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
Drug Name
Triple sulfa

Use/Spectrum

Pharmacokinetics
Admin/Absorption Distribution Metabolism/Excretion
Rapid absorption

Adverse Effects

risk of crystaluria

(sulfadiazine
sulfamerazine
sulfamethazine)
Sulfisoxazole Most commonly used single
sulfa
Sulfamethoxazole
Use in combo with trimethoprim
(cotrimoxazole)
Sulfacetamide Topical (ophthalmologic use)
ONLY
Silver sulfadiazine
Topical use only
Prophylaxis of burn patients
Sulfasalazine Ulcerative colitis
Split by intestinal flora
Crohns disease
Salicylate is anti-inflammatory
Sulfadoxine Toxoplasmosis
Rapid absorption
Pharmacology Review Sheets: Antibiotics, p.2

Highest urine solubility

Urine solubility < than
sulfisoxazole

Males: sterility
LONG t1/2 (9 days)

Allergic reactions (dermatitis)

-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 Use/Spectrum

Admin/Absorption
Adverse effects
Penicillin G S. pneumoniae, S. aureus, S. epidermidis, S. viridans, N. gonorrhoeae, N. meningitidis, Clostridia spp., Bacteroides oralis, T. pallidum
Parental admin (im, iv)
Seizures!!
Penicillin V S. pneumoniae, S. aureus, S. epidermidis, S. viridans, N. gonorrhoeae, N. meningitidis, Clostridia spp., Bacteroides oralis, T. pallidum
Oral admin
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
Drug Name

Use/Spectrum

Pharmacokinetics
Admin/Absorption
Distribution Adverse Effects

Ampicillin
Proteus mirabilis, Listeria monocytogenes, H. influenzae (alternate)
Oral
Maculopapular rashes, esp. those on allopurinol, or w/ mono.
Urasyn (ampicillin S. aureus + anaerobes
IV ONLY
+ sulbactam)
Amoxicillin B. burgdorferi, P. mirabilis, L. monocytogenes, H. influenzae (alternate) Oral
Augmentin
H. influenzae, Moraxella catarrhalis (seen in nursing homes)
Oral, IV
(amoxicillin plus
clavulanic acid)

Enters bile
Enters bile
Enters bile
Enters bile

Antipseudomonal penicillins
Drug Name

Use/Spectrum

Pharmacokinetics
Admin/Absorption
Distribution Adverse Effects

Carbenicillin Indole + Proteus sp., Enterobacter (excluding Klebsiella)

Oral (indanyl form) & Parental
aggregation
Ticarcillin
P. aeruginosa, Enterobacter (including Klebsiella)
Parental (im, iv)
aggregation, hypokalemia due to K+ excretion
Timentin
P. aeruginosa, Enterobacter (including Klebsiella)
Parental (im, iv)
(ticarcillin plus
clavulanic acid)
Piperacillin P. aeruginosa (most potent), Klebsiella spp., Serratia marcescens
Parental (im, iv)
Zosyn
P. aeruginosa (as effective as ticarcillin); Zosyn has extended spectrum Parental (im, iv)
(piperacillin +

platelet
platelet

Enters the bile

tazobactam)
Azlocillin
P. aeruginosa (but less active than piperacillin for other Gm negs)
Parental (im, iv)
Mezlocillin Similar to ticarcillin, more active vs. Klebsiella
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 +
Drug Name

Use/Spectrum

Cefazolin
Gm+ cocci (enterococci resistant); used in implant surgery
Penetrates bone well
Cefadroxil
Gm+ cocci (enterococci resistant)
Cephalexin Gm+ cocci (enterococci resistant)

Pharmacokinetics
Admininistration
Parental (im, iv)
Oral
Oral

2nd generation: Extended-spectrum

Pharmacokinetics

Distribution

Drug Name

Use/Spectrum

Admininistration

Cefaclor
Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp.
Cefuroxime Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp.
Cefuroxime acetil
Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp.
Cefoxitin
Gm+ cocci, H. influenzae, Neisseria spp., Moraxella spp., Bacteroides fragilis

Distribution

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

3rd generation: Good vs. Gm , but worse than 1st generation vs. Gm +
Pharmacokinetics
Admininistration

Drug Name

Use/Spectrum

Ceftriaxone
Cefixime
Cefotaxime
Ceftizoxime
bone well
Ceftazidine
Cefoperazone

Drug of choice for N. gonorrhoeae, N. meningitidis; H. influenzae, S. typhi, P. aeruginosa

P. aeruginosa, H. influenzae
Oral
P. aeruginosa, H. influenzae
Parental (im, iv)
P. aeruginosa, H. influenzae
Parental (im, iv)
P. aeruginosa (enhanced activity vs. other 3rd generation cephalosporins)
P. aeruginosa (enhanced activity vs. other 3rd generation cephalosporins)

Distribution

Parental (im, iv)

Penetrates

Parental (im, iv)

Parental (im, iv)

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

Drug Name

Use/Spectrum

Cefepime
Good vs. Gm+ and Gm
Penetrates prostate
Broad-spectrum, but not really a drug of choice for any specific organism
Pharmacology Review Sheets: Antibiotics, p.4

Pharmacokinetics
Admininistration

Distribution

Parental (im, iv)

-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.
Pharmacokinetics

Drug Name

Use/Spectrum

Admin/Absorption

Imipenem/cilastatin Serratia marsescens, Enterobacter, Acinetobacter, P. aeruginosa, Gm+/Gm- anerobes

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

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 Metabolism/Excretion
Adverse Effects
Vancomycin MRSA, MRSE,
Transposon containing 9 genes;
IV for systemic inf., Widely distributed, Metabolism: Not well
delineated
Shock from rapid infusion
penicillin-resistant enterococci,
sensor protein activates cascade
Oral for antibiotic- but NOT to bile or
Excretion:
Renal; t1/2 in renal
Ototoxicity from high serum levels
pts w/allergy to penicillins. of genes, changing a peptide induced colitis CSF
failure
Nephrotoxicity (esp. if given with other
C. difficile (after metronidazole
bond to an ester bond so
nephrotoxic drugs)
fails), prophylaxis for surgical
vancomycin cant bind to it.
procedures with high rates of
infections by MRSA/MRSE
Penicillin substitutes: Streptogramins
Pharmacokinetics
Drug Name Use/Spectrum
Resistance
Admin/Absorption Distribution Metabolism/Excretion
Adverse Effects
Quinupristin/ Vancomycin-resistant strains Not well known
Admin: IV Not well known
Not well known
Work
like macrolides, but effectiveness questionable
Dalfopristin
Abs: Not well known
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 Use/Spectrum
Admin/Absorption Distribution Metabolism/Excretion
Adverse
Effects
Chloramphenicol
Brain abscesses due to anaerobes; H. influenzae; non-resistant
Admin: Oral, topical Excellent throughout Metabolism:
Extensive, with
Hemolytic anemia in G6PDH deficiency; dose-related
strains of S. typhi, alternative for Rickettsial infections
for eye
body; penetrates CSF glucuronidation; metabolite
reversible anemia, leukopenia, thrombocytopenia;
Abs: Complete with even without infl.;
formed by oxidative dechlor. Doseindependent idiosyncratic aplastic anemia;
oral admin
penetrates brain
inactivates cyt. P-450
Gray baby
syndrome b/c chloramphenicol disrupts
abscesses; crosses
Excretion: Glucuronide by renal;
mitochondrial
fxn, and neonates have low glucoronyl
placental barrier
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 acidresistant)
- 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 Use/Spectrum

Admin/Absorption Distribution Metabolism/Excretion
Adverse
Effects
Erythromycin Drug of choice for Mycoplasma pneumoniae; also used for Administration:
Well distributed; gets Metabolism: Extensively by
Cramps with oral admin; jaundice with estolate;
Legionella pneumophila, C. diphtheriae, Ureaplasma urealyticum Free base: Oral
into prostate but
cytochrome P-450
system Interacts with astemizole (fatal ventricular arrythmias);
Esters: Oral NOT CSF; conc. in Excretion: Predominantly bile,
carbamazepine, valproate (antipsychotics); warfarin b/c
Lactobionate: IV liver & macrophages some metabolites in urine
erythromycin
inhibits cyt-P-450; digoxin toxicity;
Absorption:
Ototoxicity; contraindicated in pts.
with hepatic fxn
Esters: more readily
absorbed than free
Clarithromycin
Mycoplasma pneumoniae, Better for Legionella pneumophila;
Readily absorbed,
Similar to
Metabolism:
1st pass metab. GI problems; Teratogenic
C. diphtheriae, U. urealyticum, Chlamydia spp., H. influenzae,
but food delays
erythromycin but
results in an active
metabolite
Helicobacter pylori
absorption
doesnt conc. in
Excretion: Both urine and bile
liver as much
Azithromycin H. influenzae, Moraxella catarrhalis, Chlamydia trachomatis,
Readily absorbed, but
Metabolism: Not much
GI problems; less drug interactions because of altered
Mycobacterium avium-intracellulare
never given with a
Excretion: Predominantly bile
lactone
ring
meal or with Al+3 or
Mg+2 containing
antacids
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 Use/Spectrum

Admin/Absorption Distribution Metabolism/Excretion
Adverse
Effects
Clindamycin - Serious infections due to susceptible anaerobes (i.e. B. fragilis) Oral, Parental (im/iv) Penetrates bone, body Met: Oxidative
methylation by
Pseudomembranous colitis due to C. difficile;
- Topical use for acne
Almost complete
fluids well, but NOT cytochrome P-450; metabolite
contraindications with anti-peristaltic agents (i.e.
- Chloroquine-resistant malaria in combination with quinine
absorption
CSF; accumulates in has activity than
parent!!
Immodium); nausea, vomiting, diarrhea, rash,
-Toxoplasmosis in combination w/pyrimethamine
PMNs, macrophages, Excretion: Bile, urine, feces; fever;
Poss. Interactions with neuromuscular
abscesses; crosses
accumulation in pts with renal
blocking
agents
placenta
or hepatic failure; excreted into
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
Admin/Absorption Distribution Metabolism/Excretion

Drug Name Use/Spectrum

Adverse
Effects
Tetracyclines Mycoplasma pneumoniae; Chlamydia spp., Borrelia burgdorferi, Adequately absorbed Penetrates body
Metabolism:
Glucuronide GI distress
Ehrlichia spp., Yersinia pestis, Helicobacter pylori, Ureaplasma on empty stomach & fluids but not CSF; formation (esp.
doxycycline) Contraindicated in
urealyticum, Acne vulgaris/rosacea, amebiasis
duodenum w/oral
Minocycline conc. in Excretion: Doxycyline by
- Children < 8 yrs b/c of deposition in bone

admin; chelates w/

tears, saliva; Binds to feces; remainder by glomerular

Ca2+/Mg2+/Al3+

tissues undergoing

Pregnancy (crosses placenta); hepatotoxic to mother

filtration

Phototoxicity,

onycholysis (doxycycline only)

preps; pH

calcification or to

Vestibular problems

(minocycline only)
destroys tetracyclines tumors with high

Superinfection with

Candida
Ca2+ content; Conc.

Azotemia in renally impaired

in skin, Crosses

Pregnancy in women using

placental barrier

Pseudotumor cerebri: Benign

patients
oral contraceptives
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 Ca2+ ionophores)
Drug Name Use/Spectrum
Streptomycin M. tb (resistant strains), Endocarditis by Strep viridans,
Enterococcus faecalis (in combo w/-lactams)
Gentamicin E. coli, Klebsiella, Serratia, P. aeruginosa
Tobramycin E. coli, Klebsiella, Serratia, P. aeruginosa
Amikacin
E. coli, Klebsiella, Serratia, P. aeruginosa (gentamicin-resistant)
Neomycin
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 Use/Spectrum
Action
Admin/Absorption Distribution Metabolism/Excretion
Adverse
Effects
Flucytosine Cryptococcal meningitis
Inhibits thymidine synthetase Well absorbed orally Penetrates CNS
Dependent on renal fxn for
Nausea, vomiting, diarrhea, enterocolitis (25%)
Relatively selectively toxic b/c
excretion
Liver damage
(25%)
a specific permease transports
Bone marrow
suppression (15%)
flucytosine into fungal cell
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

Bioavailability

Require low pH for abs.?

Ketoconazole or
> 75%
Yes
teratogenic, dose-dependent discontinuity; inhibits host
Itraconazole
testosterone, libido, gynecomastia (males);
Fluconazole > 75%
No
dose-dependent discontinuity (less than;

Yes

No

Penetrates CSF?

Excretion

Small amount of
parent excreted

Adverse Effects

GI distress, rash, pruritis, hepatic damage,

steroid biosynthesis (esp. ketoconazole), leading to

menstrual irregularities (females)); cortisol synthesis (both), but

this doesnt manifest clinically.
80% of parent excr. GI distress, rash, pruritis, hepatic damage, teratogenic,
keto/itra); DOES NOT INTERFERE WITH HOST STEROID

BIOSYNTHESIS
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
- Oral anticoagulants: bleeding time
- Oral hyperglycemics: Hypoglycemia
- phenytoin, digoxin: Ataxia
- Rifampin, Phenytoin: levels of azoles
Antifungals: Terbinafine
Antifungals: Griseofulvin
- Fungicidal; inhibits squalene oxidase
- Must be given orally, only used for dermatophytes; LONG Rx
time
- Can be given topically or orally; used for dermatophytic infections
- Binds to newly formed keratin; inhibits microtubular
function, arrests cells in
- Adverse effects: Headache, GI symptoms
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

Use/Spectrum

Adverse Effects

Drug Interactions

Metronidazole Drug of choice for systemic amebiasis; also used for

GI problems (nausea, headache, unpleasant, metallic taste, dry mouth
(20%) Potentiates oral anticoagulants
Protozoans (Trichomonas vaginalis, Entameoba
Vomiting, weakness, etc. (12%)
Phenytoin and
phenobarbital metabolism and infections
histolytica, Giardia lamblia); also anaerobes such as Disulfuram-like effects (NO ALCOHOL!)
Cimetidine
metabolism
Bacteroides fragilis
Mutagenicity in experimental animals/bacteria, but not in humans (still, dont
risk
of lithium toxicity
give this during the 1st trimester of pregnancy).
Antiprotozoals: Antimalarials
Pharmacokinetics

Drug Name Use/Spectrum

Action
Admin/Absorption Distribution Metabolism/Excretion
Adverse
Effects
Chloroquine Erythrocytic forms of malaria Inhibits hemoglobin polymerase,
Orally active Huge volume of
Excretion: Unchanged,
GI nausea, dizziness, headaches; High dose (Diplopia,
(4-aminoquinoline) (blood schizonts, trophozoites)
a plasmodial enzyme removing
distribution; binds
70% in urine;
some
Cardiac arrhythmia, Bullseye lesion corneal
toxic heme breakdown products
to nucleoproteins
metabolites
opacities)
in liver and spleen
Primaquine Extraerythrocytic schizonts Not well known, possible
Orally active
Metabolism: Extensive
Hemolytic
anemia in G6PDH individuals (you see
(8-aminoquinoline) (tissue schizonts, gametocytes)
interference with electron
Excretion: Primarily as
darkened urine, flank pain, weakness and fatigue)
transport reactions
metabolites in urine
GI problems
t: 3-8 hours
Cardiac arrhythmias
Antiprotozoals: Rx for Leishmaniasis
Drug Name Use/Spectrum
Effects
Sodium
Leishmania; not selective
wave changes; Toxic shock/death;
stibogluconate
Pentamidine Leishmania, P. carinii
release histamine from mast cells,

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

Adverse

Muscle, joint pain; TTransaminase elevation

Severe hypotension,
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 Use/Spectrum
Admin/Absorption Distribution Metabolism/Excretion
Adverse
Effects
Mebendazole Ascaris, Unholy trinity (whipworm, hookworm, pinworm)
Excretion in urine
Make
sure to chew tablet (to get it into solution)
Trichinella
GI problems, dizziness,
headache

Albendazole Cysticercosis, hydatid disease

inflammatory response due to

Rapidly absorbed

Long half-life

Mazotti reaction

organism death; GI/CNS

disturbances; Hepatic damage
over long-term Rx
Other Antihelminthics
Pharmacokinetics
Drug Name Use/Spectrum
Action
Admin/Absorption Distribution Metabolism/Excretion
Adverse
Effects
Ivermectin
Strongyloides stercoralis, Onchocerca
Works on GABA
Oral only
Doesnt get into CNS Long life
(28 hours)
Dont prescribe to people with CNS disorders
volvulus; made from the soil
receptor to cause
Slow distr. into eye Excreted into feces (gets into
Mazotti reaction: Inflammatory response due to
actinomycete Streptomyces
paralysis of nematode
liver, then to the bile)
organism
death
muscle
Interactions: Avoid coadministration
with
benzodiazepines, barbiturates and
Valproic acid
Praziquantal Trematodes (flukes), tapeworms
Targets Ca2+ channel Rapidly absorbed
Gets into CSF, bile Short life
GI disturbances, CNS disturbances, Malaise
(but not ours) Dont chew (bitter, and breast milk
nauseating)
Pharmacology Review Sheets: Antibiotics, p.10
Antiviral drugs: Targets uncoating/surface components
Drug Name

Use/Spectrum

Action

Metabolism/Excretion

Amantadine Asian A2 influenza

Blocks H+ pumping, preventing viral uncoating
peripheral edema
Rimantadine Asian A2 influenza
Blocks H+ pumping, preventing viral uncoating
peripheral edema (but less than amantidine)
Zanamivir
Asian A and B influenza, used
Inhibits neuraminidase
with asthmatics, nausea, headache
prophylactically, or 36 hrs after
infection to duration and
severity of disease

Adverse Effects

Dependent on renal excretion Possible convulsions,

Somewhat metabolized

Possible convulsions,
Possible problems

Oseltamivir Asian A and B influenza, used

asthmatics, nausea, headache
prophylactically, or 36 hrs after
infection to duration and
severity of disease

Inhibits neuraminidase

Possible problems with

Antiviral drugs: Targets transcription

Pharmacokinetics
Admin/Absorption Distribution Metabolism/Excretion

Drug Name Structure/Properties/Action Use/Spectrum

Adverse Effects
Acyclovir
Guanine analog; must be
HSV-1, HSV-2, VZV, (CMV),
Oral (incomplete
Conc. in CSF: Excretion: Renal
Renal toxicity, neurotoxicity; with topical admin,
phosphorylated to be activated;
EBV
absorption), IV,
50% of plasma levels
burning sensation. Not teratogenic.
selectively toxic to viruses to
topical
to km of viral thymidine
Note: Valcyclovir
kinase to human counterpart;
has better oral
acts by competing with dGTP
absorption
in chain elongation (terminating
the process)
Gancyclovir Purine analog; activated by CMV (retina, GI, lungs, nerves),
Penetrates CNS,
Excretion: Renal
Bone marrow suppression (granulocytopenia,
CMV kinase PO43-transferase;prophylaxis for
aqueous & subretinal Long t:
16 hrs intracellularly,
thrombocytopenia): Treat with GM-CSF;
Affinity for CMV enzyme is immunocompromised
fluid concs similar
2-4 hrs. in plasma
Additive effects with drugs hitting bone marrow
close to our own, so its toxic
to serum levels
(zidovudine);
Azoospermia; Renal damage
to bone marrow & GI tract.
Competes with dGTP chain
in chain elongation, but can
only slow it down, not
terminate it
Foscarnet
Pyrophosphate analog; does Alternative for CMV retinitis IV administration
Excretion: Rapidly, by renal
Small therapeutic window; can also cause renal
NOT require activation;
impairment, penile ulcers,
electrolyte imbalance
Competes for pyrophosphate
(esp. hypocalcemia)
binding site of DNA and RNA
polymerases

Zidovudine (ZDV) Thymidine analog, inhibits HIV-1; (EBV)

headaches, nausea, neurotoxicity (seizures),
(azidiothymidine, reverse transcriptase at 1/100
marrow suppression (anemia, neutropenia
AZT) (NRTI)concentration needed to affect
severity based on CD4+ counts), possible association
cellular DNA polymerase
Hodgkins lymphoma

Oral, iv admin

Metabolism: Glucuronidation

Complete absorption

Excretion: Primarily renal

Severe
bone

t: 1 hr, thus requires frequent

dosing; other drugs undergoing

with Non-

glucuronidation (NSAIDs,
narcotic analgesics) can t
Didanosine (ddI)
Purine analog
marrow; adverse effects include
(NRTI)
peripheral neuropathy
Zalcitabine (NRTI)
marrow; adverse effects include

HIV-1 (alone or in combo

Not toxic to bone

with AZT)

pancreatitis,

HIV-1; Used with AZT but

Not toxic to bone

NOT didanosine
peripheral neuropathy
Lamivudine (3TC) Synergist of AZT; helps delayHIV-1; Used in combo with
insomnia, fatigue, GI upset
(NRTI)
onset of resistance
AZT
Efavirenz (NNRTI) Doesnt require activation; HIV-1; ONLY used in those Once-a-day dosing
(dizziness, headache, vivid dreams), rash,
acts at different site than NRTIs
with failed primary therapy
inducer of CYP3A4 (Note: Indinavir is

pancreatitis,
Headache,
CNS
teratogen,
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 Admin/Absorption Metabolism/Excretion

Adverse Effects
Inhibition of CYP3A4, CYP2D6
Saquinavir
Poor absorption
Extensively metabolized;
GI (nausea, vomiting, diarrhea), triglycerides (exacerbates any preexisting diabetes)
Least
primarily fecal excretion
Indinavir
Reasonable Extensively metabolized;
Nephrolithiasis, hyperbilirubinemia, rash, dry skin, taste perversion,
triglycerides
80% fecal excretion, 20% renal
Ritonavir
Reasonable 70% metabolized
GI (nausea, vomiting, diarrhea), anorexia, circumoral/peripheral paresthesia, taste
perversion,
Most; also metabolism of theophylline
90% fecal excretion, 10% renal
triglycerides
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 Structure/Properties/Action Use/Spectrum
Admin/Absorption Distribution Metabolism/Excretion
Adverse Effects
Interferon- Antiviral cytokine; suppresses
Drug of choice for HBV; HCV,
Parental (im, iv),
Metabolized by liver
and kidney
Flu-like syndrome (treated with acetaminophen and
protein synthesis when
HPV (intralesional injections),
self-administered
with
continued use)
activated by virus
Kaposis sarcoma virus,
Dose-limiting
toxicities [bone marrow suppression,
Hairy cell leukemia, malignant
neurotoxicity
(somnolence, confusion, behavioral
melanoma
changes), depression,
hyperthyroidism, hypotension,
cardiac arrhythmias)
Drug interactions: w/theophylline
HAART: A few notes
- Used to resistance, and killing of virus
- 2 nucleoside analogs, usually AZT + another RT inhibitor, protease inhibitors

Pharmacology Review Sheets: Antibiotics, p.12

Anti-tuberculosis drugs:
Pharmacokinetics
Admin/Absorption Distribution Metabolism/Excretion

Drug Name Action/Resistance

Use/Spectrum
Adverse Effects
Isoniazid (INH)
Action: Bacteriocidal; interferes
Mycobacterium tuberculosis Oral
Distributes VERY
Metabolism: Nacetyltransferase
Slow acetylator status: Has risk of peripheral
w/cell wall synthesis by
well into cells; enters in Kupffer cells (in liver)
neurotoxicity
and hepatotoxicity, drug interactions,
inhibiting mycolic acid synthesis
pleural fluid, ascitic metabolize INH
but a
better response to M. tb
Must be activated to isonicotinic
fluid, and caseous
Excretion: Metabolites, by renal
Other adverse effects: Hepatotoxicity, Drug-induced
anyl anion, then complexed w/
material
lupus
erythematosis (procainamide, hydralazine)
NADH inside the active site of
Drug interactions:
Phenytoin, Disulfuram effect,
the enzyme
inference with oral anticoagulants
Resistance: Mutations/deletion

of KatG gene (which activates

INH); mutations in ACP
reductase affinity for NADH
Rifampin
Action: Highly lipid-soluble; Mycobacterium tuberculosis, Well absorbed Well distributed
Metab.: Deacetylation (liver)
GI complaints, rash, liver enzymes, hepatitis, jaundice
Inhibits DNA-dependent RNA
Prophylaxis for meningococcal
Excretion: Biliary route
With intermittent Rx, high doses: Allergy ( risk of
Polymerase (100x affinity for H. influenzae, alternative to
Note: t with hepatic
drug-induced
fever, eosinophilia)
M. tb than us)
cotrimoxazole for Rx of MRSA
insufficiency
Colors all bodily
excretions/secretions orange-red
Resistance: Mutations so
Drug Interactions: Inducer
of CYP3A4
rifampin cant bind to -subunit
(rifampin is the best
inducer, rifabutin is poorer);
of RNA polymerase
the effectiveness of oral
contraceptives, oral
anticoagulants, methadone,
quinidine, ketoconazole,
-blockers, Protease inhibitors!
(dont use rifampin,
with HIV Rx), etc.
Pyrazinamide Bacteriocidal
Mycobacterium tuberculosis Orally active, well
Well distributed
Metabolite: 5-hydroxypyrazinoic
Hepatotoxic; metabolite can also interfere with uric
absorbed
acid
acid excretion (and may thus
produce an acute episode
of gout)
Ethambutol Bacteriostatic; inhibits
Mycobacterium tuberculosis Well absorbed Concentrates in
Excretion: Urine (renal)
Optic
neuritis (highly dose-dependent), hyperuricemia
arabinosyl transferase (cell wall
RBCs
t = 8 hrs
synthesis)
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

Pharmacology Review Sheets: Antibiotics, p.13: Lists (these may be somewhat incomplete)
Distribution to CSF:
Distributes well
Distributes well only w/ inflammation
Does not distribute well at all
Sulfonamides
Penicillins
Vancomycin
Chloramphenicol
3rd generation cephalosporins
Macrolides
Fluoroquinolones (esp. ofloxacin)
Clindamycin
Flucytosine
Tetracyclines
Fluconazole
1st generation cephalosporins
Metronidazole
2nd generation cephalosporins (except cefuroxime)
Praziquantel
Ketoconazole, Itraconazole
Acyclovir
Ivermectin
Gancyclovir
Contraindicated for Pregnancy
Enters breast milk
Sulfonamides
Penicillins
Chloramphenicol
Metronidazole
Macrolides (esp. clarithromycin b/c its a teratogen)
Praziquantal
Tetracyclines
Aminoglycosides (deafness)
Azoles (teratogenic)
Metronidazole
Efavirenz (teratogen)
Fluoroquinolones (arthropathy)

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

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

Renal Contraindications
Clindamycin
Methenamine

Zidovudine
Ethambutol
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