Pharm Drug File

7/25/2019 Pharm Drug File

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Drug Use against Cidal/static

Sulfonamides Uncomplicated UTIs, nocardia, chlamydia Static

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

!luoro"uinolones (Cipro, le#o$loxacin Cidal

Methenamine Urinary tract disin$ectant

Phenazopyridine Urinary tract analgesic (not antimicrobial

-lactams Cidal

Penicillin %/& %ram ' cocci, treponema, actinomyces

taph aureus Cidal

)ide spectrum -ampicillin, amoxicillin %ram ' and -

*nti-pseudomonal- piperacillin Pseudomonas, gram - +.

Cephalosporins

%en - ce$azolin

%en 0- ce$oxitin %ram '/- (12s P2c3 4 h $lu, 2nterobacter, neiss5, serratia

%en 6-ce$triaxone, ce$azimide %ram 4 only (eisseria, pseudomonas

%en 7- ce$epime )ide spectrum, gram '/-

Carbapenems (imi/mero %ram '/-, aerobic, anaerobic

Monobactam 4 aztreonam %ram - aerobes

&ancomycin %ram ' only Cidal

Macrolides Static

2rythromycin %ram ' cocci and atypical pneumonias

Clarithromycin ame as erythro ' 15 $lu*zithromycin C trachomatis (not $or gram ' cocci

Clindamycin Static

treptogramins &82 $aecium

inezolid

Chloramphenicol tatic

Tetracycline tatic

*minoglycosides *erobic, intracellular (pseudomon, tularemia, etc Cidal

Isoniazid TB only Cidal

C! in$x, osteomyelits, prostatitis, 2 coli, pseudomonas,almonella, Cipro $or pulm anthrax prophylaxis

*cid stable penicillin 4 na$cillin,methicillin, ox

6rdgen may be used $or empiric tx

%ram ', same as Pen % (plus P2c3 4 proteus, e coli,9elbsiell

Strep, anaerobes above the diaphram, topical for

acne!rosacea, t" for to"o # pyrimetham, bone inf"

Together cidal, alone-static

%ram ' anaerobes, &82 ($aecium and $aecalis, M8*,M8 2pidermitidis

1$lu, intracell (ric9ettsia, psittacosis, typhoid, anaerobic,meningitis

:ntracell- chlamydia, legionella, mycoplasma pneumo, lyme,ric9ettsial, rosacea, acne

3anamycin (easily inacti#ated, *mi9acin(not easily inacti#ated


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$ifampin Cidal

%yranizamide Cidal

&thambutol TB only Static

TB polytherapy, t" for leprosy, prophyla"is for 'eisseriamenin, ( flu


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*bsolute/relati#e

)bsolute

8elati#e

8elati#e (higher a$$inity $or bacteria

8elati#e

)bsolute

*bsolute

*bsolute

$elative

Metabolized by C.P7;n into ammonium and $ormaldehyde in acidic p1 (;5;

Urine turns red

Irreversibly inhibits transpeptidase, may stimulate autolysins

*moxicillin ' cla#ulanic acid ? augmentin

ame as penicillin

Mero- tx meningitis

1igh resistance to @-lactamases

=inds D-alaD-ala, inhibits T%ase $rom elongating chain

Binds % site of .S ribosome subunit, t-$') dissociates, inhibits translocation

=est $or intracellular in$ections

Binds .S subunit of ribosome, inhibits peptidyl transferase +active metabolite underoes entero-hepatic recirculation

* (dal$opristin inhibits donor/accept site on peptidyltrans$erase, changes shape5 = ("uinpristin inhibits translocation

=inds ;


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Bloc*s 1') dep $') pol- no initiation for m$') synth

%rodru is activated by TB to pyrazinoic acid

Inhib arabinosyl transferase 2 arabinoalactan is not polymerized in cell 3all


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3inetics

4ral, penetrates CS5 3ithout inflam, crosses placenta, binds albumin, acetylated and lucuronic con6

+ral, +. le#o enters C, mainly renal elim,

Time dependent *illin +above MIC 7.8 in 9: hrs, not metabolized, renal elim, enter C'S 3hen inflamed

% (intra#enousB & (oral

Methicillin- :&

+ral

:&

ame as penicillin

:& only, enters C!

:M or :&, enters C!

lo> :& admin (oral $or C5 di$, C in$lam only, not metabolized, urine

4ral, intracell, do not enter C'S, elim mainly biliary +less renal

!ormulated >ith ester or enteric coated to protect $rom stomach acid

(ih oral absorption, reaches bone, does not enter C'S, intracell, "placenta, mainly hepatic metabolism and biliary e"cretion

Continuous :& (short hal$-li$e, intracellular (PM and macros, non-enzymatic metabolism to non-acti#e metabolites

+ral,


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4ral +very lipophilic, C'S!bone, enterohep circ, de-acetylated form is elim via biliary

4ral, 3ell distributed

4ral, concentrates in $BCs, .8 metabolized, elim via *idneys


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Toxicity/*d#erse 8eactions

Crystalluria, *ernicterus +not for babies, preos, 6aundice in adults, hemolytic anemia in 0;%11

Megaloblastic anemia in people >ith poor diets/lo> $olic acid- pregnant or homeless

ong FT, tendinitis, transient arthropathy, photosensiti#e

=ladder irritation in high doses,

'euroto"ic +seizures-0)B), cation to"icity

Methicillin- nephritis

*mpicillin- macropapular rash (not allergy

:mipenem is con#ulsant at high doses

ephrotoxic and +totoxicB thrombophlebitis at site o$ admin

Motility, arrhythmia, cholestasis, rash, eosinophilia

2pigastric distress, Eaundice, trans ototoxicity

2pigastric distress, Eaundice, trans ototoxicity

'


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(epatoto"ic, hydro"y pyrazinoic acid metabolite interferes 3ith uric acid e"cretion

4ptic neuritis, decreased visual acuity and color vision +dose dep, uric acid accumulates in blood +3orse 3 out

)symptomatic elevated liver enzymes, hepatitis 3 6aundice in liver disease pts, red body fluids, hih dose therapyno loner used


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*llergy

S=S 2 necrotizin dermatitis

)naphyla"is +cross-reaction 3ith other ? lactams

!ast in$usion -K 8ed Man yndrome

$ash and fever are rare

+T !+8 hepatic insu$$iciency pts (increased ammonia, not $or renalinsu$$iciency pts (crystalluria


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Mild rash


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:nteractions

*ntacids/dairy di/tri#alent ions chelate and decrease absorption, inter$eres >ith C.P7;< metabolism (>ar$arin, theophylline

+T ):T1 sul$a drugs- $ormaldehyde $orms precipitate

Clavulanic acid +not antimicrobial inhibits ?-lactamase@ %robenecid increases half-life

:nhibits *D1 causing disul$iram-li9e e$$ect (ce$amandole/ce$operazone

:nhibits C.P-7;< metabolism o$ >ar$arin, theophylline, digoxin

:nhibits C.P-7;< metabolism o$ >ar$arin, theophylline, digoxinD+2 +T :1:=:T C.P-7;/ *mphotericin = in candidemiaand cryptococcal meningitis

$eFuires acidic environment to dissolve, does not enter CS5 3ell, hihmetabolism


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Toxicity/*d#erse 8eactions *llergy

&D, enterocolitis, ele#ated hepatic enzymes, bone marro> suppression

/&T4- less se" steroid synth, less cortisol synth, severe hepatoto"icity

5lu- very tolerable

1eadache, &D, rare hepatotoxic 8ash

1eadache, C, %:, augments alcohol e$$ect

%i distress, $lushing $rom histamine release

nephrotoxicity is dose-limiting but cant be dialyzedB in$usion reactions(chills, $e#er, muscle spasms, hypotension arrhythmias, anemia,thrombophlebitis

'


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:nteractions 8esistance

%henytoin decreases GitraconazoleH

mica$ungin increases le#els o$ ni$edipine and cyclosporine

Inhib C% dru metabolizersA increased levels of otherdrus

Cross sensiti#ity >ith penicillins5 +T !+8 acute intermittentporphyria


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Drug Use against

Metronidazole

Chloro"uine (7- amino"uinolone

Prima"uine

*rtemisinin Malaria

odium stibogluconate eshmania

Pentamidine Pneumocystis Eiro#ecii pneumonia, sleeping sic9ness

=enzimidazoles helminths

Mebendazole *scaris, >hip >orm, hoo9 >orms, pin>orm, spiralis

*lbendazole Cysticercosis, hydatid cysts

:#ermectin trongyloides, +nchocerca

Prazi"uantel Cestode, $lu9es

1ru 4bserved &ffects on (elminths

*lbendazole

Mebendazole

Pyrantel pamoate

Diethylcarbamazine

:#ermectin

Prazi"uantel

2ntamoeba, giardia, bacteroides, trichomonas #ag,clostridium, anaerobic in$x

Malaria, extra-intestinal amebiasis, high doses areanti in$lammatory $or 8*/2

Malaria in tissue schizonts and hypnozoites (not $orintra-8=C

:nhibition o$ glucose transportB depletion o$ glycogenstores, inhibition o$ $umarate reductase

:nhibition o$ glucose transportB depletion o$ glycogenstores

Muscles depolarize, increased spi9e >a#e acti#ity,spastic paralysis

1yperpolarization and paralysis o$ >ormsmusculatureB exposure o$ antigens, leading toantibody binding and attac9 by phagocytes

*lters chloride currents, resulting in death o$micro$ilariae

Depolarization o$ muscles, increased intracellularCa '' , displacement o$ schistosomes to the humanli#er, exposure o$ sur$ace antigens, binding byantibody and phagocytes, tegument disruption


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iclosamide

1ru %ossible Mechanism of )ction

Metronidazole

Paromomycin :nhibits protein synthesis

itazoxanide

Chloro"uine

Fuinine

Me$lo"uine

Pyrimethamine :nhibits dihydro$olate reductase

ul$onamides

i$urtimox

2$lornithine

Melarsoprol 8eacts >ith sul$hydryl groups, inhibits proteins

Uncouples phosphorylationB may inhibit anaerobicmetabolism

*cti#ated >hen reduced by $erredoxins, reacts >ithD* and other parasite constituents

:nhibition o$ electron trans$er reactions essential tothe metabolism o$ anaerobic organisms

Concentrated in hemoglobin-containing digesti#e#esicles, inhibits heme polymerase

Concentrated in $ood #acuoles, probably inhibitsheme polymerase

Concentrated in $ood #acuoles, may $orm toxiccomplexes >ith heme

:nhibit binding o$p -aminobenzoic acid todihydropteroate synthetase

!orms reacti#e +0species that damage cell

membranes and D*

:rre#ersibly inhibits ornithine decarboxylase, inhibitspolyamine synthesis


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Cidal/static *bsolute/relati#e

Cidal

Cidal 8elati#e 4 higher a$$inity $or helminths

Coadmin >ith steroids to reduce in$lammation

%ossible Mechanism of )ction

=inding to @-tubulin

Depolarizing neuromuscular bloc9ade

1yperpolarization and neuromuscular bloc9ade

*ltered chloride channel $unction

Uncertain

8elati#e- bacterial metabolites (+1-!8, ?+, +1xare more reacti#e than human metabolite (10

=inding to @-tubulin, pre#ents microtubulepolymerization


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Uncertain


28/46

Mechanism 3inetics

Un9no>n (maybe 2TC +ral, complete metabolize to urine

:&, #ery slo> elim

Un9no>n :& or #ia inhalation $or pneumonia, not metabolized

Coadmin o$ steroids to lo>er in$lammation +ral, acti#e metabolite, renal elim

+ral, no C, enters eye, elim unchanged in $eces

itro group on metro accepts electrons $rom ameba2TCL $orms toxic products L damages D*

+ral, enters C!, in breast mil9, al9yl chain isoxidized and glucuronidated, ;n products to hemozoin

+ral, high &d, "uic9ly binds proteins, high le#els inli#er, spleen, 9idney5 ot metabolized long hal$-li$e

:nter$eres >ith glycosome in the organism so itcannot generate *TP/%TP

=inds tubulin and bloc9s MT $ormation, bloc9glucose upta9eL no *TP

+ral tablet must be che>ed, rapid metabolism andexcretion

*cti#ates glutamate gated Cl channels, paralysis o$pharyngeal muscles

2nhances Ca in$lux, >orm contracts mucles,paralysis

+ral, D+ +T C12), binds albumin, gooddistribution to C!, mil9, bile, poo, metabolized


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Toxicity/*d#erse 8eactions *llergy

1emolytic anemia in %PDD

:n$lam (Mazotti rxn due to death o$ micro$ilariae

!e#er, sedation, itching, rash, edema

&D, headache, dry mouth, metallic taste, disul$irame$$ect, ithium toxicityQ

%:, long term use associated >ith diplopia, T >a#e,arrhythmia, death (in 8* pts, can cause #isualchanges, =ulls eye lesion

+nly gi#en in patient, muscle and Eoint pain, T >a#echanges, shoc9, death

=loc9s symp ner#es and causes hypotension,histamine release, toxic to islet cells (hypoglycemiaand then diabetes, damages 9idneys

Dead org causes headache, #omit, mental statuschange, hyperthermia5 ong term therapy- li#erdamage, leu9openia


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:nteractions 8esistance

1igh resistance #ia e$$lux pump

Dead orgs in brain release proin$lam mediators

Potentiates oral anticoags, phenytoin increases elimo$ metro, cimetidine increases RmetroS,

Do not gi#e >ith anti-seizure drugs (benzo,barbiturate or #alproic acid


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34/46

Metal Acute

Arsenic Nausea, vomiting,

"rice-water" diarrhea,

encephalopathy,

MODS, LoQS,

pain!ul neuropathy

ismuth #enal !ailure$ acute tu%ular necrosis

&admium 'neumonitis (o)ide !umes*

&hromium

&o%alt eer drin+ers (dilated* cardiomyopathy

&opper lue vomitus, . irritation/ hemorrhage, hemolysis, MODS (ingested*$ M00 (inhaled*

. hemorrhage, hemolysis, acute renal !ailure (&r12ingestion*


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.ron 3omiting, . hemorrhage, cardiac depression, meta%olic acidosis

Lead Nausea, vomiting, encephalopathy (headache, sei4ures, ata)ia, o%tundation*

Manganese M00 (inhaled*

Mercury 5lemental (inhaled*6 !ever, vomiting, diarrhea, AL.$

.norganic salts (ingestion*6 caustic gastroenteritis


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Selenium &austic %urns, pneumonitis, hypotension

Silver 3ery high doses6 hemorrhage, %one marrow suppression, pulmonary edema, hepatorenal necrosis

hallium 5arly6 3omiting, diarrhea, pain!ul neuropathy, coma, autonomic insta%ility, MODS

M00 (o)ide !umes*$ vomiting, diarrhea, a%dominal pain (ingestion*Zinc[6]


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Chronic

Dia%etes,

hypopigmentation/ hyper+eratosis,

cancer6 lung, %ladder, s+in, encephalopathy

Di!!use myoclonic encephalopathy

'roteinuria, lung cancer, osteomalacia

'ulmonary !i%rosis, lung cancer (inhalation*

'neumoconiosis (inhaled*$ goiter

vineyard sprayers lung (inhaled*$ 7ilson disease (hepatic and %asal ganglia degeneration*


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8epatic cirrhosis

5ncephalopathy, anemia, a%dominal pain, nephropathy, !oot-drop/ wrist-drop

'ar+inson-li+e syndrome,

Occupational (inhaled*6 pulmonary !i%rosis, reduced sperm count, nasopharyngeal tumors

respiratory, neuropsychiatric[5]

Nausea, metallic taste, gingivo-stomatitis, tremor, neurasthenia, nephrotic syndrome$ hypersensitivity('in+ disease*


39/46

rittle hair and nails, red s+in, paresthesia, hemiplegia

Argyria6 %lue-grey discoloration o! s+in, nails, mucosae

Late !indings6 Alopecia, Mees lines, residual neurologic symptoms

&opper de!iciency6 anemia, neurologic degeneration, osteoporosis


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Toxic Concentration

9:-h urine6

;g/L urine, or

?== >g/g creatinine

No clear re!erence standard

'roteinuria and/or ;?< >g/ g creatinine


Normal e)cretion6

=@?-?@9 >g/L (serum*

=@?-9@9 >g/L (urine*

Normal e)cretion6

9< >g/9: h (urine*


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Nonto)ic6 B== >g/dL

Severe6 Cg/dL


ac+ground e)posure "normal" limits6

?= >g/L (whole %lood*$ 9= >g/L (9:-h urine*

5)cessive e)posure6

Pediatric: symptoms or [Pb] 45 /dL b!ood"# $du!t: symptoms or [Pb] %& /dL[4]


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; >g/L (%lood*

Severe poisoning6

;g/L (-h urine*

Mild to)icity6 ESeF C?mg/L (serum*$ Serious6 C9 mg/L

Asymptomatic wor+ers have mean EAgF o! ?? >g/L (serum* and 9@1 >g/L (spot urine*

o)ic6 CB >g/L (%lood*

Normal range6

=@1-?@? mg/L (plasma*

?=-?: mg/L (red cells*


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Treatment

AL (acute, symptomatic*

Succimer

DM'S (5urope*

G

G

NA& (e)perimental*

NA&

AL

D-'enicillamine

&aNa95DA


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De!ero)amine

AL

Succimer

G

AL

Succimer

DM'S (5urope*

&aNa95DA


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G

Selenium, vitamin 5 (e)perimental*

MDA&

'russian %lue

G


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First-Line Drugs for Tuberculosis

Inhibitors of protein synthesis (Rifamycins)

Inhibitors of cell wall synthesis (Isoniazid others)

!thers

"econd-Line Drugs for Tuberculosis

Fluoro#uinolones

$minoglycosides

!thers

Drugs for Leprosy

Dapsone

Fluoro#uinolones

Rifamycins

Tetracyclines

Drugs for %ycobacterium $&ium

%acrolides

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