30307737 Pharmacology

≠CNS

Li

Vasopressin (HTN)

Aminoglutethimide

Trilostane (paresthesia)

Mitotane

≠Heart

Li

Vasopressin (HTN)

TH Agonists

Metyrapone (HTN)

Metformin

TZD

≠Lung

β Blockers

≠Liver

PTU

Ketoconazole

SU's (amide; uride; izide; iride)

TZD (troglitazones)

≠Chol

Methimazole

S'statin (g-stone)

≠GI

Somatostatin

Ketoconazole

Metyrapone

Tilostane

Mitotane

α-Glycosidase Inhibitors - Acarbose; MiglitolNausea / Vomit

≠Renal

SU's (amide; uride; izide; iride)

Metformin (lactic acidosis)

Acyclovir

↑K+

Spironolactone

Amiloride

Hydrochlorothiazide

↑Ca2+

Thiazides

≠Heme (bleed)

Spironolactone

Ketoconazole

GnRH (HA fx)

Hemolytic Anemia

Ribavirin

Megaloblastic Anemia

Zodovudine

≠Skin

Iodine (eruption)

Aminoglutethimide (rash)

≠Thyroid (itis)

Amiodarone

IFN / IL-2

≠Steroids/Adrenal Cortex

GI S.E.'s

Neuro S.E.'s

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYPENICILLINS PCN G = Strep pneumonia Bactericidal Hypersensitivity Rash PCN V = Grp A Strep (pharyngitis) Rx enters bacteria through porin AnaphylaxisPCN G (IV Form; Acid labile) Spirochetes (syphilis) A 1) Activates autolytic enzymes Hemolytic Anemia; Neutropenia 1/2 Life = 30 minutes A 2) Inhibits transpeptidase (PBP)PCN V (oral; Acid stabile) A No cross-linkage of cell wall Widespread PCN Resistance:

A 3) Inhibits cell wall synthesis β-lactamase cleavage of ringA Osmotic lysis of bacteria

PCNase-RESISTANT PCN's Staph aureus Inhibits cell wall synthesis Methicillin = I.S. nephritisSepsis; IE; Cellulitis = Nastycillin Meth Messes w/ Neph

Nafcillin (I.V.)Methicillin (I.V.) Nasty Messy OxOxacillin (Oral; I.V.)Ox Clocks Staph aureusDicloxacillin (Oral) Knocks it out!!

AMINO-PCN's Gram(+) - All Inhibits cell wall synthesis Hypersensitivity Rash (Ampicillin)Gram(-) Rods Colitis (Ampy-crampy; Colicky-amoxy)

Amoxicillin + Clavulanic acid Bronchitis; SinusitisAmpicillin + Clavulanic acid UTI's Clavulanic Acid --> Diarrhea

CA competitively inhibits β-lactamase HELPS kill entero's

TICARCILLIN Pseudomonas auruginosa Inhibits cell wall synthesis Hypersensitivity RashPIPERACILLIN Gram(-) RodsCARBINICILLIN Clavulanic Acid --> Diarrhea

Totally pseudo, dude."Toke the Pipe and Carb" + hit of Acid!Add Clavulanic acid

CEPHALOSPORINS Inhibits cell wall synthesis Hypersensitivity Rash 1st Generation Granulocytopenia1st Generation I.S. Nephritis Alex is in Alice is in Fn Group Us all in 2nd Generation ≠A-glycosides + Cephalosporin2nd Generation Fur ox β-Lactamase Resistance: Teets [use an] Cuts here β-lactamase cleavage of ring Ox tin MRSA3rd Generation 3rd Generation Enterococci X-BBB - Bacterial Meningitis

Gram(-) serious infections Gonorrhea (ceftriaxone)

4th Generation 4th Generation Cefepine Pseudomonas & Gram(+)

MONOBACTAMS Only Aerobic GNR's Inhibits cell wall synthesis Non-toxic (usually) Klebsiella GI Sx's (occasional)Aztreonam P. auruginosa

Serratia Peaceful Tree: Ok w/ Aminoglycosidesβ-Lactamase resistant Non-toxic (usually)Synergistic with Aminoglycosides Aerobic (GNR's) CARBAPENEMS Everything!!! Inhibits cell wall synthesis Seizures Skin rashImipenem + Cilastatin I'm A Pen = X all bugs out Cilistatin - ≠Dihydropeptidase GI distress

Hydrolized by Dihydropeptidase Dihydropeptidase (renal enzyme)Cilastatin inhibits above enzyme Most powerful bug drug out there A Metabolizes and inactivates imipenem

Meropenem Not hydrolized by Dihydropeptidase β-Lactamase resistant

β Lactam Rings

VANCOMYCIN Gram(+) Bactericidal Nephrotoxicity when used in combo Tx Staph aureus Binds to D-analyl-D-analine Vancomycin + aminoglycosideGlycopeptide (poorly absorbed) C. difficile A Inhibits peptidoglycan synthesis Red Neck Syndrome / Rash A Inhibits cell wall synthesis Rapid infusion"Vanc" the deaf red-neck cowboy Vancomycin Resistance Poorly absorbed A HA releaseA Kills Staph aureus and gut bugs Enterococci (plasma mediated) A Remains in gut and attacks GI bugs Ototoxicity

NastyMethy (messy)

Clocks SA

H Flu; E. Coli; List.; Prot.; Salm.

ProteusCephalexin E. coliCephalothin KlebsiellaCefazolin

H. Flu ProteusCefuroxime Enterobacter E. coliCefotetan Neisseria KlebsiellaCefoxitin Serratia

Ceftriaxone (oral) - AX 'em!!Cefotaxime - TAX 'em!!Ceftazidime - TAZ 'em!!Cefoperazone - Opera will kill too!! 1st = Pro Colie Klub

2nd = Pro Colie Klub+Sarra, Homo, Nice Aunt3rd = Serious bunch4th = Pseudo

Resistance: D-ala <-- D-lac; ↓Affinity

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITY

Cell Wall Inhibitors

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYAMINOGLYCOSIDES Aerobic GNR's (severe) Bactericidal Nephrotoxic O2 Required for uptake (aerobic orgs) Ototoxic

Aerobic organism produces metabs' Teratogen Amp-Gent Combo Tx!! A Alters membrane potential

A Allows uptake of Rx Grenade goes off A A Deaf A ≠Protein synthesis Hits kidney Ineffective Blocks initiation Anaerobes Misreading Resistance: Streptoccoci Early termination Modification of: H. Flu Acetylation

Neomycin (topical; not well-absorbed) Syphilis Adenylation Syngergistic with β-Lactams Phosphorylation

TETRACYCLINES Tet Offensive Dz's Bacteriostatic Deposited in growing bones A Stains teeth gray-brown to yellow

A Inhibits protein synthesis Inhibits bone growth in children A ≠Aminoacyl-tRNA attachment Fanconi syndrome when expired Acne Don't Take With

Milk PhotosensitivityAntacids

A Takes care of multiple diseases Fe2+ containing substances Think of newborn pups No Milk! Sharp gray-brown teeth Shut eyes (photosensitive) Resistance: ↓Uptake ↑Export

MACROLIDES Gram (+) Cocci Bacteriostatic Eosinophilia Streptoccoci

Px's w/ ≠PCN A Inhibits protein synthesis GI Nausea; Vomiting; Ab cramps 50c Big Mac Metallic taste (Clarithromycin) Chlamydia Cholestatic hepatitis (Erythromycin)

Neisseria Eat a Big Mac A GI upset + cholestatic hep

Panting = lung infection CAP Etiology Cardiac Thrusting = STD's Mycoplasma Arrhythmia (E'mycin + Terf)

Strep pneumonia Chlamydia Resistance:

Methylation of rRNA

CHLORAMPHENICOL Meningitis Bacteriostatic BM toxicity H. Flu Anemia (reversible)"Clears a meningitis Call" N. meningitis A Inhibits peptide bond formation Aplastic anemia (irreversible) S. pneumonia A Inhibits protein synthesis PancytopeniaOnly as alternative to: Anaerobes Gray Baby Syndrome PCN's Bacteroides fragilis ΦGlucuronidation Cephalosporins (3rd gen) Death Tetracycline in pregnancy Resistance: Modification of acetylation CLINDAMYCIN Anaerobes Bacteriostatic GI Clostridium Causes Pseudomembranous C.Cleans my sin[ister anaerobes] Bacteroides A Inhibits peptide bond formation Fever

Gunshot A Inhibits protein synthesis P. colitisClindamycin = ↑Diaphragm ≠O2 bugs AminoglycosidesMetronidazole = ↓Diaphragm ≠O2 bugs Clindamycin 50c for Linda Resistance Aspiration pneumonia Methylated rRNA -->no Rx binding STREPTOGRAMMINS Streptococci Bacteriostatic Myalgias Staphylococci ArthralgiasDalfopristin (Streptogrammin A) Enterococcus faecium (bact-static) A Inhibits protein synthesis PhlebitisQuinupristin (Streptogrammin B) Not E. Faecalis Bacteriocidal Resistance Strep A = Near site of Microlides Methylated rRNA -->no Rx binding Strep B = Overlaps with Microlides A Used together = synergistic A Bacteriocidal

Aerobes! (amine-O2-glycosides)"G-TANKS" w/ 30-ott Ammo

GentomycinTobramycin Rx binds to 30S RibosomeAmikacinNetilmicinKanamycinStreptomycin

The American Gent, TobyStrips "Neti" in the Kan

STD's - Chlamydia; Ureaplasma Binds 30S Ribosome subunitMinocycline Malaria - P. falciparum (doxy)Doxycycline (take w/ food; fecal elim) Tick-borne - Rickettsia; LymeDemeclocyline Diarrhea - Vibrio choleraTetracyclines

Bio-Rx - B. anthracis"Mine Doxy Demands 4 Tetes" (pups) Ellas - Pasteurella, etc.

Binds 50S (23S rRNA)AzithromycinClarithromycin Mycoplasma (#1 for CAP)Erythromycin Legionella (#1)Dirithromycin

"Big Mac ACED his women"

Binds 50S peptidyl transferase

Binds 50S ribosomal subunit

Binds 50S Ribosome subunit


RNA InhibitorsSULFANOMIDES - SMX TMP-S[MX] Bacteriostatic Displaces protein-bound Rx's (Warfarin) S.E. = Rare (common w/ AIDS Px's)Rotten eggs (oral) A ≠Folate synthesis HypersensitivityPorto-Potty (urinary excretion) A ≠Purine synthesis (bacterial)

A ≠DNA synthesis (bacterial) Hemolysis (if G6PD deficiency) A ≠Growth Blood / WBC abnormalities All Bacteria Nocardia Sulfanamide Resistance Chlamydia Altered target (plasmid-mediated) Malaria ↓Uptake: Impermeability to Rx ↑PABA synthesis UTI's PABA antimetabolite

TRIMETHOPRIM - TMP TMP-S[MX] Bacteriostatic BM Suppression Megaloblastic anemiaTMP + SMX Combo Tx A ≠Folate synthesis Leukopenia; Granulocytopenia

20-100x potency of sulfa TMP = Treats Marrow PoorlyDHFR (dihydrofolate reductase) Tx: Folinic acid

FLUOROQUINOLONES Aerobic GNR's Bactericidal S.E.'s Uncommon - Rare UTI's ≠DNA gyrase (Topoisomerase II)Quinolone A Inhibits DNA synthesis Tendonitis & Tendon ruptures

Nalidixic acid Neisseria Fluoroquinolones hurtsFluoroquinolones ≈Gram (+) Olfs are Gyrating (dancing) so much they Attachments to your bones Hurt their tendons

Headache; Dizzy GI Upset GI Upset Headaches; Dizziness Superinfections Rash

North Gate

Fluoroquinolone Resistance Mutation --> DNA gyrase / T.I.

METRONIDAZOLE Anaerobes Bactericidal ≠Alcohol! Bacteroides fragilis Forms toxic metabolites in cell wall A Disulfiram-like reaction with alcoholClindamycin = ↑Diaphragm ≠O2 bugs Clostridium difficile A Alters cell membrane e-potential HeadacheMetronidazole = ↓Diaphragm ≠O2 bugsProtozoa

Kills bugs in GI tract lumen On the metro:No drinking alcohol!Metallic taste (of train water)GI Upset (from motion)

Gee your aunt's guard tricked meto get on the metro

3X Tx (H, pylori)Metro + Amoxicillin + Bismuth

Tetracycline + PPI + Bismuth

POLYMIXINS / POLYPEPTIDES Resistant Gram (-) Cationic, basic proteins Neurotoxicity A Act like detergents Acute renal tubular necrosisPolymixin B

Colistin A Bind to cell membrane

Polymixin E A Disrupt osmotic integrity Polymixin Resistance Proteus

SerratiaImpermeable cell wallsA Rx cannot reach target

Tree (respiratory) ≠Dihydropteroate SynthaseMouth - GI tractPee - UTI; Urethritis; Prostatitis Nephrotoxicity; Kernicterus (infants)Syndrome Dz's - Toxo; PCP; I. Bella

Burns (silver sulfadiazine)

Tree (respiratory) - PCP ≠Dihydrofolate Reductase InhibitorMouth - GI tract (shig.; salm.)Pee - UTI (recurrent); UrethritisSyndrome - Toxo; PCP; I. Bella TrimethopRim = Reductase

Sulfanomide = Synthase

Pseudomonas - Cipro

Ciprofloxacin To See ProSparfloxacin SparingMortifloxacin MortifiesEnoxacin EnoughOfloxacin Olfs of theNorfloxacinGatifloxacin

Giardia (flagellate)EntamoebaGardnerella vaginalisTrichomonas (flagellate)


MISC. ANTIBIOTICSISONIAZID - INH TB ↓Mycolic acid synthesis Neurotoxicity (Tx = Pyridoxine [B6]) Solo prophylaxis Hepatotoxicity

SLE-like syndrome Hemolysis (if G6PD)

INH = Injures Neurons and Hepatocytes RIFAMPIN M. TB; M. avian ≠DNA-dependent RNA polymerase Hepatotoxic (P450) Leprosy4 R's

Always used in combo with other Rx's

Meningococcal prophylaxisH. Flu B prophylaxis

RNA polymerase inhibitorRevs up microsomal P450Red/orange body fluidsResistance (rapid) if used alone


TB DRUGS

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYBACTERIAL PROPHYLAXIS

Rifampin (1st line); Minocycline MeningococcalCeftriaxone GonorrheaPCN G SyphilisTMP/SMX Recurrent UTI'sTMP/SMX (1st line); Pentamidine PCPFluconazole Crypto prophylaxis / management

ANAEROBES

PCN + Clavulanic AcidCephalosporins (2nd Gen)ImipenemChloramphenicalClindamycinMetronidazoleOfloxacin

PSEUDOMONAS

TicarcillinPipercillinCarbenicillinCephalosporins (3rd Gen)ImipenemAztreonamQuinolones (Cipro)Aminoglycosides - Gent; Tobra; Amik

GRAM (+) TOUGHIES

Vancomycin MRSA; Staph; EnterosAmpicillin EnterosImipenem Enteros


Tough Bug Drugs

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYAMPHOTERICIN B Systemic Mycoses Binds to membrane ergosterols >> Chol. "Ampho-terrible" Cryptococcus A Forms pore in fungal cell membrane Fever; Chills = Shake & Bake (44%)I.V. Blastomyces A ↑Permeability & leakage of e'lytes Nausea; Vomiting; Ab. pain; Anorexia Not absorbed IM or orally Coccidioides A ≠Homeostasis Phlebitis (common)

≠Cross BBB Aspergillus A Cell death Heparin controls this S.E.t1/2 = 1 day Histoplasma Anemia (common)

Intrathecal Candida albicans "AmphoTears holes in membranes" Nephrotoxicity (common)Fungal meningites (rare) Mucor mycoses Monitor K+, Mg++, BUN, CRE, A-B

↓K+emia

NYSTATIN Oral Candidiasis Binds to membrane ergosterols >> Chol. A Forms pore in fungal cell membraneSwish and swallow A ↑Permeability A ≠Homeostasis A Cell death IMIDAZOLE DERIVATIVES #1 Itraconazole > Ketocanazole C14 demethylase inhibitors (via P450) Hormone synthesis inhibition Blastomycoses A ≠ Ergosterol & FA synthesis in wall A Gynecomastia (Keto)Itraconazole Cociidioides A ↑Permeability & leakage of e'lytes Liver dysfunction (via ≠P450)Ketocanazole (No Amp B!) Histoplasma A ≠Homeostasis Fever; ChillsFluconazole (X-BBB) Candidiasis (mucocutaneous) A Cell death Nausea; AnorexiaClotrimazole HypercortisolismVoriconazole Fluconazole Combo Tx - Anti-HAMiconazole (topical) Cryptococcal meningitis (L. term) A Q-T interval prolongation

Crypto prophylaxis (AIDS) A Torsade de Pointes Candida albicans Voriconazole

H2 acids or antacids ↓absorption Voriconazole / Itraconazole Visual disturbances (30min after Tx)Liver metabolism Aspergillosis!! AWarn Px's if driving,etc.

Clotrimazole / Miconazole Dermatophytosis Resistance Related to efflux pump

GRISEOFULVIN Superficial infections ≠Microtubule function Deposits in kertin-containing tissues Dermatophytes A ≠Mitosis Teratogenic / CarcinogenicOral Tx Tinea Ringworm ↑Warfarin metabolismGrizzlies are full of ringworm & tinea Grizzlies interfere with might! (mitosis)

CASPOFUNGIN Aspergillosis Inhibits Beta(1-3) glucan synthesis Well-tolerated In amphotericin intolerant Px's A Fungal cell wall disruption HA release possibleIV only Candidiasis↓Renal excretion Disseminated↓Liver metabolism No P450 Highly protein bound 5-FLUORO-CYTOSINE - 5-FC Chromomycosis RX entry into yeast cell (cytosine permease) BM suppression (#1 problem)

Candida A 5-FC --> 5-FU (via cytosine deaminase) Diarrhea (10%)Combo Tx (mostly) Aspergillosis A 5-FU inhibits transcription of RNA Watch renal failure Px's

5-FC + Ampho B Cryptococcal A Blocks tymidylate synthetaseA Stops DNA synthesis Resistance

Loss of permease or deaminaseCrypto

CNS: Headaches; Confusion


Anti-Fungal Rx's

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYIVERMECTIN Onchocerciasis (River blindness) Kills microfilariae Black flies ≠Microfilariae from leaving uteri of worms"rIVER blindness" A Fibrous nodules"rIVER es muy ancho" A Lizard skin

MEBENDAZOLE Nematode / Roundworm Paralyzes wormTHIOBENDAZOLE Whipworm A Passes out stool Pinworm"Bendy, like worms"

PYRANTEL PAMOATE Giant roundworm (Ascaris) Pinworm (Enterobius)"Pray tell, PAM ATE a GIANT WORM!!"Hookworm (Necator/Ancylostoma)

Toe rash --> Lung --> GIFe2+ def. Anemia; Wt. Loss

PRAZIQUANTEL Cysticercosis Broad spectrum antiparasitic Schistosomiasis (flukes)Praze tha Lord: Paragonimus"Christ's Sister Schisto Clonorchisis a Paragon Clone" All tapeworms

NICLOSAMIDE Cestode (tapeworm) ≠Mitochondrial Ox-Phos D. latum ≠GLU uptake by parasite

Hymenolepsis nana Toad with nickle tape Taenia solium (#2 Rx)A Making a "teeny lata"

PENTAVALENT ANTIMONY Leishmania "Leechman is Anti-Money" ie he will leech off you

CHLOROQUINE Malaria (chloroquine) P. falciparum = AggressiveQUININE vivax Human resistance to Vivax & Falciparim A 30% of RBC'sMEFLOQUINE ovale Vivax = ΦDuffy a + b Mefloquine resistant malariae Falcip: SSD-->rupture-->Φinfxn Chloroquine resistant Quinine (if chloro-resistant) Quinine resistant Tx = Artemethol for severe P. falc.PRIMAQUINE Malara (latent hypnozoite--liver) Exo-RBC cycle: vivax; ovale Chloroquine resistant Plasmodium vivax A Liver Hemolysis in G6PDPrima Viva Ova!! Plasmodium ovale GI upset

METRONIDAZOLE Giardia Metallic taste Entameba histolyticaSitting on the METRO gives you Gardnerella vaginalis Diarrhea Trichomonas (nasty vadge discharge)

Vadge infections"Gee-ur Aunt's Guard Tricked me to get on the metro"

PENTAMIDINE Prophylaxis: Pneumocystis carinii pneumonio I'm all Pent up I might die [AIDS PCP]

NIFURTIMOX Chagas Dz (Trypanosoma cruzi) SURAMIN Sleeping sickness (African tryp) Tripanosomiasis (tsetse fly)" I Sure Am Sleepy; I might trip"

"Nickle = ¢es-toad / Tapeworm"


Antiparasitics

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYAMANTADINE Influenza A (prophylaxis) ≠Viral penetration / uncoating CNS Parkinson's Dz Ataxia

Rubella Dizziness He has A Flu (sneeze on your dish) Slurred speech

He's got Parkinson's (throw food)He's dizzy, ataxic, slurring

ZANAMIVIR Influenza Virus A ≠Influenza Neuraminidase Bronchoconstriction (asthma)Zanamivir (inhaled) Influenza Virus B A Use Oseltamivir, not ZanamivirOseltamivir (oral) ≠Asthmatics (use Oseltamivir)

RIBAVIRIN RSV ≠IMP dehydrogenase Hemolytic anemia A ≠Synthesis of guanine nucleotides Teratogen (severe)!!Ribavirin is rabid

Eats the IMPRabid and bloody (hemolytic)

ACYCLOVIR HSV Phosphorylated by viral thymidine kinase Delerium VZV A Diphosphate --> Triphosphate (active) TremorA cycle of Di-p --> Tri-p --> ≠DNA EBV A Competes w/ Deoxyguanose TRFP NephrotoxicityZovirax Prophylaxis (compromised Px's) A ≠Viral HSV DNA polymeraseACV A ≠DNA synthesisValacyclovir (pro-drug)

FAMCYCLOVIR HSV-1 (labialis) Potent inhibitor of HBV DNA P-ase Rarely side effects Denavir cream (oral) A Nucleoside Analogue Headache; NauseaZovirax HSV-2 A Deacylated + oxidized in liverACV Acute (3x/day) A Converted to PencyclovirValacyclovir (pro-drug) Recurrent; Suppression (2x/day) A Taken up by infected cells

VZV (3x/day) A Phosphorylated by viral TKHBV A ↑Affinity for P-ase

GANCICLOVIR CMV Phosphorylated by viral thymidine kinase Leukopenia; Thrombocytopenia A ≠Viral CMV DNA polymerase Nephrotoxicity"C MoVe the GAN GAN (kankan)"

Toxicity: Ganciclovir > AcyclovirDHPG (dihydroxy-2-propoxymethyl guanine)GCV GCSF: G'cyle stim. FactorCtyoveneValgancyclovir (pro-drug)

FOSCARNET Use when Ganciclovir fails Binds to pyrophosphate binding site ≠E'lytes CMV A ≠Viral CMV DNA polymerase ThrombophlebitisIV only CMV retinitis in immunocomrpomised

No need for phosphorylationFoscavir

INTERFERONS HBV (chronic) ≠Viral RNA and DNA synthesis Neutropenia HBC (cronic)Glycoproteins from Leukocytes Kaposi's Sarcoma

Don't ask "a man to dine" with you if:

Rimantidine = derivative w/ few S.E.'s

RSV (RibaVirin)

Resistance: CMV

Pyrophosphate analog (Foscarnet)


Antivirals

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYBETHANECHOL Ileus (Post-op / Neuro) Cholinergic Agonist Urinary Retention (Post-op / Neuro) Activates bowel + bladder smooth muscle"Bet you it's In the colin (retention)" CARBACHOL Glaucoma Cholinergic AgonistPILOCARPINE Activates ciliary muscle of eye (open angle) Activates Pupillary sphincter (narrow angle)

DIRECT AGONISTS

NEOSTIGMINE Myesthenia gravis Carbamylation of AnticholinesteraseOral; Injection Ileus (Post-op / Neuro) A ≠ACh -Esterase

Urinary Retention (Post-op / Neuro) A ↑Ach (endogenous)Antidote - NMJ blockade

PYRIDOSTIGMINE Myesthenia gravis Carbamylation of AnticholinesteraseOral A ≠ACh -EsteraseInjection A ↑Ach (endogenous)

A ↑StrengthEDROPHONIUM Dx of Myesthenia gravis Anticholinesterase / Cholinesterase inhibitor

ie v. short acting A ↑Ach (endogenous)

PHYSOSTIGMINE Glaucoma (crosses BBB) Anticholinesterase / Cholinesterase inhibitorEye drops Atropine overdose A ↑Ach (endogenous)OintmentPhyso for my Eyes, Oh! "Eyes are 'fizzing' from pressure"

ECHOTHIOPHATE Glaucoma Anticholinesterase / Cholinesterase inhibitor"Echothio = Echo in my eye, Oh!" Esotropia (X-eyed) A ↑Ach (endogenous)DemelariumIsoflurophate INDIRECT AGONISTS

PRALIDOXIME Antidote - ACh-Esterase Toxicity ACh-Esterase RegeneratorAntidote - Pesticides; Nerve gas

Pray + Lie = Doxology of DUMBBELLS

Injection

ACh-E ANTIDOTE

ATROPINE Muscarinic Antagonist Red as a beat - ↑Temperature; Pulse Dilate pupil Hot as a hare - ↑Temperature; Pulse"A troop blocking SLUD" ↓Secretions (Acid; Airway) Dry as a bone - Dry mouth / Flushed

Mad as a hatter; Hot as a hare ↓GI Motility Mad as a hatter - DisorientationDry as a bone; Blind as a bat Tx organophosphate poisoning Blind as a bat - Cycloplegia; Mydriasis

HEXAMETHONIUM Nicotinic Antagonist Ganglionic blocker

ANTIMUSCARINICS - R-BLOCK

BENZTROPINE Parkinson's Anti-Muscarinic"Park the Benz - Slowly and smoothly" Tx Sx's of Reserpine; Haloperidol Anti-Dyskinetic (↓Stiffness)

SCOPOLAMINE Motion Sickness Anti-Muscarinic Pupil Dilator

ANTIMUSCARINICS - CNS

HOMATROPINE Pupil Dilator Anti-Muscarinic Mydriasis Uveitis Cycloplegia

Post-synechiae (iris sticks to cornea)TROPICAMIDE Pupil Dilator Anti-Muscarinic MydriasisEye drops Uveitis CycloplegiaOintment Post-synechiae (iris sticks to cornea) ANTIMUSCARINICS - EYE

IPRATROPIUM Asthma Anti-MuscarinicInhalant COPD Bronchodilator

ANTIMUSCARINICS - LUNG

DiarrheaUrinationMiosisBronchospasmBradycardiaExcitation of skeletal muscleLacrimationSweatingSalivation

SalivationLacrimationUrinationDefecation


CholinergicsSUCCINYLCHOLINE Muscle paralysis in: Neuromuscular blockade (depolarizing)

SurgeryIt "sucks" to be paralyzed Mechanical ventilation Antidote = None

Antidote = Neostigmine

X-CUR-X Muscle paralysis in: Neuromuscular blockade (non-depolarizing)Surgery Antidote = Neostigmine; Edrophonium

Tubocurarine Mechanical ventilation PyridostigmineAtracuriumMivacuriumPancuroniumVecuroniumRapacuronium

NEUROMUSCULAR BLOCKADE

DANTROLENE Halothane + Succinylcholine ≠Ca2+ release from SR of skeletal muscleA Malignant hyperthermia

"Gets Dan to Lean (relax from rigidity)" Antipsychotic Rx (Phenothiazines)A Neuroleptic Malignant Syndrome

Phase I - Prolonged depolarization

Phase II - Repolarized, but blocked


NM BlockadeEPINEPHRINE Anaphylaxis Agonist (direct)

Asthma α1; α2; β1; β2Epidemic: It gets all the receptors Hypotension

Glaucoma (open angle)NOREPINEPHRINE Hypotension Agonist (direct) ↓Renal perfusion

α1; α2; β1Near-Epidemic: Almost gets all receptorsBut it be too (β2) weak

ISOPROTERENOL AV Block (rare use) Agonist (direct)β1 = β2

Iso = Equal; Erenol = β Agonist ≈No α effects

DOPAMINE Shock (DA --> ↑Renal perfusion) Agonist (direct)Heart failure D1 = D2; > β > α

DOPA = DDβα

DOBUTAMINE Shock Agonist (direct)Heart failure β2 > β1

X-BU-X = β2 > β1CATECHOLAMINES

AMPHETAMINE ADD Agonist (indirect)Obesity Releases stored catecholamines

Aderol Narcolepsy A α1; α2; β1; β2

EPHEDRINE Nasal Congestion Agonist (indirect)Urinary incontinence Releases stored catecholamines

Eep! Head run Hypotension A α1; α2; β1; β2Head run = head:snot; dick:urine A Constricts (no fluid flow)

Pseudophed CATECHOLAMINES

PHENYLEPHRINE Hypotension Agonist (direct)Nasal Congestion α1 > α2

≈NE Eye exam (Pupil dilator)α AGONIST

ALBUTEROL Asthma Agonist (direct)TERBUTALINE β2 > β1

X-BU-X = β2 > β1β AGONIST

COCAINE Local anesthesia ≠Re-Uptake of Chatecholamine VasoconstrictionA Agonist (indirect) Tachycardia; Arrhythmias

CLONIDINE α Agonist (central)α-METHYLDOPA

A ↓Central adrenergic outflow"Clones NE" (fakes presynaptic-R's)

OTHER

α1 B.V. Vasoconstriction

α2 B.V. Vasoconstriction

Pre-Synaptic ≠NE Release - (-) Feedback

β1 Heart ↑HR

β2 Bronchial BronchodilationSmooth M.

Skeletal M. ??Arterioles


SympathomimeticsPHENOXYBENZAMINE Pheochromocytoma - HTN Non-Selective Blocker Irreversible

α Irreversible Orthostatic Hypo-TN"Pheno = Pheo" Reflex tachycardia

PHENTOLAMINE Pheochromocytoma - HTN Non-Selective Blocker Reversibleα Reversible Orthostatic Hypo-TN

"Phento = Pheo" Reflex tachycardia

X-ZOSINS HTN α1-Selective Blocker 1st-Dose Orthostatic Hypo-TNBPH urinary retention Dizziness

Zosin - Sauce In; HTN Headache

PrazosinTerazosinDoxazosin

YOHIMBINE Impotence (controversial) α2-Selective Blocker Arrhythmias (no (-) feedback)

α-BLOCKERS

β-BLOCKERS (X-OLOL) HTN ↓CO; ↓Renin secretion ImpotenceAngina pectoris ↓HR; ↓Contractility --> ↓O2 demand Asthma exacerbation

Non-Selective Blockers MI ↓HR; ↓Contractility --> ↓O2 demand; ↓Death Bradycardia; AV block; CHFPropranolol SVT (propranolol; esmolol) ↓AV conduction velocity CNS: Sedation; ΔSleep; ≠DiabeticsPindolol CHF ↓Progression to CHFTimolol Glaucoma ↓Secretion of aqueous humorNadololLabetalol

β1-Selective Blockers

"A BEAM of β1's"

β-BLOCKERS

AtenololBetaxololEsmololAcebutololMetoprolol


Sympathetic Blockers

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYBARBITURATES (BARBITALS) Sedative ↑Cl- channel open duration Dependence Anxiety A ↓Neuronal firing CNS depression w/ alcohol --> DeathPhenobarbital Seizures A GABAa facilitator Cyt. P450 - Rx interactionsPentobarbital InsomniaThiopental Anesthesia induction (thiopental)Secobarbital

≠PorphyriaBENZODIAZEPINES (EPAMS) Anxiety ↑Cl- channel open duration Sedation Spasticity A ↓Neuronal firing DependenceDiazepam Status epilepticus (diazepam) A GABAa facilitator CNS depression w/ alcohol --> DeathLorazepam Detoxification (delerium tremens) Benzo's < Barb's in CNS depressionTemazepam ie respiratory depressionChlordiazepoxide Insomnia Flumazenil (overdose Tx)

≠GABA-r (competitive antagonist)Short-Acting

like "TOM's thumb"Tri = three

↑Frequency

ANTIPSYCHOTICS Schizophrenia (excess DA) ≠D2-r Sedation; Extrapyramidal S.E.'s Psychosis Endocrine S.E.'s"Clears thy halo fluff, Psycho!" Neuroleptic Malignant Syndrome ≠Muscarinic-r's; ≠HA-r's; ≠α-r's

Rigidity; Autonomic instability; HyperreflexChlorpromazine Tardive dyskiniesia Dystopnia (4 hrs)Thioridazine Stereotyped oral-facial mvnts (chr. use) A Akinesia (4 days)Haloperidol A Akathisia (3 wks)Fluphenazine A Tardive dyskinesia (4 mos)

ATYPICAL ANTIPSYCHOTICS Schizophrenia - (+) & (-) Sx's ≠5HT2-r's + ≠DA-r's Fewer extrapyramidal S.E.'s Olanzapine O lands! OCD (olanzapine) Clozapine = agranulocytosis (monitor)Clozapine A Close! Anxiety (olanzapine)Risperidone A respite! Depression (olanzapine)

LITHIUM Bipolar affective disorder ??PIP Cascade?? Tremor Acute manic events (≠relapse) Hypothyroidism Mood stabilizer Polyuria (ADH antagonist) Teratogen / Toxic!

TRICYCLIC ANTIDEPRESSANT Depression ≠NE & SE reuptake Sedation(IPRAMINE; TRIPTYLINE) Bed wetting (imipramine) α-Blocking S.E.'s

OCD (clomipramine) Anticholinergic S.E.'sHoly trinity / TRI-C TRI - C'sNor trippingDoxology ClompingAm IDesciple 3' > 2' (Amitriptyline > Nortriptyline)

Desipramine is least sedating

SSRI's Depression ≠SE reuptake (serotonin-specific) SSRI's < TCA's 2-3 wks for effectFluoxetine Nausea; VomitingSertraline Serotonin Syndrome w/ MAOI'sParoxetine Hyperthermia; Rigidity; CV collapseCitalopram

HETEROCYCLICS Major depressive disorders

Heterosexuals Depression; α2 Antagonist --> ↑NE & SE release; 5HT2-r antogonistSedation; ↑Cholesterol; ↑Appetite"Mirt & Bupee Depression; Smoking cessation ??? Tachycardia; Dry mouth; PsychosisVem la pra Tranzar" Depression; Anxiety disorder ≠DA & SE reuptake; 5HT2-r antagonist Anxiety; Agitation; Headache; Insomnia

Depression; ≠SE reuptake Sedation; Nausea; Priapism; HypoTN

Barbiturates ↑DURATion of Cl- ch.

Overdose Tx = Flumazenil

TriazolamOxazepamMidazolam

Frenzodiazepines (FREquent)

Nortriptyline (2')Doxepin ConvulsionsClomipramine ComaAmitriptyline (3') Cardiotoxicity (arrhythmias)ImipramineDesipramine

CNS - Anxiety; Insomnia; Tremor

MirtazapineBuproprionVenlafaxineTrazodone


CNS Rx'sMOA INHIBITORS (GENERAL) Atypical depressions ≠Monoamine Oxidase Inhibition MAO I + Tyramine + Meperidine Depression + Psychosis A ↓Degredation of monamines A HTN crisisPhenylzine Depression + Phobias CNS stimulationTranylcypromine Anxiety ≠SSRI's; ≠β-Agonists

HypochondriasisMAO-B INHIBITOR Parkinson's adjuvant Rx ≠MAO-B selective inhibition Enhances L-DOPA S.E.'s L-DOPA + Selegiline A ↑DA availabilitySelegiline (Deprenyl)

L-DOPA + CARBIDOPA Parkinson's L-DOPA Arrhythmias (from periferal conversion)L-DOPA crosses BBB DyskinesiasA Dopa decarboxylase conversionA DA (in brain)

Carbidopa≠Dopa decarboxylase in peripheryA ↓S.E.'s; ↑Bioavailability of DA in brain

OPIOID ANALGESICS Pain Opioid-r Agonists AddictionCough (dextromethorphan) mu = morphine CNS depression

"MMM, Dexter Fenan's Code is Heroin"Diarrhea (loperamide; diphenoxylate) delta = enkephalin Respiratory distressAcute pulmonary edema kappa = dynorphin Pinpoint pupilsWithdrawal (methadone) Modulate synaptic transmission Constipation

Toxicity AntidoteNaloxoneNaltrexone

Heroin

SUMATRIPTAN Acute migraine 5-HT1d Agonist Chest discomfortCluster headache attacks 1/2 life < 2 hrs Mild tingling

A Headaches; Migraines ≠Prinzmetal's Angina; ≠CAD

ONDANSETRON Vomiting (control) 5-HT3 Antagonist HeadachePost-op vomit control A Central-acting anti-emetic Diarrhea

"On Dan it runs (vomit)" Cancer Tx vomit control

MorphineMeperidineMethadoneDextromethorphanFentanylCodeine

I assume a trip and you 5HiT your head


CNS Rx'sPHENYTOIN Grand mal seizures ≠Na+ Channels (use-dependent) Nystagmus; Diploplia

Ataxia; Peripheral neuropathy"Fee Na+ To In" Lethargy; Megaloblastic Anemia (↓B12)

Na+ has a fee to enter so it can't Gingival hyperplasiaHirsutismTeratogenic - Fetal hydantoin syndrome


CNS Rx's

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYACETAZOLAMIDE Glaucoma ≠Carbonic anhydrase in PCT Acidosis (hyperchloremic metabolic) Alkalosis (metabolic; urinary) A NaHCO3 diureses Neuropathy"Aceta acidifies" Altitude sickness A HCO3 excretion NH3 toxicity Sulfa allergy

"Aceta acidifies"

FEROSEMIDE Edema (CHF; Cirrhosis; Pulm) ≠Na+ / K+ / 2Cl- Cotransporter in TAL ↓K+-emia HTN A ↓Hypertonicity of medulla ↓Ca2+-emiaSulfonamide loop diuretic ↑Ca2+-emia A ≠Concentration of urine Ototoxicity

A Diuresis / Dilute urine I.S. NephritisA ↑Na+ to DT --> K+ swapping Allergy (sulfa)A ↓K+-emia Gout

A ↑Ca2+ excretion --> ↓Ca2+-emia Dehydration

ETHACRYNIC ACID Edema ≠Na+ / K+ / 2Cl- Cotransporter in TAL ↓K+-emia HTN A ↓Hypertonicity of medulla ↓Ca2+-emiaPhenoxyacetic acid derivative ↑Ca2+-emia A ≠Concentration of urine OtotoxicityNot sulfonamide A Diuresis / Dilute urine I.S. Nephritis

NOTE: A ↑Na+ to DT --> K+ swapping Dehydration"Ferocious Etha cryin" cuz Diuresis in Px's w/ sulfa allergies A ↓K+-emia No uricemia (no gout)she got sulfa allergies A ↑Ca2+ excretion --> ↓Ca2+-emia No sulfa allergies

HYDROCHLOROTHIAZIDE HTN ≠NaCl reabsorption in early DT ↓K+ metabolic alkalosis CHF A ↓Diluting capacity of nephron ↓Na+emiaThiazide diuretic ↑Ca2+uria A ↓Ca2+ excretion ↑Ca2+emia Nephrogenic Diabetes Insipidus ↑GLU HyperGLUC

↑Lipids↑UricemiaSulfa allergy

K+ SPARING DIURETICS ↑ALD Competitively binds ALD-r in CCT (Spiro) ↑K+emia K+ Depletion ≠Na+ channel in CCT (Triam; Amilo) Endocrine effects - gynecomastia"Try and Sprint A mile" - Km sparing CHF Blocks ALD --> backflow

MANNITOL Shock Osmotic Diuretic Pulmonary edemaDrug overdose DehydrationIntraocular pressure (decreases it)

≠Anuria≠CHF

DIURETIC E'LYTE CHANGES URINE BLOOD Carbonic Anhydrase Inhibitors ↑NaCl (All) ↓pH (acidosis) - Carb-A Inhib.; K+ sparingK+ Sparing ↑K+ (except K+ sparing) ↑pH (alkalosis) - Loops; ThiazidesLoops ↑Ca2+ (loops)Thiazides ↓Ca2+ (thiazides)

TriamtereneSpironolactoneAmiloride


Diureticsβ-BLOCKERS Impotence

Bronchospasmβ1 Selectivity (heart only) HTN ↓CO; ↓Renin Bradycardia; AV block Angina ↓HR; ↓Contractility Sedation; Sleep alterations MI ↓Mortality ↑TG's and ↓HDL SVT ↓AV conduction velocity

CHF ↓Progression Glaucoma ↓Secretion

β1 = β2 Propranolol ≠Asthma Pindolol !Diabetics! Nadolol Labetalol

↓cAMP A ↓Ca2+ influx A ↓HR, Contractility A ↑Refractory period

HYDRALAZINE HTN (severe) ↑cGMP Nausea; Headache CHF A Smooth muscle relaxation Hypotension; Reflex tachycardia"Hydra-relaxing" A Arterioles > Veins Relaxation Fluid retention A ↓Afterload SLE-like syndrome

Hydra (H2O-retention)

ACE INHIBITORS HTN ≠Antiotensin-converting enzyme CHFCaptopril Diabetic Renal Dz Angiotensin IEnalaprilLisinopril ACE

Angiotensin II-R Antagonist ↓AT IILosartan (no cough S.E.) A ≠Vasoconstriction

≠↑Na+/H2O≠↓Bradykinin Hyperkalemia≠↓Sympathetics

A ↑Renin release (compensatory) CAPTOPRIL

NITRATES Angina NO release from smooth muscle TachycardiaEdema (pulmonary) A ↑cGMP Hypotension

Nitroglycerin Aphrodesiac; Erection enhancer A Smooth muscle relaxation "Monday Dz"Isosorbide Dinitrate A Vasodilation (veins > arteries) Tolerance during work week

Intolerance on weekendsA Tachycardia

Dizziness; Headache

GLYCOSIDES CHF ≠Na+/K+ ATPase Nausea; Vomiting; DiarrheaAtrial Fib A ↑Na+ I.C. Blurry yellow vision (Van Gogh)

Digoxin A Na+ / Ca2+ swap Arrhythmia75% bioavailability 25% protein-bound Renal Failuret1/2 = 3 days A ↓ExcretionPeed out A ↑Risk for toxicity

↑K+ A Potentiates glycosides --> Toxic!! Quinidine A ↓Clearance of digoxin

↑Na+ (IC) Anti-dig Fab fragmentsA ↑Ca2+ (IC)

PHOSPHODIESTERASE INHIB

AtenololBetaxololEsmololAcebutololMetoprolol

CoughAngio-edemaProteinuriaTaste changesHypO-TNPregnancy problems (fetal renal injury)RashIncreased ReninLower A-II

Antidote = K+; Lidocaine; Pacer;

Na+

K+

Ca2+

Na+ Na+ Na+ Na+ Na+

Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Na+ Ca2+ Ca2+

Na+ Na+ Na+ Na+

ATP

cAMP

β1

AMP

P-Diesterase

ATP

cAMP

β1

Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+

P


CardiovascularCLASS IA Atrial arrythmias Local anasthetics Quinidine:

Ventricular arrhythmias ↓ / ≠ Conduction Headache; TinnitusQuinidine Queen A ↓Slope of phase 4 depolarization ThrombocytopeniaAmiodarone Amy A ↑Threshold in abnormal pacemaker cells Torsade de pointes (↑QT)Procainamide Proclaims Slectively depress frequent depolarizers Procainamide:Disopyramide Dis Ol' pyramid SLE-like syndrome (reversible)

≠K+ ChannelA ↑K+ (IC)A ↑↑Repol.A ↑PR

↑QRS↑↑QT

CLASS IB Acute ventricular arrhythmias ↓AP duration Local anestheticPost-MI A Affects ischemic or depolarized CNS stimulation/depression

Lidocaine Digitalis-induced arrhythmias Ventricula tissue Cardiovascular depressionMexiletine Purkinje tissueTocainide

CLASS IC Last resort b/c of toxicities ProarrhythmicVentricular Tach / Fib

Flecainide SVT (intractable)Encainide No effect on AP durationPropafenone

CLASS II - β-BLOCKERS Suppress abnormal pacemakers ↓caMP; ↓Ca2+ currentsA ↓Phase 4 slope

Esmolol (short acting) Esmo A ↓Abnormal pacemakersMetoprolol Met A ↑PR intervalTimolol Tim AV Node sensitiveAtenolol A 10Propranolol Pro

CLASS III - K+ CH. BLOCKERS Use when other antiarrythmics fail ↑AP duration Sotalol - Torsade de pointes↑ERP Ibutilide - Arrhythmias; HypoTN

Sotalol ↑QT interval BretyliumIbutilide Amiodarone - Pulmonary fibrosisBretylium HepatotoxicityAmiodarone Hypo/Hyper-Thyroidism

Neuro; Skin; Photoderm

CLASS IV Ca2+ CH. BLOCKERS Nodal arrhythmias (ie SVT) Affect AV nodal cells ConstipationPrevention A ↓Conduction velocity Flushing

Verapamil ↑ERP EdemaDiltiazem ↑PR interval CHF; AV block; SN dep.

Torsades de pointes (bepridil)

Ca2+ CHANNEL BLOCKERS HTN ≠L-type Ca2+ channels (cardiac; smooth m) Cardiac depression Angina A ↓Contractility Peripheral edema"Knife Dealt [you] A Vera!!" Arrhythmias Flushing; Dizziness

ConstipationNifedipine > Diltiazem > Verapamil Smooth muscle: Knife dealt you a vera

Verapamil > Diltiazem > Nifedipine Heart: Vera dealt a knife

MISCELLANEOUS

Adenosine #1 Rx for AV nodal arrhythmiasK+ Ectopic pacemakers; Digoxin toxicity

K+ K+ K+ K+ K+ K+ K+ K+

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYMg+ Torsades de pointes; Digoxin toxicity

Antiarrhythmics

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYSILDENAFIL Erectile dysfunction ≠cGMP phosphodiesterase Headache A ↑cGMP Flushing"Sildenafil FILLS the penis" A Relaxation of smooth muscle Dyspepsia A Corpus Venosum fills with blood Blue-green vision

A Erection!!Hypotension!! (Heart Px's; Nitrates)

H2 BLOCKERS PUD ≠H2-r (reversible blockage) Anti-androgenic effect (cimetidine) Gastritis A ↓H+ production ↑CRE (cimetidine)Cimetidine GERDRanitidine Z-E Syndrome ≠P450 (potent inhibitor)FamotidineNizatidine

OMEPRAZOLE PUD ≠H+/K+ ATPase in parietal cells (irreversible)LANSOPRAZOLE Gastritis A ↓H+ Production in stomach GERD Z-E Syndrome

SUCRALFATE PUD Polymerizes in ↓pH (stomach env.) A Binds necrotic peptic ulcer tissueAluminum sucrose sulfate Cannot work w/ A Barrier to acid, pepsin, and bile Antacids

PPI's; H2 blockers

MISOPROSTOL NSAID-Peptic-Ulcer prevention PGE1 Analog Diarrhea Induce labor A ↑Mucous secretion of GI mucosa ≠Childbearing potential (abortative)

ANTACIDS GERD pH buffers PUD ↓K+ (all)Al2+ hydroxide Al2+ hydroxide = Constipation; ↓PO4-Mg2+ hydroxide Mg2+ hydroxide = DiarrheaCa2+ carbonate Ca2+ carbonate = ↑Ca2+; ↑Acid

Can affect absorption of other Rx's


GI Rx's

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYHEPARIN IMMEDIATE anticoagulation Catalyzes activation of antithrombin III Bleeding Pulmonary embolism A AT II Activation ThrombocytopeniaLMWH Storke Rx-Rx Interactions Better bioavailability Angina

Longer hal-life MISubcutaneous w/o lab monitoring DVT (+) charged molecule

A Binds HA(-) Follow PTTShort 1/2 life Pregnancy = OK Check aPTT

WARFARIN Chronic coagulation ≠ γ carboxylation of Vit K-dependent Factors Bleeding Hypercoagulable state (prolonged) ≠Protein C & S (via vit. K antagonism) TeratogenicCoumadin Follow PT values Rx-Rx interactions II, VII, IX, XLong 1/2 life ≠Pregnancy (X-placenta)

IIa, VIIa, IXa, Xa ≠NADPH oxidation

A ↓Reduced Vit. K A ↓Activation of II, VII, IX, and X "War-far-in hits 2, 7, 9 and 10"

ANTICOAGULANTS

THROMBOLYTICS Early MI ↑Plasminogen --> Plasmin (direct/indirect) BleedingA Plasmin cleaves thrombin & fibrin

StreptokinaseUrokinaset-PA (ALTEPLASE)APSAC (anistreplase)

THROMBOLYTICS

CLOPIDOGREL Acute Coronary Syndrome ≠ADP pathway Neutropenia (ticlopine)TICLOPIDINE Coronary stenting A ≠Binding of fibrinogen

Prevention of thrombotic stroke A ≠Platelet aggregation Use only for Aspirin intolerant Px'sUse only for Aspirin intolerant Px's

ANTIPLATELETS

Antidote = Protamine sulfate Antidote = Protamine sulfate

Vit K

NADP

NADPH

O2

CO2


AnticoagulantsBILE ACID RESINS ≠Reuptake of bile acids in lumen Px's HATE it!! A ↓↓LDL Tastes badCholestyramine =HDL GI discomfortColestipol ~↑TG

HMG-CoA REDUCTASE INHIB. ≠HMG CoA Reductase $$$ A ≠CE synthesis in liver Myositis; Muscle stiffnessSimvastatin Sim the A ↓↓↓LDL ↑LFT's (reversible)Atorvastatin Actor ↑HDLPravastatin Prays for ↓TGLovastatin Love

HMG Studios onStatin Island

NIACIN ≠Hepatic release of VLDL Flushing; Red face; Tx w/ aspirin A ↓↓LDL ↑↑HDL ↓TG

LIPOPROTEIN LIPASE STIM ↑↑LPL activity Myositis; Muscle stiffness A ↑Breakdown of VLDL --> IDL --> LDL ↑LFT'sGemfibrozil A ↓LDLClofibrate ↑HDL

↓↓↓TG


Lipid-Lowering

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYMETHOTREXATE Leukemias Folic acid analog Myelosuppresion

Lymphomas A ≠Dihydrofolate reductase Reverse w/ Leucovorin orS Phase antimetabolite Choriocarcinoma A ↓dTMP Folinic acid Sarcomas A ↓DNA + Protein synthesis Liver macrovesicular fatty change

AbortionEctopic pregnancyRheumatoid ArthritisPsoriasis

5-FU (5-FLUOROURACIL) Colon CA Pyrimidine analog activated --> 5F-dUMP Myelosuppresion (not reversible)Solid tumors A Complexes to folic acid Photosensitivity

S Phase antimetabolite Basal Cell CA (topical) A ≠Thymidylate synthase≈Effects as Methotrexate A ↓dTMPSynergy w/ methotrexate

6-MP (6-MERCAPTOPURINE) Leukemias ≠Purine synthesis ≠BMLymphomas (ΦCLL or HD) ≠Liver

Metabolized by xanthine oxidase ≠GIA ↑Toxicity w/ Allopurinol

↑Toxicity w/ Allopurinol

BUSULFAN CML Alkylating agent Pulmonary fibrosisA X-links DNA ↑Pigmentation

CYCLOPHOSPHAMIDE Non-Hodgkin's Lymphoma Alkylating agent MyelosuppressionBreast CA A Liver bioactivation Hemorrhagic cystitisOvarian CA A X-links DNA at guanine N-7Immunosuppressant

NITROSOUREAS Brain tumors Alkylating agent CNS toxicityGlioblastoma multiforme A Liver bioactivation Dizziness

Carmustine A X-links DNA AtaxiaLomustineSemustine X-BBBStreptozocin

CISPLATIN Testicular CA ≈Alkylating agent (acts like one) NephrotoxicityBladder CA A Hydrolysis of Cl- groups ≠CN VIIIOvary CA A X-links DNA Lung CA

DOXORUBICIN Intercalates DNA strands (non-covalent) ≠HeartMyelomas A ↓Replication and transcription Myelosuppression

Adriamycin Sarcomas A Free radical generation AlopeciaSolid Tumors (Breast; Lung; Ovary) A Breakage Toxic extravasation

BLEOMYCIN Testicular CA Intercalates DNA strands Pulmonary fibrosisLymphomas A Free radical generation ≠Skin

A Strand breaks

ETOPOSIDE Lung CA (Oat cell) ≠Topoisomerase II (G2-phase) MyelosuppressionProstate CA A ≠Break repair in DNA ≠GITesticular CA A Degradation of DNA Alopecia

PREDNISONE #1 Corticoid in CA Tx ???; Triggers apoptosis Cushing Syndrome; ImmunosuppresionCLL Osteoporosis; HTN; Peptic ulcers

Cataracts; Acne; Autoimmune Dz's ↑GLU; Psychosis

TAMOXIFEN / RALOXIFENE Breast CA Estrogen mixed Agonist / Antagonist ↑Risk of endometrial cancerA ≠Binding of estrogen to ER+ cells Hot flashes

VINCRISTINE / VINBLASTINE M-phase alkaloid NeurotoxicityWilm's tumor A Binds to tubulin Areflexia

Oncovin / Vincristine Choriocarcinoma A ≠Polymerization of microtubules Peripheral neuritisA ≠Mitotic spindle formation Paralytic ileus

PACLITAXEL Ovarian CA M-phase alkaloid MyelosuppressionBreast CA A Binds to tubulin Hypersensitivity

A Hyperstabilizes polymerized microtublesA ≠Mitotic spindle breakdownA ≠Anaphase

HD (ABVD)

Hodgkin's (MOPP)

Lymphomas (MOPP)

≠BM (Vinblastine BLASTS BM)


Cancer Drugs

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYINSULIN Diabetes Mellitus Binds Insulin-R (liver; muscle; adipose) ↓GLU ↑K+ (life-threatening) A Tyrosine Kinase activity Allergy (rare) ↑GLU A GLU --> Glycogen (Liver) A Synthesis of glycogen + protein (Muscle)

A Tryglyceride storage (Fat)

SULFONYLUREAS DM II (NIDDM) Close K+ channels in β-cell membrane ↓GLU A Cell depolarization Disulfiram-like effectsSo fun you'll race a Car (hyperglycemic) A Ca2+ influx Glyburide; Glipizide

A Insulin release stimulatedChlorpropamide Chlar poolGlyburide Glide your ride Ca2+ / Car releaseGlipizide Glip the side [of the]Tolbutamide Toll booth

METFORMIN ↑GLU ??Unknown?? Lactic acidosis ≠Gluconeogenesis (liver)Oral Biguanide A ↓GLU levels "Metformin = Stops GLU Formin' "

GLITAZONES DM II MonoTx ↑Targe cell response to insulin Hepatotoxic (troglitazone) Combo + Above agents Weight gainPioglitazoneRosiglitazone Glitazone = Lit a zone up (↑sensitivity) Glitazone = Glutton zone --> Wt. Gain!Troglitazone

α-GLUCOSIDASE INHIBITORS DM II MonoTx ≠Inestinal brush border α-glucosidase GI Disturbances Combo + Above agents A ↓Sugar hydrolysis and absorptionAcarbose A ↓GLU serum levels (post-prandial)Miglitol

DIABETIC Rx's

LEUPROLIDE Infertility (pulsatile) Continuous Anti-androgen Prostate cancer (continuous) A LH and FSH Burst (transient) Nausea; VomitingGnRH Analog / Agonist Leuprolide + Flutamide Uterine fibroids

PROPYLTHIOURACIL Hyperthryoidism ≠TH synthesis coupling Skin rash ≠T4 --> T3 conversion in periphery Aplastic anemiaThio = Thyro Agranulocytosis

FINASTERIDE Benign Prostastic Hypertrophy ≠5α-reductase A ≠Testosterone --> DihydrotestosteroneAnti-androgen Finasteride = Fine ass rubber ball

Big prostate = rubber ball in ass Finasteride = Final steroid (no conversion)

FLUTAMIDE Prostate Carcinoma Competitive inhibitor of Testosterone-rA ≠Androgens

Non-steroidal Anti-androgen

KETOCONAZOLE Polycystic ovarian syndrome ≠Steroid synthesisSPIRONOLACTONE (Prevents hirsutism)

Anti-androgen

Leuprolide = Leutonizing H / Follicle SH


EndocrineCLOMIPHENE Infertility Pituitary ER(+) Estrogen agonist (partial) Hot flashes A Prevents (-)feedback Ovarian enlargement A ↑LH & FSH release Multiple spontaneous pregnancies A Ovulation stimulation ≠Visual

MIFEPRISTONE (RU-486) Abortifacient ≠Progestin (competitive inhibitor) Heavy vaginal bleeding A ↓Hospitality of uterus for enpregnation ≠GI (nausea; vomiting; anorexia) Abdominal pain

ORAL CONTRACEPTIVES Contraception ↑TG'S Regulation of menses DepressionEstrogen ↓Endometrial & Ovarian CA risk ↑WeightProgestins ↓Ectopic pregnancy incidence Nausea

↓Pelvic infections HTN< 1% Failure ↑Coagulable state

PROGESTERONE Converts endometrium to decidualized state ≠Non-REM sleepWithdrawal --> Endometrial shedding Fatigue; Sedation

Produced by corpus luteum Maintains pregnancy ↓Sleep onset↓Myometrial excitability; Uterine relaxation Night wakenings↑Thick mucus production (inhibits sperm)↑Temp Immunosuppressant(-) Feeback (LH; FSH)Competitively Inhibits aldosteroneA ↑Ald secretion (compensatory)

ESTROGEN Menopause (replacement Tx) Growth of follicle Excessive / Unopposed Estrogen TxA ↓Hot flashes Endometrium proliferation A ↑Risk of endometrial cancer

Estradiol (ovary) ↓Bone loss Genitalia development Tx = Progesterone to balanceEstriol (placenta) Breast stroma development; Lactation prepAromatizaztion (in blood) Fat distribution (women) ≠REM sleepEstrogen (Testes) Protein synthesis and transport (liver) ≠Sleep wake cycle

(-) Feedback (FSH)Estradiol > Estione > Estriol (potency) (+) Feedback (LH)

↑Myometrial excitabilityOvarian & ExtraovarianA Estrone (E1) = Estradiol (E2) Estriol Test = tests fetoplacental function

Placental Sulfatase deficienyA Pregnenolone (mother; placenta) X-linked metabolic Dz in malesA Post-date pregnanciesA DHA --> E1; E2 (placenta) ≠Labor inducement

A ↓Estriol in motherA Estriol (E3); (placenta; mother) ↑DHEA-S in amniotic fluid

ANDROGENS Finasteride inhibits Test --> DHT Wolffian duct differentiation --> Gonads2' Sex characteristics

Testosterone (testes; adrenal) Growth spurt (puberty)DHT (prostate; peripheral conversion) SpermatogenesisAndrostenedione (adrenal) Anabolic function

A ↑MuscleDHT > Testosterone > Andro ↑RBC's

↑LibidoTargetsA Skin; Prostate Testosterone + 5α-reductase

Epididymis; Seminal vesicles A DHTLiver; Muscle; Brain Testosterone / Androstenedione + Aromatase

A Estrogen (convertsion in adipose tissue)

hCG ↑hCG in Choriocarcinoma Maintains corpus luteum (1st tri.)↑Hydatidiform Mole Stimulates CL secretion

Human Chorionic Gonadotropin A ProgesteronProduced by syncytiotrophoblasts EstrogenA Placenta (2nd & 3rd Tri) Relaxin≈LH

Pregnancy Test hCG(+) < 8 days

hPL Anti-insulin effects on momA Facilitates GLU delivery to fetus

Human Placental Lactogen

Cholesterol (mother)

DHA sulfate (fetus)

16αOH DHA sulfate (fetus --> placenta)


HormonesOCP's Endometriosis Pseudopreganncy state

↓Menstrual flowEthinyl Estradiol ↓PG's in Luteal phaseProgestine

GnRH AGONISTS Endometriosis (-) Feeback on Hypothalamus Hypoestrogenic state (profound)A Inhibition of GnRH Hot flushes

Leuprolide Acetate ↓Bone densityNafarelin Costly drugGoserelin

GnRH ANTAGONISTS Endometriosis (-) Feeback on HypothalamusA Inhibition of GnRH

Antagonists > Agonists (efficacy)

GanirelixCetrorelix

PROGESTINS Endometriosis (-) Feeback on HypothalamusA Inhibition of GnRH

Norethindrone acetateMedroxyprogesterone Acetate

≈GnRH Analogs

ANDROGENS Endometriosis Antigonadotropic action VirilizationEstrogen deficiency

Danazol

AROMATASE INHIBITORS Endometriosis ↓Androgen --> Estrogen conversion

MIFEPRISTONE Anti-progestin


Contraceptives

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYPREDNISONE #1 Corticoid in CA Tx ≠Phospholipase A2 & ≠COX-2 Expression Cushing Syndrome; Immunosuppresion CLL A ↓LKT's & PG's Osteoporosis; HTN; Peptic ulcers Cataracts; Acne; Autoimmune Dz's ↑GLU; PsychosisCYCLOSPORINE Transplant immunosuppression Binds to peptidyl proline cis-trans isomerase Prone to viral infections Autoimmune disorders A ≠IL-2 synthesis & ≠IL-2-r Prone to lympomas

A ≠Diff. & Activation of T Cells Nephrotoxic (Tx = mannitol diuresis)

AZOTHIOPRINE Kidney transplant I-suppression Anti-metabolite derivative of 6-MP Autoimmune disorders A ≠Metabolism & Synthesis of nucleic acid GN A ≠L'cyte proliferation

Hemolytic Anemia Antigenic stimulationA Toxic to L'cytes

METHOTREXATE Leukemias Folic acid analog MyelosuppresionLymphomas A ≠Dihydrofolate reductase Reverse w/ Leucovorin or

S Phase antimetabolite Choriocarcinoma A ↓dTMP Folinic acid Sarcomas A ↓DNA + Protein synthesis Liver macrovesicular fatty change

DACTINOMYCIN

CYCLOPHOSPHAMIDE Non-Hodgkin's Lymphoma Alkylating agent MyelosuppressionBreast CA A Liver bioactivation Hemorrhagic cystitisOvarian CA A X-links DNA at guanine N-7Immunosuppressant

ANTI-L'CYTIC GLOBULIN

Monoclonal anti-T L'cyte Ab's

Rh3(D) Ig

TACROLIMUS (FK506) Transplant immunosuppression Binds FK-binding protein Nephrotoxicity A ≠Secretion of cytokines (IL-2; others) Peripheral neuropathy≈Cyclosporine A ≠Diff. & Activation of T Cells HTN

Pleural effusion↑GLU

IMMUNOSUPPRESSANTSGLUCOCORTICOIDS Addison's Dz ≠Phospholipase A2 & ≠COX-2 Expression Cushing's SyndromeHydrocortisone Inflammation A ↓LKT's & PG's Dorsal fat pads; Turnkal obesityPrednisone Immune suppression Moon faciesTriamcinolone Asthma Muscle waisting; OsteoporosisDexamethasone BruisingBeclomethasone Adrenocortical atrophy

Hodgkin's (MOPP)


ImmunosuppressantsASPIRIN Anti-pyretic Acetylation action GI ulceration

Analgesic A ≠COX-1 & COX-2 (IRREVersible inhibition)BleedingNSAID Anti-inflammatory A ≠Arachidonic acid --> PGE's Hyperventilation

Antiplatelet Reye's syndromeTinnitus (CN VIII)

OTHER NSAIDS Anti-pyretic Acetylation action GI ulcerationAnalgesic A ≠COX-1 & COX-2 (REVersible inhibition) Bleeding

Ibuprofen Anti-inflammatory A ≠Arachidonic acid --> PGE's HyperventilationNaproxen Antiplatelet Reye's syndromeIndomethacin Tinnitus (CN VIII)

Patent ductus arteriosus (Indomethacin)NSAIDS

COX-2 INHIBITORS Rheumatoid arthritis ≠COX-2 (cyclo-oxygenase isoform 2) NO GI ulcerationOsteoarthritis A ≠Inflammation Bleeding

Celecoxib ≠Pain HyperventilationRofecoxib A Spares COX-1 Reye's syndrome

A OK = GI Mucosa maintenance Tinnitus (CN VIII)

COX INHIBITORS

ACETAMINOPHEN Anti-pyretic ≠COX (CNS mostly) - Reversible Hepatic necrosis (overdose)Analgesic Glutathione depletion!!ΦAnti-inflammatory!! Inactivated peripherally A Toxic adducts in liver


NSAIDS & ≠COX

INDICATIONS MECHANISM OF ACTION SIDE EFFECTS / TOXICITYINHALED ANESTHETICS Inhaled Heart depression ↑Lipid solubility = ↑Potency = 1 / MAC Respiratory depressionHalothane (hepatotoxic) ↓Blood solubility = Rapid induction Nausea; VomitingEnflurane (convulsant) ↑CNS blood flowIsofluraneSevoflurane Hepatotoxicity (halothane)Methoxyflurance (nephrotoxic) Nephrotoxicity (methoxyflurane)Nitrous oxide Convulsant (enflurane)

I.V. ANESTHETICS

BARBITURATES Anesthesia induction (thiopental) ↑Cl- channel open duration DependenceShort surgical procedures A ↓Neuronal firing CNS depression w/ alcohol --> Death

Thiopental A GABAa facilitator Cyt. P450 - Rx interactionsSedativeAnxietySeizuresInsomnia ↑Lipid solubility --> X-BBB≠Porphyria

BENZODIAZEPINES (EPAMS) Anesthesia induction ↑Cl- channel open duration Post-operative respiratory distress Endoscopy (#1 Rx) A ↓Neuronal firing AmnesiaShort-Acting A GABAa facilitator

Anxiety SedationSpasticity Dependence

Midazolam Status epilepticus (diazepam) Flumazenil (overdose Tx) CNS depression w/ alcohol --> DeathDetoxification (delerium tremens) ≠GABA-r (competitive antagonist) Benzo's < Barb's in CNS depressionInsomnia ie respiratory depression

OPIOID ANALGESICS Anesthesia induction Opioid-r Agonists Addictionmu = morphine CNS depressiondelta = enkephalin Respiratory distress

Pain kappa = dynorphin Pinpoint pupilsCough (dextromethorphan) Modulate synaptic transmission ConstipationDiarrhea (loperamide; diphenoxylate)Acute pulmonary edema Toxicity AntidoteWithdrawal (methadone) Naloxone

Naltrexone

KETAMINE Dissociative anesthetic DisorientationCardiovascular stimulant Hallucinations

PCP analog ↑CNS blood flow Bad dreamsPROPOFOL Anesthesia induction (RAPID) Less post-op S.E. than thiopental

Short procedures

LOCAL ANESTHETICS Local pain numbing ≠Na+ channels (via inner channel receptors) Allergies to Esters Minor surgical procedures A ≠Action potential conduction A Give AmidesEsters Anesthetic + Epinephrine (v. const.) A ≠Pain signal

Progaine Spinal anesthesia A Small fibers > Large fibers CNS excitationCocaine A Myelanted > Unmyelinated Cardiovascular toxicity (bupivacaine)Tetracaine ≠Infected (acidic) tissue A Pain > Temp. > Touch > Pressure HTN

Charged anesthetics cannot X Arrhythmias (cocaine)A More anesthetic needed 3' Amines penetrate membrane

A Bind to channel-r's on inner side

Barbiturates ↑DURATion of Cl- ch.

TriazolamOxazepam

Overdose Tx = Flumazenil

MorphineFentanyl

AmidesLidocaineBupivacaine


Anesthetics

MECHANISM OF ACTION SIDE EFFECTS / TOXICITYPARKINSON'S Benz SLAB Dopamine Agonists

MAO Inhibitors

Anti-Muscarinic

MOTION SICKNESS

Scopolamine

ENCEPHALOPATHY ≠Growth of GI bacteria OtotoxicityLactulose ↓Ammonia forming bacteria in GI NeurotoxicityNeomycin Nephrotoxicity

COMA

Rule Out

DON'T Tx (in that order)

Bromocriptine (partial DA agonist)Amantadine (↑DA release)L-Dopa / Carbidopa

Selegiline (selective MAO B inhibitor)

Benztropine (improves tremors)

Airway (protect)Breathing (assist) InfectionsCirculation (assist) TraumaDextrose (and thiamine; Naloxone IV) Seizure

Carbon MonoxoideOverdose / Opioids

Dextrose Metabolic disturbanceO2 AlcoholNaloxoneThiamine

MECHANISM OF ACTION SIDE EFFECTS / TOXICITY

CNS RxEYE EXAM (PUPIL DILATION)

Atropine Anti-MuscarinicHomatropine Anti-MuscarinicTropicamide Anti-Muscarinic

GLAUCOMA

"ABCD P"

↑Outflow of aqueous humor Mydriasis + Stinging (epi)Epinephrine ≠Closed-angle glaucoma (epi)Brimonidine No pupillary or vision changes (brimo)

↓Secretion of aqueous humor No pupillary or vision changesTimololBetaxololCarteolol

Ciliary muscle contraction MiosisPilocarpine A Opening of trabecular meshwork CyclospasmCarbachol A ↑Outflow of aqueous humorPhysostigmineEchothiophate

↓HCO3- (via ≠carbonic anhydrase) No pupillary or vision changesAcetazolamide A ↓Secretion of aqueous humorDorzalamideBrinzolamide

↑Outflow of aqueous humor Iris darkening (browning)Latanoprost

α-Agonists

β-Blockers

Cholinomimetics

Diuretics

Prostaglandins


Eye RxCHF

β-Blockers ↓Progression to CHF

ANGINA

β-Blockers ↓HR; ↓Contractility --> ↓O2 demand

MI

β-Blockers ↓HR; ↓Contractility --> ↓O2 demand

HTN

β-Blockers ↓CO; ↓Renin secretion

SVT β-Blockers ↓AV conduction velocity


Heart RxASTHMA

Isoproterenol β Agonist (non-specific) ↑HRA Relaxes bronchial smooth muscle

Albuterol Acute attack β2 Agonist (acute attack)A Relaxes bronchial smooth muscle

Salmeterol Long-acting β2 Agonist (acute attack) ArrhythmiaA Relaxes bronchial smooth muscle Tremor

Theophylline ≠Phosphodiesterase Narrow TIA ↓Hydrolysis of cAMP CardiotoxicityA Bronchodilation Neurotoxicity

Ipratropium ≠Muscarinic (competitive antagonist)A ≠Bronchoconstriction

Cromolyn Prophylaxis only ≠Release of Mast cell mediators Rare S.E.

Corticosteroids Inactivates NF-κBBeclomethasone A ≠Synthesis of Cytokines (TNF-α & other cytokines)Prednisone

ZileutonA ≠Arachidonic acid --> LKT's

Zafirlukast ≠LKT-r's

≠5-Lipoxygenase


Lung RxCHRONIC HBVImmunolo-Tx BindS membrane-R's

A ≠Viral replication; ↓Prolif; ↑Phago.Nucleoside Analogs Incorporates into viral DNA Adefovir = Renal tubular injury

≠Priming; ≠R-transcriptase; ≠RNAse ≠DNA polymerase; ≠Chaperone Deoxyguanosine analog

CHRONIC HCVImmunolo-Tx BindS membrane-R's

A ≠Viral replication; ↓Prolif; ↑Phago.Nucleoside Analogs Enhances IFN; ??Mechanism

RibavirinPRIMARY BILIARY CIRRHOSISImmunomodulator Folic Acid antagonist Nausea; BM Suppression

A ≠DNA synthesis --> Apoptosis Hepatotoxic; Tx = Glucovorin to reverseBiliary Product (Brown Bear)

ASCITESDiuretics Furosemide SpironolactoneSpontaneous Bacterial Peritonitis Cephalosporins Quinolones

VARICEAL BLEEDNon-Selective β-Blockers Non-Selective β-Blockers ≠Indications Propanolol Splanchnic vasoconstriction Hypersensitivity; HypoTN Naldolol ↓Heart rate and CO Cardio shock, block, bradycardiaNitrates Vasodilator ≠Indications: HypotensionSomatostatin Analogs Inhibits Serotonin, Gastrin, VIP release

Octreotide (#1 Emergency bleed Rx) A ≠VasodilationVasopressin A Splanchnic ConstrictionAngiotensin II Inhibitors A ↓Portal HTN

IFN-α (high dose)

LamivudineAdefovirTenofovir

Entecavir

Interfere before it's too LATE

IFN-α (high dose)

Methotrexate

Ursodeoxycholic acid

CholchicineAntibiotics


GI RxENDOMETRIOSIS Estrogen antagonistsNSAIDSDanazol (Androgens)Oral contraceptivesMifepristone (anti-progestins)Aromatase InhibitorsE.C. Matrix ModulatorsImmunotherapy

WILSON'S DISEASE Trientine D-PCN Weaker chelator of copper? Hypersensitivity; RashCopper Chelators Zinc Acetate Proteinuria D-PCN ↑E'cytes metallothionein production Blood dyscrasias Trientine Binds Copper > Zinc Anorexia; Nausea; VomitingCopper Absorption Reducers A Traps copper inside enterocytes Trientine Zinc Acetate Enterocyte sloughing Less SE's than D-PCN Tetrathiomolybdate A Copper eliminated in stools Zinc Acetate Does not chelate copper from tissues Well-tolerated Non-specific epigastric irritation Pancreatitis

MENOPAUSE Φestrogen production

α w/ ↓Ovarian follicles with age↓Estrogen Age of onset = 51 yrs old↑GnRH Early onset in smokers↑↑FSH; ↑LH

HAVOC

DIABETESINSULIN Binds Insulin-R (liver; muscle; adipose) ↓GLUTo Tx DM A Tyrosine Kinase activity Allergy (rare)

A GLU --> Glycogen (Liver)↑K+ (life-threatening) A Synthesis of glycogen + protein (Muscle)↑GLU A Tryglyceride storage (Fat)

SULFONYLUREAS Close K+ channels in β-cell membrane ↓GLUTo Tx DM II (NIDDM) A Cell depolarization Disulfiram-like effects

A Ca2+ influx Glyburide; GlipizideSo fun you'll race a Car (hyperglycemic) A Insulin release stimulatedChlorpropamide Chlar poolGlyburide Glide your ride Ca2+ / Car releaseGlipizide Glip the side [of the]Tolbutamide Toll booth

METFORMIN ??Unknown?? Lactic acidosisTo Tx ↑GLU ≠Gluconeogenesis (liver)

A ↓GLU levelsOral Biguanide "Metformin = Stops GLU Formin' "

GLITAZONES ↑Targe cell response to insulin Hepatotoxic (troglitazone)DM II MonoTx Weight gainCombo+Above Rx's

PioglitazoneRosiglitazone Glitazone = Lit a zone up (↑sensitivity) Glitazone = Glutton zone --> Wt. Gain!

Hot flashesAtrophy of VaginaOsteroporosisCAD

MECHANISM OF ACTION SIDE EFFECTS / TOXICITYTroglitazone

α-GLUCOSIDASE INHIBITORS DM II MonoTx ≠Inestinal brush border α-glucosidase GI Disturbances Combo+Above Rx's A ↓Sugar hydrolysis and absorptionAcarbose A ↓GLU serum levels (post-prandial)Miglitol

DIABETIC Rx's

Endocrine RxGOUT

Colchicine Acute Gout Depolymerizes microtubules ≠GIIndomethacin (more common) Acute Gout A ≠Lk'cyte chemotaxis & degranulation Indomethacin < toxicProbenecid Chronic Gout ≠Absorption of uric acid

≠PCN secretionAllopurinol Chronic Gout ≠Xanthing oxidase

A ↓Xanthine --> uric acid


CT Dz Rx'sTUBERCULOSIS

Combo Tx: RESPIre Hepatotoxicity (all Rx's)

ProphylaxisIsoniazid - INH used alone

Cyclosporine (2nd line Tx)

Tx TB before it's RIPE

BACTERIAL PROPHYLAXISMeningococcal Rifampin (1st line); MinocyclineGonorrhea CeftriaxoneSyphilis Benzathine PCN GRecurrent UTI's TMP/SMXPCP TMP/SMX (1st line); Pentamidine

HIV Tx - 2Nucleosides + 1Protease Rx initiated at low CD4+ Count < 500 or high viral loadProtease Inhibitors ≠Protease enzymes

A ≠Viral assembly Nausea; Diarrhea"When it RAINS it pro's" Hyperglycemia

Lipid abnormalitiesThrombocytopenia (Indinavir)

Reverse Transcriptase Inhibitors ≠Reverser transcriptase BM Suppression: Neutropenia; AnemiaA ≠HIV incorporation into host DNA Peripheral neuropathy

"Nevir Efa Delete!" Lactic acidosis (nucleosides)A Non-nucleoside Rash (non-nucleosides)

Megablastic anemia (AZT)"Get N ZZ (in the) SADDLE and ride reverse"

INFLUENZA A VIRUS

AmantadineZanamivir

Zany Man fights A Flu

CMV

CMV = EFGFoscarnetGanciclovir

HSV Target = Viral DNA PolymeraseCommon in normal and compromised

RifampinIsoniazidPyrazinamideEthambutolStreptomycin

RESPIre

RitonavirAmprenavirIndinavirNelfinavirSaquinavir

NevirapineZidovudine (AZT)Zalcitabine (ddC)Stavudine (d4T)AbacavirDidanosine (ddI)DelavirdineLamivudine (3TC)Efavirenz

MECHANISM OF ACTION SIDE EFFECTS / TOXICITYHerpes Simplex Virus (HSV) Key to AbbreviationsVaricella Zoster Virus (VZV) TK = Thimadine Kinase

Common in immunocompromised P-ase = Polymerase Cytomegalovirus (CMV) RT = Reverse Transcriptase

RETROVIRUSES NRTI's Nucleoside analogue Lactic acidosisNucleoside Analogues Target = Viral RT Severe hepatomegaly with steatosis

Cornerstone of 3X Tx for HIV Nucelotide RT inhibitor A May be fatalTarget = Viral RT

Guidelines Non-Nucleoside RT Inhibitor (NNRTI) Use > 3 drugs against virus Target = Viral RT Start and stop all drugs at same time Protease Inhibitor Evaluate risk/benefit Target = Viral Protease Simpler regimen = better adherence Entry Inhibitor Resistance Target = Viral Entry Base-pair mutations in RT

Infectious Dz Rx

MECHANISM OF ACTION DOSAGE SIDE EFFECTS / TOXICITYTETANUS - DTP Vaccine = toxoid treated w/ formaldehyde Infancy Rare

A Altered virulence 3 DosesClostridium tetani Unaltered immunogenicity W/ Diphtheria and Pertussis Pre-exposed adults A ≈100% effective A Allergic reaction Booster every 10 yrs Wound / Trauma Passive Ab's Active Vaccine

DIPHTHERIA - DTP Toxoid vaccine Infancy Toxicity minimal for infants Given with Tetatnus and Pertussis Reactions at injection site (older kids)Corynebacterium diphtheriae DT = Kids dT = Adults (less toxins) Booster every 10 yrs

PERTUSSIS - DTP DTP > 6 mo's Febrile & local reactions (mild) > 1 killed bacteria 1% mortality < 6mo's of age High feverBordetella pertussis Impure Given with Tetatnus and Pertussis Convulsions Highly contagious Recommended > 6 yrs Encephalopathy DTaP Serious reactions (DTP) > 1 purified Ag's of B pertussis Milder reactions (DTaP) P toxoid Filamentous hemagglutinin, etc. Better

H. FLU VACCINE Ab of Hib cap. polysacch. (> 2 yrs old) Purified PRP = > 2 yrs old A Purified PRPType B (Hib) A T-L'cyte activation (age limited) Conjugate = 2 mo's oldA Bacterial meningitis > 18-24 months of age A Ab production Conjugate Vaccine (Infants) A PRP conugated to protein carrier A Creates T-L'cyte dependent Ag's that infant can make Ab's to

STREP PNEUMONIA CPS's (multivalent) (> 2yrs old) CPS's (multivalent) (> 2yrs old) A Purified CPS's of 23 types (~95%)#1 cause of bacterial infections T-independent Ag's ineffective <2yrs old Bacteremia Elderly > 65yrs old; Immunocomp. URTI Underlying Dz Meningitis Pneumonia Protein-CPS Conjugate (Infants) Protein-CPS Conjugate (Infants) A 7 valent with 80% serotype coverage Bronchitis A Immunogenic in infants Otitis media Sinusitis

POLIOMYELITIS OPV (oral live-attenuated) OPV (oral live-attenuated) 3 serotypes 4 dose schedulePoliovirus 4 dose schedule Herd immunity IPV (parenteral, killed) IPV (parenteral, killed) 3 serotypes 4 dose schedule 4 dose schedule

MECHANISM OF ACTION DOSAGE SIDE EFFECTS / TOXICITY

Vaccines

ACTION DISEASE S.E. / CONTRA-INDIC.Anterior Pituitary Releasing Hormones GnRH ↑LH, FSH --> Est, Prog, Test ≠Hypothalamus; Replacement Tx Suppression Test GHRH ↑GH (G; cAMP) GH Deficiency

LHRH ↑LH --> Prog, TestTRH ↑TSH; ↑PrlCRH ↑ACTH

Stimulating Hormones ACTH (cosyntropin) ACTH (corticotropin) FSH

TSHhCG Insulin ResistanceHMG

Target HormonesGH GH Deficiency; RF; Turner; PW ≠Neoplasia; DM; Carpel TSomatostatin ↑Pituitary Dz - AcromegalySomatotropinProlactin Insulin Resistance

Posterior PituitaryVasopressin Agonists

Vasopressin (ADH) V1 Agonist Hypo-TN; Septic shock; GI Bleed Cardio; CVA; Short t1/2Desmopresssin (DDAVP) V2 Agonist DI; Bed wetting; Hemophliacs

Vasopressin AntagonistsOxytocin ↑Uterine cont.; Milk eject

Dopamine AgonistsBromocriptine Binds D2-r --> Blocks Prl ProlactinomaCabergoline Binds D2-r --> Blocks Prl Prolactinoma

Anterior Pituitary

ThyroidThyroxine (T4)Triiodothyronine (T3)IodidePTU (Propylthiouracil) ≠Thyroid peroxidase --> ≠T4-->T3Hyperthyroidism

ParathryroidHypo-Ca2+

Ca2+ Gluc/Lac/Citrate Ca2+ SupplementThiazied Diuretic Ca2+ Sparing diureticMg2+ Mg2+ SupplementDrisdol Vit D2 SupplementDihydrotachysterol (DHT) Vitamin D analogCalciferol Vitamin D analog: 1,25-OHDCalcitriol Vitamin D analogHydroxyapatitePTH (teriparatide)

OsteoporosisCalcitonin (salmon)Alendronate AminobisphosphonateRisedronate AminobisphosphonateRaloxifene Selective Estrogen-R Mod.Estradiol

Paget's DzAlendronate Bisphosphonate; ↓Resorption Upper GI Sx'sRisedronate Bisphosphonate; ↓ResorptionPamidronate Bisphosphonate; ↓Resorption Acute phase reactionMithramycin (Caution!) Bisphosphonate; ↓Resorption Caution!Tiludronate Bisphosphonate; ↓Resorption

OsteomalaciaVit D (1,25 OHD or DHT)Ca2+ SupplementsPhosphate Supplements Soft tissue Ca2+

Thyroid / Parathyroid

PancreasFast

LisproAspartIGF-1

RegularZinc Insulin (Regular)Insulin Zinc Suspension

IntermediateLente Insulin

LongGlargine

SlowUltralente insulin UnpredictableGlimepirideGlipizideGlyburideNPHAcarboseMetforminRepaglinideRosiglitazoneSemilente InsulinTolbutamide

Pancreas

Adrenal CortexCorticosteroids

Hydrocortisone Adrenal I; Surgery; Inflammation Adrenal Insuff; O-Porosis; ↓GHCortisone ShortCortisol ShortPrednisone IntermediatePrednisolone IntermediateDexamethasone Long TEST: CAH; Adrenal Dz

Mineral CorticoidFludrocortisone 10X Cortisol!!Aldosterone

≠Steroid Genesis CushingsMitotane Adrenotoxic --> ≠Enzymes GI; Neuro; Severe!!Ketoconazole ≠Multiple enzymes GI; Hepatic dysfunctionAminoglutethimide ≠Multiple enzymes Neuro; Fever; RashMetyrapone ≠11-β-hydroxylase GI; HTN; Acne; HirsutismTrilostane ≠3-β-Hydroxysteroid dehyd. GI; Parasthesias

Kidney

Dexomethazone Suppresses ACTH 1' ↑ALD 2' Adrenal insufficiencyOctreotide

K+ Sparing DiureticAmiloride ≠Na+ reabsorption in DT / CD 1' ↑ALD ↑K+Spironolactone ≠p450; ≠ALD-r; ≠Androgen-r 1' ↑ALD; ↑Androgenism Gynecomastia; ↑K+

Adrenal Cortex / Kidney

GonadsTestolactoneTestosteroneEstradiolEthinyl EstradiolNorgestrelProgesterone Insulin ResistanceFluoxymesteroneMedroxyprogesteroneMestranol

Male Dev't HormonesMIS Anti-mullerian hormoneTestosterone Testicular descent; Wolff duct dev'tDihydrotestosterone

Gonads

ANTIBIOTICS - SITES OF ACTION

Antibacterial TreeANTIBIOTICS - SITES OF ACTION

AntibioticsANTIVIRALS - SITES OF ACTION

Antivirals


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