‘Sympathetic Activity arasympathetic tivity organ ‘Aetion* ‘Receptor’ Action ‘Receptor? Be Iris radial muscle Contacts “ - - fais creuer muscle - - Contracts ™, Clary muscle (Relaxes B Contracts ™ Heart Sinoatal node Accelerates Bud Deceleates ™, Ectopic pacemakers Accelerates Buds - - Contactity Incres Bubs Decreases (ta) ™ Blood vessels Skin, splanchnic vessels Contracts « - - Skeletal muscle vessels Relanes bs = = {contracts « = - elas! Mm, S - Endothelium of vessels in heart bran, viscera — - Syresies and releases EDRF! MM, Bronchiolar smooth muscle Aelaees Contracts ™, Gastrointestinal tract smooth muscie wal Relaxes Bs Contacts” ™ Sphincter Contacts “ Relaxes ™ Secretion (Decrees) « Increases ™ Genitourinary smooth muscle ‘Blodder wal Relaces b Contacts! ™, Sphincter Contracts « Relaxes ™, Uterus, pregnant Relaces b, - - Contacts « Contacts ™ Penis, seminal vesicles fiacuation « tection M skin Pilomotor smooth muscle Contacts « - - ‘Sweet glands - - Fccine Increases ” - - Apoctine (tess) Increases « - - Metabolic functions Liver Gluconeogenes’s yar - - Liver Glycogenciis yt - - Fat cells Lipalysis S - Renin release = - ineSUMMARY Drugs Used for Cholinomim Subclass, Drug Mechanism of A DIRECT-ACTING CHOLINE ESTERS * Bethanechol | Mascarnicegonist neglect at nestine receptors + CarbackotNorstetvemuscaricané lectin agony eerwise sila to bthan Coed Activates M, Mand M, ‘eceptersinall pepheal fees caus increased secretin smooth muscle contaction (except vascuer ttrooth muscle rans), and changes in heart rate fa 17 co) ro Postoperative and neuregencleus and tnay retention ral end parenteral duration -30 in oes not ‘enter cerval nervoussystem (NS) Toxcye tacerehe parseymeatnommatc effects, ‘expecially bronchospasm inasthnatis, “Interactions: Rdgeve wth other parasympathomimetics echo used rpcoy amos: excel fr glaucoma DIRECT-ACTING MUSCARINIC ALKALOIDS OR SYNTHETICS + Piecing | Like bethanecho} partial agonist Uke bethanechal + Cevimetne Synthetic M,slectve: sma toplcarpine Glaucoma: Sgrens syrerame ral lozenge and topical Tony interactions Like betnanechal DIRECT-ACTING NICOTINIC AGONISTS + Mctine ‘Agonist at both My ard Ny eceptct Activates autonomic posiganglione neurone (oth sympathetic ane paresympethetia end elt mule euomuscul end plates encersCNS and acates Ny rectors Medial usein smoking cessation nonmees tee in smatng ain insecticides Varricine Selective partial agonist at afB2 nicotine receptor used excuse forsaking cesction ‘ral gun petch for smoking cessation Toile ‘Aeutelyncreazee gaerointetinal (acy, ‘nausea vomting dathea-Ineased blood pressure high doses cause seizures ong-term (Glandearsovacusr reactor Interactions ‘ase wth CHS simatans ‘SHORT-ACTING CHOLINESTERASE INHIBITOR (ALCOHOL) + Edtephonium |. Ako, binds biy ‘Amplifesallactions of Ch | Disgnossand acte | Parenteral-quatemmyamine doesnot eer twoactve ste of increases paesympacheic | treatment of myasthenia | CNS Tovey: Parasympathomimetic excess acehycholnesterase actity and somatic gras Ticerctoes: Adie wit (ACHE and prevents ewomuscular parasympathomimetics sccessefacetyehoine | tranemizsion (ach INTERMEDIATE-ACTING CHOLINESTERASE INHIBITORS (CARBAMATES) “ Neostigmine | Fermsecvalent bond wth | Ukeccrophenium but |. Myasthenia gravis (ral and parenteral quatemry amine, does rot ACME but hysalaed nd | longeracting postoperative and | enterCNS,Duratlon 24h Tk released neurogencileusand | interactions Lk edrophonium Urinary retention « Pyidstigmin: Uke cei but longer cig (4-6 hi used myasthenia Physostigmine: Lie nese, but natural kad trary amine enersCNS {LONG-ACTING CHOLINESTERASE INHIBITORS (ORGANOPHOSPHATES) + Echothioghate | Like neostigmin, but released more slovly Lkeneostigmine but Iongeracting| Obsolete was used in gaucoma “Topical onl Ty Brow ache vets lures von + Melathon nsec, lately sate for manmek enc because metbolzed by other enzymes to active procs some media us cxetoparasie + Parton ether: Insecticide, dangerous fora animalstocty portent becouse of earcutural use and expose o farm workers sett) + Sal others: ‘Nerve gas wid exciely a werfare and tremSUMMARY Drugs with Anticholinergic Actions ra Pa oad co [MOTION SICKNESS DRUGS + Scopolamine | Unknown mechan in | Reduces vertigo, Prevention of motion ‘Trandemel patch wed for motion skness as postopertverausea | sidess and postoperative | «IM rjction fer postoperative use» Tay: nauees and voming Tachyeard tured vision serstoria, dir interactions: With ther intmuscarnie ‘GASTROINTESTINAL DISORDERS. + Dicjchamine | Compettive antagonism | Reduces smooth muscle | able bowel symdrome, |. Avalalein orl and parenteral forms = shot, SEM, receptors andsecetor acy of | minor dishes butacton lsu to G hours Ty cut Tachycardia, conus, urinary etonton, Increases mirage pressure» tracions ‘th otherancinuscarns, + yjamine Longer aurcin faction ‘OPHTHALMOLOGY + opine Competiveantagonisn | Causesmydiasisand Retin examination Used as drops «long (5-6 day) action «oxilye seal receptors odopiega prevention ofsmechiae | Increased trocar pressure dosed angle aersurgery sieucoma- Inaction Wth other + Homatepine Sharer duretionefocton (2-248) an ctopne + Qyopertolre: shorter duration faction 3-6) + Topica Shortest dation of acon (15-601in) antrscannics RESPIRATORY [ASTHMA COPD) + Iratopium | Compettive nonselective antagonist tM receptors + Titropium,acinium,andumecldniur: Langer duction cf cction used onedaly Reducesorpevenis | Prevention and elefof bronchospasm ‘acute episodes of bronchospasm ‘Aerosol canister, up to gid Toc Xerstomia cough interactions WA ether anemone URINARY + Onybutyrin | Sight Mselactve muscarinic aniagonst Reduces dens smooth ‘muscetone, pass Ugeincortinence; postoperative spasms + Darifenacin solfenacn ond toltrodine Tertiary amires wt somenhat grec sect fr My receplrs Tiesium: Quateraryaminevith ess CNS effect ‘oat1¥ patch formations Toy “Tachycara, constipation, nceased Inada pressure xerostomi Patch Prats introctons With ober antimuscarinics “CHOLINERGIC POISONING + Avopine Nonselecive compettive amiagons ata mmuscanicreceptorsin (CNS and peihery Yer igh frit for phossherusatom but foes not ener CNS + Prabdoxme Blocks muscarin excess | Mandatory amt for atevocrne ands hear, | severe cholinesterase smooth moc Inhibitor poisoning Regenerates active ACHE | Usual antidote fr eny- ‘anraieveseletal stage (481) cholinesterase ‘muscieend plate block | inhibitor posening Iravenousinfsion unl artuscarinc slgnsappeat continue 2s ong as necessary “Torii insignia along a ACHE Inhibition continues Ietravenous every4-6h Twi: Con couse muscle weaknessin overdose [AcE,aeaehotnaserac CAS, canta eras yom; COPD, cron obenathe pers ehaaieyM, MAM atTau Pharmacokinetics, Toxicities Seat Mice euaba cies Ce sean! ‘9, AGONISTS. " Midodrine | Actes phospholipase, | Yaseuarsmoothmusce | Orthostatichypotension | Ora-produg converted active dug ‘esutig in nceesed ‘contetion ieessng blood tha Fh peak fet: Tay: Supine Iinraceltr calcu and | presure (BP) peterson ploerection (goosebumps). sasocostcton tnd urinary eteton| + Phrygian beused Vos tem mcntenanc of 8 acute ypetenson and trea produce local woconsicion ave decangestnt ‘o,AGONISTS *Gonidine | Inhbasacemyyleycase | Yatoconstcion smashed Hypertension (ral transdermal» peakeffeet 1-30 andinteracs ath other | by ental sympatholte ofl tug ~12h- produces dry meuth Inracel pathways fe, which lowers BP ana seeation + wMetyiopa, guorfacine, aed quonabenz Ao sed ascerva sympethays + Dexmedetomidine: Prominent sedative efectsondused in anesthesia + Teondne:Used aso muscle relent + Aeradonidre an bameniaine Used topical in glaucoma to reduceinteecuapresure acon Dobutanire! | Achetesaderyhyi cle, | Posvelnavopc effect | Caageni shock acute | Ns teues dos tatoo deselect Irereasing myocardal heartaue conacity BLAGONISTS| ‘butorol | AcwatesadenyWicylase | Bronenalsmoothmuscle Asthma Inhation- uration 4-6. Tess diaton Tremor tacyeacla + Seecther agonists in Chapter 20 BAGONSTS| * Minbegion | Actatsaderyhy gcse | Reduces blader tone Lina gency Charan 3h Tc Posse ‘hypertension DOPAMINE AGONISTS Agonists “Fendopam | Acvotesaderyyceze | Vsersmoathmusde | Hypertens emeigeney | eure os treton to deed eet reoton ,Agoints “ Wemectpine | Inhbtsodenfylcychse | Mines dopamine aeions | Parensons ease, Oe Tepe Nawien esche Ancinersrwntorwer | inthe os preacnersa nose ypetesion inact pata + Se aterD,agoistsh Chant 2637 "Dobuemnne has oer actansin adaion to -agons ete Seen dtsBETAAGONISTS: ‘Aiba! | Selene agonist, + Saimeteroh | Selective agonist + Metprteeno terbtane: Shnlart but teruien valde as anol ug + Fortran Simro slnetrcl ‘ epinephine | Nonsalective and agonist + bopoteenol_ | Band 8, agonist ‘ronchodistion pl al ther sympathomimetic eects on ‘aionascular and other organ systems (see Chapter) Bronchodistion plus powerful cardovaiclr eect CT Applications Asthma, conic obsuctve pulmonary disease (COPD) ug of cho insane ‘ethmatl bronchespazm Bronchod ation, prevention of thea exacerbations drapes aoa, others (se Copter 9) rarely used for asthma (selective ages prefer) ‘Asthma but selective agents referee a ‘Aero ination «uration several hour» alo aval for naculzer and parenteral uses Toxic remor, factycaaln- Overdue aytrmiat ‘ero inhlation «uation 12-24 “Toy Teor tachycarha «Overdose exis ‘Aerosol, nebulizer or parenteral see Chapters ‘Aerosol neblzetor parenteral see ChapterS| ‘CORTICOSTEROIDS, INHALED s Flutkatone | Aker gene expression Reduces meltor of nammation + power propia of, ‘racerbatlons + Beclomethasone budesonide furs ethers Snir tofuticasone Asta adjunct COPD hay ever asl ‘Aerotal uation hous Toy: United by asorl aplication «cand Infection, vocal cord changes ‘CORTICOSTEROIDS, SYSTEMIC rednione | Ukefutcasone Uke furasone + Meth prednisolone: Parenteral gent ike prednisone Asthma adjunct COPD (ra curation 12-26 Toy: Makipe- se Chapter 39 STABILIZERS OF MAST AND OTHER CELLS ‘Cromol, | Aterfuncion of | Prevention of bronchospastic ‘Asta (other outs used or | Aerosl- duration 6-8 hoy: Cough redocoml | deayed corde | raszensetoallegenirhaistion | cela nasal and ‘not absorbed ther once ae Inolonger | channels inhbt (estrone ler) rinimal swalsbiein | bfammstoryce theusa) | aeration METHYLXANTHINES * Theophline | Uncertain Bronceinvion, cardiac stimulation, | Asthra, COPD (ral duration 8-12 hb extended sphosphodlestrase | Incestd skeletal muscle strength teleose preparations cen used Fly: inhibten (daphrag) Maile etx) ‘adeno {eceptor antagonist + Rofuniast Sarto theptyine but wih beter therapeutic roto LEUKOTRIENE ANTAGONISTS + Montalutat, | Blecklaukatione | Block airway reponsetooxrcse | Prophfaxs of ara, (ral craton hour Toy Minis zafiutast | Dj reeptors and aigen challenge speci in chien and in achrininduced asta stor: inhisYponcenas reduces shes luloienes Wye ANTIBODY. = Omazumab | Hurenzed gf antibody reduces cating ge Reduces frequency of asthma exacerbations Severe ath adequately contofedby above ages Parenteral «dation 2-4 week Tvey Injection site reactions (nephyacs cemtemely rate (oontirued)re Mechanism of Cees or od Effects ec ieed ANT/-INTERLEUKIN-S PATHWAY ANTIBODIES AND OTHER ANTIBODIES. * Mepslaursb | Humanzedani-t-5 | Reducsrequency of astima Severessthms adequately | Parenteral duration 2-4 wk Toit anvbodysreduces | eacerbations ‘ontoledby above agens, | Iecton ste reaction (anaphyans ‘eulauing and ‘th assecated eosmophls | eter rae| tissue esinophis + Duplumab | Humanized Reduces frequency fastens Severeastha indequiely | Pareneainjection every 2-4 wk antibody against | exacerbations:improves pulronsry | contol by KSILABA therapy ‘éerecepot or | function stand IL Aesteumab and benraexrnas Siar to mepotaunad SUMMARY Drugs U: CCRT ry Be eeake Milicecenceukilacicoculiaesed oa ‘OPIOID RECEPTOR ANTAGONIST + Nalevene Nonseective antagonist of | Reversesthe acute eflectsof | Opiid overdose fect much shorter than morphine opledrceptor ‘pio cn pecptate severe abstinence syndrome (1-2 hy therfore sever injections required + Nalrexon Amvagonis of pls receptors Bock ets of ter opis Treatment of alcoholism, pied adction Hate 10h (ra 5=10 days (ep jection) SYNTHETIC OPIOID ‘Methadone | Slowsactng agonist of ‘este effects smiarto Substitution therapy for | High oa bioavasbilty shale high opioid receptor ‘morphine se ext) plod adits valle amang india (ange 4-130) - Tony Respiratory epresion, constipation mics, tolerance dependence, ayia anc withdrawal symptoms ‘ Levomethadone | “Trertopue' methadone | Similartomorphineand | Substitution therapy Les toxic compared to racic containing onlythelt- | methadone, but at half the methadone prtcary related fenamiomerofthemolecule | dose ofthe iter ‘adc adverse fects (ong T intra) + Morphine ‘Asateontsning morphine | Slow-leasevesion wth a | Substtuten therapy sulphate sulfate penahydiate longer action than marphee PARTIAL j-OPIOID RECEPTOR AGONIST Buprenophine | Partial agonist aty-opiod | Attenuates acute effects of | Oralsubstution thetapy for) Long half 40) formulated receptors morphine plod adits together uth naloxone avoid ict ectons [NICOTINIC RECEPTOR PARTIAL AGONIST Varenicine | arta agonist ofricotine | Occiudes"ewarding’efiects | Smoking casation Tey: Nausea and vorting slurs, acetyichotneeceprorofthe_| of smoking «heightened psjcinc changes caR2 ne anareness felons + thine Natwel analog fecracted fom burn lowers) of arenene Sa) acu od a [BENZODIAZEPINES * Orazepam, | Pesltive modulators ofthe |. Enhances GABRerge Detrum ernens Hafele 4-15 pharmacokinetics not thers GABA receptor increase | syrapictwansision: affected by decreased iver function frequency of channe attenuates withdranal cpeting symtoms remo, halacations anxiety) in aleaholis- prevents ‘withdrewal Slee + Lorazepam: Alternate to cxizepar wth sini properties [W-METHYL-2- ASPARTATE (NIMDA| ANTAGONIST + Aeamprosate | Antagonist of NMDA slaamate receptors “Treatment akoholsm fective onyin combination ‘ith counselng ‘lege eactonsarthythmia nd low 1 igh blood pressure headeches, Insomnia, end impotence» hallucinations particulary in lcery patients May etrtere with forms of syapticplasicty thet calc cleum dinenyrines | chewed + Nydalane Caesnicarderdene | Vacdiaton-recicesvatcdar | Hypatasion-minasat | Onl-Todc Angina + Moe ees cecerg tarp ae [rece ete lect ste hoe Petree tee invecrsroath made | sense tan vena efx Lipustke yrdeme ovis Ninn perrenotfibanceiaet Cae) erencekaboc Cd eae taneeers PARENTERAL AGENTS + Nivoprsside Releases ic orde Powerful vascaton Hypertesive emergencies | Pareteral short duration + Fenoldopam Aatnats D receptors «diazoxide now used only | Tony: Excessive + Diazoxse (pens K channel Intypogiycema hypotension shock + Labetalol vp biocer ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS. + Captopril many | Inhibit angitensirconverting | Reduce angiotensin levels | Hypertension heat fie, | Oral» Txt: Cough, others engyme reduce vsoconstecionané | clabetes angicedems hyperialeria akostrone secretion «increase ‘renal impatient teratogenic badykin ANGIOTENSIN RECEPTOR BLOCKERS (ARBS) + Lonartan any Block AT anditersin Same asACEinhibtors but no Hypetersion-heatfaiure | Oral=Toity Same as ACE others receptors Increase in bvadykin Inbar but es cough RENIN INHIBITOR. + Alsen Inhibs enzyme acy Reduces angiotensin andl and_ | Hypertersion (ra ont Hyperkalemia, ofrenin aldosterone renal impairment - potential teratogenNG anu ead Cee Miicoiinubedecad Effects Clinical Applications Doubs meres “Nhu | Selene iin semates guanyyl cjlae fndincreases cGMP Smooth muscle relation, especialy in vesel other smooth mule ersned but nots markedly = esodlatin deeoses ‘enous retumend heat size “may inerasa coronary flow knsome areas andi varsrt angha Aone Suing form for eve pisos ora and teanecermal for for ‘ropa IV or for ‘acute cxonary syndrome + orrbde dintcte Very smlartontraghcery sight ionger duction of ection tansdemel form + oxide mononiate: Ate metabole ofthe trate; used oral fo prophylas High fist pass efect so sublingual dose ‘emuch snl than oral hgh iid Selubty ensures rapid absorpicn ‘Tox Orbestatic hypotension, tachycardia, headache nations Synergistic hyatesion with Dhoschodiestase type 5 inhibitors ‘slderati et ote Er ee Meet bados calcined Cla aaeineiiieie oad BETA BLOCKERS ‘+ Propranclol | Nonselective competitive | Dacensed heat at, Propiylaisofanginasfor |. Onl ad pereteral 4-6 h duration of antogonst at caicincoutpuand blood | other applications see | action Tac: Asthma atrioventricular ectenocepirs resure decreases ‘Chapters 10,11,and 13. | block acute hear fala, sedation myocardial ogygen demand *Imeractions deve with al cardioe depressants + Menlo metoprolol oes lective Blockers less of bronchospasm, but sil sanfcant + See Chapters and 1 for ote blocker cr ther app ection: ‘CALCIUM CHANNEL BLOCKERS + Verapami Nonsslectivebockof Reduced vascular restance, | Prophyan of angina, Cray duration 4-8 «Toye dane Lerypecalcumchanrlsin | cardac rate andcaciac "| hypertension, others ‘Avioventcular block aco heart fare: ‘eset anc heart | force results in decreed constipation, era nteractons: Ave ‘oxygen demand vith ther carne depresants and Frypotensive dogs Nfedipee || Blockot vascuisr type | Like verapamil anc Propiylatsof angina and | Oral duration 4-6 Towry Excessive ydropyridin) | calcu channels> cardiac | ditazeriesscardaceffect_ | testmentcf hypertension | hypotension berrecepor rele chunne’s but prorat release tachycardia interactions: Alive with rien is othe vasaetors ‘onanaicates + Anon elope other dhydopidnes Like nifedipine but slower orset ard longer duration fp to 12or mor) MISCELLANEOUS + Ranclaine Inf ate sodium curent Inheart-aiso may moaiy faty sod ondation a such higher doses Reduces carcnconygen demand fay aid oxestion modcaton could improve wfciency of arc anygenutlzaion Prophylaxis angina + InabredineInibor of sno pacemekr eduction of heart rate reciesongen demand + Timetazidnealopurical phen fesudlt See ext (ra, duration 6-8» Tc: OT interval rolongaton (outro increaseoftorsades de pines nausea, constipation czziness ‘Interactions inhbtos of CYPBA crease ‘anolaine concentration and duration of actionSUMMARY Drugs Used in Heart Failure Gonos eae eae euro Clinical Applications ‘wuRETics + Fuoceide Loop duet: Decreaes NaCl | Inreated exertion ofsalt Acute and chronic hear ‘2nd KCirbsorpionntick | and waters reduces cardiac | flue «severe hypertension ascending Lib ofthe bop of | preload andaftroud edematous conditions Henleinthe nepnvon Gee | sreduces pulmonary anc Chapter 15) petipneralederm + Hyorochorthiade | Decreases NaCireabiorption in| Some afurcemid out | id ehrone fare: mi ‘thedial convauted use | muchles effescous ‘moderst hypertension Irypercakia as nt been shawn to reduce martalty + Tre other oop drei: Bumetonide ond tose silat fveserie;ethacync acd not asufonamide + Many other thladeAl basal sna to hytocNoohlalde, dering ony npharmacoknes ‘al and Ve duraton 2-4h ‘Tac: Hypovolela hypokalemia, rthostatic hypotension, ototoxic, silenamide ergy (rally: duration 10-12 ‘Taxcy Hyponatremia, hypokalemia, hypealyemi, hyperuricemia hyperipidemia, ssenamideaetgy ‘ALDOSTERONE ANTAGONISTS: + Spienolctone Bocks cytoplasmic aldosterone | Increased salt and water | Chronic heart falure receptor incollectng tubules | excretion reduces ‘alostoronism (rho, ‘fephion- posible temocelg areal ume membrane eet ‘hypectension hasbeen ‘hat to reduce meray el -duation 4-72 ison ‘onset and oft) Toe: Hyperkalemia antiandrogen actions + Eplerenone: Srila tosironolctone more selective artininrlocrtcot fet no sian ariandegen actor has been shown to reduce moray [ANGIOTENSIN ANTAGONISTS Angiotensn-converting | Inhibits ACE» reduces A ‘Arttioar and venous Crronicheat failure fenzyme|A@Dinhibiters:| formation by inhibiting ‘dltion «reduces hypertension» diabetic Boren ‘conversion ofl to ‘dosterone secretion renal diate hat been duces card remodeling | shown toreckce marty ‘Angiotensin receptor | Antagonize Affects 2t AT, |_Like ACE nhibkore Le ACE inion used in blockers (ARBs) receptors Pals nce to ACE : inhibitors -has been shown ‘orate toreduce mortaity + Ealapl many ether ACE motor: Like capt + Candesartan vosator, ary other ARBs: Lik satan (al habe 2-4 h bt given Inlarge doses so duration Ta-athn Tnoty Cough, hypetalemia, angoneurotie ‘edema = rterction: Additive ‘th other angiotensin antagonist ol duration 6-8 enc Hyperkalemia anglonewoci: ‘edems=irtrcton: Adve ‘th other angiotensin antagonistsae) ‘BETA BLOCKERS + Cane! Cadac Comperively blocs 8 recaps se Chater 10) Effects Sows heat ate -recuces ood pressure poorly understood other effects Ce maacen Cenihear fax: Tosiow program reduce mortalty Inmodetate end severe heart. fale -mary other Inaeatonsin Chapter 10 (ra dration 10-12 Tony Bronchospasm traded, atioventeulr lock acute ‘ardacdecomperston see (Chapter Of verti: andinveations = Merpreto bsoproll ebivlo Select aroup of blockers thethav bean shown to reduce heat falure mrtlty ‘CARDIAC GLYCOSIDE. + Digoxin ther Na‘A-ATPaginhibiton results | ieressescardaccontactity | Chronisymptomatc heart | Ora parenteral- duration ‘lcosdes ae used | nreduced Ca” expulsion and | «cardiac falresrapidvenicuiar tate | 36-40 Tory Nausea, Cutsidethe USA) | increased Ca” stored in ‘ect (lowedsius heat rate, | inatral fbilation -hesnot | vomiting ciathea-cerdac ssicopasmic eticutin slowedstiovertcuer been shown to reduce ayahmins concton) moray but does recuce rehospkalzation ‘VASODILATORS Venodilates: eeaesritc oxide (NO) Venodtation reduces ewe and chvonicheat | Oras dation 4-6h Tol: ‘ tosorbide dinitrate | sactNatesguanyyleydase | preloadand vewicuar | fae-angina Postural hypeterson, (see Chapter 12) stretch tachyearda headaches ‘Arveioar datos: + Hydlalaaine Probably increases NO symhess in enelom (see Chapter 1) Reduces blood presse are afteroad results increased cardiac output Hydraaane plas neates may reduce mortality in ican Ameticans Interactions Adve wth other asodistorsand synergistic lth phesphodiestrase ype inkitors (ral uration $12» Toon Tachyar, hed recension, lupuske syndrome Combined areolar | Releases NOspomaneousy | Mate vatoletion heute cede |W ony duration 1-2 min and venodilaor: actvetesuanyyleyelae | «reduce preload and decompensation Tock acess hypatensen, ” Nigprisie ereed ‘hypertensveemergencies | thicrateand cyanide (magnant hypertension) | tcricty- teractions Active wrth other vasoditers ‘BETA ADRENOCEPTOR AGONISTS. + Dobutamine 2telecve agonist Increases eardlac ‘cute decompensated [Nonly= duration few increases cAMP synthesis | contract output heartfalre minutes Tv Athos Inieracons Rive with othe sympathomimeties Dopamine Dopamine receptoragonist_ | Incresesteralbioodfiow | Acute decompensatedheat | Nonly-duationa few shighercosesacivate Band | higher dosesincrease | falureshock minutes Txt Arhythmias bwadienoceptors ‘ardac foe and biood "Interactions Ave with pressure sympathomimetic ‘IPYRIDINES. Milinone Phosohodestersetype3 | Vasodlatorlowerperipheral_| Acute decompensatedheart |W only-duration3-6h Inhlonor:decreaes cam> | vasclarressnce» aso | falure-incesesmeraltyin | -Toecly:Amythmias breakdown Increases earlae vont falure ‘Interactions: Adve with ceonvaciy otherarthythagenicagents [NATRIURETIC PEPTIDE Nesitide Aetnates BNP receptors Vesodlation diuresis Jeute decompensatedfaltre | Nonly- duction 18min Inereasas GMP has notbeenshownto | = Tox Renal damage, reduce matalty hypotension may increase mortality [NEPRILYSIN INHIBITOR Sacubitl used onty incombiraton with valartan ARN Inhibits nee thus reducing broatdoum of ANP ded BAP alan ibis action of anlatensin omits receptor. Vasodilator Chronictatze- combination reduces morealty and rehosplalzations Oral duration 12h- used only Imcombination wth ARE "Toxdly:Hypacesion, sgioedernaBain er Subclass, Drug of Action Effects ead CLASS 1A + Procainamide | ly (pray) and, | Slowsconductonvelocty nd | Mostatraland verricular | Oral IM -elminaed by hepatic (econdary blockade | pacematerrae prolongs acion | arrhyihmiasediug ofsecond_| metals to Nacetlprcanaride potenti duetionanddssocates | choiceferest sustained | (NAPA, see tet] and renal eininaton ffomy,chennel wth intermediate | verirulararythmias | NAPA implceted in tosades de ines Kinetic crect depesanteects | ssiacated with acute inpatients with renal faire» Toy: ‘on snostal(SA|andatioventicuar | myocardial efarctin Hypotension -Iong term therapy (WW) nodes produces rverile irueraltes symptoms += Quinine Slr to procainamide but more to (anchonam torsade} orl usedin ayn see Chapa $2 fer mala + Dispyramile Sia to rocohamide but significant antinascarnc feta pret heart flue not carmony used Lass 18 + Udocane | Sodiumchannel(,,)_ | Blocksaciated andinactvated | Terminates veicular 10 fs pass hepatic metabolism Blockade camels wth fsthinetics-does | tachycardias and prevents | reduce dose inpatients mith heart ‘nat prolong and may shorten action | vertculrfbriltion ater | failure or Ber csease~Taniy, potential ceariovesion Newolege symptoms + Metletine Cally octvecongereof doce; used in vertu ati chronic pain syadomes eng [tunes Bon rey Coe Clinical Applications ‘CLASS 1¢ + Fecalide | Sodiumchannl fy! | Dissocistes from channel ith slow | Supraveniclerartythmias. | Oral: hepatic and kidney metabolism bleckode netics «no change inaction in patents wih normal heart «hal Me ~20- Towiy:Proorhythmic potent duration * donot uso chomic ondtons (ost myocaal Infretion) + Propfenone Gray activ, weck blocking oct supraventiculr arth epaicmetaboliry + MorcznePhenthiacne derivative oral active eiculararythmias,proothythm,Whdrann in USA. ‘cLASS2 + Propranolol | rAdenoceptor Direct membrane fects (odlum |. Aulalaythnisand ‘a patente: duration 4-61 blockade channel biock) and prclongation of | prevention ofrecuret "Toy Asthma, AV blockade, acute action potential duration-slowsSA | infaeionandsuddendeath | heart falureIneactons With ether node automaticity and AY nodal Carine depressots andhypotensive conduction vlocty drugs + smoot Shooting onl ued for ntraopratie ard othe acute anfythmas ‘CLASS: + Amiodwrone | Block nga. | Prolongsacton potential duration | Serious ventricular ‘ra N+ vaiabl absorption ae tissue channels and CT interad-slowsheartrate | arhythmissand ‘scumuletion + hepaticmetablism, adrenoceptors 14 AV node conduetion low supraventricular elimination comolexand iw «Tevet Imidence of torsades de pointes | anhythmias Badyardla and heartblckIn seco heart priherl vaso, pulmonary and hepatic txt «hyper Or hypothyroidism interactions: Many, based on CYP mecabosism = dotetide — | 1, bio relongs acton poten efectve | Maintenance or restoration | Ora-renalexcrevon=TonloyTosades refactor period ofsius rhythm natal | de ponte (ntate hosstal with fie monitoring) Interactions: Adetive with other apionging tugs + Sol Adrenergic andl acer direc actin potent prolongation properties se or ventral bition + lout: Potassium chanel blocker may athat Inward cunt se fo conversion ial ute and fbinion + Dronedaroe: Amiodarone dative mutchonnel cons, recsces mrtltyn patents with ata Abilaion + Venatalennvestationlin the USA, mutichanne actions oa, prolongs ail reactrnes fective ina filationCLASS 4 + Verepamil | Caldumcamnel | SlonsSAnade akomatiy and AY |. Supravenscusrtachycardas, | Oral hepatic metabolism caution n ‘aa type) blockade | node conduction velcty-decrenses | hypertension angina Patient ith hepatic dfuncton Tay eardseconacly reduces bead ‘imeractions See Chapt 12 pressure + bitiaze: Equivalent to verazat ‘MISCELLANEOUS + Aer Actateinvard | VerybieLusalycompleteAY | Paroxysmal supraveniciar | Mon satin 10-15 5: Ty rectifier bleds|, | blockade tacycacas Flushing ches ihe, zines + interactions: Minimal + Megnesim | Poorvundesteed: | Nomalixsorinceases Torades de pits dgtali- |W duntion dependent on dosage feencs with nae | plasma ig inde aryas + Toney Me weakest novrdose [Pose Kanda” chars + Potassium | erases? Slons ecoplepaceraters-sons | Digtalsihaueed anhytamas | Ora -Towoy:Reentant arth, pemeabity,x° | condutonveoaty neat santas asedated wth | ean oanet overdone curets hypokaleia SUMMARY Diuretic Agents ‘CARBONIC ANHYDRASE INHIBITORS. ‘+ Aceaolamide, | Inhibition oftheerzyme | Reduce reabsorption of HCO; casing | Glaucoma, ountaln|_ Orlane topical preparations others prevents dehycation of | sliinteddivess-hyoercioremic | sickness edema with | avalable curation of ction H,CO,and hydration ofCO, | metabolic access» reduce body pH | alaloss -8-12h- Tovey Metabolic inehe penimalcenvones | reduce intaoclr pressure acidosis renal stones, ‘ubue hyperammonemi chats + frnzlamide,dorzokmie: Tope glaucoma ‘SGLr2 WHIBITORS + Canaan iin csedum/suone | bbtoncfghcoreeabetontowes | Oubtesmalitas | ae cry Hie ‘eotranspeter(SGU2| inthe | serum glucose concentaton, approvedforthe | 10-12h=not recommended Riethicsawertst | mavatnnasgseneuensd | teamenet In severe rena rer tnd glucose reabsorption | dies Fypersycemia,notas | dsease adiretie + Dapogifozempagiocn: sna tocanogifochcre) Subclass, Drug Mechanism of A cin Applications Loop DIURETICS + Furosemide Inhibton ofthe Nat/201 | Markadincreassin NaC excretion some | Purmonaryedema, | Oslandprertaral ‘wansporerinthe ascending | wasting hypotalemic meabolcalalss | peripheral edema | preparations duration of limbot Henle loop ‘creased une Caard Mg heart fale, fection 2-4 Tit hypertension 2cte | Orotencty, typoveemia, yparake’s anion | Kwastng,nyporuicemia overdose hypomagnesemia + Bumetnietorsemide Su¥onanize oop agen ie arse + Ethecynic act: Notosfonamide but hos tpicelop act and seme wicesuic ation TTHIAZIDES + Hysrochiorothiande | Inhibition ofthe Na“ Modest increasein NG exretonesome | Hyperension,mild | Oraledutaton8-12 ‘wansporter inthe distal X wasting «hypokalemic metabolic ert flue, +Tax: Hyzokelemic ‘convoluted tubule silos decreed urine Ca septs metabolicakalsis, neptrogeniecabetes | hyperuricemia, insipidus hypesgheemia hyponatiemia + Metlazone: Popular fous wit lop agents for synerosc eflcs + Chlortisie Only parenteral tise abl) + Ghlortadore: Lang hae (50-60 de to binding to red bood cls POTASSIUM -SPARING DIURETICS + Spenclacone | Pharmacologicantagonst_ | adueesNaretemtion and Kvastingin | Aldosterorism tem | Slow onstand ote of fofakicsieroneincolecing | kney-peoiy understood antagonsmet | any cause effect uation 26-3 ‘ubules-weskantagonism | akesteronetheart and vessels sypokalemiadueto | «Tot Hyperkalerie, cof androgen rcaptors other diuretics gynecomastia “pasimecertal | penolacone not ‘sfrction eplerenone -addive Interaction wth other Kraning cugs + Atos Bloc epithelial sodium Rodces Na rtention and K wasting Yypotatemiatram — | Oray active duration 24 ‘channels in colecting tubules. | «increases Ithum clearance other duets “Tally: Hyperkaieric sreduceslithium- | metabolic acidosis ‘nauced pera «Liles syndiome + Bolerenone Like spirorolatore more selectve fr ldosteronerecetor + Tancerene: Mechanism ike alo much ess potent maretone ‘OSMOTIC DIURETICS + Mannital Physica osmeticafocten | Marked ncraseinurne om reduced | Renaltallure dueto | administration «Txt: tive waterdstrbution | bain volume, deceased intraocular Increased solute load | Nausea yomtng, headache becaueit retained in the | pressure inital Ryonatrema, then tembdornyahss, veal compartment Fyperaters | chemetrapy incensed intacerial pressure glaucoma "VASOPRESSIN (ADH] ANTAGONISTS. + Conivaptan AntagonistatV,2nd Vs ADH | Reduces water resorption, inceases | Hyponatremia, Wonly usualy continuous receptors Plsema laconcertation,vatcciston | cengestveneat | «Taweryeintusion ste taikze reaction thst polyuria, hypematersa + Tevaptan Solective antagonist at Reduces water reabsorption inceasas | Hyponatremia, SIADH | Oral- duration 12-24 Ve ADH recepors Plasma Na concervation “Tol Pour frequency ‘ist hyperrateiaPharmacokinetics, Toxicities, Drug Mechanism of Action Effects Ciel STATINS. + Morvastainy | WnhibitHMG-Coh reductase | Reduce cholesterol synthes'sand | Atheroscleroticvascular | Oral» duration 12-24 ay: Myopathy, simvastatn, ‘pregulte low deny Ascase (primary and | eat dyshanetion- traction: rosuvastat, poproten (104 receptorson | secondary prevention) | CYPdepencent metabolism (3A 28) pitvestatin hepatocytes-modest reduction | «acute coronary Interacts with CYPinhibitors/competors in rgiycondes syndromes + Rurestatnprovastatn, lovastatin: Sina but somewhat essefcacious FIBRATES + Fenofiate | Pereskomeprolfeator- |. Dacease secretion of Hypertighceidemia, | Oral» duration 3-24) Tx: Myopathy, gemfibroct | actvatedreceptorelpha | verylow-density lipoproteins | low HDL hepate drfunction (Poatea) agoniss (ULDU «nrease lipoprotein pase activity «increase high-ensy ipopretains OL) CT Interactions BILE ACID SEQUESTRANTS Colesipol | Bndsbieacesinaut Decreases LOL Erated LDL digits | Oel-taken with meals not absorbed | preventsresbroton toxity, pros *Tesley: Constipation, boating incrfres “increases cholesterol with absorption of some drugs and viterins ‘atabotsm-uregubtes DL recep: + Cholera, colesevel: Snir to cleat STEROL ABSORPTION INHIBITOR Ezetmibe | Blocks ster transporter | Inhibits reabsorption of Erated OL, ‘Ol - duration 24h Tw: Low incdonce NCILIinitesine rush | cholester excreted ble Prytosteoimia of hepatic dysfunction myosts| border + decreases LOL and phytosterols NIACIN Decreases catabolimof | InteasesHDL «decreases Low HOL elevated VLDL, | Oral lage doses» Toy Gast tation, ‘60 A= reduces DL ‘ipopetsns (pla), LDL Ll elevated Lin" | fushing low indence of heptictxity feeteton fom ber stati-unresponsve or | «may aduce glucose tolerance Intterart patients + Bxtended release ac: Siar to regula + Sustare release mci (nt the same os extended velar produc): shouldbe avoided CEK® HUMANIZED MONOCLONAL ANTIAODIES Erlecurab | ComelenesPCSKO Inhibits cabot oftOL Fania Pernt Cost $14000H¢e- Fy: meer ryperhoesecleninet_| iyectonste scien raxophaynat, teqpnivetoordtaapy| Alta mgcons uy maga ‘newrocognitive and ophthalmologic events + Alrocameb Smit evolucumabSUMMARY Hypothalamic & Pituitary Hormones’ nism of Subclass,Drug Action Clinical Applications ‘GROWTH HORMONE (GH) + Somatropin | Recombinantform of | Restores nermalgiowthanc | Replacementin GH deficiency SCinjacton «ory: reudotumor human GH acts metabo GH effects ‘increased nal aduthelghtin | cere sipped capital femoral troush GH receptors | GHdefcentincivuals | children with certain condtions | epiohysis edema, yperahycamia, raereaseproducton | «increases final aduithelght | astocared wth shortsaure fee | progression of solos, kk of of GF insome chidien nih short | Table37-4)-astingin IN ‘sph inseverely obese patents stature not due to GH Infecton short bowelsyndreme | wt Pra Nil syndrome and upper eficency alway obstruction or sles apnea IGF AGONIST + Mecasermin | Recombinantform of | Improves growth ne Replacement in IG dfcienc that] SC njction- Toxicity Hypoclycamia, (cF-\shatstimulies | metabolic IGF efecs in| snotresponsiveto exogenous GH | iniacraniaypertenson ceased 1F-\recepters Invcuas with IGE Tverensymes ‘eficancy due to severe GH resistance Sar) ‘SOMATOSTATIN ANALOGS * Ociretie Aorist somatostatin receptors Inhibits production of GH and,toaleser ete of TH, glucagon. insulin and gastin Actomegay and several ther hormone-secretng tumors: acute Conirl of bleeding fiom esophageal sates + Lanreote Siar ocreoe avatobe oa long-acting frmulatcn fr ocromegaly ‘Cor W nection slong acting formulation injected Mi monty “Toric, Gastrointestinal disturbances, glstones,brcycardi, ‘ancla eduction prodiens (GH RECEPTOR ANTAGONIST Pegyisomant Blocks GH receptors Amolerates flocs of xcs GH production Deromeay ‘Cinjecton + Tvl Increased Wer cenymes ‘GONADOTROPINS: FOLLICLESTIMULATING HORMONE (FSH) ANALOGS + Folitropin fa Actuate FSH rectors ‘Minis wees of| endogenous FH Contleg varia stimulation +nferty du to hypogonadtropic hypogeracism in men SCinjecton + Toei Ovanan Inyperstimaaton syrome and ‘mule pregnancies n women * gynecomasta in men headache, . | cuceptlebacens suse | Grmportivebacers | 6h) sartngdoreof39mghgfd nto cree Aatermnusctmascese | ethan lactam Incig spas endocy, | ade dose n patents witha eal Peptisoghcan ardent cafe | func tough cores of Cals orfermuston) | 10-15 megfLsufcient for most infections TeecyRed man syndrome nephrotoxic ‘Tecoplani: nraveos snr vanconycin except hat long hale 45-70 permits orcedaly dosing + DobowancInttavenou verlag hai (>10dop) peritsonceweey dosing + Ortovancilntrverous, ver lrg halite (>10 day) permits once wes dosing + Teaver Iravenous, once daly desing LUPOPEPTIDE + Deptomyen | Binds to callmembrane, | Bactericidal activity against | Infections caused by Gam | Vatminitration renal clearance (allie 8h) Causing depolarzaton | susceptible baiena-more | postive bacetainduding | dosed once daly «inactivated by pulmonary Sand rapdcel cesty fepldlybacencéal than | Saale and endocrde turfctant0 ant be uses to test poeumon’s vancomycin “Toy Myepathys mentoring of weeldy Creatine phosphokinase levels commendedSe Moe Us ee col Streptogramins, & Oxazolidinones kine eae) acid Cees ee TETRACYCLINES Tetacyclne | Prevents bactel poten | Bactelostai acy | Infeccons caused by Cras mised clearance hale Bh) =cosed symthesisy binding tothe | aganst susceptible | mycoplasma chlarydlaa, | evry @hedualentctlons impair 30S bosomalsubumt | bactea ‘eke some sprochetes | absorption» Tact Gastontestinal upset, ‘mola +H pfs aoe hepatotoccy,photosenstvy, depostion ky bone and te + Doryyine: Ort and longer ha He 18 0 dosed ce dl nonrena elinaticn absorptions minimally ceted by valent cations wsed oreo community ‘cequredpneuroniaand exacerbations ofbronchits + Mincyine: rand longer hae 16 0 dosed vie dl requertlycuses reversible vestibular tchy + Taser unafeced by commen tetaeycne resistance mechani vr/boad specu cect agains Gra postive, Gram-negatveendanaerobic ‘bacteria; nausea and vomiting are the einer oes (MACROLIDES + Eexthramycin | Prevents acter poten | Bactelosaacivty | Community acquted Ota V hepatic clearance hale 151) ‘yrthesisty binding tothe | against susceptible | pneumonia pertussis dosed ery 6h -tactrome Paso inhibitor 50S toosomalsubunt | bacteria eoryebacteral ans “Tent Gastrlcasiealupsat,hapatotoiy, ‘lama infections (T, prolongation + Carton: Ora lorger hal fe) dosed tice ay added acti versus avium compl, toroplesma and M epre + Aatvomyein: ro er fong hae (allows for nce day dosing and $day course therapy communty-acaed pneumonia does rot inhi todo PaSdersyres + Teron tnt by eee reteset wes any enrony-et sas peut castor pa LINCOSAMIDE: + Clndaryein Skinand sot tesue infections | Ora V=hepat clearance ale 25) sanserobicinfeciont * doued every 6-8 hove Tn. Gastloestinal upset Cie cots Prevents bacteria proteln synthesis binding othe 50 osomal subumt Bacstosace acevty aganst susceptible bacteria STREPTOGRAMINS “= Qunupristn- | Prevents bacterl protein Infections caus by Iv -hepai earance- dosed every 8-12 dtsfopisen | syrthesisty nang tothe | acy Staphyococcl or vancomycin | « ctocreme 450 inbitor-Tencty Severe 50S foosomalsubunt | surcernbe reditanesvains ef Efaecum | sion rdated myalgias and atlas ‘CHLORAMPHENICOL Preventsbaceil pote | Bacteistatcectviy | Use'sareinthe deveped | Nshepatie dearance tale 25): dosage s synthesisby binding tothe | apenst susceptible | world becuse of sereus 50-100 mg/hg/din fou dvded doses 50S bosoms subunit | baeteie tones “Tost Dose telted anemia, iesycrtc aplastic anemia, gray baby syndrome [OXAZOLIDINONES. + Unezald | Prevents bacteria poten | actostatcactivty | nfctlons caused by Cra Vs hepaticclexance hae Gh doved ‘yrthesisty Dndg tothe | agains: susceptible” | methelinvesitant ‘ce-dly Tony Duratlon-dependent bone 28S oosomal NA 0S | bacteria Saphyococl and vancomycin | marrow suppression newopathy,andoptie subunt reshtantenterocac ‘eu serotonin syndrome may occur when ‘coudminsteres th other serotonergic Sgt {eg selective serotonin reuptake nos) Teco Cra and longer half (12 so dosed anced creased potency versus starhyococc copreved for sein skin and sof tise nectionsSUMMARY Aminoglycosides ad ed Drug ron Effects Clinical Applications interactions AMINOGLYCOSIDES & SPECTINOMYCIN, * Gentamlcn | Prevensbaceris | Bacterial acy galt Sepsis caused by seroble | erenalclarance (raf. 25) sconvetonal proeinsymibests | suscepuble bacteria» synergistic Geamnegativebacteia | dosing 1-1. mg/g gh wih goal peak levels bybinding tothe | effects against Gampostve bacteia | «smegsticactay in | S-8mcy/mL. trough eves <2 meginL 305riboromal | whencombined with rectarsor | endocardtiscaused by | «oncedady dosing a 5-7 mgg as fective and subunit vencomycin-concentation- strptoczc staphyloceed, | may have ls toy than conventional dosing ‘dependent ling anda signtiant | and enterococe “Tory, Nephtancy (ever) totodaty postantbiote afct (reverse neuromuscular blockade + Tobramycintevenous ore active than gentamicin resus Pseudomonas ay aso have es neprotxcy + AmikacrIntavenousresstantt many eneymes that inactivate gentamicin andtebramycin; het dose and trget peaks and troughs than genamin and tobranycn + Streptomycin: iiramuscolr widespread reshtonce lent set specie heats suchas tubercles and enterococctendocrdts + Neorycin-Grt or topical oor beavelbiity used before bowel sugey to decrease aerobic fra + Specinomyciinvarusculr soe wes or teatmentofantbiote-esistent gonocaccalinctins or ganecocalinfectionsinpenklinalegic patients not avalable inthe ust MARY Sulfonamides, Trimethoprim, and Fluoroquinolones Pharmacokinetics, Toxicities, Subclass, Drug Ce Lae eee FOLATE ANTAGONISTS. + Threthoprin Symergitic combination of | Bacterial etity | Urinary tacinfectons soft | Oral N-renacesrance hal if h sullemethoaaole | felateantagoriss blocks | aganstsusceptbie | tisuernfecions-boneand | =¢oted every8-12 forulatedina purine roduction ard bacteria Jpheinfections-Pjroect” |S ratio fsfamethoraale to nucleic acd synthesis ‘meurreni-toxopasmosis | timethopsn Tork Rash, ever, bone ecards ‘martow suppression hyperalemia, ephotenicy| + Sulfadiazine Or fistne therapy for torplasmoss when combined wih primethamine *Timethoprin: ra sed alone ol fr leer wer) tact infections may bsfeyprescrbe o patents wth sufonamide aeray + Pyrmetherine Orkney fr toxoplasmosis when combined th sedlzane; code with leucovorin toni one marow todcty + Pyrimettaineslfacoxne Ora secondineralra teat FLUOROQUINOLONES + Ciprofloxacin Inhibits DNA replication by | Bactericidal activity | Urinary tactinfectons Orel, Ns med clearance baie 4h) bindeotoONA gyaseand | againstsusceptibe | -castroentetis dosed every 12h dvalnt and tivalent teposomerse bacteria sesteonyelis-arttrae | cations ingalroral absorption Toc: Gastrointestinal upset, neurtcacty, tendons + Levefoncln: Ora isomer ofofloxach once aly desig renal dearanc,‘esplatay"vorequirolne wlth improved actly versus poeumococus + Moxifocace: Or respttory”Muorauiolone:once ly dos: improved actinty versus anoerobes ond M tuberculoss hepatic derance resus in fowe urinary levels useinurnay tact infectonsisnetecoramended + Gemttoeacin: Oat ‘resictor'fucrouinoloneSUMMARY Sulfonamides, Trimethoprim, and Fluoroquinolones es Brae ieee aa uc Clinical Applications Interactions FOLATE ANTAGONISTS + Timethoprin Symerisiccombination of | Bactericidal acthity | Urinary tratinfections-soft | Oral V-renal clearance (life) sulfamethonzele | folate amagonstsblocts | aganstsuscoptble | vssueirfeciors -boneand | «dosed every8-12h: fermulstod ina purine production and bacteria joint infections» Pjrove’ | 5:1 ato of sifanethorazole to chi acd synthesis ppreumonia-tcreplasmosis | wimethopre Tony Rash, fv, bone rocarsose ‘marow suppression, hypertalem, nephvotanicy + Suen Ora esi therapy fo txoplasmoss wher combined wit pyrimethamine Trimethoprim: Oc: ued alone only frlower urinary ac infections my be sofeyereserbed to patients wh satonamdealery + Byrimethamine: Oro ostsne they fer toxoplsross wnen contired ih sulfates; oadminse ith kucovortn ln bane marrow ty + Brimethamine slledvine: Oak second Ire malaria weatnent FLUOROQUINOLONES: + Clprotocacn Inhibits DNA replication by | Bactericidal acety | Usnarytactinfections (fal V +m clearance (rate binding to DNAgyraseand | againstsuscestible | -gastroentertis «dosed every 12 divalent ae talent toposomerase bacea esteomyeltis antvax | cations impair oral absorption Toxin. Gastrointestinal upset. neurotoxic, tendonitis + Levofowacin Ora tomer ofofxccin,once- daly doting renal dearance;"espittory roquinolone wth improved ect versus peumcccis + Moutiexccn- Or; YespatrySuorequralone once daly dosing imeroved ectwity versus anceober nd M tuberculosis herctic clearence ests n lower urinary Teves so usehn urinary ra infectons isnot recommended + Geriflenacin: Ort "esiatoryfuoroauinaloneSUMMARY Antifungal Drugs See reakt Mileueinikadacliaeced POLYENE MACROLIDE + Amphotericin | Forms pores in fungal Loss ofinraceidh contents | Locales andsystenie | Oralforisnot absorbed for rmembranes(whicreontain | through poresis fungicidal | candidemia Crptococas | systemic use intrathecal forfuncal ergesao) but notin sbroadspectumetacion | -Hiteplarma-Bletomyces | meningitis topical for oodar ane ‘mammalian (holesterl- Coceidetdes-ssperus | baer infections «uration, d+ containing) membranes Tukey infusion actions onal ipaiment = terocons Additive with ‘other enaltoxicdrugs + Lipid formations Lower tay, higher doses can bevsed PYRIMIDINE ANALOG + Flustosie | Intefreswith ONAand AVA | Synertie with Cenpococu and (ral ution hous renal exon syivesssdectveyinking! | amphoceicn systemic | cvomobhstomyenss | «Ten Myelosppreson tonotynhos.duer@ NA | infections and ANA eects ‘AZOLES ~Ketoconazle | Blockfungl asvenzymes | Poo selective ato Grand pecrumbuttoxcy. | Oral topel-Txctyendinetens: are inert with intefereswth manmalan | restetsusetotepcal | Interferes wth stecidhormone crgesae syntess aso functon theapy symhess and phase | rug metatolsm -traconazie | Samessforketoconole | Muchmocestlectvettan | droadspecure Cardia, | OalandV- dation, 1-26- poor ety etoconaoie Gptoocu stones, | int central eres ster) covoditionyes, “Tencty diners Low tony Histplasmos + Fionn, vorconaraepesecenarole sannezele: ccrazolehar excelent CNS penton wed nfnga megs ECHINOCANDINS + Cspfungn | BlodksPfucansmiase | Pevenssymhesoffongal | Fungal Conta spas0 | W ony» dation 11-15 Txt: cela sed ergs Winr geste fect using +intrectons: creases cyosporine Tov (void combination) + Micnginanisaturan Mcafungin incase lero npn, yclosgerin slim; nidulans elately feof tisnteractn ALLYLAMINE “Terbinafine | Inhibits epenidaton of Recuces ergosterol Mucocutancoustungsl | Ol - duration, days Toy squalene mfung-inceased_ | = proventssymthess of Infeciens Gaswoiestial upset headache, Tess are tonctofunge | fungalcell memtyane bepatatoxcy sImerction None reportedBU aa es Subclass, Drug Mechanism of Action Effects Cay oa [NITROINIDAZOLE ‘+ Metronidazole | Otsnpton af secon | Bacteriil actwty | Anaerobic infections vagins | OrlorV+hepatic dlearance(, 8h) transport chain aginst suseptble | «Cafclecotis + disdcamke reaction when given with anaerobic bacteria nd aleshol Tv: Gastontstinal upset protazse ‘metalic taste- neuropathy seizes + Thidace Ort similar to retroniczle but dosed once daly opprved for ichomanas, las, and anebiois ‘MACROLIDE + Fdaxomicin | inibtsbacter AVA | acterdain tle cots Ora biood levels nelle Toy: abymerase Gran-postivebacters Nonspectic gastrointestinal upset IFAMYCIN. + Ridin Inhibits bacterial AWA | Bacterldaacvty in| Trav’ aarhea,hepate | Ort blood Ives nage» Touchy: polymerase Grarrposiveand | encephalopathy Clffele | Nausea Grarr-esatvebacteis_| coli irtable Bowel syndrome ‘URINARY ANTISEPTICS + Nitcuranion | Not fly understood Bacterostate or Uncomplicated uinay tact | Ora-ropid eral clearance (f,0.5h)- Blood ‘darts protelnsymthess | bactercdal actwty | infections «longtem levels are negligible» convalndested nena and hits mokiple agaistsisceptble | prophyleds fares Toi Gasoitestnal upset bacteralenzymesystems | bactera ‘neuropathies: hypersensivty pneumonitis + Metin ippraeanemetenarie mclaren ther sed on fps, nt emer, of arya nctonsTABLE 51-1 Empiric antimicrobial therapy based on microbiologicetiology. Suapectedor Proven Disease orPathogen Drage of it Choice ‘Alternative Drage “Gram-negative ccd ferobie) Moret ronhamela cotrhols “TWP-5Mz| cepalosprin uecond- Quinolone? macro! ‘etsera gonorhoeae Netsara meningitis Gram-negative rds (aerobic) £ cal Rebel, Proteus Enercbacer Grebe Serato Stiga Campybobocter un Hetcobocter ot so species Predomones coucinesa atholera cepacia lormety Prutomonos epee), Stencvophorene matophits ormesy Xanthomonas mato) Leglnalaseces Gram postive coed (aerobic) Strptcecespreuronioe Sreptcoceusprogenes laroup A) Streproceccsoalotioe (rou 8) iidanssrptocoec Sophococasaures [Btsctamase negate Bactamase postive eshte ‘Gram postive reds (aerobic) acs species ron-aerac) Lista speces Nocardia species Anaerobic bacteria Gram poste lst epoca, Aetnomyces, eposreprocaces) Css tte aces gis Fusobocterum, Preval, Porphyromonas orthia-generion™ Cetraxone, fame Penicin Cephulospotn into acon (generation! TWP SWZ "TWP intone caroapenen* uncle! Quinolone carisone Esttuomein orators sumone Proton pump inhibitor + amoxil *earthomyc| Tevacyline ‘Asipseutomonal penii + ‘aninogheesae™ wes! “we sue ‘axtromyein o quinolone! Peni Perici nda Peni (¢aminegycosie") Penvciin Pein Periclineseresitat peri? Yancomyen Pic + aminoglycoside! Yancomein -Ampictin aminoglycoside’ Saison TMP SN2" Plc cada Metroncale Metvoridasle cindy, pena Spectromycnatvomycn Chloramphenicol cfirasonecefocanine unclone aminoghosie? Anspueudomena pencil eminogiyeouise eeepie ‘TMP SZ ampiclin, acvonyeincefelnone Chlsempheriea ampli, TP. 5M2" “evap quinolone? Chleemphencal + sminagycoise! or W052" Bismuth + mewaniszoie+teracyctne + proton pump inhibitor Quinolone THF Sz! -Antpseudoronal pein: quinlons? cefepime, ‘etaidime anpseudomonal carbapeneno zreonan aminonlyosice’ Cehiime cero Minooylngtearclin-davulanate,Sgecying etasine, suoloe Canktomycn, enthromycin Desyeycing cefraxone,amipreumocaccal quncone” rytworycn cephalosporin fist ge oncom Cephelosorn iso hie generation vancomycin ton? Cephslosporin ist. generton vancomycin Pasko "MPS minacyce inezo, dopey oecyine Vancomycin + aminoglycoside! Imipenem, quinolone damn esi! ‘Minocyine imipenem, amis, ez Vancomycin catbapenem’ oranphenieal \oncomycn brecn Chloramphenicol crbapenem’ actam—Blscamase Inintor combinations einsamyjein Astor BagiPavcbaclny| Depsone amin | | | lathromycatwomycin | i i i “Teuacycine,athvomycin, cefttaxone [ ‘Aspegivs species Anpotarcn 8 iuaconaole, caspeturginkavuconazole onc oes “Amphotricin edinecndn'” —__Fuconaol, racanazoe vericonzole eects ins Amphoticin 8 Fuconaol, racnazee verconzole posaconzole ‘cracee (Meeps, Abid) Amphotwicin 8 Posaconzoeiavucorazle “Tmateprey sarah TMPSIZ ba mate clone par wien pts tie pet amhoazle “Toe grwaten cephscigons fcon ren rns aterce tnt epee, ene emo cpp cere rev usr cto ene a ceo foal mien. The gerrston epaliermeatasme een ckatre pater em [Satan ef poser fiber a etre loro Fast geneton epg cleme srero warns epee “cuoines byrne gemfoac leoteach moses erent oleae Nora rat flit wena stme beens Geran ‘eroncn ard nfnnan hae ecient acy pratense Coram and wrfoecn hare gs aly enn seman sete “Mugoidesactomencevonyen avon ebm ‘cena sectarian gentmc we aed at econ th Gam po ganas wher etary and arian edo a con wwihnm gater "cebiperems dabtoa, rape penn meopeer {rage inks tty spitenaocec Actas rd Panis “somerset. iperiivsbcian vewchn clone ‘steers an tanlest-2fr gale onthe Use of pel ean peumocacalmenngt "petra ool concn “mts novegimen a ey bce vncrenestan each heehee expe dtm as bate ety n ‘se fens thos nen eperes tobe taco oderarfon ornnwy vo netn poner rte ae dane, nea “aepatygumpn epmoandns tra casptinn mtonah