Pharmacology Antibiotics

7/25/2019 Pharmacology Antibiotics

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Sulfadoine &ooplasmosis $apid absorption 87!* t5;( < days) Allergic reactions (dermatitis)

Pharmacology Review Sheets: Antibiotics, p.+

lactams: Penicillins

Common Properties

- 1-aminopenicillanic acid4 al"yl group off of chain at position 1 determines drug susceptibility to penicillinase or acid hydrolysis

- -acteriocidal4 binding to penicillin-binding proteins interfering +ith transpeptidationcrosslin%ing

/step in cell +all synthesis

- $esistance:

Chromosomally5plasmid-encoded -lactamaseProtection: changing side chain at C1 or adding a -lactamase inhibitor (sulbactam clavulanic acid tazobactam)

- 'mmunity for organisms lac"ing a cell +all (mycoplasma fungi protozoans viruses)

- penetrability (channels allo+ing entry modified)- binding to PBPs

- istribution: By circulation

- oes !7& distribute +ell to prostate eye CS=4 entry to CS= facilitated by meningitis

- Crosses the placenta (nonteratogenic

) enters breast mil"

- ,etabolism: >ery little4 cretion: Primarily renal (organic acid secretory system)4 probenecid interferes +ith ecretion

- Adverse effects: 0ypersensitivity: Anaphyla*is, rashes Allergy to one may result in crossallergy to other drugs in that class224 diarrhea

- Synergistic +ith aminoglycosides4 but 7!#& mi them because they inactivate each other chemically?

BenzylpenicillinsP h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Admin'Absorption Adverse effectsPenicil lin * S/ pneumoniae S/ aureus S/ epidermidis S/ viridans !/ gonorrhoeae !/ meningitidis Clostridia spp/ Bacteroides oralis &/ pall idum Parental admin (im iv) Seizures??

Penicillin > S/ pneumoniae S/ aureus S/ epidermidis S/ viridans !/ gonorrhoeae !/ meningitidis Clostridia spp/ Bacteroides oralis &/ pallidum 7ral admin

Anti-staphylococcal: =or penicillinase-producing Staphylococcus aureus/ 'ncludes methicillin (prototype@no longer used) dicloacillin cloacillin oacillin nafcillin- ,$SA is resistant to all ecept vancomycin (and maybe not even that no+)??

- !afcillin enters bile4 ecreted by biliary route

tended-spectrum penicillinsP h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Admin'Absorption Distribution Adverse )ffects

Ampicillin Proteus mirabilis 8isteria monocytogenes 2/ influenzae (alternate) 7ral nters bile ,aculopapular rashes esp/ those on allopurinol or +5 mono/

%rasyn(ampicillin S/ aureus 3 anaerobes '> 7!89 nters bile 3 sulbactam)

Amoicillin B/ burgdorferi P/ mirabilis 8/ monocytogenes 2/ influenzae (alternate) 7ral nters bileAugmentin 2/ influenzae ,oraella catarrhalis (seen in nursing homes) 7ral '> nters bile (amoicillin plus

clavulanic acid)

Antipseudomonal penicillinsP h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Admin'Absorption Distribution Adverse )ffects

Carbenicillin 'ndole 3 Proteus sp/ nterobacter (ec luding 0lebsie lla) 7ral ( indanyl form) Parental platelet aggregation

&icarcillin P/ aeruginosa nterobacter (including 0lebsiella) Parental (im iv) platelet aggregation hypo"alemia due to 03ecretion

&imentin P/ aeruginosa nterobacter (including 0lebsiella) Parental (im iv) (ticarcillin plus clavulanic acid)

Piperacillin P. aeruginosa(most potent) 0lebsiella spp/ Serratia marcescens Parental (im iv) nters the bile

osyn P/ aeruginosa (as effective as ticarcillin)4 osynhas etended spectrum Parental (im iv) (piperacillin 3

tazobactam)


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Azloci llin P/ aeruginosa (but l ess act ive than p iperaci ll in for o ther *m neg#s) Parental ( im iv)

,ezlocillin Similar to ticarcillin more active vs/ 0lebsiella Parental (im iv)

Pharmacology Review Sheets: Antibiotics, p.$

lactams: 3ephalosporins

Common Properties

- -aminocephalosporanic acid4 al"yl group off of chain at position determines drug susceptibility to penicillinase or acid hydrolysis

- Substitutions at position ; determine pharmaco"inetics

- Action: 'nhibit the transpeptidation (cross-lin"ing) step of cell +all synthesis (same as penicillins)

- $esistance: plasmid-encoded5chromosomal cephalosporinase

- Cefuroime cefoitin Drd5Ethgen/ cephalosporins are most resistant to cephalosporinases

- Absorption: 8ongest t5;: ceftriaone (follo+ed by cefonicid cefotetan)

- istribution: 'n general distributes +ell into pleural pericardial and synovial fluid

- Cefazolin cefamandole ceftizoime penetrate bone +ell

- Cefepime gets into the prostate

- ,etabolism: ster groups at CD can be hydrolyzed

- cretion: All by "idney ecept ceftriaone (biliary ecretion)

- Adverse ffects

- Allergy: 4f patients are allergic to penicillins, cephalosporins are A-S5)56 contraindicated22

- iarrhea

- Ceftriaone: Biliary sludge and pseudolithiasis

- Cefamandole cefoperazone cefotetan: possess methylthiotetrazole side chain on CD

- isulfuram effect (FAntabuseG) @ alcohol-containing substances contraindicated

- 2ypothrombinemia due to interference in >it 0-dependent carboylation involved in clotting cascade

st generation: !arro+ spectrum %sed for *m 3 P h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Admininistration Distribution

Cefazolin *m3 cocci (enterococci resistant)4 used in implant surgery Parental (im iv) Penetrates bone +ellCefadroil *m3 cocci (enterococci resistant) 7ral

Cephalein *m3 cocci (enterococci resistant) 7ral

;nd generation: tended-spectrum P h a r m a c o % i n e t i c s


Cefaclor *m3 cocci 2/ influenzae !eisseria spp/ ,oraella spp/ 7ralCefuroime *m3 cocci 2/ influenzae !eisseria spp/ ,oraella spp/ Parental (im iv)Cefuroime acetil *m3 cocci 2/ influenzae !eisseria spp/ ,oraella spp/ 7ral

Cefoitin *m3 cocci 2/ influenzae !eisseria spp/ ,oraella spp/ Bacteroides fragilis Parental (im iv)

Drd generation: *ood vs/ *m @ but +orse than stgeneration vs/ *m 3 P h a r m a c o % i n e t i c s


Ceftriaone Drug of choicefor !/ gonorrhoeae !/ meningit idi s4 2/ influenzae S/ typhi P/ aeruginosa Parental ( im iv)Cefiime P/ aeruginosa 2/ influenzae 7ral

Cefotaime P/ aeruginosa 2/ influenzae Parental (im iv)Ceftizoime P/ aeruginosa 2/ influenzae Parental (im iv) Penetrates bone +ell

Ceftazidine P/ aeruginosa (enhanced activity vs/ other Drdgeneration cephalosporins) Parental (im iv)Cefoperazone P/ aeruginosa (enhanced activity vs/ other Drdgeneration cephalosporins) Parental (im iv)

Eth generation: *ood vs/ *m 3 and *m @ (ecept ,$SA of course) P h a r m a c o % i n e t i c s


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Cefepime *ood vs/ *m3 and *m @ Parental (im iv) Penetrates prostate

-roadspectrum but not really a drug of choice for any specific organism

Pharmacology Review Sheets: Antibiotics, p.7

lactams: 3arbapenems 4mipenem'cilastatin (eropenem/

Common Properties

- 8ac" an amine group at position 1 but are intrinsically resistant to penicillinase

- -roadest spectrum antibiotic used to R* fevers of un%nown origin !# effective vs. (RSA

- $esistance to carbapenems by P/ aeruginosa is rapid

- 'mipenem can be bro"en do+n by host dehydropeptidase '4 the metabolite produced is toic/ Cilastatin is a dehydropeptidase ' inhibitor protecting imipenem/

- ,eropenem is !7& affected by dehydropeptidase '/ P h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Admin'Absorption

'mipenem5cilastatin Serratia marsescens nterobacter Acinetobacter P/ aeruginosa *m35*m- anerobes Parental (im iv)

,eropenem Serratia marsescens nterobacter Acinetobacter P/ aeruginosa *m35*m- anerobes Parental ( im iv)

lactams: (onobactams A8treonam is the only one/

Properties of Aztreonam

- Stable to penicillinase

- Hor"s for enterobacteriacea P/ aeruginosa

- 8ac"s activity vs/ *m3 organisms anaerobes/

Penicillin substitutes: 9ancomycin- rug of last resort (prudent use is "ey???)

- 'nhibits transglycoslase step of cell +all synthesis (-lactams inhibit the transpeptidase step)P h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Resistance Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

>ancomyc in ,$SA ,$S &ransposon conta ining < genes4 '> for systemic inf / Hidely distr ibuted ,etabolism: !ot +e ll delineated Shoc" f rom rapid infusion

penicillin-resistant enterococci sensor protein activates cascade 7ral for antibiotic- but !7& to bile or cretion: $enal4 t5;i n renal 7totoicity from high serum levelspts +5allergy to penicillins/ of genes changing a peptide induced colitis CS= failure !ephrotoicity (esp/ if given +ith otherC/ difficile (after metronidazole bond to an ester bond @ so nephrotoic drugs)

fails) prophylais for surgical vancomycin can#t bind to it/procedures +ith high rates ofinfections by ,$SA5,$S

Penicillin substitutes: StreptograminsP h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Resistance Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

Iuinupristin5 >ancomycin-resistant strains !ot +ell "no+n Admin: '> !ot +ell "no+n !ot +ell "no+n Hor" li"e macrolides but effectiveness Juestionable

alfopristin Abs: !ot +ell "no+n 7ther toicities not +ell "no+n

Penicillin substitutes: 3hloramphenicol

- Propanediol segment binds to KLS subunit (different binding site than clindamycin)

- $esistance by plasmid-encoded acetyl-CoA transferase penetrance affiinity- Broad-spectrum4 bacteriostatic5bacteriocidal depending on organism

P h a r m a c o % i n e t i c sDrug !ame &se'Spec trum Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

Chloramphenicol Brain abscesses due to anaerobes4 2/ influenzae4 non-resistant Admin: 7ral topical cellent throughout ,etabolism: tensive +ith 2emolytic anemia in *1P2 deficiency4 dose-relatedstrains of S/ typhi alternative for $ic"ettsial infections for eye body4 penetrates CS= glucuronidation4 metabolite reversible anemia leu"openia thrombocytopenia4

Abs: Complete +ith even +ithout infl/4 formed by oidative dechlor/ ose-independent idiosyncratic aplastic anemia4


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oral admin pene tr ate s br ain inactivates cyt/ P-EKL *ray baby syndrome b5c chloramphenicol disruptsabscesses4 crosses cretion: *lucuronide by renal4mitochondrial fn and neonates have lo+ glucoronyl

placental barrier liver failure affects ecretion transferase activity4 oral5vaginal candidiasis

but renal failure doesn#t? tMof +arfarin dicumarol phenytoin tolbutamidechlorpropamide4 phenobarbital5rifampin tMofchloramphenicol

Pharmacology Review Sheets: Antibiotics, p.

Penicillin substitutes: (acrolides

- 8actone ring +ith ; sugars attached4 azithromycin has a slightly larger ring +ith a nitrogen atom incorporated (this ma"es it more acid-resistant)

- Polar but +ell absorbed

- Prototype is erythromycin4 clarithromycin is a methylated form4 azithromycin has an ! replace a CN7

- rythromycin has free form ethylsuccinate lactobionate estolate esterol

- 'nhibits protein synthesis by binding irreversibly to KLS subunit of ribosome4 relatively selective

- Bacteriostatic

- $esistance: mainly byaffinity of KLS ribosome also by penetrance efflu or a plasmid-encoded esterase


rythromycin Drug of choicefor ,ycoplasma pneumoniae4 also used for Administration: Hell distributed4 gets ,etabolism: tensively by 3ramps+ith oral admin4 Oaundice +ith estolate48egionella pneumophila C/ diphtheriae %reaplasma urealyticum =ree base: 7ral into prostate but cytochrome P-EKL system 'nteracts +ith astemizole (fatal ventricular arrythmias)4

sters: 7ral !#CS=4 conc/ in cretion: Predominantly bile carbamazepine valproate(antipsychotics)4 +arfarin b5c

8actobionate: '> liver macrophages some metabolites in urine erythromycin inhibits cyt-P-EKL4 digoin toicity4

Absorption: 7totoicity4 contraindicated in pts/ +ith hepatic fn

sters: more readily absorbed than free

Clari thromycin ,ycoplasma pneumoniae -etter for8egionella pneumophila4 $eadily absorbed Similar to ,etabolism: stpass metab/ *' problems4 #eratogenic

C/ diphtheriae %/ urealyticum Chlamydia spp/ 0. influen8ae but food delays erythromycin but resul ts in an act ive metabol it e0elicobacter pylori absorption doesn#t conc/ in cretion: B oth urine and bile

liver as much

Azithromycin 2/ influenzae ,oraella catarrhalis 3hlamydia trachomatis $eadily absorbed but ,etabolism: !ot much *' problems4 less drug interactions because of altered

,ycobacterium avium-intracellulare never given +ith a cretion: Predominantly bile lactone ringmeal or +ith Al3Dor

,g3;@ containingantacids

Penicillin substitutes: 3lindamycin

- Chlorinated analog of lincomycin4 stable to acid

- 'nhibits KLS subunit by interfering +ith peptidyl transferase reaction and translocation step of protein synthesis- Bacteriostatic

- $esistance:

,utation of ;DS subunit on KLS subunit affinity- 7-nucleotidyl transferase inactivates antibiotic

- 'nability to enter organism

3rossresistance to macrolides may occur22


Clindamycin - Serious infections due to susceptible anaerobes (i/e/ B/ fragilis) 7ral Parental (im5iv) Penetrates bone body,et: 7idative methylation by Pseudomembranous colitisdue to C/ difficile4

- &opical use for acne Almost complete fluids +ell but !7& cytochrome P-EKL4 metabolite contraindications +ith anti-peristaltic agents (i/e/

- ChloroJuine-resistant malaria in combination +ith Juinine absorption CS=4 accumulates in has

activity than parent22 'mmodium)4 nausea vomiting diarrhea rash

-&ooplasmosis in combina tion +5p yr ime thamine P,!s macrophages cretion: Bile ur ine feces4 feve r4 Poss/ 'nte ractions +ith neuromuscula r abscesses4 crosses accumulation in pts +ith renal bloc"ing agents

placenta or hepatic failure4 ecreted into


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breast mil"

Pharmacology Review Sheets: Antibiotics, p.;

Penicillin substitutes: #etracyclines

- oycycline and minocycline are most lipophilic

- 'nhibits protein synthesis by binding to DLS subunit bloc"ing initiation of translation

- iffuses through pores4 also active transportmediated upta%e responsible for selective to*icity- Broad-spectrum4 bacteriostatic

- $esistance by accumulation of drug (active transport efflu)4 affinity for DLS subunit4 3rossresistance for members of this family may occur2


&etracyclines ,ycoplasma pneumoniae4 Chlamydia spp/ Borrelia burgdorferi AdeJuately absorbed Penetrates body ,etabolism: *lucuronide *' distress

hrlichia spp/ 9ersinia pestis 0elicobacter pylori %reaplasma on empty stomach fluids but not CS=4 formation (esp/ doycycline) Contraindicated inurealyt icum Acne vulgaris 5rosacea amebias is duodenum +5oral ,inocycline conc/ in cretion: oycyl ine by - Children 6 Q yrs b5c of depos it ion in bone

admin4 chelates w' tears saliva4 Binds to feces4 remainder by glomerular - Pregnancy (crosses placenta)4 hepatotoic to mother

3a+estibular ototoicity (streptomycin gentamicin)4 cochlear ototoicity (gentamicin tobramycin ami"acin)4 contraindicated in pregnancy b5c fetus may be born deaf4nephroto*icity(ranges from mild impairment to severe toicity depending on dose)4 neuromuscular paralysis (b5c aminoglycosides act li"e Ca ;3ionophores)


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Drug !ame &se'Spec trum

Streptomycin ,/ tb (resistant strains) ndocarditis by Strep viridans

nterococcus faecalis (in combo +5-lactams)*entamicin / coli 0lebsiella Serratia P/ aeruginosa&obramycin / coli 0lebsiella Serratia P/ aeruginosaAmi"acin / coli 0lebsiella Serratia P/ aeruginosa (gentamicin-resistant)

!eomycin &opically or orally in bo+el surgery5hepatic coma

Pharmacology Review Sheets: Antibiotics, p.>

R*"s: ?luoro=uinolones

- =luoride at position 1: Confers resistance4 =luoride at position Q: ris" of phototoicity

- 'nhibits topoisomerase '' (!A gyrase)- Bacteriocidal

- $elatively selectively toic (due to bacterial affinity cp/ human affinity)

- $esistance by point mutation in !A gyrase also by an efflu pump (S/ aureus P/ aeruginosa some ,ycobacteria)

- Spectrum: s(/ coli 0lebsiella Proteus P. aeruginosa)4 Prostatitis4 S&s (!/ gonorrhoeae Chlamydia spp/)4 *' (/ coli Shigella)4 $espiratory (2/ influenzae

resistant S/ pneumoniae ,$-&B C=)4 Alternative to infections of bone5Ooints4 &rovofloacin used vs/ anaerobes

- rallyactive vs/ *m@ *m3(S/ pneumoniae)

- 8evofloacin (iv oral admin) mostly used for infections other than %&'s

- Pharmaco"inetics:

- Administration5Absorption: 7rally active (ciprofloacin (1KR) 6 trovafloacin (


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- $apidly absorbed from *' tract

- cretion: Parent in urine

- Can be given to pregnant +omen +ith %&'s

- pensive??

Pharmacology Review Sheets: Antibiotics, p.@

Antifungals: Amphotericin AmphoterribleB/ - !ystatin- Amphipathic4 multiple forms eist (lipid formulation colloidal dispersion)

- 'nterfere +ith cell +all synthesis4 Q molecules of amphotericin B ma"e a pore in the membrane4 03lea"s out "illing the cell

tremely toic4 selective toicity is narro+ and based on ergosterol#s greater binding affinity (than cholesterol) for amphotericin B @ the pores last K times as long- Spectrum: =ungicidal4 only used for life-threatening fungal infections in +hich the alternative is @ A & 2@

- Pharmaco"inetics

- !ot used orally ecepting fungal infections in the gut4 preparation is freshly done and protected from light

- !ystatin is only used topically to $ Candidiasis of the mouth anus vagina and nose

- 2uge volume of distribution (E85"g)4 high seJuestering in membranes

- 8ong tM(K days)

- Adverse effects:

- Chills fever vomiting

- $enal toicity (lipid formulations are slightly less nephrotoic)

- Anemia (normocytic normochromic)

- 2ypo"alemia (ris" of cardiac arrhythmias)- C!S symptoms (pain headache impaired vision chemical meningitis) +ith intrathecal administration- &hrombophlebitis at site of infection

Antifungals: ?lucytosine

- Pyrimidine analog4 used in combination +ith amphotericin B to dose of it/P h a r m a c o % i n e t i c s

Drug !ame &se'Spectrum Action Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

=lucytosine Cryptococcal meningitis 'nhibits thymidine synthetase Hell absorbed orally Penetrates C!S ependent on renal fn for !ausea vomiting diarrhea enterocolit is (;KR)$elatively selectively toic b5c ecretion 8iver damage (;KR)

a specific permease transports Bone marro+ suppression (KR)flucytosine into fungal cell

Antifungals: A8oles

- =ungistatic4 inhibits cyt/ P-EKL-dependent E--demethylation of sterols (bloc"ing sterol formation ergosterol synthesis rate of replication)- Selective toicity due to affinity of triazole or imidazole group for heme iron

Drug !ame -ioavailability Re=uire low p0 for abs.C Penetrates 3S?C )*cretion Adverse )ffects

0etoconazole or KR 9es !o Small amount of *' distress rash pruritis hepatic damage teratogenic dose-dependent discontinuity4 inhibits host

'traconazole parent ecreted steroid biosynthesis (esp. %etocona8ole) leading to testosterone libido gynecomastia (males)4menstrual irregularities (females))4 cortisol synthesis (both) but this doesn#t manifest clinically/

=luconazole KR !o 9es QLR of parent ecr/ *' distress rash pruritis hepatic damage teratogenic dose-dependent discontinuity (less than4"eto5itra)4 D)S !# 4!#)R?)R) 4#0 0S# S#)R4D -4S6!#0)S4S

Drug !ame &ses

0etoconazole Pseudal lescheriasi s

=luconazole Candidiasis (especially candidemia)4 coccidioidomycosis4 cryptococcus chronic suppression'traconazole Blastomycosis (+hich affects males females)4 histoplasmosis4 sporotrichosis

rug interactions:

- &erfenadine and astemizole: Cardiac arrhythmias- levels of cyclosporine: $enal damage


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- 7ral anticoagulants: bleeding time- 7ral hyperglycemics: 2ypoglycemia

- phenytoin digoin: Ataia- $ifampin Phenytoin: levels of azoles

Antifungals: #erbinafine Antifungals: Eriseofulvin- =ungicidal4 inhibits sJualene oidase - ,ust be given orally only used for dermatophytes4 87!* $ time

- Can be given topically or orally4 used for dermatophytic infections - Binds to ne+ly formed "eratin4 inhibits microtubular function arrests cells in

- Adverse effects: 2eadache *' symptoms metaphase

Pharmacology Review Sheets: Antibiotics, p.F

Antiproto8oals: (etronida8ole- Bacteriocidal4 acts by accepting electrons from special mechanisms of energy generation (by certain organisms)

- =ormation of hydroy radicals hydroyl amines nitrosos interact and cleave !A "illing the organism/

- 7rally effective

- istributes into CS= and breast mil"

Drug !ame &se'Spec trum Adverse )ffects Drug 4nteractions

,etronidazole Drug of choice for systemic amebiasis4 also used for *' problems (nausea headache unpleasant metallic taste dry mouth (;LR) Potentiates oral anticoagulants

Protozoans (&richomonas vaginalis ntameoba >omiting +ea"ness etc/ (;R) Phenytoin and phenobarbital metabolism and infectionshistolytica *iardia lamblia)4 also anaerobes such as isulfuram-li"e effects (!7 A8C7278?) Cimetidine metabolismBacteroides fragilis ,utagenicity in eperimental animals5bacteria but not in humans (still don#t ris" of lithium toicity

give this during the sttrimester of pregnancy)/

Antiproto8oals: Antimalarials

P h a r m a c o % i n e t i c sDrug !ame &se'Spectrum Action Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

ChloroJuine rythrocyt ic forms of malaria 'nhibit s hemoglobin polymerase7rally act ive 2uge volume of cretion: %nchanged *' nausea d izziness headaches4 2igh dose (iplopia

(E-aminoJuinoline) (blood schizonts tr ophozoites) a pla smod ia l enzyme removing distributi on4 binds LR in urine 4 some Cardiac arrhythmia FBullseye le sionG @ cornea ltoic heme brea"do+n products to nucleoproteins metabolites opacities)

in liver and spleen

PrimaJuine traerythrocytic schizonts !ot +ell "no+n possible 7rally active ,etabolism: tensive 2emolytic anemia in *1P2 individuals (you see (Q-aminoJuinoline) (tissue schizonts gametocytes) interference +ith electron cretion: Primarily as dar"ened urine flan" pain +ea"ness and fatigue)

transport reactions metabolites in urine *' problems

tM: D-Q hours Cardiac arrhythmias

Antiproto8oals: R* for 5eishmaniasisP h a r m a c o % i n e t i c s

Drug !ame &se'Spec trum Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

Sodium 8eishmania4 not selective Small vol/ 7f ,uscle Ooint pain4 &-+ave changes4 &oic shoc"5death4

stibogluconate distribution &ransaminase elevationPentamidine 8eishmania P/ carinii Parental inhalation Severe hypotension release histamine from mast cells

&oic to pancreatic islet cells (initial release of insulin

+5diabetes chronically) renal toicity (hyper"alemiahypocalcemia)

Antihelminthics: -en8imada8oles- Bind to tubulin bloc"ing microtubule formation4 this bloc"s glucose upta"e depletes A&P immobilization of organism leads to death

- Selective toicity: >ery slim ; affinity for helminths than us


,ebendazole Ascaris F%nholy trinityG (+hip+orm hoo"+orm pin+orm) cretion in urine ,a"e sure to che+ tablet (to get it into solution)&richinella *' problems dizziness headache

Albendazole Cysticercosis hydatid disease $apidly absorbed 8ong half-life ,azotti reaction @ inflammatory response due to

organism death4 *'5C!S disturbances4 2epatic damage

over long-term $


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ther Antihelminthics

P h a r m a c o % i n e t i c sDrug !ame &se'Spectrum Action Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

've rmectin Strongyloides stercora lis 7nchocerca Hor"s on *ABA 7ral only oesn#t get into C!S 8ong M lif e (;Q hours) on#t presc ribe to people +ith C!S disorde rsvolvulus4 made from the soil receptor to cause Slo+ distr/ into eye creted into feces (gets into (a8otti reaction: 'nflammatory response due toactinomycete Streptomyces paralysis of nematode liver then to the bile) organism death

muscle 'nteractions: Avoid coadministration +ithbenzodiazepines barbiturates and >alproic acid

PraziJuantal &rematodes (flu"es) tape+orms &argets Ca;3c hannel $apidly absorbed *ets into CS= bile Short M life *' disturbances C!S disturbances ,alaise

(but not ours) on#t che+ (bi tt er and breas t mi l" nauseating)

Pharmacology Review Sheets: Antibiotics, p.1G

Antiviral drugs: #argets uncoating'surface components

Drug !ame &se'Spec trum Action (etabol ism')*cretion Adverse )ffects

Amantadine Asian A;influenza Bloc"s 23pumping preventing viral uncoating ependent on renal ecretion Possible convulsions peripheral edema

$imantadine Asian A;influenza Bloc"s 23pumping preventing viral uncoating Some+hat metabolized Possible convulsions peripheral edema (but less than amantidine)

anamivir Asian A and B influenza used 'nhibits neuraminidase Possible problems +ith asthmatics nausea headacheprophylactically or D1 hrs after

infection to duration andseverity of disease

7seltamivir Asian A and B influenza used 'nhibits neuraminidase Possible problems +ith asthmatics nausea headache

prophylactically or D1 hrs after

infection to duration andseverity of disease

Antiviral drugs: #argets transcriptionP h a r m a c o % i n e t i c s

Drug !ame Structure'Proper ties'Action &se'Spec trum Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

Acyclovir *uanine analog4 must be 0S91, 0S9+, 9H9 (C,>) 7ral ( incomple te Conc / in CS=: cretion: $ enal $ena l toicity neurotoic ity4 +ith topical adminphosphorylated to be activated4 B> absorption) '> KLR of plasma levels burning sensation/ !ot teratogenic/selectively toic to viruses to topical

to "mof viral thymidine !ote: >alcyclovir"inase to human counterpart4 has better oralacts by competing +ith d*&P absorptionin chain elongation (terminating

the process)

*ancyclovi r Purine analog4 act ivated by 3(9(retina *' lungs nerves) Penetrates C!S cretion: $enal Bone marro+ suppression (granulocytopeniaC,> "inase P7E

D-transferase4 prophylais for aJueous subretinal 8ong tM: 1 hrs intracellularly thrombocytopenia): &reat +ith *,-CS=4

Affinity for C,> enzyme is immunocompromised fluid conc#s similar ;-E hrs/ in plasma Additive effects +ith drugs hitting bone marro+close to our o+n so it#s toic to serum levels (zidovudine)4 Azoospermia4 $enal damage

to bone marro+ *' tract/Competes +ith d*&P chainin chain elongation but canonly slo+ it do+n not

terminate it

=oscarnet Pyrophosphate analog4 does Alternative for C,> retinitis '> administration cretion: $ apidly by renal Small therapeutic +indo+4 can also cause renal

!#reJuire activation4 impairment penile ulcers electrolyte imbalanceCompetes for pyrophosphate (esp/ hypocalcemia)

binding site of !A and $!Apolymerases

idovudine (>) &hymidine analog inhibits 04914 (B>) 7ral iv admin ,etabolism: *lucuronidation Severe headaches nausea neurotoicity (seizures)

(azidiothymidine reverse transcriptase at 5LL Complete absorption cretion: Primarily renal bone marro+ suppression (anemia neutropenia @ A&) (!$&') concentration needed to affect tM: hr thus reJuires freJuent severity based on CE

3counts) possible associationcellular !A polymerase dosing4 other drugs undergoing +ith !on-2odg"in#s lymphoma

glucuronidation (!SA's

narcotic analgesics) can tM

idanosine (dd') Purine analog 2'>- (alone or in combo !ot to*ic to bone marrow4 adverse effects include


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(!$&') +ith A&) pancreatitis peripheral neuropathy

alcitabine (!$&') 2'>-4 %sed +ith A& but !ot to*ic to bone marrow4 adverse effects include!7& didanosine pancreatitis peripheral neuropathy

8amivudine (D&C) Synergist of A&4 helps delay 2'>-4 %sed in combo +ith 2eadache insomnia fatigue *' upset

(!$&') onset of resistance A&

favirenz (!!$&') oesn#t reJuire activation4 2'>-4 !56 used in those 7nce-a-day dosing C!S (dizziness headache vivid dreams) rash

acts at different site than !$&'s with failed primary therapy teratogen inducer of 36P$A7(!ote: 'ndinavir isone of C9PDAE#s substrates so dosage +ill need to beadOusted/

Pharmacology Review Sheets: Antibiotics, p.11

Antiviral drugs: Protease 4nhibitors- Site-directed analogs of 2'> protease

- 'nhibits protease @ resulting in non-infective virions (because they can#t mature)

- Structural components affected: matri protein capsid nucleocapsid p1

- >iral enzymes affected: protease reverse transcriptase integrase

P h a r m a c o % i n e t i c sDrug !ame Admin'Absorption (etabol ism')*cretion Adverse )ffects 4nhibition of 36P$A7, 36P+D;

SaJuinavir Poor absorption tensively me tabolized4 *' (nausea vomiting diarrhea ) t rig lycer ides (eacerbates any pre-eist ing d iabetes) 8eas tprimarily fecalecretion

'ndinavi r $easonable tens ively metabolized4 !ephrol ithiasis hyperbi li rubinemia rash dry s"in t as te pervers ion triglyceridesQLR fecal ecretion ;LR renal

$itonavir $easonable LR metabolized *' (nausea vomiting diarrhea ) anoreia c ircumoral5pe riphe ra l paresthesia taste pe rve rsion ,ost4 also metabolism of theophylline

$ regimen?

Antiviral drugs: 4nterferonsP h a r m a c o % i n e t i c s

Drug !ame Structure'Proper ties'Action &se'Spec trum Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

'nterferon- Antiviral cyto"ine4 suppresses Drug of choice for 0-94 2C> Parental (im iv) ,etabolized by liver and "idney ?luli%e syndrome(treated +ith acetaminophen andprotein synthesis +hen 2P> (intralesional inOections) self-administered +ith continued use)activated by virus 0aposi#s sarcoma virus Doselimiting to*icitiesTbone marro+ suppression

2airy cell leu"emia malignant neurotoicity (somnolence confusion behavioralmelanoma changes) depression hyperthyroidism hypotension

cardiac arrhythmias)

Drug interactions: +5theophylline

0AAR#: A few notes

- %sed to resistance and "illing of virus- ; nucleoside analogs usually A& 3 another $& inhibitor protease inhibitors


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Pharmacology Review Sheets: Antibiotics, p.1+

Antituberculosis drugs:P h a r m a c o % i n e t i c s

Drug !ame Action'Resistance &se'Spec trum Admin'Absorption Distribution (etabol ism')*cretion Adverse )ffects

'soniazid ( '!2) Action: Bacteriocidal 4 interferes ,ycobacterium tuberculos is 7ral ist ributes >$9 ,etaboli sm: !-acetyl transferase Slow acetylator status: 2as ris" of peripheral+5cell +all synthesis by +ell into cells4 enters in 0upffer cells (in liver) neurotoicity and hepatotoicity drug interactionsinhibiting mycolic acid synthesis pleural fluid ascitic metabolize '!2 but a better response to ,/ tb,ust be activated to isonicotinic fluid and caseous cretion: ,etabolites by renal ther adverse effects: 2epatotoicity rug-inducedanyl anion then compleed +5 material lupus erythematosis (procainamide hydralazine)

!A2 inside the active site of Drug interactions: Phenytoin isulfuram effectthe enzyme inference +ith oral anticoagulants$esistance: ,utations5deletion

of 0at* gene (+hich activates'!2)4 mutations in ACP

reductase affinity for !A2

$ifampin Action: 2ighly lipid-soluble4 ,ycobacterium tuberculos is Hel l absorbed Hel l d ist ributed ,etab/: eacetylation ( liver) *' complain ts rash liver enzymes hepatitis Oaundice'nhibits !A-dependent $!A Prophylais for meningococcal cretion: Biliary route Hith intermittent $ high doses: Allergy (ris" ofPolymerase (LL affinity for 2/ influenzae alternative to !ote: tM +ith hepatic drug-induced fever eosinophilia),/ tb than us) cotrimoazole for $ of ,$SA insufficiency Colors all bodily ecretions5secretions orange-red$esistance: ,utations so Drug 4nteractions: 4nducer of 36P$A7

rifampin can#t bind to -subunit (rifampin is the best inducer rifabutin is poorer)4of $!A polymerase the effectiveness of oral contraceptives oral

anticoagulants methadone Juinidine "etoconazole

-bloc"ers Protease inhibitors2 don"t use rifampinwith 049 R*) etc/

Pyrazinamide Bacteriocidal ,ycobacterium tuberculos is 7rally act ive +el l Hel l d ist ributed ,etaboli te : K-hydroypyrazinoic 2epatotoic4 metabol it e can also interfere +i th uricabsorbed acid acid ecretion (and may thus produce an acute episode

of gout)

thambutol Bac te riostatic 4 inhibits ,ycobac terium tuberculosis Hell absorbed Concentr ates in cretion: %r ine (renal) 7ptic neuritis (highly dose -dependent) h yperuricemia

arabinosyl transferase (cell +all $BCs tMN Q hrssynthesis)

R* of #- for real/:

- %se coc"tail of E drugs for ; months ('!2 $ifampin Pyrazinamide thambutol)

- &hen '!2 and $ifampin for E more months

- irectly observed therapy (7&) b5c of patient non-compliance leading to ,$-&B

- $ for ,$-&B based on sensitivity

- =or ,ycobacterium avium-intracellulare (,AC): $ifabutin 3 Azithromycin


13/14

Pharmacology Review Sheets: Antibiotics, p.1$: 5ists these may be somewhat incomplete/

Distribution to 3S?:

Distributes well Distributes well only w' inflammation Does not distribute well at all

Sulfonamides Penicillins >ancomycin

Chloramphenicol Drdgeneration cephalosporins ,acrolides

=luoroJuinolones (esp/ ofloacin) Clindamycin

=lucytosine &etracyclines

=luconazole stgeneration cephalosporins

,etronidazole ;ndgeneration cephalosporins (ecept cefuroime)

PraziJuantel 0etoconazole 'traconazole

Acyclovir 'vermectin

*ancyclovir

3ontraindicated for Pregnancy )nters breast mil%

Sulfonamides Penicillins

Chloramphenicol ,etronidazole

,acrolides (esp/ clarithromycin b5c it#s a teratogen) PraziJuantal

&etracyclines

Aminoglycosides (deafness)

Azoles (teratogenic)

,etronidazole

favirenz (teratogen)

=luoroJuinolones (arthropathy)

3helation

Azithromycin

&etracyclines (also p2 +ill destroy them)=luoroJuinolones

Disulfuramli%e effect

Cefamandole

Cefoperazone

Cefotetan

,etronidazole

'soniazid!ote: *riseofulvin doesn#t have a disulfuram-li"e effect but it does potentiate the effects of alcohol/


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(a8otti reaction inflammation due to lots of dead bacteria/

'vermectin

Albendazole

Pharmacology Review Sheets: Antibiotics, p.17: 5ists these may be somewhat incomplete/

Renal )*cretion route Renal to*icities Renal 3ontraindications

Sulfonamides Sulfonamides (crystaluria) Clindamycin

Penicillins >ancomycin ,ethenamine

Cephalosporins (ecept ceftriaone) Aminoglycosides

Aminoglycosides Amphotericin B

=luoroJuinolones Acyclovir

=osfomycin =oscarnet

Amphotericin B Pentamidine

=lucytosine

Antimalarials

,ebendazole

AmantidineAcyclovir

*ancyclovir

=oscarnet

idovudine

thambutol

0epatic )*cretion -iliary'fecal e*cretion

Chloramphenicol Ceftriaone

rythromycin ,acrolides

Clindamycin $ifampin

,ethenamine oycycline

Azoles (also hepatic toicity due to these) 'vermectin'soniazid Protease inhibitors

$ifampin

Pyrazinamide (hepatotoic)

P7G activators P7G inhibitors

favirenz rythromycin

$ifampin Protease inhibitors (especially $itonavir)

$ifabutin Chloramphenicol

*riseofulvin Azoles

Documents

Pharmacology Antibiotics