Drug

Sulfonamides

Use against
Uncomplicated UTIs, nocardia, chlamydia

Cidal/static
Static

Trimethoprim

TMP- bacterial, pyrimethamine- protozoa (toxo, malaria)

Fluoroquinolones (Cipro, levofloxacin)

CF infx, osteomyelits, prostatitis, E coli, pseudomonas,

Salmonella, Cipro for pulm anthrax prophylaxis

Methenamine

Urinary tract disinfectant

Phenazopyridine
-lactams

Urinary tract analgesic (not antimicrobial)

Penicillin G/V
Acid stable penicillin nafcillin,
methicillin, ox

Gram + cocci, treponema, actinomyces

Staph aureus

Wide spectrum -ampicillin, amoxicillin

Gram + and -

Anti-pseudomonal- piperacillin

Pseudomonas, gram - ONLY

Cephalosporins
Gen 1- cefazolin

3rd gen may be used for empiric tx

Gram +, same as Pen G (plus PEcK) proteus, e coli,
kelbsiell

Gen 2- cefoxitin

Gram +/- (HENs PEcK) h flu, Enterobacter, neiss., serratia

Gen 3-ceftriaxone, cefazimide

Gen 4- cefepime
Carbapenems (imi/mero)
Monobactam aztreonam
Vancomycin
Macrolides

Gram only (Neisseria, pseudomonas)

Wide spectrum, gram +/Gram +/-, aerobic, anaerobic
Gram - aerobes
Gram + only

Erythromycin
Clarithromycin
Azithromycin
Clindamycin

Gram + cocci and atypical pneumonias

Same as erythro + H. flu
C trachomatis (not for gram + cocci)
Strep, anaerobes above the diaphragm, topical for
acne/rosacea, tx for toxo + pyrimetham, bone infx

Streptogramins

VRE faecium

Linezolid

Gram + anaerobes, VRE (faecium and faecalis), MRSA,

MRS Epidermitidis

Chloramphenicol

Hflu, intracell (rickettsia, psittacosis, typhoid), anaerobic,

meningitis

Tetracycline

Intracell- chlamydia, legionella, mycoplasma pneumo, lyme, Static

rickettsial, rosacea, acne

Aminoglycosides

Aerobic, intracellular (pseudomon, tularemia, etc)

Cidal

TB only

Cidal

Cidal

Cidal

Cidal

Cidal
Static

Static

Together cidal, alonestatic

Static

Kanamycin (easily inactivated), Amikacin

(not easily inactivated)
Isoniazid

Rifampin

TB polytherapy, tx for leprosy, prophylaxis for Neisseria Cidal

mening, H flu

Pyranizamide
Ethambutol

Cidal
TB only

Static

Absolute/relative
Absolute
Relative
Relative (higher affinity for bacteria)

Relative

Absolute

Absolute

Absolute
Relative
Metabolized by CYP450
CYP450 makes active metabolite
Relative

relative
Relative

Relative (active uptake by bacteria, not by humans),

higher affinity for non-host ribosomes)

Absolute- humans do not make mycolic acid

Relative- less affinity for human enzyme

Mechanism
Compete for dipydropteroate synthetase (PABA analog)
Competes for DHF reductase
Inhibit DNA gyrase/topo 4

Breakdown into ammonium and formaldehyde in acidic pH (5.5)

Urine turns red
Irreversibly inhibits transpeptidase, may stimulate autolysins

Amoxicillin + clavulanic acid = augmentin

Same as penicillin

Mero- tx meningitis
High resistance to -lactamases
Binds D-alaD-ala, inhibits TGase from elongating chain
Binds P site of 50S ribosome subunit, t-RNA dissociates, inhibits translocation

Best for intracellular infections

Binds 50S subunit of ribosome, inhibits peptidyl transferase (active metabolite undergoes entero-hepatic recirculation)

A (dalfopristin) inhibits donor/accept site on peptidyltransferase, changes shape. B (quinpristin) inhibits translocation
Binds 50S and prevents formation of 70S initiation complex
Blocks peptidyl transferase at 50S
Binds 30S, blocks attachment of aminoacyl tRNA

Binds 30S, blocks formation of initiation complex, premature mRNA termination, forces misreading

Prodrug amines are cleaved by KatG to INA-radical or anion ACP reductase linked to NADH, blocks mycolic fatty acid synthesis

Blocks DNA dep RNA pol- no initiation for mRNA synth

Prodrug is activated by TB to pyrazinoic acid

Inhib arabinosyl transferase arabinogalactan is not polymerized in cell wall

Kinetics
Oral, penetrates CSF without inflam, crosses placenta, binds albumin, acetylated and glucuronic conj

Oral, ONLY levo enters CNS, mainly renal elim,

Time dependent killing (above MIC 70% in 24 hrs), not metabolized, renal elim, enter CNS when inflamed
G (intravenous); V (oral)
Methicillin- IV
Oral
IV
Same as penicillin

IV only, enters CSF

IM or IV, enters CSF
Slow IV admin (oral for C. dif), CNS inflam only, not metabolized, urine
Oral, intracell, do not enter CNS, elim mainly biliary (less renal)
Formulated with ester or enteric coated to protect from stomach acid

High oral absorption, reaches bone, does not enter CNS, intracell, xplacenta, mainly hepatic metabolism and biliary excretion

Continuous IV (short half-life), intracellular (PMN and macros), non-enzymatic metabolism to non-active metabolites
Oral, 100% bioavailability, non-enzymatically broken down to 2 inactive metabolites, 65% biliary excretion
Oral/parenteral, enters CNS, xplacenta, glucuronic conj, renal elim
Oral, range of bioavailability (doxy is best), crosses placenta, all but doxy are glucuronidated and undergo EHC), doxy-feces, rest-renal

IV only, dose dependent killing, xplacenta, QD, ECF only, NO CSF, no metabolism, elim is dependent on renal filtration only*

Oral, penetrates all tissues (CSF, placenta, pleural fluid, intracell, caseous material), high metabolism, elim via kidney in 24 hours

Oral (very lipophilic), CNS/bone, enterohep circ, de-acetylated form is elim via biliary

Oral, well distributed

Oral, concentrates in RBCs, 50% metabolized, elim via kidneys

Toxicity/Adverse Reactions
Crystalluria, kernicterus (not for babies, preggos), jaundice in adults, hemolytic anemia in G6PDD
Megaloblastic anemia in people with poor diets/low folic acid- pregnant or homeless
Long QT, tendinitis, transient arthropathy, photosensitive

Bladder irritation in high doses,

Neurotoxic (seizures-GABA), cation toxicity

Methicillin- nephritis
Ampicillin- macropapular rash (not allergy)

Imipenem is convulsant at high doses

Nephrotoxic and Ototoxic; thrombophlebitis at site of admin
Motility, arrhythmia, cholestasis, rash, eosinophilia
Epigastric distress, jaundice, trans ototoxicity
Epigastric distress, jaundice, trans ototoxicity
NVD, allergy, C dif infection, high dose causes NMJ blockage (poor contraction)

Incompatible with saline (must use glucose), myalgia, arthralgia, inhibits 3A4 metabolism. Non-enzyme breakdown,
biliary elim
NVD, tongue color change, anemia, TCPenia, neutropenia (weekly tests), c dif infx
Hemolytic anemia in G6PDD, reversible anemia, irreversible aplastic anemia, grey baby syndrome
Deposits in tissues undergoing calcification (bone, teeth), NVD (not for kids <8), toxic in preg, phototoxic, minocyclineCN8 problems
CN 8 damage, fetal CN8 damage, nephrotoxic, NMJ toxic (not for weak muscles)

Peripheral neuropathy due to increased elim of B6, convulsions in seizure disorder, hepatotoxic with age, drug
induced SLE

Asymptomatic elevated liver enzymes, hepatitis w jaundice in liver disease pts, red body fluids, high dose therapy
no longer used

Hepatotoxic, 5 hydroxy pyrazinoic acid metabolite interferes with uric acid excretion
Optic neuritis, decreased visual acuity and color vision (dose dep), uric acid accumulates in blood (worse w gout)

Allergy
SJS necrotizing dermatitis

NOT FOR hepatic insufficiency pts (increased ammonia), not for renal
insufficiency pts (crystalluria)
Anaphylaxis (cross-reaction with other lactams)

Fast infusion -> Red Man Syndrome

Rash and fever are rare

Mild rash

Interactions

Antacids/dairy di/trivalent ions chelate and decrease absorption, interferes with CYP450 metabolism (warfarin, theophylline)

NOT WITH sulfa drugs- formaldehyde forms precipitate

Clavulanic acid (not antimicrobial) inhibits -lactamase; Probenecid increases half-life

Inhibits ALDH causing disulfiram-like effect (cefamandole/cefoperazone)

Inhibits CYP-450 metabolism of warfarin, theophylline, digoxin

Inhibits CYP-450 metabolism of warfarin, theophylline, digoxin
DOES NOT INHIBIT CYP-450
GOOD: for beta-lactam allergy, prophylaxis for oral procedures (no endocarditis)

Inhibits CYP450
Dairy, antacids, iron chelates and blocks absorption; Tetracycline lowers normal flora and may cause digoxin to reach toxic levels; Less normal flora causes
warfarin activity
Synergism with -lactams and used for life threatening infx (use two different IVs because they will react and precipitate out)

Alters CYP metabolism of other drugs; Rifabutin has less inducing ability

Absorption delayed by PABA, induces CYP450 and decreases half-lives of other drugs

Resistance
Efflux pump, enzyme mt, increased PABA synth

Efflux, pt mt

Altered PBPs, plasmid/chrom encoded -lactamase, down-reg porins, efflux

Same as - lactams

Plasmid encodes D-ala D-lactate (9 genes)

Methylation of 23S subunit adenine decreases affinity for binding site, efflux, esterase

Methylation decreases affinity, inactivated by S aureus (O-nucleotidyl TFase)

Methylation of 23S prevents B from binding. Enzyme inactivation of group A.

Some strains of S. aureus bind less drug (but no cross resistance)
Plasmid acetyl transferase
Active efflux (MDR transposable gene cassette)

Anaerobes, mutated binding site, plasmid for enzyme to inactivate drug

Chrom pt mt of KatG decreases affinity, delete KatG (non essential), or mt ACP reductase so INH
is not linked to NADH

Mutation in polymerase decreases affinity to subunit

Drug
Amphotericin B (polyene)

Nystatin (polyene)
Flucytosine

Azoles
Imida- keto/clotrima
Traizoles- flu/itra
Keto/Itraconazole
Fluconazole
Voriconazole
Posaconazole
Terbinafine
Griseofulvin

Echinocandins (Caspofungin, Micafungin)

Use against
Systemic mycoses

Cidal/static
Cidal

Cutaneous mycoses, candida

Cidal

Cryptococcus neoformans

Cidal

Systemic (oral) and Cutaneous (topical)

Static

Topical- cutaneous

Fungal kidney infections-parent drug is active in urine

Aspergillosis
Mucormycosis
Onycomycosis, dermatophyte infx
Only dermatophytes

Candidemia and Aspergillosis

Cidal

Absolute/relative
Relative, increased affinity for ergosterol, pore half-life is longer in fungi

Relative, increased affinity for ergosterol, pore half-life is longer in fungi

Relative- fungi actively pump in

Relative- increased affinity for fungal CYPs, humans get sterols from
diet

Relative human enzyme is less sensitive

absolute

Mechanism
Hydrophobic portion associates with ergosterol to form a pore --> loss of K and other
electrolytes

Hydrophobic portion associates with ergosterol to form a pore --> loss of K and other
electrolytes
Fungi convert to 5-flurouracil to 5-FdUMP, inhibits thymidylate synthase no cell division

Inhibit CYP450 14 demethylase, no ergosterol synthesis

Inhib squalene epoxidase --> toxic intermediate accumulates

Binds mitotic spindles, blocks cell division

inhibits -glucan synthase, decreasing cell wall synthesis

Kinetics
IV or intrathecal (does not dissolve in water), sequestered in tissues; 15 day
half life, liposomal administration is less nephrotoxic but $$$$; no metabolism

topical
Oral, renal elim, enters CNS --> synergistic w/ Amphotericin B in candidemia
and cryptococcal meningitis

Requires acidic environment to dissolve, does not enter CSF well, high
metabolism
Does not need acidity, enters CSF well, low metabolism

Topical and oral (oral for nail infx- 12 week therapy); accumulates in keratin

Toxicity/Adverse Reactions
nephrotoxicity is dose-limiting but can't be dialyzed; infusion reactions
(chills, fever, muscle spasms, hypotension) arrhythmias, anemia,
thrombophlebitis

Allergy

NVD, enterocolitis, elevated hepatic enzymes, bone marrow suppression

NVD, rash, elevated hepatic enzymes, all are teratogens (contra for
preg)

KETO- less sex steroid synth, less cortisol synth, severe hepatotoxicity
Flu- very tolerable

Headache, NVD, rare hepatotoxic

Rash

Headache, CNS, GI, augments alcohol effect

Rare serum
sickness,
angioedema

Gi distress, flushing from histamine release

Interactions

Inhib CYP drug metabolizers: increased levels of other

drugs

Phenytoin decreases [itraconazole]

Cross sensitivity with penicillins. NOT FOR acute intermittent

porphyria
micafungin increases levels of nifedipine and cyclosporine

Resistance

Drug
Metronidazole

Use against
Entamoeba, giardia, bacteroides, trichomonas vag,
clostridium, anaerobic infx

Chloroquine (4- aminoquinolone)

Malaria, extra-intestinal amebiasis, high doses are

anti inflammatory for RA/SLE

Primaquine

Malaria in tissue schizonts and hypnozoites (not for

intra-RBC)

Artemisinin
Sodium stibogluconate

Malaria
Leshmania

Pentamidine

Pneumocystis jirovecii pneumonia, sleeping sickness

Benzimidazoles

helminths

Mebendazole

Ascaris, whip worm, hook worms, pinworm, spiralis

Albendazole

Cysticercosis, hydatid cysts

Ivermectin

Strongyloides, Onchocerca

Praziquantel

Cestode, flukes

Drug
Albendazole

Observed Effects on Helminths

Inhibition of glucose transport; depletion of glycogen
stores, inhibition of fumarate reductase

Mebendazole

Inhibition of glucose transport; depletion of glycogen

stores

Pyrantel pamoate

Muscles depolarize, increased spike wave activity,

spastic paralysis

Diethylcarbamazine

Hyperpolarization and paralysis of worm's

musculature; exposure of antigens, leading to
antibody binding and attack by phagocytes

Ivermectin

Alters chloride currents, resulting in death of

microfilariae

Praziquantel

Depolarization of muscles, increased intracellular

Ca ++ , displacement of schistosomes to the human
liver, exposure of surface antigens, binding by
antibody and phagocytes, tegument disruption

Niclosamide

Uncouples phosphorylation; may inhibit anaerobic

metabolism

Drug
Metronidazole

Possible Mechanism of Action

Activated when reduced by ferredoxins, reacts with
DNA and other parasite constituents

Paromomycin
Nitazoxanide

Inhibits protein synthesis

Inhibition of electron transfer reactions essential to
the metabolism of anaerobic organisms

Chloroquine

Concentrated in hemoglobin-containing digestive

vesicles, inhibits heme polymerase

Quinine

Concentrated in food vacuoles, probably inhibits

heme polymerase

Mefloquine

Concentrated in food vacuoles, may form toxic

complexes with heme

Pyrimethamine
Sulfonamides

Inhibits dihydrofolate reductase

Inhibit binding of p-aminobenzoic acid to
dihydropteroate synthetase

Nifurtimox

Forms reactive O 2 species that damage cell

membranes and DNA
Irreversibly inhibits ornithine decarboxylase, inhibits
polyamine synthesis

Eflornithine

Melarsoprol

Reacts with sulfhydryl groups, inhibits proteins

Cidal/static
Cidal

Absolute/relative
Relative- bacterial metabolites (OH-FR, N=O, OHx)
are more reactive than human metabolite (NH2)

Cidal

Relative higher affinity for helminths

Coadmin with steroids to reduce inflammation

Possible Mechanism of Action

Binding to -tubulin, prevents microtubule
polymerization
Binding to -tubulin
Depolarizing neuromuscular blockade
Hyperpolarization and neuromuscular blockade

Altered chloride channel function

Uncertain

Uncertain

Mechanism
Nitro group on metro accepts electrons from ameba
ETC forms toxic products damages DNA

Kinetics
Oral, enters CSF, in breast milk, alkyl chain is
oxidized and glucuronidated, 50% metabolized,

Inhib Hb polymerase (plasmodium enzyme converts Oral, high Vd, quickly binds proteins, high levels in
toxic heme breakdown products to hemozoin)
liver, spleen, kidney. Not metabolized long half-life

Unknown (maybe ETC)

Oral, complete metabolize to urine

Interferes with glycosome in the organism so it

cannot generate ATP/GTP

IV, very slow elim

Unknown

IV or via inhalation for pneumonia, not metabolized

Binds tubulin and blocks MT formation, block

glucose uptake no ATP
Oral tablet must be chewed, rapid metabolism and
excretion
Coadmin of steroids to lower inflammation

Oral, active metabolite, renal elim

Activates glutamate gated Cl channels, paralysis of

pharyngeal muscles

Oral, no CNS, enters eye, elim unchanged in feces

Enhances Ca influx, worm contracts mucles,

paralysis

Oral, DO NOT CHEW, binds albumin, good

distribution to CSF, milk, bile, poo, metabolized

Toxicity/Adverse Reactions
Allergy
NVD, headache, dry mouth, metallic taste, disulfiram
effect, Lithium toxicity?
GI, long term use associated with diplopia, T wave,
arrhythmia, death (in RA pts), can cause visual
changes, Bulls eye lesion
Hemolytic anemia in G6PDD

Only given in patient, muscle and joint pain, T wave

changes, shock, death
Blocks symp nerves and causes hypotension,
histamine release, toxic to islet cells (hypoglycemia
and then diabetes), damages kidneys

Dead org causes headache, vomit, mental status

change, hyperthermia. Long term therapy- liver
damage, leukopenia
Inflam (Mazotti rxn) due to death of microfilariae

Fever, sedation, itching, rash, edema

Interactions
Potentiates oral anticoags, phenytoin increases elim
of metro, cimetidine increases [metro],

Resistance

High resistance via efflux pump

Dead orgs in brain release proinflam mediators

Do not give with anti-seizure drugs (benzo,

barbiturate or valproic acid)

Metal

Acute

Arsenic

Nausea, vomiting,

"rice-water" diarrhea,

encephalopathy,

MODS, LoQTS,

painful neuropathy

Bismuth

Renal failure; acute tubular necrosis

Cadmium

Pneumonitis (oxide fumes)

Chromium

GI hemorrhage, hemolysis, acute renal failure (Cr6+ ingestion)

Cobalt

Beer drinkers (dilated) cardiomyopathy

Copper

Blue vomitus, GI irritation/ hemorrhage, hemolysis, MODS (ingested); MFF (inhaled)

Iron

Vomiting, GI hemorrhage, cardiac depression, metabolic acidosis

Lead

Nausea, vomiting, encephalopathy (headache, seizures, ataxia, obtundation)

Manganese

MFF (inhaled)

Mercury

Elemental (inhaled): fever, vomiting, diarrhea, ALI;

Inorganic salts (ingestion): caustic gastroenteritis

Nickel

Dermatitis; nickel carbonyl: myocarditis, ALI, encephalopathy

Selenium

Caustic burns, pneumonitis, hypotension

Silver

Very high doses: hemorrhage, bone marrow suppression, pulmonary edema, hepatorenal necrosis

Thallium

Early: Vomiting, diarrhea, painful neuropathy, coma, autonomic instability, MODS

Zinc[6]

MFF (oxide fumes); vomiting, diarrhea, abdominal pain (ingestion)

Chronic
Diabetes,

hypopigmentation/ hyperkeratosis,

cancer: lung, bladder, skin, encephalopathy

Diffuse myoclonic encephalopathy

Proteinuria, lung cancer, osteomalacia
Pulmonary fibrosis, lung cancer (inhalation)
Pneumoconiosis (inhaled); goiter

vineyard sprayers lung (inhaled); Wilson disease (hepatic and basal ganglia degeneration)

Hepatic cirrhosis

Encephalopathy, anemia, abdominal pain, nephropathy, foot-drop/ wrist-drop

Parkinson-like syndrome,

respiratory, neuropsychiatric[5]

Nausea, metallic taste, gingivo-stomatitis, tremor, neurasthenia, nephrotic syndrome; hypersensitivity

(Pink disease)

Occupational (inhaled): pulmonary fibrosis, reduced sperm count, nasopharyngeal tumors

Brittle hair and nails, red skin, paresthesia, hemiplegia

Argyria: blue-grey discoloration of skin, nails, mucosae
Late findings: Alopecia, Mees lines, residual neurologic symptoms

Copper deficiency: anemia, neurologic degeneration, osteoporosis

Toxic Concentration
24-h urine:

50 g/L urine, or

100 g/g creatinine

No clear reference standard

Proteinuria and/or 15 g/ g creatinine
No clear reference standard
Normal excretion:

0.1-1.2 g/L (serum)

0.1-2.2 g/L (urine)

Normal excretion:

25 g/24 h (urine)

Nontoxic: < 300 g/dL

Severe: >500 g/dL

Pediatric: symptoms or [Pb] 45 /dL (blood); Adult: symptoms or [Pb] 70 /dL[4]

No clear reference standard

Background exposure "normal" limits:

10 g/L (whole blood); 20 g/L (24-h urine)

Excessive exposure:

8 g/L (blood)

Severe poisoning:

500 g/L (8-h urine)

Mild toxicity: [Se] >1mg/L (serum); Serious: >2 mg/L

Asymptomatic workers have mean [Ag] of 11 g/L (serum) and 2.6 g/L (spot urine)
Toxic: >3 g/L (blood)

Normal range:

0.6-1.1 mg/L (plasma)

10-14 mg/L (red cells)

Treatment
BAL (acute, symptomatic)

Succimer

DMPS (Europe)

*
*
NAC (experimental)
NAC

CaNa2 EDTA

BAL

D-Penicillamine

Succimer

Deferoxamine

BAL

CaNa2 EDTA

Succimer

BAL

Succimer

DMPS (Europe)

*
Selenium, vitamin E (experimental)
MDAC

Prussian blue

First-Line Drugs for Tuberculosis

Inhibitors of protein synthesis (Rifamycins)
Inhibitors of cell wall synthesis (Isoniazid, others)
Others
Second-Line Drugs for Tuberculosis
Fluoroquinolones
Aminoglycosides
Others
Drugs for Leprosy
Dapsone
Fluoroquinolones
Rifamycins
Tetracyclines
Drugs for Mycobacterium Avium
Macrolides