ID drugs

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Key Words : Ototoxicity, Nephrotoxicity or Renal toxicity, Hepatotoxicity, Hematopoietic toxicity, Bactericidal, CYP3A4 Inducer/inhibitor, Cross-react

Antibacterial ChemotherapyClass Drug Name Mechanism/pharmacokinetics/Resistance Indications Adverse effects

Inhibitor of Cell Wall Synthesis (ICWS)

B - L a

c t a m s P e n i c i l

l i n s

M e c h a n i s m

o f A c t i o n s :

1 -

C o v a

l e n

t b i n d i n g t o

t r a n s p e p

t i d a s e s

/ P B P s

2 -

I n h i b i t t r a n s p e p

t i d a

t i o n

r x n

( c r o s s - l

i n k i n g o

f c e

l l w a

l l )

3 -

A c

t i v a

t i o n o

f M u r e

i n h y

d r o

l a s e s

( a u

t o l y s

i n s

)

A l l a r e

b a c

t e r

i c i d a

l ! ! ! !

Pen G

Pen V

Pen G oral/parenteral, Pen V oral; Benzathine depot ; acid labile

Pen G: particularly for Group B Strep (GBS)

Gram(+) cocci In general to all penicillin:-Hypersensitivity reaction

is the major penicillinadverse effect. About 5-8% claim allergic to pens.

Seizure by high dose penicillins (particularly

renal failure )

Nafcillin ,Methicillin ,

Isoxazolyl penicillins(ox-, clox-)Oxacillin

Cloxacillin

Oral; nafcillin and oxacillin parenteral too; ox- clox- and diclox acid-stable

All B-Lactams: Bactericidal Time dependent .PharmK: poor distribution to eye, prostate, and CNS.

Anti-Staphyloccocal penicillins

B-lactamaseresistant!! , Staph.

aureus

Carbenicillin indanyl ,Piperacillin ,Ticarcillin ,

Mezlocillin

Effective against Proteus , Pseudomonas . Problem: rapid emergencew/Pseudomonas, so use in combo w/ aminoglycosides or

fluoroquinolones . Note: these are powerful Rx, use only whenindicated to protect their therapeutic value

Anti-PseudomonalPenicillins

Ampicillin,Amoxicillin ,

Increased gram(-) activity Extended SpectrumPenicillins

Gram +/-

Ampicillin Rash (10%incidence, 90% in ptx w/

mononucleosis)

-Same general contra asabove

B-Lactamaseinhibitor

Clavulanic acid ,

Sulbactam ,Tazobactam

Resistance to Penicillins by B-lactamase production (major

mechanism). Use B-lactamase-resistant penicillin (Nafcillin, oxacillin,cloxacillin) + Co-administer w/ B-lactamase inhibitors!

B-lactamase

resistant

Cephalosporins-In general

Cephalosporins areMore toxic than

penicillins particularly Renal

Toxicity Some

cross-reactivity w/pen-sensitive pts.

1st generationCephalothin Cephalexin (o)Cefazolin

Less sensitive to B-lactamase . Broader spectrum of activity.Clinical use: chemoprophylaxis for surgery , alternative to anti-staph

penicillin.

(ph)

Greater gram-activity

Gram +

5-10% cross-reactivitywith penicillins.

Hypersensitivity, some GI,Renal Toxicity ; plateletinhibition and Disulfram

effect.2nd gen

Cef uroxime(o)CefotetanCef aclor (o)

Intermediate Spectrum

F?

More gram- than 1 st.Less Gram (+)

activity

Cefotetan &cefoperazone: Disulfram

effect

3 rd gen

Broad spectrum. Better for CNS Reserve for Gram-

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Cefotax imeCeftriaxoneCef taz idime

tax, triax, tazactivity

4 th genCefepime

Broad Spectrum. Better distribution (CNS).Cephalosporinase-resistant .

Reserve for gram- activity

Mono-bactams(still b-lactams)NEWER DRUGS!

Aztreonam Gram (-) activity; virtually inactive against Gram (+) or anaerobes.

Resistant to B-lactamase . No cross-reactivity in pen-sensitive

patients

Only good againstGram- activity , B-

lactam resist

Carbapenems

Imipenem Broad spectrum . IV only. Pseudomonas develops resistance rapidly, souse w/ aminoglycosides . Inactivated by renal dipeptidase , co-administer Cilastatin (inhibits enzyme from blocking Imipenem)

Gram (-/+),anaerobes May Cross-reactivity w/penicillins.

Meropenem Dipeptidase-resistant carbapenem. So you give this one as a secondline to Imipenem

May Cross-reactivity w/penicillins.

Other ICWS

Non-B-Lactams

VancomycinBactericidalOtotoxicity

Renal Toxicity

Inhibits transglycosylation (step before transpeptidation). Previouslyclassed as too toxic for systemic use. IV drug cleared through kidney enhances oto- & renal toxicity of aminoglycosides. Red man or red

neck syndrome = histamine release. Misuse/overuse can be aproblem.

Bactericidal forGram (+).

Systemic MRSAVancymycin-d

Nephrotoxic andototoxicity .

Some thrive on thisdrug!!!: Vancomycin-

dependent Enterococci Fosfomycin Newest ICWS. Inhibits cell-wall synthesis from within! At the

cytoplasmic step in cell wall precursor synthesis. Active uptake byglycerophosphate or G6P-transporter. Only oral approved in USA.

Active drug excreted by kidney. Approved for single-dose therapy ofUTI. Synergistic w/ B-lactams , aminoglycosides , or fluoroquinolones .

Gram (-) UTI

Some Gram+ too

BacitracinBactericidal

Topical antibiotic only!!!! Markedly nephrotoxic

Other Polymixin B This agent affects cell membranes. Not sure how. Inhibits G-Polymyxin E Old drug, now used as new drug as last resort. Mech: solubilizes

bacterial membrane.Anti-Pseudomonal

How come the class of anti-staph can be used to treat b-lactamase producing pneumococci?

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Class Drug Name Mechanism/pharmacokinetics/Resistance Indications Adverse effects

Inhibitor of Protein Synthesis (IPS)Aminoglycosides

Mechanism:irreversible

inactivation ofribosome

(30S).

Irreversible = thinkBactericidal!! !

OtotoxicityRenal Toxicity

Streptomycin

Gentamicin

Tobramycin

Amikacin

BactericidalOtotoxicity

Renal Toxicity

Multiple effects on translation misreading of mRNA, interfere w/ initiation , break up polysomes (streptomycin monosomes) PharmK: poor oral absorption usually given IV, sometimes IM.

Good distribution except for eye and CNS. No significant hostmetabolism. Excretion glomerular filtration. Very high

concentration in proximal tubule cells!!!!.

Administer: One Dose a Day at HIGH CONCENTRATION!!!! Once a day gives us a brief time to kill bacteria and gives us the

rest of the day to relax and avoid the adverse effects: ototoxicity & Nephrotoxicity

Nephrotoxicity: Exacerbated by Vancomycin, cyclosporine

Neuromuscular blockade : seen at very high dose phenomenon.Most common during surgery (d/t other NM blockers), also in

Myasthenia gravis ptx.

Resistance: emerges rapidly if AG used alone.

Non-resistant Gram(-) infections: E. coli,

Proteus,Pseudomonas

For Pseudomonas :

use Gent>Tobra>Amika

Nephrotoxicity!!! : high

concentrations of AG inrenal cortex. 5-25%receiving AG >3 days

shows progressive renalimpairment . Ampho B, or

cisplatinOtotoxicity : high conc ofAG in inner ear. 5-25% of

ptx. Loss of vestibularand/or auditory fxn. May

be reversible.Dose- and Time-

dependent

Neuromuscular

Blockade!!!!!!

Spectinomycin Spectinomycin Related to aminoglycosides. Used againstPenicillin-resistant

gonococci

TetracyclinesHepatotoxicity

Reversible binding to30S subunit.

Bacteriostatic .

Tetracycline

Usually given orally, but absorption variable. Tetracyclines chelatemetal ions : Ca2+, Al3+, Fe2+, Mg2+. Poorly absorbed therefore

DO NOT administer with food, milk, antacids. Rarely given IV.

Well distributed, except to CNS, synovial fluid. Concentrates inteeth, bone, liver (bile), kidney .

Tetracyclines crosses the placenta and are excreted in milk .

Bacterial resistance to Tetracyclines by:-increased efflux pumps are major resistance .

-altered ribosomal proteins or RNA are secondary mechanisms.-Especially common in Pseudomonas, proteus

-indiscriminate use/overuse (clinical & agricultural)

Broad spectrumantibiotics.

Gram (+/-)Mycoplasma ,Chlamydia ,Rickettsiae ,

Lyme disease

Intracellular bugsincluding

spirochetes .

Tick-borne diseases?

GI direct irritation.Superinfections:

Pseudomonas, Proteus,Staph, Clostridia, Candida

Impaired liver function high doses, during

pregnancy, pre-existingliver dz

Photosensitization

Calcium chelation :deposit in teeth & bone leads to discoloration,

growth retardation,deformity.

Doxycycline Excreted mostly fecal; others mostly urine

Glycylcyclines (part Newer generation of tetracyclines. Retain antibacterial spectrum

Tetracycline

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of Tetracyclines)

Tigecycline

of tetracyclines but overcome resistance .

NOT affected by Efflux pump EXCEPT in Proteus andPseudomonas .

resistant bacteria!!

MacrolideAntibiotics

(older)

Blocks translocation by binding to 50S

subunit

Macrolide Antibiotics (newer)=

50S

Erythromycin ,Clarithromycin,Azithromycin

Clari- and Azi- (broaderspectrum)

Hepatotoxicity

Bacteriostatic or bactericidal , depending on dose

Absorbed from GI tract, but acid-labile. Therefore, we use entericcoating or erythromycin esters to increase stability. Can also beadmin IV. Excellent distribution except to CNS. Crosses placenta.

Excreted in bile ( 50x higher than in plasma ). Half-life 2-5hrs exceptfor azithromycin (a little longer).

Resistance: Staph, some strept- and pneumococci. By altered(methylated) rRNA, efflux pump, esterases

Gram (+),some Gram (-), some

mycobacteria.

Think Atypical

pneumonia !

Mycoplasma or

Legionnaires disease, chlamydia

1. GI distress 2. Microsomal enzymeinhibition (Rx-Rx interx:

oral anti-coagulants,digoxin, non-sedating anti-

histamines)3. Hepatotoxicity esp.erythromycin estolate

cholestatic jaundice!!!! .

Clarithromycin Higher availability ~Less GI effects

Azithromycin Minimal P450-based interactions

Tissue level 10-100x plasma levels!!!T1/2 = 2-4 days.

Higher availability~Active against mycobacterium avium-intracellulare (MAC) in

AIDS patients

Chlamydia

Active against(MAC) in AIDS

patients

High intracellular concentration !!!

Ketolides(macrolide-like)

50S

Telithromycin

Semi-synthetic macrolide. Oral, well absorbed and distributed.Metabolized in liver, excreted in both bile and urine. Poor

substrate for efflux pump . ONCE daily dosing !!

Used for respiratory tract infections (community-acquiredpneumonia, bronchitis, sinusitis). Inhibits CYP3A4

Doesnt have thatefflux problem

macrolides have. QT Prolongation!!

Other Proteinsynthesis inhibitors

50SChloramphenicol

Hematopoietictoxicity

Reversible inhibitor of protein synthesis. Bacteriostatic . Broadspectrum. Well absorbed from all routes, CNS levels = Serum .

100% excreted in urine (10%filtrate, 90% tubular sec).Glucuronidation in liver is rate-limiting step for

inactivation/clearance for drug.

Resistance: key mechanism is plasmid-mediated . Chloramphenicol

Acyl Transferase (CAT). Slow development. Only slight resistance(2-4x). Ideal drug; however, too many adverse effects.

Typhoid fever, RockyMountain spotted

fever in children.

1) GI disturbances followed by fungal

superinfections.2) Anemia d/t BM

depression .3) Aplastic Anemia

usually irreversible & oftenfatal.

4) Gray Baby syndrome (poor glucuronidators)

5) Drug-drug interactions inhibits microsomal

enzymes.ClindamycinHepatotoxicity

Lincosamide antibiotic . Bacteriostatic . Well-absorbed anddistributed, except for CNS.

Bacteroides fragilis,other anaerobes.

GI upset,Clostridium

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Endocarditisprophylaxis

superinfection ,

Hepatotoxicity Other

Streptogramins :50S

Newer drugs!

QuinupristinDalfopristin(Synercid TM)Bactericidal

Peptide macrolactones. IV, 80% excreted in bile, 20% in urine.POTENT Protein inhibitor of CYP3A4.

Bacteriostatic against Enterococcus faecium. Bactericidal againstother organisms.

Approved for use against Vanco- and multi-drug resistantEnterococcus faecium, Methicillin-resistant Staph. Aureus (MRSA).

VRE, MRSA SERIOUS INDICATIONSHERE FOR DRUG-DRUG

INTERACTIONS

OtherOxazolidinones

Prevents formation of70S ribosomes

(unique!)

Linezolid(can inhibit MAOI)

Bactericidal

No cross-resistance w/ other IPS. Bactericidal againststreptococci .

Bacteriostatic against staph and enterococci.IV or oral, Oral AUC = IV AUCGood distribution to tissues.

Primary: Vanc -resistant E. faecium (Limit to multi-drug

resistant Gram+infections)

BM suppression ,Thrombocytopenia (reversible & mild)


Inhibitor of Folate Dependent Pathwaysp-Aminobenzoic Acid

analogs ( PABA)

Inhibitors of FolateSynthesis

SulfonamidesHematopoietic toxicity

Renal Toxicity

Silver Sulfadiazine PABA analog . Enter into a normal metabolic pathway, butthen blocks that pathway. Competitive inhibitor of

dihydrofolate synthesis . Biostatic

Oral, some topical (burns), rarely IV. Well absorbed in GI, welldistributed including CNS. Variable metabolism, depending on

drug and patient. Acetylation yields inactive metabolite .Excreted in urine (90% by glomerular filtration). 10-20x blood

concentration in urine.

Topical application forburns

Allergic reaction: fever,rash (up to 5% incidence)-May cross react w/ othersulfonamides carbonic

anhydrase inhibitors,thiazides, furosemide,

sulfonylureahypoglycemic.

SodiumSulfacetamide

Ophthalmic preparations

Sulfasalazine(not absorbed-split bygut bacteria to release

aminosalicylate)

Ulcerative colitis

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Inhibits Pteridinesynthetase UTI uncomplicated, untreated, acute.

Sulfonamides are now combined with trimethoprim.

Resistance: mutations overproduction of PABA. Loss ofpermeability. New form of dihydropteroate synthetase

enzyme can discriminate b/t PABA vs sulfonamide.

Stevens-Johnsonsyndrome (fever, malaise,

rare but can be fatal).-Crystalluria/ hematuria -Hematopoietic effects

-Hemolytic anemias (G6PDH deficiency)

Inhibitor of Folate use:

Dihydrofolatereductase (DHFR)

inhibitors

Trimethoprim

Blocks bacterial enzyme. Blocks dihydrofolate reductase . Readily absorbed from GI. Wide distribution including CNS.

Excreted in urine. Can be used alone for UTI, but usuallycombined w/ sulfonamide (TMP-SMX). Combination is often

bactericidal.10,000x more effective against bacterial DHFR than againstmammalian enzyme, but still may see anti -folate effects.

Pneumocystispneumonia, complicated

UTI.

Megaloblastic anemia ,

leukopenia ,

granulocytopenia . Treat

w/ folinic acid . (easyfix!)

CombinationBactrim

orTrimethoprim-

Sulfamethoxazole (Co-trimoxazole) aka

TMP-SMX

Combo = bactericidal.

Typical sulfonamideeffects.

AIDS ptx receiving Co-

trimoxazole = higherincidence of adverseeffects . Fever, rashes ,leukopenia , diarrhea


DNA Gyrase InhibitorQuinolones

bactericidal

Nalidixic Acid Prototype quinolone antibiotic.

Inhibits transcription and DNA replication .Oral admin, rapidly absorbed, rapidly metabolized (glucuronidation),

and excreted in urine

Anti-malarial drugs??

Fluoroquinolones

Bactericidal!

Ciprofloxacin Levofloxacin

Ofloxacin

Fluorinated analogues of nalidixic acid. Well absorbed & distributedafter oral administration. Only 20% is metabolized (liver). Excreted

in urine, blocked by probenicid . Effective systemically after oraldose, parenteral forms also available.

Resistance: altered (mutated) DNA gyrase, especially Pseudomonas ,Staph, Serratia

Broad-spectrum

Excellent against Gram-. Useful in GI & UTIs.Shows promise for

treatment of respiratory,skin, soft tissue

infections, esp. multi-drug resistant organisms.

Moderate-good:Gram(+)

Some GI: nausea,vomiting, diarrhea.

HA, dizziness, insomnia,abnormal liver fxn tests .

Blocks theophyllineclearance (cannot be co-admin, duh!). Connective

tissue dsd?

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Urinary Tract Antiseptics-Use systemic agents, which are efficiently cleared in the urine: Penicillins, Aminoglycosides, Sulfonamides, Fluoroquinolones.

Resistance and re-infections are common. May need to suppress bacteria for a long time.Nitrofurantoin Mechanism is unknown, but may involve oxidative stress.

Bacteriostatic or cidal depends on bug. Rapidly absorbed (oral),metabolized, and excreted in urine (50% as active drug). Even IV does

not have a systemic effect.

Resistance: all Pseudomonas , some Proteus

UTI, Gram+/- ,most effective ifurine pH

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Ethambutol Inhibits synthesis of mycobacterial cell wall glycan (arabinogalactan ?). Well absorbed and distributed. CNS level

variable, 4-60% of serum. Most excreted in urine accumulates inrenal failure.

Resistance: rapid, therefore use in combo

Dose-dependent opticneuritis , decreased acuity ,

loss of red -green differentiation .

Streptomycin Was only for severe ( life-threatening ) cases, now used morefrequently. PK.

adverse effects typical ofaminoglycoside

IV every day forprophylaxis.. not an ideal

drug choice!2nd line Anti-TB

drugsPara-

aminosalicylate (PAS)

Currently a resurgence in TB, highly resistant strains are common.2nd line may become 1 st line. Other drugs include: amikacin,

Ciprofloxacin, OfloxacinCycloserine

EthionamideSulfone Dapsone Similar to sulfonamide. Well absorbed and distributed.

Concentrates in skin, muscle, liver, and kidney. Acetylated; excretedin feces and urine.

Dr. Z: inhibits folic acid synthesis.

Used in combination w/rifampin and clofazimine

for M. Leprae . Also may beused for P. jiroveci

pneumonia.

Hemolysis andmethemoglobinemia

common.

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Anti-Fungal ChemotherapyDrug Mechanism/Phamacokinetics Clinical Use Adverse effect

Class: Systemic Anti-Fungal Agents Amphotericin B ampotherrible drug lotsof side effects

Binds Ergosterol (essential component of fungal membrane)

A: IV or intrathecal (into CSF)D: good (except CNS)t 1/2 = 2 weeks (slow)- (side effects dont stop until drug is

gone).Add to Liposomes drug will have higher affinity to liposomethan to OUR memb lower side effects. Liposome = buffer

Most important drug for severesystemic mycosesBroad spectrumUse initially then switch (toxic)

Concentration is greatest:Fungi > liposome > our cell membrane

Chills, fever, nausea, vomiting,headache

(premedicate: antipyretics,antihistamines, analgesics)

Nephrotoxicity

FlucytosineInhibitor of nucleic acidsynthesis! Anti-cancerdrug.

Only fungi have cytosinedeaminase!

Antimetabolite! Fungal cytosine deaminase converts 5-Fluorocytosine to 5-fluorouracil (5-FU)Block DNA & RNA syn

Use is limited because only some fungi are susceptible andonly given independently = rapid resistance!A: Orally effective,D:widely distributed ( even CNS ),E:urine (10x serum)

Cryptococcus, some CandidaRapid resistance use w/ AmphotericinB or itraconazole

Low toxicity

Anti-Fungal Azoles Azoles all inhibit Ergosterol synthesis (blocks fungal CYP450) Ketoconazole Inhibit Ergosterol synthesis

A: 1 st oral antifungal for systemic diseaseD: Not into CNS

Not widely used anymore

Used as adjunct therapy for prostatecancer (androgen dependent)Systemic fungal diseaseNot used often b/c of side effects.

GI, hepatotoxicityBlock OUR adrenal steroidogensis

(Gynecomastia )Alters drug metabolism ofcyclosporine, non-sedating

antihistaminesItraconazole Inhibit Erogosterol synthesis

A: Oral and IVHistoplasms, blastomyces, sporothrix Fewer adverse effects than

ketoconazoleFluconazole Inhibit Erogosterol synthesis

Water soluble good CSF deliveryMore selective for fungal P450s

Most widely used. Cryptococcalmeningitis, candidemia,mucocutaneous candidiasis

Voriconazole Inhibit Erogosterol synthesis . Newest triazoleA: Oral and IV M: liverCleanest/purist drug.

Aspergillosis, Candida, Dimorphicfungi

Fewer adverse effects thanketoconazole

Visual disturbances in 30% ofpatients

Inhibitors of cell wall synthesisCaspofungin Inhibits synthesis of cell wall b(1-3) glucan

-Incomplete wall causes lysisLarge cyclic peptide linked to fatty acidIV, highly protein bound, slow metabolism.

Candida , Emperic anti-fungal(neutrophenia)Salvage therapy for amphotericin-resistant Aspergillus

Minor GI

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E: Urine, feces

Anti-fungal agents for mucocutaneous infections Drug Mechanism/Phamacokinetics Clinical Use Adverse effectTopical Nystatin Similar to Amphotericin B Topical antifungal agent

Can be given orally for intestinal tractToo toxic for systemic use. You

cannot achieve systemicconcentration safe enough for

this drug WORST thanamphotericin B!

Systemic Griseofulvin A: Orally concentrates in keratinized tissue ringworm & athletes foot Terbinafine Similar to Griseofulvin, concentrates in keratinized tissue BUT it does not ACTIVATE until it REACHES TOPICALLOCATION!-Inhibits Squalene epoxidase (ergosterol synthesis)

More commonly used than

Anti-Parasitic Chemotherapy

Drug Mechanism/Phamacokinetics Clinical Use Adverse effectAnti-Malarials

(Plasmodium falciparum, P. malariae, P. vivax, P. ovale) 1st 2 = single cycle; 2 nd 2 = multiple cycles Chloroquine Alters metabolism of hemoglobin by parasite & blocks nucleic acid

synthesisA: Oral or parenteral. Rapid, completeD: wideE: urine, 25% as metaboliteGive loading dose for acute tx (long t1/2)Resistance: in SA, Africa, Asia, common in P.falciparum, in P.

vivax, from P -glycoprotein pumping mechanism

highly effective blood schizonticide Acute: clears parasitemia from all 4

plasmodiaCures: P. falciparum & p. malariae

Use w/ primaquine for P. vivax &ovaleProphylactic of choice : 1 wk before

travel and continue till 4 wk after

Well tolerated Pruritis ; GI, mildheadache; may exacerbatepsoriasis or porphyria

Biggest problem is resistance(efflux pump)

Block efflux w/verapamil (Ca2+channel blocker-so it has side

effects)

Mefloquine UnknownA:oral (to irritating for parenteral) well absorbed,M: liver, excreted in feces

Prophylaxis or tx of chloroquineresistant

GI, CNS, possible psychotropic effects (used in murder defenses!)*Nightmares!

Quinine Inhibits nucleic acid and protein synthesis. Doesnt cross BBB,metabolized by CYP3A4 and CYPs

Back up for Chloroquine-resistant P.falciparum

Cinchonism (HA, nausea, sweating,tinnitus, dizziness, blurred vision)

QT prolongation Atovaquone /

Proguanil (Malarone)Atovaquone : Inhibits ETC, poor oral absorption, high proteinbinding 2-3 half life.

Proguanil : inhibits protozoal dihydrofolate reductase, wellabsorbed, half life 12 hrs, extensive metabolism by CYP2C19, activemetabolite is cycloguanil

Prophylaxis or treatment for P.falciparum resistant.

GI, HA, anorexia, dizziness

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Fansidar

(pyrimethamine-sulfadozine)

Anti-folate combinationBlocks synthesis/utilization of folic acidWell absorbed, excreted in urine

Use for P. FalciparumSlow acting (Not for acute attacks)

GI distress, cutaneous rxns

Steven-Johnson symptoms

Primaquine This fights protozoans in the LIVER Oral, well absorbed, metabolites are intracellular oxidants

Tissue Schizonticide (goes after liver)Use in combination w/ chloroquinefor prophylaxis or cure of P. vivax orovale

Some GI distress, hemolyticanemia in G6PDH deficiency

Artemisinin Traditional Chinese medicineActivated by oxidative metabolism free radicals, alkylationVery short t 1/2 , oral

Rapidly acting blood schizonticideFor multi-drug resistant P. Falciparum

Artesunate Available through CDC only! Cannot get through pharmacy. Used for severe P. falciparum orwhen oral meds cannot be given!

Other Anti-Protozoal Drugs: Metronidazole

bactericidal Tissue amebicide, Nitroimidazole (activated by electron donation),effective for anaerobic/hypoxic sites Oral or IV, well absorbed and distributed, including CNS, boneCleared in urine (hepatic metabolism)

Intestinal, extraintestinal, urogenitalprotozoal infections (Trichomoniasis,Giardiasis, Amebiasis)Anaerobic Infctions (C. Diff)

Nausea, headache, dry mouth,leucopeniaDisulfram effect (cant drinkalcohol)

Nitozoxanide Inhibits electron transport system pyruvate ferridoxinoxidoreductase (PFOR).

Tx: Giardia lamblia andCryptosporidia parvum. Usefulagainst metronidazole-resistantstrains

Few far better tolerated thanmetronidazole

Pentamidine UnknownIV, IM or aerosol Concentrates in liver, spleen, kidneysDoesnt enter CNS

Aerosol: used for tx & prophylaxis forPneumocystis pneumonia

Respiratory stimulation depression; hypotension, anemiaLess common w/ aerosol

Anti-HelminthicAnti-Helminthic Chemotherapy

Mebendazole Blocks microtubule synthesis , blocks vesicle and organellemovementGiven orally,

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Rapidly metabolized, excreted in urineAlbendazole Interferes w/ microtubule aggregation, alters glucose uptake

Rapidly and completely metabolized in liver, conjugates excreted inurine

Wide-spec anti-helminthic

Ivermectin Oral treatment for all intestinal Strongyloidiasis andOnchocercasiasInhibits Cl channel and paralyzes worm and they die!

Praziquantel Parent is active species membrane permeability to Ca 2+ resulting in contraction andparalysis80% bioavailability from oral dosingRapidly and extensively metabolized, cleared in urine

Schistosomes, some trematodes andcestodes

Headache, dizziness, drowsiness

Diethylcarbamazine(DEC)

Destroys adult nematodes particularly filarial lymphatic wormsthat causes elephantiasis.

Drug may have severe side effects.

Pyrimethamine-SulfonamideClass Drug Name Mechanism/pharmacokinetics/Resistance Indications Adverse effects

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