose-independent idiosyncratic aplastic anemia;

oral admin

penetrates brain
abscesses; crosses
placental barrier

inactivates cyt. P-450

Gray baby syndrome b/c chloramphenicol disrupts
Excretion: Glucuronide by renal;mitochondrial fxn, and neonates have low glucoronyl
liver failure affects excretion,
transferase activity; oral/vaginal candidiasis
but renal failure doesnt!
t of warfarin, dicumarol, phenytoin, tolbutamide,
chlorpropamide; phenobarbital/rifampin t of
chloramphenicol

Pharmacology Review Sheets: Antibiotics, p.5

Penicillin substitutes: Macrolides
- Lactone ring with 2 sugars attached; azithromycin has a slightly larger ring with a nitrogen atom incorporated (this makes it more acid-resistant)
- Polar, but well absorbed
- Prototype is erythromycin; clarithromycin is a methylated form; azithromycin has an N replace a C=O
- Erythromycin has free form, ethylsuccinate, lactobionate, estolate esterol
- Inhibits protein synthesis by binding irreversibly to 50S subunit of ribosome; relatively selective
- Bacteriostatic
- Resistance: mainly by affinity of 50S ribosome, also by penetrance, efflux, or a plasmid-encoded esterase
Pharmacokinetics
Drug Name
Erythromycin

Use/Spectrum
Admin/Absorption Distribution
Drug of choice for Mycoplasma pneumoniae; also used for
Administration:
Well distributed; gets
Legionella pneumophila, C. diphtheriae, Ureaplasma urealyticum Free base: Oral
into prostate but
Esters: Oral
(antipsychotics); warfarin b/c
Lactobionate: IV liver & macrophages
Absorption:
Esters: more readily
absorbed than free
Clarithromycin
Mycoplasma pneumoniae, Better for Legionella pneumophila;
Readily absorbed,
Similar to
C. diphtheriae, U. urealyticum, Chlamydia spp., H. influenzae,
but food delays
erythromycin but
Helicobacter pylori
absorption
doesnt conc. in
liver as much
Azithromycin
H. influenzae, Moraxella catarrhalis, Chlamydia trachomatis,
Readily absorbed, but
Mycobacterium avium-intracellulare
never given with a
meal or with Al+3 or
Mg+2 containing
antacids

Metabolism/Excretion
Metabolism: Extensively by
cytochrome P-450 system
NOT CSF; conc. in Excretion:

Adverse Effects
Cramps with oral admin; jaundice with estolate;
Interacts with astemizole (fatal ventricular arrythmias);
Predominantly bile, carbamazepine, valproate

some metabolites in urine

erythromycin inhibits cyt-P-450; digoxin toxicity;

Ototoxicity; contraindicated in pts. with hepatic fxn

Metabolism: 1st pass metab.

results in an active metabolite
Excretion: Both urine and bile

GI problems; Teratogenic

Metabolism: Not much

Excretion: Predominantly bile

GI problems; less drug interactions because of altered

lactone ring

Penicillin substitutes: Clindamycin

- Chlorinated analog of lincomycin; stable to acid
- Inhibits 50S subunit by interfering with peptidyl transferase reaction and translocation step of protein synthesis
- Bacteriostatic
- Resistance:
Mutation of 23S subunit on 50S subunit affinity
- O-nucleotidyl transferase inactivates antibiotic
- Inability to enter organism
Cross-resistance to macrolides may occur!!
Pharmacokinetics
Drug Name
Clindamycin

Use/Spectrum
- Serious infections due to susceptible anaerobes (i.e. B. fragilis)
- Topical use for acne
- Chloroquine-resistant malaria in combination with quinine
-Toxoplasmosis in combination w/pyrimethamine

Admin/Absorption
Oral, Parental (im/iv)
Almost complete
absorption

Distribution
Metabolism/Excretion
Penetrates bone, body Met: Oxidative methylation by
fluids well, but NOT cytochrome P-450; metabolite
CSF; accumulates in has activity than parent!!
PMNs, macrophages, Excretion: Bile, urine, feces;
abscesses; crosses
accumulation in pts with renal
placenta
or hepatic failure; excreted into

Adverse Effects
Pseudomembranous colitis due to C. difficile;
contraindications with anti-peristaltic agents (i.e.
Immodium); nausea, vomiting, diarrhea, rash,
fever; Poss. Interactions with neuromuscular
blocking agents

breast milk

Pharmacology Review Sheets: Antibiotics, p.6

Penicillin substitutes: Tetracyclines
- Doxycycline and minocycline are most lipophilic
- Inhibits protein synthesis by binding to 30S subunit, blocking initiation of translation
- Diffuses through pores; also active transport-mediated uptake responsible for selective toxicity
- Broad-spectrum; bacteriostatic
- Resistance by accumulation of drug ( active transport, efflux); affinity for 30S subunit; Cross-resistance for members of this family may occur!
Pharmacokinetics
Drug Name
Tetracyclines

Use/Spectrum
Mycoplasma pneumoniae; Chlamydia spp., Borrelia burgdorferi,
Ehrlichia spp., Yersinia pestis, Helicobacter pylori, Ureaplasma
urealyticum, Acne vulgaris/rosacea, amebiasis

Admin/Absorption
Adequately absorbed
on empty stomach &
duodenum w/oral
admin; chelates w/
Ca2+/Mg2+/Al3+
preps; pH
destroys tetracyclines

Distribution
Penetrates body
fluids but not CSF;
Minocycline conc. in
tears, saliva; Binds to
tissues undergoing
calcification or to
tumors with high
Ca2+ content; Conc.
in skin, Crosses
placental barrier

Metabolism/Excretion
Metabolism: Glucuronide
formation (esp. doxycycline)
Excretion: Doxycyline by
feces; remainder by glomerular
filtration

Adverse Effects
GI distress
Contraindicated in
- Children < 8 yrs b/c of deposition in bone
- Pregnancy (crosses placenta); hepatotoxic to mother
Phototoxicity, onycholysis (doxycycline only)
Vestibular problems (minocycline only)
Superinfection with Candida
Azotemia in renally impaired patients
Pregnancy in women using oral contraceptives
Pseudotumor cerebri: Benign intracranial hypertension
(headaches, blurred vision)
Fanconi-like syndrome (electrolyte loss and
proteinuria), esp. outdated preps w/ascorbic acid

Penicillin substitutes: Aminoglycosides

- POLAR!!; coprecipitates with heparins
- Enters bacteria through pores; taken up by an oxygen-requiring, energy-dependent (active transport) system
- Strict anaerobes are thus IMMUNE to aminoglycosides!
- Inhibits protein synthesis by binding to 30S subunit to interfere with assembly of 70S ribosome; basically depletes the 30S subunit pool
- Also attaches to 30S subunit causes misreading of mRNA defective proteins incorporated into cell membrane makes it leaky
- Bacteriocidal!!
- Resistance by plasmid-encoded inactivating enzymes (Gm bacilli, S. aureus, S. epidermidis)
- 20 enzymes identified with unique specificity leading to variable and unpredictable cross-resistance!
- Synergism with -lactams (but still doesnt work vs. MRSA)
- Administration/Absorption: All parental except neomycin (which is topical)
Once-a-day dosing:
- Aminoglycosides exhibit concentration-dependent killing
- Aminoglycosides have long post-antibiotic effect (PAE)
- Dosing once a day initial levels are toxic, but quickly fall back into therapeutic range
- Distribution: Penetrates body fluids well but doesnt penetrate CSF under any circumstances; crosses placenta, penetrates renal cortex, ear endolymph
- Poor penetration into bronchial secretions (thus tobramycin spray is used to Rx P. aeruginosa in cystic fibrosis)
- Dose depends on lean body weight b/c of ECF-dependent distribution (obese people have ECF, edematous people have ECF)
- Blood level monitoring required to make sure that trough levels arent
- Underdosing is bad, mkayleads to hospital stay, duration of Sx, risk of complications
- Metabolism: None (aminoglycosides are metabolically stable)
- Excretion: Renal; accumulation in patients with renal failure
- Adverse effects: Vestibular ototoxicity (streptomycin, gentamicin); cochlear ototoxicity (gentamicin, tobramycin, amikacin); contraindicated in pregnancy b/c fetus may be born deaf;
nephrotoxicity (ranges from mild impairment to severe toxicity, depending on dose); neuromuscular paralysis (b/c aminoglycosides act like Ca 2+ ionophores)

Drug Name
Streptomycin
Gentamicin
Tobramycin
Amikacin
Neomycin

Use/Spectrum
M. tb (resistant strains), Endocarditis by Strep viridans,
Enterococcus faecalis (in combo w/-lactams)
E. coli, Klebsiella, Serratia, P. aeruginosa
E. coli, Klebsiella, Serratia, P. aeruginosa
E. coli, Klebsiella, Serratia, P. aeruginosa (gentamicin-resistant)
Topically, or orally in bowel surgery/hepatic coma

Pharmacology Review Sheets: Antibiotics, p.7

UTI Rxs: Fluoroquinolones
- Fluoride at position 6: Confers resistance; Fluoride at position 8: risk of phototoxicity
- Inhibits topoisomerase II (DNA gyrase)
- Bacteriocidal
- Relatively selectively toxic (due to bacterial affinity cp. human affinity)
- Resistance by point mutation in DNA gyrase, also by an efflux pump (S. aureus, P. aeruginosa, some Mycobacteria)
- Spectrum: UTIs (E. coli, Klebsiella, Proteus, P. aeruginosa); Prostatitis; STDs (N. gonorrhoeae, Chlamydia spp.); GI (E. coli, Shigella); Respiratory (H. influenzae,
resistant S. pneumoniae, MDR-TB, CF); Alternative to infections of bone/joints; Trovofloxacin used vs. anaerobes
- Orally active vs. Gm, Gm+ (S. pneumoniae)
- Levofloxacin (iv, oral admin) mostly used for infections other than UTIs
- Pharmacokinetics:
- Administration/Absorption: Orally active (ciprofloxacin (65%) < trovafloxacin (90%) < levofloxacin (95%))
- Distribution: Can get into body fluids and CNS, only ofloxacin gets into CNS with enough efficacy
- Metabolism: Maximum of 20% of total dose
- Excretion: Renal
- Adverse effects: Rare; includes GI (nausea, abdominal discomfort, vomiting, diarrhea); CNS (headache, dizziness, agitation, insomnia); Photosensitivity (esp
with sporofloxacin due to fluorine at position 8); arthropathy (contraindicated in pregnancy for this reason); sudden, unexpected tendon rupture; crystaluria,
hepatic necrosis (trovafloxacin)
- Drug interactions: Antacids, mineral supplements oral absorption due to chelation by Mg2+, Al3+, Zn3+, Fe3+; Ciprofloxacin & levofloxacin interfere with renal
clearance of theophyllin and warfarin (Note: Trovofloxacin doesnt!!)
UTI Rxs: Methenamine
- Action depends on dissociation of methenamine to formaldehyde at site of action (bladder/ureters), which is also pH-dependent (Proteus may thus be immune)
- Bacteriocidal; formaldehyde denatures the surface proteins of organisms, leading to cell death
- Orally active
- Adverse effects: GI upset
- Contraindications: Renal insufficiency/Hepatic insufficiency; Sulfonamides
UTI Rxs: Nitrofurantoin
- Bacteriostatic
Used because resistance is rare
- Adverse reactions: Nausea, pneumonitis, nystagmus, vertigo, headache, colors urine brown; High doses may lead to polyneuropathy of motor, sensory nerves;
Hemolytic anemia in those with G6PDH deficiency
UTI Rxs: Phenazopyridine (NOT AN ANTIBIOTIC!!)
- Alleviates symptoms only; Colors urine orange red
UTI Rxs: Fosfomycin
- Inhibits pyruval transferase (inhibits cell wall synthesis)
- Pharmacokinetics:

- Rapidly absorbed from GI tract

- Excretion: Parent, in urine
- Can be given to pregnant women with UTIs
- Expensive!!

Pharmacology Review Sheets: Antibiotics, p.8

Antifungals: Amphotericin (Amphoterrible) B; Nystatin
- Amphipathic; multiple forms exist (lipid formulation, colloidal dispersion)
- Interfere with cell wall synthesis; 8 molecules of amphotericin B make a pore in the membrane; K + leaks out, killing the cell
Extremely toxic; selective toxicity is narrow, and based on ergosterols greater binding affinity (than cholesterol) for amphotericin B the pores last 5 times as long
- Spectrum: Fungicidal; only used for life-threatening fungal infections in which the alternative is D E A T H
- Pharmacokinetics
- Not used orally, excepting fungal infections in the gut; preparation is freshly done, and protected from light
- Nystatin is only used topically, to Rx Candidiasis of the mouth, anus, vagina, and nose
- Huge volume of distribution (4L/kg); high sequestering in membranes
- Long t (15 days)
- Adverse effects:
- Chills, fever, vomiting
- Renal toxicity (lipid formulations are slightly less nephrotoxic)
- Anemia (normocytic, normochromic)
- Hypokalemia ( risk of cardiac arrhythmias)
- CNS symptoms (pain, headache, impaired vision, chemical meningitis) with intrathecal administration
- Thrombophlebitis at site of infection

Antifungals: Flucytosine
- Pyrimidine analog; used in combination with amphotericin B to dose of it.

Pharmacokinetics
Drug Name
Flucytosine

Use/Spectrum
Cryptococcal meningitis

Action
Inhibits thymidine synthetase
Relatively selectively toxic b/c
a specific permease transports
flucytosine into fungal cell

Admin/Absorption Distribution
Well absorbed orally Penetrates CNS

Metabolism/Excretion
Dependent on renal fxn for
excretion

Adverse Effects
Nausea, vomiting, diarrhea, enterocolitis (25%)
Liver damage (25%)
Bone marrow suppression (15%)

Antifungals: Azoles
- Fungistatic; inhibits cyt. P-450-dependent 14--demethylation of sterols (blocking sterol formation, ergosterol synthesis, rate of replication)
- Selective toxicity due to affinity of triazole or imidazole group for heme iron
Drug Name
Ketoconazole or
Itraconazole

Bioavailability
> 75%

Require low pH for abs.?

Yes

Penetrates CSF?
No

Excretion
Small amount of
parent excreted

Fluconazole

> 75%

No

Yes

80% of parent excr.

Drug Name
Ketoconazole
Fluconazole
Itraconazole

Uses
Pseudallescheriasis
Candidiasis (especially candidemia); coccidioidomycosis; cryptococcus chronic suppression
Blastomycosis (which affects males > females); histoplasmosis; sporotrichosis

Drug interactions:
- Terfenadine and astemizole: Cardiac arrhythmias
- levels of cyclosporine: Renal damage

Adverse Effects
GI distress, rash, pruritis, hepatic damage, teratogenic, dose-dependent discontinuity; inhibits host
steroid biosynthesis (esp. ketoconazole), leading to testosterone, libido, gynecomastia (males);
menstrual irregularities (females)); cortisol synthesis (both), but this doesnt manifest clinically.
GI distress, rash, pruritis, hepatic damage, teratogenic, dose-dependent discontinuity (less than;
keto/itra); DOES NOT INTERFERE WITH HOST STEROID BIOSYNTHESIS

- Oral anticoagulants: bleeding time

- Oral hyperglycemics: Hypoglycemia
- phenytoin, digoxin: Ataxia
- Rifampin, Phenytoin: levels of azoles

Antifungals: Terbinafine

Antifungals: Griseofulvin

- Fungicidal; inhibits squalene oxidase

- Can be given topically or orally; used for dermatophytic infections
- Adverse effects: Headache, GI symptoms

- Must be given orally, only used for dermatophytes; LONG Rx time

- Binds to newly formed keratin; inhibits microtubular function, arrests cells in
metaphase

Pharmacology Review Sheets: Antibiotics, p.9

Antiprotozoals: Metronidazole
- Bacteriocidal; acts by accepting electrons from special mechanisms of energy generation (by certain organisms)
- Formation of hydroxy radicals, hydroxyl amines, nitrosos interact and cleave DNA, killing the organism.
- Orally effective
- Distributes into CSF and breast milk
Drug Name
Metronidazole

Use/Spectrum
Drug of choice for systemic amebiasis; also used for
Protozoans (Trichomonas vaginalis, Entameoba
histolytica, Giardia lamblia); also anaerobes such as
Bacteroides fragilis

Adverse Effects
GI problems (nausea, headache, unpleasant, metallic taste, dry mouth (20%)
Vomiting, weakness, etc. (12%)
Disulfuram-like effects (NO ALCOHOL!)
Mutagenicity in experimental animals/bacteria, but not in humans (still, dont
give this during the 1st trimester of pregnancy).

Drug Interactions
Potentiates oral anticoagulants
Phenytoin and phenobarbital metabolism and infections
Cimetidine metabolism
risk of lithium toxicity

Antiprotozoals: Antimalarials
Pharmacokinetics
Drug Name
Use/Spectrum
Chloroquine
Erythrocytic forms of malaria
(4-aminoquinoline) (blood schizonts, trophozoites)

Primaquine
Extraerythrocytic schizonts
(8-aminoquinoline) (tissue schizonts, gametocytes)

Action
Admin/Absorption Distribution
Inhibits hemoglobin polymerase, Orally active
Huge volume of
a plasmodial enzyme removing
distribution; binds
toxic heme breakdown products
to nucleoproteins
in liver and spleen
Not well known, possible
Orally active
interference with electron
transport reactions

Metabolism/Excretion
Excretion: Unchanged,
70% in urine; some
metabolites

Adverse Effects
GI nausea, dizziness, headaches; High dose (Diplopia,
Cardiac arrhythmia, Bullseye lesion corneal
opacities)

Metabolism: Extensive
Excretion: Primarily as
metabolites in urine
t: 3-8 hours

Hemolytic anemia in G6PDH individuals (you see

darkened urine, flank pain, weakness and fatigue)
GI problems
Cardiac arrhythmias

Antiprotozoals: Rx for Leishmaniasis

Pharmacokinetics
Drug Name
Sodium
stibogluconate
Pentamidine

Use/Spectrum
Leishmania; not selective
Leishmania, P. carinii

Admin/Absorption Distribution
Small vol. Of
distribution
Parental, inhalation

Metabolism/Excretion

Adverse Effects
Muscle, joint pain; T-wave changes; Toxic shock/death;
Transaminase elevation
Severe hypotension, release histamine from mast cells,
Toxic to pancreatic islet cells (initial release of insulin,
w/diabetes chronically), renal toxicity (hyperkalemia,
hypocalcemia)

Antihelminthics: Benzimadazoles
- Bind to tubulin, blocking microtubule formation; this blocks glucose uptake, depletes ATP, immobilization of organism leads to death
- Selective toxicity: Very slim 2x affinity for helminths than us

Pharmacokinetics
Drug Name
Mebendazole
Albendazole

Use/Spectrum
Ascaris, Unholy trinity (whipworm, hookworm, pinworm)
Trichinella
Cysticercosis, hydatid disease

Admin/Absorption Distribution

Metabolism/Excretion
Excretion in urine

Rapidly absorbed

Long half-life

Adverse Effects
Make sure to chew tablet (to get it into solution)
GI problems, dizziness, headache
Mazotti reaction inflammatory response due to
organism death; GI/CNS disturbances; Hepatic damage
over long-term Rx

Other Antihelminthics
Pharmacokinetics
Drug Name
Ivermectin

Use/Spectrum
Strongyloides stercoralis, Onchocerca
volvulus; made from the soil
actinomycete Streptomyces

Action
Admin/Absorption Distribution
Works on GABA
Oral only
Doesnt get into CNS
receptor to cause
Slow distr. into eye
paralysis of nematode
muscle

Metabolism/Excretion
Long life (28 hours)
Excreted into feces (gets into
liver, then to the bile)

Praziquantal

Trematodes (flukes), tapeworms

Targets Ca2+ channel Rapidly absorbed

(but not ours)
Dont chew (bitter,
nauseating)

Short life

Gets into CSF, bile

and breast milk

Adverse Effects
Dont prescribe to people with CNS disorders
Mazotti reaction: Inflammatory response due to
organism death
Interactions: Avoid coadministration with
benzodiazepines, barbiturates and Valproic acid
GI disturbances, CNS disturbances, Malaise

Pharmacology Review Sheets: Antibiotics, p.10

Antiviral drugs: Targets uncoating/surface components
Drug Name
Amantadine
Rimantadine
Zanamivir

Oseltamivir

Use/Spectrum
Asian A2 influenza
Asian A2 influenza
Asian A and B influenza, used
prophylactically, or 36 hrs after
infection to duration and
severity of disease
Asian A and B influenza, used
prophylactically, or 36 hrs after
infection to duration and
severity of disease

Action
Blocks H+ pumping, preventing viral uncoating
Blocks H+ pumping, preventing viral uncoating
Inhibits neuraminidase

Inhibits neuraminidase

Metabolism/Excretion
Dependent on renal excretion
Somewhat metabolized

Adverse Effects
Possible convulsions, peripheral edema
Possible convulsions, peripheral edema (but less than amantidine)
Possible problems with asthmatics, nausea, headache

Possible problems with asthmatics, nausea, headache

Antiviral drugs: Targets transcription

Pharmacokinetics
Drug Name
Acyclovir

Gancyclovir

Foscarnet

Zidovudine (ZDV)
(azidiothymidine,
AZT) (NRTI)

Didanosine (ddI)

Structure/Properties/Action
Guanine analog; must be
phosphorylated to be activated;
selectively toxic to viruses to
to km of viral thymidine
kinase to human counterpart;
acts by competing with dGTP
in chain elongation (terminating
the process)
Purine analog; activated by
CMV kinase PO43-transferase;
Affinity for CMV enzyme is
close to our own, so its toxic
to bone marrow & GI tract.
Competes with dGTP chain
in chain elongation, but can
only slow it down, not
terminate it
Pyrophosphate analog; does
NOT require activation;
Competes for pyrophosphate
binding site of DNA and RNA
polymerases
Thymidine analog, inhibits
reverse transcriptase at 1/100
concentration needed to affect
cellular DNA polymerase

Use/Spectrum
HSV-1, HSV-2, VZV, (CMV),
EBV

Purine analog

HIV-1 (alone or in combo

Admin/Absorption Distribution
Metabolism/Excretion
Oral (incomplete
Conc. in CSF:
Excretion: Renal
absorption), IV,
50% of plasma levels
topical
Note: Valcyclovir
has better oral
absorption

CMV (retina, GI, lungs, nerves),

prophylaxis for
immunocompromised

Penetrates CNS,
Excretion: Renal
aqueous & subretinal Long t: 16 hrs intracellularly,
fluid concs similar
2-4 hrs. in plasma
to serum levels

Adverse Effects
Renal toxicity, neurotoxicity; with topical admin,
burning sensation. Not teratogenic.

Bone marrow suppression (granulocytopenia,

thrombocytopenia): Treat with GM-CSF;
Additive effects with drugs hitting bone marrow
(zidovudine); Azoospermia; Renal damage

Alternative for CMV retinitis

IV administration

Excretion: Rapidly, by renal

Small therapeutic window; can also cause renal

impairment, penile ulcers, electrolyte imbalance
(esp. hypocalcemia)

HIV-1; (EBV)

Oral, iv admin
Complete absorption

Metabolism: Glucuronidation
Excretion: Primarily renal
t: 1 hr, thus requires frequent
dosing; other drugs undergoing
glucuronidation (NSAIDs,
narcotic analgesics) can t

Severe headaches, nausea, neurotoxicity (seizures),

bone marrow suppression (anemia, neutropenia
severity based on CD4+ counts), possible association
with Non-Hodgkins lymphoma

Not toxic to bone marrow; adverse effects include

(NRTI)
Zalcitabine (NRTI)
Lamivudine (3TC)
(NRTI)
Efavirenz (NNRTI)

with AZT)
HIV-1; Used with AZT but
NOT didanosine
Synergist of AZT; helps delay
HIV-1; Used in combo with
onset of resistance
AZT
Doesnt require activation;
HIV-1; ONLY used in those
acts at different site than NRTIs with failed primary therapy

pancreatitis, peripheral neuropathy

Not toxic to bone marrow; adverse effects include
pancreatitis, peripheral neuropathy
Headache, insomnia, fatigue, GI upset
Once-a-day dosing

CNS (dizziness, headache, vivid dreams), rash,

teratogen, inducer of CYP3A4 (Note: Indinavir is
one of CYP3A4s substrates, so dosage will need to be
adjusted.

Pharmacology Review Sheets: Antibiotics, p.11

Antiviral drugs: Protease Inhibitors
- Site-directed analogs of HIV protease
- Inhibits protease resulting in non-infective virions (because they cant mature)
- Structural components affected: matrix protein, capsid, nucleocapsid, p6
- Viral enzymes affected: protease, reverse transcriptase, integrase

Pharmacokinetics
Drug Name
Saquinavir
Indinavir
Ritonavir

Admin/Absorption Metabolism/Excretion
Poor absorption
Extensively metabolized;
primarily fecal excretion
Reasonable
Extensively metabolized;
80% fecal excretion, 20% renal
Reasonable
70% metabolized
90% fecal excretion, 10% renal

Adverse Effects
GI (nausea, vomiting, diarrhea), triglycerides (exacerbates any pre-existing diabetes)

Inhibition of CYP3A4, CYP2D6

Least

Nephrolithiasis, hyperbilirubinemia, rash, dry skin, taste perversion, triglycerides

GI (nausea, vomiting, diarrhea), anorexia, circumoral/peripheral paresthesia, taste perversion,
triglycerides

Most; also metabolism of theophylline

and ethinyl estradiol

- Drug Interactions:
- Ritonavir has the most.
- There is a VERY long list, including some drugs taken as part of an HIV Rx regimen!

Antiviral drugs: Interferons

Pharmacokinetics
Drug Name
Interferon-

Structure/Properties/Action
Antiviral cytokine; suppresses
protein synthesis when
activated by virus

Use/Spectrum
Admin/Absorption Distribution
Drug of choice for HBV; HCV, Parental (im, iv),
HPV (intralesional injections), self-administered
Kaposis sarcoma virus,
Hairy cell leukemia, malignant
melanoma

HAART: A few notes

- Used to resistance, and killing of virus
- 2 nucleoside analogs, usually AZT + another RT inhibitor, protease inhibitors

Metabolism/Excretion
Adverse Effects
Metabolized by liver and kidney Flu-like syndrome (treated with acetaminophen and
with continued use)
Dose-limiting toxicities [bone marrow suppression,
neurotoxicity (somnolence, confusion, behavioral
changes), depression, hyperthyroidism, hypotension,
cardiac arrhythmias)
Drug interactions: w/theophylline

Pharmacology Review Sheets: Antibiotics, p.12

Anti-tuberculosis drugs:
Pharmacokinetics
Drug Name
Isoniazid (INH)

Action/Resistance
Use/Spectrum
Action: Bacteriocidal; interferes Mycobacterium tuberculosis
w/cell wall synthesis by
inhibiting mycolic acid synthesis
Must be activated to isonicotinic
anyl anion, then complexed w/
NADH inside the active site of
the enzyme
Resistance: Mutations/deletion
of KatG gene (which activates
INH); mutations in ACP
reductase affinity for NADH

Admin/Absorption Distribution
Oral
Distributes VERY
well into cells; enters
pleural fluid, ascitic
fluid, and caseous
material

Rifampin

Action: Highly lipid-soluble;

Inhibits DNA-dependent RNA
Polymerase (100x affinity for
M. tb than us)
Resistance: Mutations so
rifampin cant bind to -subunit
of RNA polymerase

Mycobacterium tuberculosis,
Well absorbed
Prophylaxis for meningococcal
H. influenzae, alternative to
cotrimoxazole for Rx of MRSA

Well distributed

Pyrazinamide

Bacteriocidal

Mycobacterium tuberculosis

Orally active, well

absorbed

Well distributed

Ethambutol

Bacteriostatic; inhibits
Mycobacterium tuberculosis
arabinosyl transferase (cell wall
synthesis)

Well absorbed

Concentrates in
RBCs

Rx of TB (for real):
- Use cocktail of 4 drugs for 2 months (INH, Rifampin, Pyrazinamide, Ethambutol)
- Then, INH and Rifampin for 4 more months
- Directly observed therapy (DOT) b/c of patient non-compliance, leading to MDR-TB
- Rx for MDR-TB based on sensitivity
- For Mycobacterium avium-intracellulare (MAC): Rifabutin + Azithromycin

Metabolism/Excretion
Metabolism: N-acetyltransferase
in Kupffer cells (in liver)
metabolize INH
Excretion: Metabolites, by renal

Metab.: Deacetylation (liver)

Excretion: Biliary route
Note: t with hepatic
insufficiency

Adverse Effects
Slow acetylator status: Has risk of peripheral
neurotoxicity and hepatotoxicity, drug interactions,
but a better response to M. tb
Other adverse effects: Hepatotoxicity, Drug-induced
lupus erythematosis (procainamide, hydralazine)
Drug interactions: Phenytoin, Disulfuram effect,
inference with oral anticoagulants

GI complaints, rash, liver enzymes, hepatitis, jaundice

With intermittent Rx, high doses: Allergy ( risk of
drug-induced fever, eosinophilia)
Colors all bodily excretions/secretions orange-red
Drug Interactions: Inducer of CYP3A4
(rifampin is the best inducer, rifabutin is poorer);
the effectiveness of oral contraceptives, oral
anticoagulants, methadone, quinidine, ketoconazole,
-blockers, Protease inhibitors! (dont use rifampin,
with HIV Rx), etc.
Metabolite: 5-hydroxypyrazinoic Hepatotoxic; metabolite can also interfere with uric
acid
acid excretion (and may thus produce an acute episode
of gout)
Excretion: Urine (renal)
Optic neuritis (highly dose-dependent), hyperuricemia
t = 8 hrs

Pharmacology Review Sheets: Antibiotics, p.13: Lists (these may be somewhat incomplete)
Distribution to CSF:
Distributes well
Distributes well only w/ inflammation
Sulfonamides
Penicillins
Chloramphenicol
3rd generation cephalosporins
Fluoroquinolones (esp. ofloxacin)
Flucytosine
Fluconazole
Metronidazole
Praziquantel
Acyclovir
Gancyclovir
Contraindicated for Pregnancy
Sulfonamides
Chloramphenicol
Macrolides (esp. clarithromycin b/c its a teratogen)
Tetracyclines
Aminoglycosides (deafness)
Azoles (teratogenic)
Metronidazole
Efavirenz (teratogen)
Fluoroquinolones (arthropathy)

Does not distribute well at all

Vancomycin
Macrolides
Clindamycin
Tetracyclines
1st generation cephalosporins
2nd generation cephalosporins (except cefuroxime)
Ketoconazole, Itraconazole
Ivermectin

Enters breast milk

Penicillins
Metronidazole
Praziquantal

Chelation
Azithromycin
Tetracyclines (also pH will destroy them)
Fluoroquinolones
Disulfuram-like effect
Cefamandole
Cefoperazone
Cefotetan
Metronidazole
Isoniazid
Note: Griseofulvin doesnt have a disulfuram-like effect, but it does potentiate the effects of alcohol.

Mazotti reaction (inflammation due to lots of dead bacteria)

Ivermectin
Albendazole

Pharmacology Review Sheets: Antibiotics, p.14: Lists (these may be somewhat incomplete)
Renal Excretion route
Sulfonamides
Penicillins
Cephalosporins (except ceftriaxone)
Aminoglycosides
Fluoroquinolones
Fosfomycin
Amphotericin B
Flucytosine
Antimalarials
Mebendazole
Amantidine
Acyclovir
Gancyclovir
Foscarnet
Zidovudine
Ethambutol

Renal toxicities
Sulfonamides (crystaluria)
Vancomycin
Aminoglycosides
Amphotericin B
Acyclovir
Foscarnet
Pentamidine

Hepatic Excretion
Chloramphenicol
Erythromycin
Clindamycin
Methenamine
Azoles (also hepatic toxicity due to these)
Isoniazid
Rifampin
Pyrazinamide (hepatotoxic)

Biliary/fecal excretion
Ceftriaxone
Macrolides
Rifampin
Doxycycline
Ivermectin
Protease inhibitors

P-450 activators
Efavirenz
Rifampin
Rifabutin
Griseofulvin

P-450 inhibitors
Erythromycin
Protease inhibitors (especially Ritonavir)
Chloramphenicol
Azoles

Renal Contraindications
Clindamycin
Methenamine