First Aid 2008 Pharmacology

(A loving compilation by the University of Maryland class of 2010)

NB: SE = side effect C/I = contraindication There are graphics in FA that have not been included in this document

Participants: Eddie Ahn, Tala Al-Talib, Mona Bahouth, Richie Bryson, Sarah Bui, Niloo Ghassemzadeh, Nidhi Goel, Jen Han, Kyle Hatten, Ashley Huber, Anita Katikineni, Jessica Lue, Thom Reznik, Justin Waltrous, Felicia Washington, Melissa Wisner, Danielle York, Zombor Zoltani

CLASS/NAME Bacteriostatic vs bactericidal antibiotics

CLINICAL USE Bacteriostatic Bactericidal

ANTIBACTERIAL THERAPY (pp 176-183) MECHANISM

SIDE EFFECTS / MISC

Erythromycin, Clindamycin, Sulfamethoxazole, Trimethoprim, Tetracyclines, Chloramphenicol ("We're ECSTaTiC about bacteriostatics") Vancomycin, Fluoroquinolones, Penicillin, Aminoglycosides, Cephalosporins, Metronidazole ("Very Finely Proficient At Cell Murder") 1. Bind penicillin-binding proteins -Prototype -lactam antibiotics 2. Block transpeptidase cross-linking of cell wall -Not penicillinase resistant 3. Activate autolytic enzymes -SE: hypersensitivity reactions, hemolytic anemia -Same as penicillin -Narrow spectrum -Penicillinase-resistant -Penicillinase resistant because of bulkier R group -SE: hypersensitivity reactions; methicillin - interstitial nephritis -Penicillinase-sensitive -Also combine with clavulanic acid (penicillinase inhibitor) to enhance spectrum. -amOxicillin has greater Oral bioavailability than ampicillin -SE: hypersensitivity reactions; ampicillin rash; pseudomembranous colitis

Penicillin G (IV) Penicillin V (oral)

-Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes.

Penicillinase-resistant -S. aureus (except MRSA; resistant penicillins because of altered pencillinMethicillin binding protein target site) Nafcillin ("Use naf (nafcillin) for staph") Dicloxacillin Aminopenicillins Ampicillin Amoxicillin -Extended spectrum penicillin: certain gram-positive bacteria and gram-negative rods (Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, enterococci) (Coverage: ampicillin/amoxicillin HELPS kill enterococci) -Pseudomonas spp. and gram-negative rods

-Same as penicillin -Wider spectrum

Antipseudomonals Ticarcillin Carbenicillin Piperacillin (TCP: Takes Care of Pseudomonas)

-Same as penicillin -Extended spectrum

-Susceptible to penicillinase; use with clavulanic acid -SE: hypersensitivity reactions

Cephalosporins

--lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases

-Bactericidal -SE: -hypersensitivity reactions -cross-hypersensitivity with penicillins occurs in 5-10% of patients - nephrotoxicity of aminoglycosides -disulfiram-like reaction with ethanol (in cephalosporins with a methylthiotetrazole group, e.g. cefamandole)

1st generation Cefazolin Cephalexin 2nd generation Cefoxitin Cefaclor Cefuroxime

-Gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae (PEcK) -Gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens (HEN PEcKS) -Serious gram-negative infections resistant to other -lactams -Meningitis (most penetrate the blood-brain barrier) -Examples -ceftazidime for Pseudomonas -ceftriaxone for gonorrhea - activity against Pseudomonas and gram-positive organisms

3rd generation Ceftriaxone Cefotaxime Ceftazidime

4th generation Cefepime

Aztreonam

-Gram-negative rods: -A monobactam resistant to -lactamases Klebsiella spp. -Inhibits cell wall synthesis (binds to PBP3) Pseudomonas spp. Serratia spp. -No activity against gram-positives or anaerobes. -Use for penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides -Gram-positive cocci, gram-negative rods, and anaerobes. -Drug of choice for Enterobacter -Imipenem is a broad-spectrum, -lactamase-resistant carbapenem

-Synergistic with aminoglycosides -No cross-allergenicity with penicillins -No cross-sensitivity with penicillins or cephalosporins -SE: usually nontoxic; occasional GI upset

Imipenem / cilastatin, Meropenem

-Always administered with cilastatin (inhibitor of renal dihydropeptidase I) to inactivation in renal tubules (With imipenem, "the kill is LASTIN' with ciLASTATIN") -The significant side effects limit use to life-threatening infections, or after other drugs have failed. Meropenem, however, has a reduced risk of seizures and is stable to dihydropeptidase I. -SE: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels. -Bactericidal -Resistance occurs with amino acid change of D-ala D-ala to D-ala D-lac -SE: Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing - "red man syndrome" (can largely prevent by pretreatment with antihistamines and slow infusion rate). (Well tolerated in general - does NOT have many problems)

Vancomycin

-Used for serious, gram-positive multidrug-resistant organisms, including S. aureus and Clostridium difficile (pseudomembranous colitis)

-Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors

-Severe gram-negative rod Aminoglycosides infections Gentamicin, -Synergistic with -lactam Neomycin, antibiotics Amikacin, -Neomycin for bowel surgery Tobramycin, Streptomycin ("Mean" GNATS canNOT kill anaerobes) Tetracyclines Tetracycline, Doxycycline, Demeclocycline, Minocycline

-Inhibit formation of initiation complex and cause misreading of mRNA

-Bactericidal -AminO2glycosides require O2 for uptake; therefore ineffective against anaerobes -SE: Nephrotoxicity (esp. when used with cephalosporins), Ototoxicity (esp. when used with loop diuretics), Teratogen -Bacteriostatic -Limited CNS penetration -Doxycycline is fecally eliminated and can be used in patients with renal failure -Demeclocycline - ADH antagonist; acts as a Diuretic in SIADH -Must NOT take with milk, antacids, or iron-containing preparations because divalent cations inhibit its absorption in the gut -SE: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity -C/I: pregnancy -Bacteriostatic -SE: GI discomfort (most common cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rashes. Increases serum concentration of theophyllines, oral anticoagulants. -Bacteriostatic -Conservative use owing to toxicities -SE: anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase) -Bacteriostatic -SE: pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea

Vibrio cholerae, Acne, Chlamydia, -Bind to 30S and prevent attachment of aminoacyl-tRNA Ureaplasma Urealyticum, Mycoplasma pneumoniae, Tularemia, H. pylori, Borrelia burgdorferi (Lyme disease), Rickettsia (VACCUUM THe BedRoom)

Macrolides Erythromycin Azithromycin Clarithromycin

-URIs, pneumonias, STDs gram-positive cocci (streptococcal infections in patients allergic to penicillin), Mycoplasma, Legionella, Chlamydia, Neisseria -Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae)

-Inhibit protein synthesis by blocking translocation -Bind to the 23S rRNA of the 50S ribosomal subunit

Chloramphenicol

-Inhibits 50S peptidyltransferase activity

Clindamycin

-Treat anaerobic infections (e.g. Bacteroides fragilis, Clostridium perfringens) -Treats anaerobes above the diaphragm

-Blocks peptide bond formation at 50S ribosomal subunit

Sulfonamides Sulfamethoxazole (SMX), Sulfisoxazole, Triple sulfas, Sulfadiazine, Trimethoprim

-Gram-positive, gram-negative, Nocardia, Chlamydia -Use triple sulfas or SMX for simple UTI

-PABA antimetabolites inhibit dihydropteroate synthetase

-Bacteriostatic -SE: hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. warfarin) -Bacteriostatic -SE: Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folic acid) ( Trimethoprim = TMP : "Treats Marrow Poorly )

-Used in combination with sulfonamides (trimethoprimsulfamethoxazole (TMP-SMX)), causing sequential block of folate synthesis. -Combination used for recurrent UTIs, Shigella, Salmonella, Pneumocystis jiroveci pneumonia

-Inhibits bacterial dihydrofolate reductase

Sulfa drug allergies

-Patients who do not tolerate sulfa drugs should not be given sulfonamides or other sulfa drugs, such as sulfasalazine, sulfonylureas, thiazide diuretics, acetazolamide, or furosemide -Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram-positive organisms -Inhibit DNA gyrase (topoisomerase II) -Bactericidal -Must not be taken with antacids -SE: GI upset, superinfections, skin rashes, headache, dizziness. In adults, tendonitis and tendon rupture. In kids, leg cramps and myalgias -C/I: pregnant women, and in children because animal studies show damage to cartilage (FluoroquinoLONES hurt attachment to your BONES)

Fluoroquinolones Ciprofloxacin, Norfloxacin, Ofloxacin, Sparfloxacin, Moxifloxacin, Gatifloxacin, Enoxacin, (fluoroquinolones), Nalidixic acid (a quinolone) Metronidazole

-Antiprotozoal. Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, Clostridium). -Used with bismuth and amoxicillin (or tetracycline) for "triple therapy" against H. pylori (GET GAP on the Metro!) -Treats anaerobes below the diaphragm

-Forms toxic metabolites in the bacterial cell that damage DNA

-Bactericidal -SE: Disulfiram-like reaction with alcohol; headache, metallic taste

Polymyxins Polymyxin B, Polymyxin E

-Resistant gram-negative infections

-Bind to cell membranes of bacteria and disrupt their osmotic properties -Polymyxins are cationic, basic proteins that act like detergents ('MYXins MIX up membranes)

-SE: Neurotoxicity, acute renal tubular necrosis

Antimycobacterial drugs M. tuberculosis M. avium-intracellulare M. leprae Anti-TB drugs Streptomycin, Pyrazinamide, Isoniazid (INH), Rifampin, Ethambutol (INH-SPIRE (inspire)) Cycloserine (2nd-line therapy) Isoniazid (INH) -Mycobacterium tuberculosis -The only agent used as solo prophylaxis against TB

-prophylaxis: -treatment: -prophylaxis: -treatment: -prophylaxis: -treatment:

Isoniazid Isoniazid, rifampin, ethambutol, pyrazinamide Azithromycin Azithromycin, rifampin, ethambutol, streptomycin N/A Dapsone, rifampin, clofazimine -important SE of ethambutol is optic neuropathy (red-green color blindness). -for other drugs, hepatotoxicity

- synthesis of mycolic acids

-Different INH half-lives in fast vs slow acetylators. -SE: Hemolysis if G6PD deficient, neurotoxicity, hepatotoxicity, SLE-like syndrome. Pyridoxine (vitamin B6) can prevent neurotoxicity. (INH Injures Neurons and Hepatocytes) -SE: Minor hepatotoxicity and drug interactions (P450); orange body fluids (nonhazardous side effect). (Rifampin's 4 R's: RNA polymerase inhibitor Revs up microsomal P450 Red/orange body fluids Rapid resistance if used alone)

Rifampin

-Mycobacterium tuberculosis -Delays resistance to dapsone when used for leprosy -Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B

-Inhibits DNA-dependent RNA polymerase

Resistance mechanisms Penicillins / cephalosporins for various antibiotics Aminoglycosides Vancomycin Chloramphenicol Macrolides Tetracycline Sulfonamides Quinolones Meningococcal infection Nonsurgical antimicrobial prophylaxis Gonorrhea Syphilis History of recurrent UTIs Pneumocystis jiroveci pneumonia Endocarditis with surgical or dental procedures Treatment of highly resistant bacteria MRSA VRE

-lactamase cleavage of -lactam ring, or altered PBP in case of MRSA Modification via acetylation, adenylation, or phosphorylation Terminal D-ala of cell wall component replaced with D-lac; affinity Modification via acetylation Methylation of rRNA near erythromycin's ribosome-binding site uptake or transport out of cell Altered enzyme (bacterial dihydropteroate synthetase), uptake, or PABA synthesis Altered gyrase or reduced uptake Rifampin (drug of choice), minocycline Ceftriaxone Benzathine penicillin G TMP-SMX TMP-SMX (drug of choice), aerosolized pentamidine Penicillins Vancomycin Linezolid and streptogramins (quinupristin / dalfopristin)

CLASS/NAME Amphotericin B

CLINICAL USE -Used for wide spectrum of systemic mycoses. -Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). -Intrathecally for fungal meningitis; does not cross blood brain barrier. "Swish and swallow" for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis. -Systemic mycoses. -Fluconazole for cryptococcal meningitis in AIDS patients (because it can cross the blood-brain barrier) and candidal infections of all types (i.e., yeast infections). -Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans ; hypercortisolism. -Clotrimazole and miconazole for topical fungal infections. -Used in systemic fungal infections (e.g., Candida, Cryptococcus ) in combination with amphotericin B. -Invasive aspergillosis -Used to treat dermatophytoses (especially onychomycosis) -Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm).

ANTIFUNGAL THERAPY (p 184) MECHANISM -Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes

SIDE EFFECTS / MISC -SE: Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis ("amphoterrible"). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity. -Misc. notes: Amphotericin "tears" holes in the fungal membrane by forming pores.

Nystatin

-Binds to ergosterol, disrupting fungal membranes.

Misc. notes: Too toxic for systemic use.

Azoles Fluconazole, Ketoconazole, Clotrimazole, Miconazole, Itraconazole, Voriconazole

-Inhibit fungal steroid (ergosterol) synthesis.

-SE: Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills.

Flucytosine

-Inhibits DNA synthesis by conversion to fluorouracil, which competes with uracil.

-SE: Nausea, vomiting, diarrhea, bone marrow suppression.

Caspofungin Terbinafine

-Inhibits cell wall synthesis. -Inhibits the fungal enzyme squalene epoxidase. -Interferes with microtubule function; disrupts mitosis -Deposits in keratin-containing tissues (e.g., nails).

-SE: GI upset, flushing

Griseofulvin

-SE: Teratogenic, carcinogenic, confusion, headaches, P-450 and warfarin metabolism.

CLASS/NAME Amantadine

CLINICAL USE -Prophylaxis and treatment for influenza A -Parkinson's disease

ANTIVIRAL THERAPY (pp 185-187) MECHANISM -Blocks viral penetration / uncoating (M2 protein); -May buffer pH of endosome. -Also causes the release of dopamine from intact nerve terminals. ("A man to dine" takes off his coat)

SIDE EFFECTS / MISC -Mechanism of resistance: Mutated M2 protein. 90% of all influenza A strains are resistant to amantidine, so not used. -Amantadine blocks influenza A and rubellA and causes problems with the cerebellA -SE: Ataxia, dizziness, slurred speech. -Rimantidine is a derivative of amantadine with fewer CNS side effects. Does not cross the blood-brain barrier

Rimantidine Zanamivir Oseltamivir Ribavirin Acyclovir -Both influenza A and B -RSV, chronic hepatitis C -HSV, VZV, EBV -HSV induced mucocutaneous and genital lesions, and encephalitis -Prophylaxis in immunocompromised pts. -For herpes zoster- use related agent famciclovir. -No effect on latent forms of HSV and VZV. -CMV, especially in immunocompromised. -Inhibit influenza neuraminidase, decreasing the release of progeny virus. -Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase. -Monophosphorylated by HSV/VZV thymidine kinase. -Triphosphate formed by cellular enzymes. -Preferentially inhibits viral DNA polymerase by chain termination.

-SE: Hemolytic anemia. Severe teratogen. -Mechanism of resistance: Lack of thymidine kinase. -SE: Generally well tolerated

Ganciclovir

-5`-monophosphate formed by CMV viral kinase or HSV/VZV thyrmidine kinase. -Triphosphate formed by cellular kinases. -Preferentially inhibits viral DNA polymerase. -Viral DNA polymerase inhibitor that binds to the pyrophosphate binding site of enzyme -Does not require activation by viral kinase. (FOScarnet=pyroFOSphate analog) -Glycoproteins from human leukocytes that block various stage of viral RNA and DNA synthesis -Induce ribonuclease that degrades viral mRNA.

-Mechanism of resistance: Mutated CMV DNA polymerase or lack of viral kinase. -SE: Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir. -Mechanism of resistance: Mutated DNA polymerase -SE: Nephrotoxicity -SE: Neutropenia.

Foscarnet

-CMV retinitis in immunocompromised patients when ganciclovir fails. -Acyclovir resistant HSV. -IFN- : chronic hepatitis B, C, Karposi's sarcoma -IFN- : MS -IFN- : NADPH oxidase deficiency.

Interferons

-HIV Protease Inhibitors Saqunavir, Ritonavir, Indinavir, Nelfinavir, Amprenavir -all end in -navir (NAVIR (never) TEASE a proTEASE) -HIV Reverse -HAART (highly active Transcriptase antiretroviral therapy) usually a Inhibitors protease inhibitor + RT inhibitor. Initiated when patients Nucleosides have low CD4 (<500) or high Zidovudine (ZDV viral load. formerly AZT), -ZDV is used for general Didanosine (ddI), prophylaxis and during Zalcitabine (ddC), pregnancy to reduce risk of Stavidine (d4T), fetal transmission. Lamivudine (3TC), Abacavir Non-Nucleosides Nevirapine, Efavirenz, Delaviridine. (Never Ever Deliver nucleosides) Fusion Inhibitors Enfuvirtide

HIV THERAPY -Inhibit assembly of new virus by blocking protease in progeny virions.

-SE: GI intolerance (nausea, diarrhea), hyperglycemia, lipodystrophy, thrombocytopenia (indinavir)

-Preferentially inhibit reverse transcriptase of HIV. -Prevent incorporation of DNA copy of viral genome into host DNA.

-SE: -Bone marrow suppression (neutropenia, anemia) (give GM-CSF + Erythropoetin to reduce marrow suppression) -Peripheral neuropathy -Nucleosides: lactic acidosis -Non-nucleosides: rash -ZDV: megaloblastic anemia.

-HIV -In patients with persistent viral replication in spite of antiretroviral therapy. -Use in combo with other drugs.

-Bind viral gp41 subunit; inhibit conformational change required for fusion with CD4 cells. -Therefore block entry and subsequent replication.

-SE: -Hypersensitivity reactions -Reactions at subcutaneous injection site - risk of bacterial pneumonia

CLASS/NAME

CLINICAL USE

IMMUNOLOGY (pp 204-205) MECHANISM -Binds to cyclophilins -The resulting complex blocks the differentiation and activation of T cells by inhibiting calcineurin, preventing the production of IL-2 and its receptor

SIDE EFFECTS / MISC -SE: -predisposes patients to viral infections and lymphoma -nephrotoxic (preventable with mannitol diuresis)

Immunosuppressants Cyclosporine -Suppresses organ rejection after transplantation -Selected autoimmune disorders

Tacrolimus (FK506)

-Potent immunosuppressive used -Similar to cyclosporine in organ transplant recipients -Binds to FK-binding protein, inhibiting secretion of IL-2 and other cytokines -Kidney transplantation -Autoimmune disorders (including glomerulonephritis and hemolytic anemia) -Antimetabolite precursor of 6-mercatopurine that interferes with the metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes.

-SE: Significant-nephrotoxicity, peripheral neuropathy, hypertension, pleural effusion, hyperglycemia.

Azathioprine

-SE: -Bone marrow suppression -Active metabolite mercaptopurine is metabolized by xanthine oxidase; thus, toxic effects may be by allopurinol -SE: Cytokine release syndrome, hypersensitivity reaction

Muromonab-CD3 (OKT3)

-Immunosuppression after kidney -Monoclonal Ab that binds to CD3 (epsilon transplantation chain) on the surface of T cells. Blocks cell interaction with CD3 protein responsible for T cell signal transduction. -Immunosuppression after kidney -Binds to mTOR (molecular target of transplantation in combo with rapamycin). cyclosporine and corticosteroids -Inhibits T cell proliferation in response to IL-2 -Inhibits de novo guanine synthesis and blocks lymphocyte production. -Monoclonal Ab with high affinity for the IL-2 receptor on activated T cells.

Sirolimus (rapamycin)

-SE: Hyperlipidemia, thrombocytopenia, leukopenia

Mycophenolate mofetil Daclizumab

Recombinant cytokines Aldesleukin (IL-2)

-Renal cell carcinoma -Metastatic melanoma Erythropoietin (epoetin) -Anemias (esp in renal failure) Filgrastim -Recovery of bone marrow (granulocyte colonystimulating factor) Sargramostim (granulocytemacrophage colonystimulating factor) -interferon -Recovery of bone marrow

-Hepatitis B and C -Kaposi's sarcoma -Leukemias Malignant melanoma -Multiple sclerosis -Chronic granulomatous disease -Thrombocytopenia -Thrombocytopenia

-interferon -interferon Oprelvekin (IL-11) Thrombopoietin

CLASS/NAME Cholinergic agents

(DIRECT, INDIRECT)

CLINICAL USE

PHARMACOLOGY (pp 227-232) MECHANISM

SIDE EFFECTS / MISC

Direct agonists Bethanechol -Postoperative and neurogenic ileus and urinary retention -Glaucoma -Pupilary contraction - Intraocular pressure -Potent stimulator of sweat, tears, saliva -Emergency treatment for open and narrow glaucoma -Contracts ciliary muscle of eye (open angle), pupillary sphincter (narrow angle) -Challenge test to diagnose asthma -Direct cholinergic agonist -Activates Bowel and Bladder smooth muscle -Direct cholinergic agonist (muscarinic and nicotinic agonist) Direct cholinergic agonist -Resistant to AchE (Pile on the sweat and tears) -Resistant to AChE (Beth Anne, call (bethanechol) me if you want to activate your bowels and bladder)

Carbachol

Pilocarpine

Methacholine

-Direct cholinergic agonist -Stimulates muscarininc receptors in airway when inhaled

Indirect agonists (anticholinesterases) Neostigmine -Postoperative and neurogenic ileus and urinary retention -Myasthenia gravis -Reversal of neuromuscular junction blockade (postop) -Myasthenia gravis (long acting) -(Indirect agonist (anticholinesterase)) = - endogenous Ach -No CNS penetration (NEO CNS = NO CNS) -Shorter acting than pyridostigmine

Pyridostigmine

- endogenous Ach therefore increases strength -No CNS penetration - endogenous Ach - endogenous Ach -Crosses the BBB to CNS - endogenous Ach

-Long acting

Edrophonium Physostigmine Ecothiophate

-Diagnosis of myasthenia gravis -Glaucoma (b/c crosses BBB) -Atropine overdose -Glaucoma

-Extremely short acting (PHYS is for EYES)

Cholinesterase inhibitor -Causes: Parathion and other organophosphates. Irreversible inhibitors. -Symptoms: (DUMBBELSS) poisoning -Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation skeletal muscle and CNS; Lacrimation, Sweating, Salivation (also abdominal cramping) -Antidote: Atropine (muscarinic antagonist) plus pralidoxime (chemical antagonist used to regenerate active cholinesterase)

Muscarinic antagonists Atropine, Homatropine, Tropicamide Benztropine Scopolamine Ipratropium Methoscopolamine, Oxybutynin, Glycopyrrolate Pirenzepine, Propantheline Glaucoma drugs Epinephrine

-Produce mydriasis and cycloplegia -Parkinson's disease (PARK my BENZ) -Motion sickness -Asthma, COPD -Reduce urgency in mild cystitis and reduces bladder spasms -Peptic ulcer treatment

-(Organ system) = -Eyes -CNS -CNS -Respiratory -Genitourinary

-Gastrointestinal

-Glaucoma

--agonist - aqueous humor synthesis due to vasoconstriction --agonist - aqueous humor synthesis --blockers - aqueous humor synthesis -Diuretic - aqueous humor secretion due to HCO3 (via inhibition of carbonic anhydrase) -Cholinomimetics - outflow of aqueous humor -Contract ciliary muscle and opens trabecular meshwork -Use pilocarpine in emergencies -Very effective at opening the canal of Schlemm -Prostaglandin - outflow of aqueous humor

-SE: Mydriasis; stinging -C/I: Do not use in closed angle glaucoma -No pupillary or vision changes -No pupillary or vision changes

Brimonidine Timolol, Betaxolol, Carteolol Acetazolamide

-Glaucoma -Glaucoma

-Glaucoma

-No pupillary or vision changes

Pilocarpine, Carbachol, Physostigmine, Echothiophate

-Glaucoma

-SE: Miosis; cyclospasm

Latanoprost (PGF 2-)

-Glaucoma

-SE: Darkens color of iris (browning)

Atropine

(Blocks DUMBBELLS) -Eye: -pupil dilation, cycloplegia -Airway - secretions -Stomach - acid secretions -Gut - motility -Bladder - urgency in cystitis -Ganglionic blocker - used in experimental models to prevent vagal reflex responses to changes in blood pressure (e.g. prevents reflex bradycardia caused by NE)

Muscarinic antagonist

-SE: - body temp, rapid pulse, dry mouth, dry flushed skin, cycloplegia, constipation, disorientation -(Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter) -Acute angle-closure glaucoma in elderly -Urinary retention in men with prostatic hypertrophy -Hyperthermia in infants

Hexamethonium

Nicotinic antagonist

-SE: Severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction

Sympathomimetics
(DIRECT, INDIRECT, SYMPATHOPLEGICS)

Direct sympathomimetics Epinephrine NE Isoproterenol Dopamine Dobutamine Phenylephrine -Anaphylaxis, glaucoma (open angle), asthma, hypotension -Hypotension (but renal perfusion) -AV block (rare) -Shock ( renal perfusion), heart failure -Shock, heart failure, cardiac stress testing -Pupillary dilation, vasoconstriction, nasal decongestion -Albuterol for acute asthma -Terbutaline reduces premature uterine contractions -Reduces premature uterine contractions 1, 2, 1, 2, low doses selective for 1 1, 2 > 1 1 = 2 D1 = D2 > > 1 > 2 1 > 2

-Inotropic and chronotropic -Inotropic but not chronotropic

Albuterol, Terbutaline Ritodrine Indirect sympathomimetics Amphetamine Ephedrine Cocaine Sympathoplegics Clonidine, -methyldopa Selective 2-agonists Metaproterenol, Albuterol, Salmeterol, Terbutaline

2 > 1

-Narcolepsy, obesity, attention deficit disorder -Nasal decongestion, urinary incontinence, hypotension -Causes vasoconstriction and local anesthesia -Hypertension, especially with renal disease (no in blood flow to kidney)

-Indirect general agonist, releases stored catecholamines -Indirect general agonist, releases stored catecholamines -Indirect general agonist, uptake inhibitor -Centrally acting 2-agonist, central adrenergic outflow 2-agonist MAST: Metaproterenol, Albuterol, Salmeterol, Terbutaline

-blockers
(NONSELECTIVE, 1 SELECTIVE, 2 SELECTIVE)

Nonselective Phenoxybenzamine (irreversible) and Phentolamine (reversible)

-Pheochromocytoma (use phenoxybenzamine before removing tumor, since high levels of released catecholamines will not be able to overcome blockage) -Hypertension, urinary retention in BPH

Nonselective -blocker

-SE: Orthostatic hypotension, reflex tachycardia

1-selective Prazosin, Terazosin, Doxazosin 2-selective Mirtazapine -blockers Propranolol, Metoprolol, Atenolol, Nadolol, Timolol, Pindolol, Esmolol, Labetalol

1 selective -blocker

-SE: 1st-dose orthostatic hypotension, dizziness, headache

-Depression

2 selective -blocker

-SE: Sedation, serum cholesterol, appetite

-Hypertension cardiac output, renin secretion -Angina pectoris heart rate and contractility, resulting in O2 consumption -MI -blockers mortality -SVT (propranolol, esmolol) AV conduction velocity (class II antiarrhythmic) -CHF Slows progression of chronic failure -Glaucoma (timolol) secretion of aqueous humor

-Nonselective antagonists (1 = 2) propranolol, timolol, nadolol, pindolol, and labetalol -1-selective antagonists (1 > 2) Acebutolol (partial agonist), Betaxolol, Esmolol (short acting), Atenolol, Metoprolol (A BEAM of 1-blockers) -Nonselective - and - antagonists carvedilol, labetalol -Partial -agonists acebutolol, pindolol

-SE: -impotence -exacerbation of asthma -cardiovascular adverse effects (bradycardia, AV block, CHF) -CNS adverse effects (sedation, sleep alterations) -use with caution in diabetics

CLASS/NAME Antihypertensives Hydrochlorothiazide (HCTZ) Loop Diuretics

CLINICAL USE -Hypertension

CARDIOVASCULAR (pp 266-272) MECHANISM -Thiazide diuretic (prevents NaCl resorption in early DCT) -Loop diuretic (blocks NKCC channel in TALH) -Sympathoplegic

SIDE EFFECTS / MISC -SE: Hypokalemia, mild hyperlipidemia, hyperuricemia, lassitude, hypercalcemia, hyperglycemia -SE: Potassium wasting, metabolic alkalosis, hypotension, ototoxicity -SE: Dry mouth, sedation, severe rebound HTN -SE: Sedation, positive Coomb's test -SE: Severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction -SE: Sedation, depression, nasal stuffiness, diarrhea -SE: Orthostatic and exercise hypotension, sexual dysfunction, diarrhea -SE: 1st dose orthostatic hypotension, dizziness, headache -SE: Impotence, flushing, Cardiovascular effects (bradycardia, CHF, AV block), CNS effects (sedation, sleep alterations)

-Hypertension

Clonidine

-Hypertension

Methyldopa

-Hypertension

-Sympathoplegic

Hexamethonium

-Hypertension

-Sympathoplegic

Reserpine

-Hypertension

-Sympathoplegic

Guanethidine

-Hypertension

-Sympathoplegic

Prazosin

-Hypertension

-Sympathoplegic

Blockers

-Hypertension

-Sympathoplegic

Hydralazine

-Severe hypertension -CHF -First-line therapy for HTN in pregnancy, with methyldopa

-Vasodilator - cGMP smooth muscle relaxation. -Vasodilates arterioles > veins; afterload

-SE: Nausea, headache, lupus-like syndrome, reflex tachycardia, angina, salt/fluid retention. -C/I: angina/CAD -Use with blockers to prevent reflex tachycardia, diuretic to block salt retention -SE: Hypertrichosis, pericardial effusion, reflex tachycardia, angina, salt retention -Use with blockers to prevent reflex tachycardia, diuretic to block salt retention -SE: Dizziness, nausea, flushing, constipation (verapamil), AV Block (verapamil), cardiac depression, peripheral edema

Minoxidil

-Severe hypertension

-Vasodilator -K+ channel opener - hyperpolarizes and relaxes vascular smooth muscle

Nifedipine Verapamil Diltiazem

-Hypertension -Angina -Arrhythmias (not nifedipine) -Prinzmetal's angina -Raynaud's

-Vasodilator -Block voltage-dependent L-type Ca channels of cardiac and smooth muscle and thereby reduce muscle contractility -Vascular smooth muscle: Nifed > Dilt > Verap -Heart: Verap > Dilt > Nifed -Vasodilator -Short acting; cGMP via direct release of NO -Vasodilator -K+ channel opener - hyperpolarizes and relaxes vascular smooth muscle -ACE Inhibitor

Nitroprusside

-Hypertension -Malignant HTN (see below) -Hypertension -Malignant HTN (see below)

-SE: Cyanide toxicity (releases CN) -SE: HypER*glycemia (reduces insulin release), hypotension *Annotate your FA- this is on the errata list -SE: Hyperkalemia, cough, angioedema, taste changes, hypotension, pregnancy problems (fetal renal damage), rash, renin -SE: Fetal renal toxicity, hyperkalemia -SE: -Tachycardia, hypotension, flushing, headache, -"Monday Disease" in industrial exposure - development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend, resulting in tachycardia, dizziness, and headache on re-exposure.

Diazoxide

Captopril Enalapril Fosinopril Losartan Nitroglycerin, Isosorbide dinatrate

-Hypertension

-Hypertension -Hypertension -Angina -Pulmonary edema -Also used as an aphrodesiac and erection enhancer

Angiotensin II Receptor Inhibitor (ARB) -Vasodilate by releasing nitric oxide in smooth muscle, causing in cGMP and smooth muscle relaxation. -Vasodilates veins >> arteries; preload

Malignant HTN treatment Nitroprusside Fenoldopam

Malignant HTN Malignant HTN

-Vasodilator -Short acting; cGMP via direct release of NO -Vasodilator -Dopamine D1 receptor agonist - relaxes renal vasuclar smooth muscle -Vasodilator -K+ channel opener - hyperpolarizes and relaxes vascular smooth muscle

-SE: Cyanide toxicity (releases CN)

Diazoxide

Malignant HTN

-SE: HypER*glycemia (reduces insulin release), hypotension *Annotate your FA- this is on the errata list

Antianginal therapy

-Goal = reduction of myocardial O2 consumption (MVO2) by decreasing 1 or more of the determinants of MVO2: end diastolic volume, blood pressure, heart rate, contractility, ejection time -Calcium channel blockers: Nifedipine is similar to Nitrates in effect; Verapamil is similar to blockers in effect. -Labetalol, pindolol, and acebutolol are partial agonists- CONTRAINDICATED in angina Nitrates (affect preload) (Reflex response) (Reflex response) Blockers (affect afterload) Nitrates + Blockers No effect or Little/No Effect Little/No Effect

Component EDV BP Contractility HR Ejection time MVO2

Lipid lowering agents

HMG-CoA reductase inhibitors Lovastatin Pravastatin Simvastatin Atorvastatin Niacin

-LDL "bad cholesterol" -HDL "good cholesterol -triglycerides = TG HDL TG LDL

-Inhibit cholesterol precursor, mevalonate

-SE: expensive, reversible LFTs, myositis

-Inhibits lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation -Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more -Prevent cholesterol reabsorption at small intestine brush border -Upregulate LPL TG clearance

-SE: red, flushed face, which is reduced by aspirin or long-term use -SE: pts hate it (tastes bad and causes GI discomfort), absorption of fat-soluble vitamins -SE: rare, LFTs

Bile acid resins Cholestyramine Colestipol Cholesterol absorption blockers Ezetimibe "Fibrates" Gemfibrozil Clofibrate Bezafibrate Fenofibrate Cardiac glycosides Digoxin

slightly

slightly

--

--

-SE: myositis, LFTs

-CHF (increase contractility) -Atrial fibrillation (conduction at AV node and depression of SA node)

-Direct inhibition of Na/K ATPase leads to indirect inhibition of Na/Ca exchanger/antiport [Ca] positive inotropy

-Misc: 75% bioavailability 20-40% protein bound t1/2 = 40 hrs urinary excretion -SE: -cardiac: may cause PR, QT, scooping of ST segment, T-wave inversion of ECG, arrhythmia -parasympathetic activity - nausea, vomiting, diarrhea, blurry yellow vision (think Van Gogh) - toxicity if : -Renal failure (excretion) or -Hypokalemic (potentiates drug effects) or -Quinidine (digoxin clearance; displaces drug from tissue binding) -Antidote: Slowly normalize K+, lidocaine, cardiac paper, anti-dig Fab fragments, Mg2+

ANTIARRHYTHMICS Na+ channel blockers (Class I)

-Block Na channel -Slow or block () conduction (esp in depolarized cells) - slope of phase 4 depolarization, - threshold for firing in abnormal pacemaker cells -Affect both atrial and ventricular arrhythmias, especially reentrant and ectopic supraventricular and ventricular tachycardia - AP duration - effective refractory period (ERP) - QT interval

-These are local anesthetics -Are state dependent - selectively depress tissue that is frequently depolarized, eg fast tachycardia -Hyperkalemia toxicity for all class I drugs

Class IA Quinidine Amiodarone Procainamide Disopyramide (Queen Amy Proclaims Diso's pyramid) Class IB Lidocaine Mexiletine Tocainide (I'd Buy Lidy's Mexican Tacos) Class IC Flecainide Encainide Propafenone ANTIARRHYTHMICS Beta-blockers (Class II) Propanolol Esmolol Metoprolol Atenolol Timolol

-SE: -quinidine -cinchonism (headache, tinnitus, thrombocytopenia) -torsades de pointes due to QT interval; -procainamide -reversible SLE-like syndrome

-Affect ischemic or depolarized Purkinje and ventricular tissue -Useful in acute ventricular arrhythmias (esp. post-MI) and in digitalis-induced arrhythmias

- AP duration

-SE: Local anesthetic, CNS stimulation/depression, cardiovascular depression -phenytoin can also fall into the IB category

-Useful in V-tachs that progess to VF and in intractible SVT -Usually used only as last resort in refractory tachyarrhythmias

-No effect on AP duration

-SE: proarrhythmic, especially post MI (contraindicated), significantly prolongs refractory period in AV node

-V-tach -SVT -Slowing ventricular rate during atrial fibrillation and atrial flutter

-cAMP, Ca currents -Suppress abnormal pacemakers by slope of phase 4 -AV node particularly sensitive: PR interval

-Esomolol is very short acting -SE: Impotence, exacerbation of asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations); May mask signs of hypoglycemia; Metoprolol can cause dyslipidemia

ANTIARRHYTHMICS K+ channel blockers (Class III) Sotalol Ibutilide Bretylium Amiodarone

-Used when other antiarrhythmics - AP duration, fail - effective refractory period - QT interval -SE: torsades des pointes, excesssive block -SE: torsades des pointes -SE: new arrhythmias, hypotension -Safe to use in Wolff-Parkinson-White Syndrome -SE: -pulmonary fibrosis, corneal deposits, hepatotoxicity, skin deposits resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, CHF), hypothyroidism/hyperthyroidism (Remember to check PFTs, LFTs, and TFTs when using amiodarone)

ANTIARRHYTHMICS Ca2+ channel blocker (Class IV) Verapamil Diltiazem -Primarily affect AV nodal cells -Used in prevention of nodal arrhythmias (eg SVT) - conduction velocity - effective refractory period - PR interval -SE: constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression), torsades de pointes (bepridil)

OTHER ANTIARRHYTHMICS Adenosine

K+

-Drug of choice in diagnosis/abolishment of AV nodal arrhythmias -Depresses ectopic pacemakers in hypokalemia (e.g. digoxin toxicity) -Effective in torsades de pointes and digoxin toxicity

- K+ out of cells hyperpolarizing the cell

-Very short acting (~15 sec) -SE: Flushing, hypotension, chest pain

Mg+

CLASS/NAME Diabetic drugs Insulins Lispro (short-acting) Aspart (short-acting) NPH (intermediate) Lente (long-acting) Ultralente (long-acting) Sulfonylureas First generation Tolbutamide Chlorpropamide Second generation Glyburide Glimepiride Glipizide Biguanides Metformin

CLINICAL USE -Type 1 DM -Also: life-threatening hyperkalemia & stress-induced hyperglycemia

ENDOCRINE (pp 287-288) MECHANISM -Bind insulin receptor (tyrosine kinase activity) -Liver: glucose stored as glycogen -Muscle: glycogen & protein synthesis, K+ uptake -Fat: aids TG storage

SIDE EFFECTS / MISC -SE: hypoglycemia, hypersensitivity reaction (very rare)

-Stimulate release of endogenous -Close K+ channel in -cell membrane, so insulin in type 2 DM. cell depolarizes triggering of insulin -Require some islet function, so release via Ca2+ intake useless in type 1 DM.

-SE: -1st gen: disulfiram-like effects. -2nd gen: hypoglycemia.

-Used as oral hypoglycemic -Can be used in patients without islet function

-Exact mechanism is unknown -Possibly: gluconeogenesis glycolysis serum glucose levels. - target cell response to insulin

-SE: Most grave adverse effect is lactic acidosis.

Glitazone Pioglitazone Rosiglitazone -glucosidase inhibitors Acarbose Miglitol

-Used as monotherapy in type 2 DM or combined with above agents. -Used as monotherapy in type 2 DM or combined with above agents.

-SE: Weight gain, edema, hepatotoxicity, CV toxicity

-Inhibit intestinal brush-border -glucosidases -Delayed sugar hydrolysis & glucose absorption lead to postprandial hyperglycemia.

-SE: GI disturbances

Misc endocrine drugs Orlistat Sibutramine Propylthiouracil, Methimazole -Long-term obesity management (in conjunction with modified diet) -Short-term & long-term obesity management -Hyperthyroidism -Alters fat metabolism by inhibiting pancreatic lipases. -Sympathomimetic serotonin & norepinephrine reupake inhibitor. -Inhibit organification and coupling of thyroid hormone synthesis. -Propylthiouracil also peripheral conversion of T4 to T3 -Thyroxine replacement. -SE: Steatorrhea, GI discomfort, reduced absorption of fat-soluble vitamins, headache. -SE: Hypertension, tachycardia. -SE: Skin rash, agranulocytosis (rare), aplastic anemia.

Levothyroxine, Triiodothyronine Hypothalamic / pituitary drugs GH Somatostatin (octreotide)

-Hypothyroidism, myxedema.

-SE: Tachycardia, heat intolerance, tremors, arrhythmias

-GH deficiency -Turner's syndrome -Acromegaly -Carcinoid -Gastrinoma -Glucagonoma -Stimulates labor, uterine contractions, milk let-down -Controls uterine hemorrhage -Pituitary DI (central, not nephrogenic)

Oxytocin

ADH (desmopressin) Glucocorticoids Hydrocortisone Prednisone Triamcinolone Dexamethasone Beclomethasone

-Addison's disease -Inflammation -Immune suppression -Asthma

- the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2

-SE: Iatrogenic Cushing's syndrome - buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic).

CLASS/NAME H2 blockers Cimetidine Ranitidine Famotidine Nizatidine (take H2 blockers before you DINE) Proton pump inhibitors Omeprazole, Lansoprazole

CLINICAL USE -Peptic ulcer -Gastritis -Mild esophageal reflux

GASTROINTESTINAL (pp 317-318) MECHANISM -Reversible block of histamine H2 receptors causing secretion of H+ from parietal cells

SIDE EFFECTS / MISC -SE of cimetidine: -Cimetidine is a potent inhibitor of P-450 -it also has antiandrogenic effects (prolactin release, gynecomastia, impotence) -can cross BBB (confusion, dizziness, headaches) and placenta -SE of cimetidine & ranitidine: - renal excretion of creatinine -Other H2 blockers are relatively free of these effects

-Peptic ulcer -Gastritis -Esophageal reflux -ZES

-Irreversibly inhibit H+/K+ ATPase in stomach parietal cells

Mucosal protectants Bismuth, Sucralfate

-Improve ulcer healing -Traveler's diarrhea

-Bind to ulcer base, providing physical protection, and allow HCO3- secretion to reestablish pH gradient in the mucous layer -a PGE1 analog - production and secretion of gastric mucous barrier - acid production -Block M1 receptors on ECL cells ( histamine secretion) -Block M3 receptors on parietal cells ( H+ secretion)

Misoprotol

-Prevention of NSAID-induced peptic ulcers -Maintenance of a patent ductus arteriosus. -Induction of labor

-Triple therapy for H. Pylori ulcers : Metronidazole, Amoxicillin (or Tetracycline), Bismuth. -Can also use a PPI (Please MAke Tummy Better) -SE: Diarrhea -C/I: contraindicated in women of childbearing potential (abortifacient)

Muscarinic antagonist -Peptic ulcer Pirenzepine, Propantheline

-SE: Tachycardia, dry mouth, difficulty focusing eyes

Antacid use

-SE of all: -Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying -All cause hypokalemia -SE: Constipation and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures (Aluminimum amount of feces) -SE: Diarrhea, hyporeflexia, hypotension, cardiac arrest (Mg = Must go to the bathroom) -SE: Hypercalcemia, rebound acid ; can chelate and effectiveness of other drugs (e.g. tetracycline)

Alumninum hydroxide (AlOH3) Magnesium hydroxide Calcium carbonate

Infliximab

-Crohn's disease -Rheumatoid arthritis -Ulcerative colitis -Crohn's disease -Control vomiting postoperatively and in patients undergoing cancer chemotherapy

-A monoclonal antibody to TNF, which is a proinflammatory cytokine (INFLIXimab INFLIX pain on TNF) -A combination fo sulfapyridine (antibacterial) and mesalamine (anti-inflammatory) -Activated by colonic bacteria -5-HT3 antagonist -(Powerful central-acting antiemetic)

-SE: Respiratory infection, fever, hypotension

Sulfasalazine

-SE: Malaise, nausea, sulfonamide toxicity, reversible oligospermia -SE: Headache, constipation
(You will not vomit with ONDANSetron, so you can go ON DANCing)

Ondansetron

Prokinetic agents Cisapride

Metoclopramide

-Diabetic and post-surgery gastroparesis

-Acts through 5HT receptors to ACh release at the myenteric plexus. - esophageal tone - gastric and duodenal contractility, improving transit time (including through the colon) -D2 receptor antagonist - resting tone, contractility, LES tone, motility -Does not influence colon transport time

-No longer used -SE: Serious interactions (torsades des pointes) with Erythromycin, Ketoconazole, Nefazodone, Fluconazole

-SE: - Parksonian Effects. -Restlessness, drowsiness, fatigue, depression, nausea, diarrhea. -Drug interaction with digoxin and diabetic agents -C/I: pts with small bowel obstruction

CLASS/NAME Heparin

CLINICAL USE -Immediate anticoagulation for pulmonary embolism, stroke, angina, MI, DVT -Used during pregnancy (does not cross placenta)

HEMATOLOGY AND ONCOLOGY (pp 336-340) MECHANISM SIDE EFFECTS / MISC -Catalyzes activation of antithrombin III, thrombin and Xa -Short half-life -Follow patient's PTT when on heparin -Newer low-molecular-weight heparins (enoxaparin) act more on Xa, have better bioavailability and 2-4 times longer half-life. Can be administered subcutaneously and without laboratory monitoring. Not easily reversible. -SE: -bleeding -osteoporosis -drug-drug interactions, -heparin-induced thrombocytopenia (HIT): heparin binds platelets, causing autoantibody production that destroys platelets and overactivates the remaining ones, resulting in a thrombocytopenic, hypercoagulable state. -for rapid reversal of heparinization, use protamine sulfate (positively charged molecule that acts by binding negatively charged heparin) -Hirudin derivatives

Lepirudin, Bivalirudin Warfarin (Coumadin)

-Used as an alternative to heparin for anticoagulating patients with HIT -Chronic anticoagulant -Not used in pregnant women (because warfarin, unlike heparin, can cross the placenta)

-Directly inhibit thrombin

-Interferes with normal synthesis and -carboxylation of vitamin K-dependant clotting factors (II, VII, IX, X, protein C & S) -Affects Extrinsic pathway and PT -Long half-life (The EX-PaTriot went to WAR(farin))

-Follow patient's PT/INR values when on warfarin -Metabolized by cytochrome P450 -SE: bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions

Heparin vs. warfarin Structure Route of administration Site of action Onset of action Mechanism of action Duration of action
Inhibits coagulation in vitro

Heparin Large anionic polymer, acidic Parenteral (IV, SC) Blood Rapid (seconds) Activates antithrombin III, which the action of IIa (thrombin) and Xa Acute (hours Yes Protamine sulfate PTT (intrinsic pathway) No -Early MI -Early ischemic stroke -Directly or indirectly aids conversion of plasminogen to plasmin, which is the major fibrinolytic enzyme that cleaves thrombin and fibrin clots. -PT, PTT, no change in platelet count

Warfarin Small lipid-soluble molecule Oral Liver Slow, limited by half-lives of normal clotting factors Impairs the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X (vitamin K antagonist) Chronic (days) No IV vitamin K and fresh frozen plasma PT/INR (extrinsic pathway) Yes (teratogenic) -SE: bleeding -C/I: Patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension -Treatment of toxicity is with aminocaproic acid, an inhibitor of fibrinolysis

Treatment of acute OD Monitoring Crosses placenta Thrombolytics Streptokinase, Urokinase, tPA (alteplase), APSAC (anistreplase)

Antiplatelet drugs Aspirin (ASA)

Clopidogrel, Ticlopidine

Abciximab

-Antipyretic -Analgesic -Anti-inflammatory -Antiplatelet drug -Acute coronary syndrome -Coronary stenting - incidence or recurrence of thrombotic stroke -Acute coronary syndromes -Percutaneous transluminal coronary angioplasty

-Acetylates and irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) to prevent conversion of arachidonic acid to thromboxane A2. -Inhibit platelet aggregation by irreversibly blocking ADP receptors. -Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression. -Monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation.

- bleeding time. -No effect on PT, PTT. -SE: Gastric ulceration, bleeding, hyperventilation, Reye's syndrome, tinnitus (CN VIII) -SE: Neutropenia (ticlopidine)

-SE: bleeding, thrombocytopenia

Cancer drugs Methotrexate (MTX)

5-Fluorouracil (5-FU)

-Leukemias -Lymphomas -Choriocarcinoma -Sarcoma -Abortion -Ectopic pregnancy -Rheumatoid arthritis -Psoriasis -Colon cancer and other solid tumors -Basal cell carcinoma (topical) -Synergy with MTX -Leukemias -Lymphomas (not CLL or Hodgkin's) -AML -Non-Hodgkin's lymphoma -Breast and ovarian carcinoma -Immunosuppressant -Brain tumors (including glioblastoma multiforme)

-S-phase-specific antimetabolite. -Folic acid analog that inhibits dihydrofolate reductase, resulting in dTMP and therefore DNA and protein synthesis.

-SE: -Myelosuppression, which is reversible with leucovorin (folinic acid) "rescue." -Macrovesicular fatty change in liver -Mucositis

-S-phase-specific anti-metabolite -Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thmidylate synthetase, resulting in dTMP and same effects as MTX -Blocks de novo purine synthesis -Activated by HGPRATase -Inhibit DNA polymerase -Alkylating agent '-Covalently cross-link (interstrand) DNA at guanine N-7 -Alkylate DNA

-SE: -Myelosuppression (NOT reversible with leucovorin). Can "rescue" with thymidine -Photosensitivity -Metabolized by xanthine oxidase; thus toxicity with allopurinol -SE: Bone marrow, GI, liver -SE: Leukopenia, thrombocytopenia, megaloblastic anemia -Requires bioactivation in liver -SE: Myelosuppression; hemorrhagic cystitis. Hemorrhagic cystitis can be partially prevented with mesna -Requires bioactivation -Crosses blood-brain barrier CNS -SE: CNS toxicity (dizziness, ataxia)

6-mercaptopurine (6-MP) Cytarabine (ara-C) Cyclophosphamide, Ifosfamide

Nitrosoureas Carmustine Lomustine Semustine Streptozocin Cisplatin, Carboplatin Busulfan Doxorubicin (adriamycin), Daunorubicine Dactinomycin (actinomycin D)

-Testicular, bladder, ovary, and lung carcinomas -CML -Part of ABVD combo for Hodgkin's and for myelomas, sarcomas, solid tumors (breast, ovary, lung) -Wilm's tumor -Ewing's sarcoma -Rhabdomyosarcoma (ACTinomycin D is used for childhood tumors (children ACT out)

-Act like alkylating agent -Alkylates DNA -Generate free radicals and noncovalently intercalate in DNA (creating breaks in DNA strand to replication) -Intercalates in DNA

-SE: Nephrotoxicity, acoustic nerve damage -SE: Pulmonary fibrosis, hyperpigmentation -SE: Cardiotoxic, myelosuppression, marked alopecia, toxic extravasation

-SE: Myelosuppression

Bleomycin

Hydroxyurea

Etoposide (VP-16)

Prednisone

Tamoxifen, Raloxifene

-Testicular cancer -Lymphoma (part of ABVD regimen for Hodgkin's) -Melanoma -CML -Sickle cell disease -Small cell carcinoma of lung and prostate -Testicular carcinoma -Most commonly used glucocorticoid in cancer therapy -CLL -Hodgkin's lymphoma (part of the MOPP regimin) -Immunosuppressant used in autoimmune disease -Breast cancer -Osteoporosis prevention

-Induces free radical formation, which causes breaks in DNA strands -Inhibits Ribonucleotide Reductase DNA Synthesis (S-phase specific) -G2-phase-specific agent -Inhibits topoisomerase II and DNA degradation -May trigger apoptosis -May even work on dividing cells

-SE: Pulmonary fibrosis, skin changes, but minimal myelosuppression -SE: Bone marrow suppression, GI upset

-SE: Myelosuppression, GI irritation, alopecia

-SE: Cushing-like symptoms, immunosuppression, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

-Estrogen receptor antagonist in breast -Agonist in bone -Block the binding of estrogen to estrogen receptor-positive cells

Trastuzumab (Herceptin)

-Metastatic breast cancer

-Monoclonal antibody against HER-2 (erb-2) -Helps kill breast cancer cells expressing HER-2 possibly through antibody-dependent cytotoxicity -Philadelphia chromosome (bcr-abl) tyrosine kinase inhibitor -M-phase specific alkaloids -Bind to tubulin and block polymerization of microtubules so mitotic spindle cannot form (Microtubules are the vines of your cells) -M-phase specific agents -Bind to tubulin and hyperstabilize polymerized microtubules so mitotic spindle cannot break down (anaphase cannot occur)

-SE: -Tamoxifen may risk of endometrial carcinoma via partial agonist effects; -Roloxifen does not cause endometrial carcinoma because it is an endometrial antagonist -"Hot flashes" -SE: Cardiotoxic

Imatinib (Gleevec) Vincristine, Vinblastine

-CML -GI stromal tumors -Part of MOPP (Oncovin = vincristine) regimen for lymphoma -Wilm's tumor -Choriocarcinoma -Ovarian and breast carcinoma

-SE: Fluid retention -SE: -Vincristine : -Neurotoxicity (areflexia, peripheral neuritis), -Paralytic ileus -VinBLASTine : BLASTs Bone marrow (suppression) -SE: Myelosuppression and hypersensitivity

Paclitaxel, other taxols

CLASS/NAME NSAIDs Ibuprofen Naproxen Indomethacin Ketorolac COX-2 inhibitor Celecoxib

CLINICAL USE -Antipyretic -Analgesic -Anti-inflammatory -Indomethacin: closure of PDA -Rheumatoid and osteoarthritis

MUSCULOSKELETAL (pp 358-359) MECHANISM -Reversibly inhibit cyclooxygenase (both COX-1 & COX-2) -Block prostaglandin synthesis

SIDE EFFECTS / MISC -SE: Renal damage, aplastic anemia, GI distress, ulcers

-Reversibly inhibit specifically the cyclooxygenase (COX) isoform 2, which is found in inflammatory cells and mediates inflammation and pain -Spares COX-1, which helps maintain the gastric mucosa. Thus, should not have the corrosive effects of other NSAIDs on the GI lining. -Depolymerizes microtubules, impairing leukocyte chemotaxis & degranulation -Inhibits reabsorption of uric acid in PCT (also inhibits secretion of penicillin) -Inhibits xanthine oxidase, conversion of xanthine to uric acid.

-SE: - risk of thrombosis -Sulfa allergy. -Less toxicity to GI mucosa (lower incidence of ulcers, bleeding).

Gout drugs Colchicine

-Acute gout

Probenecid Allopurinol

-Chronic gout -Chronic gout -Also used in lymphoma & leukemia to prevent tumor lysis-associated urate nephropathy -Antipyretic -Analgesic -Lacks anti-inflammatory properties -Rheumatoid arthritis -Psoriasis -Ankylosing spondylitis. -Crohn's disease -Rheumatoid arthritis -Ankylosing spondylitis

-Do not give salicylates -SE: GI side effects, especially if given orally. (Indomethacin is less toxic, more commonly used in acute gout). -C/I: should not be used to treat an acute episode of gout -Interacts with azathioprine & 6-MP -C/I: should not be used to treat an acute episode of gout

Misc drugs Acetaminophen

-Reversibly inhibits cyclooxygenase, mostly in CNS. -Inactivated peripherally. -Recombinant form of human TNF receptor that binds TNF (EtanerCEPT is a TNF decoy reCEPTor) -Anti-TNF antibody (INFLIXimab INFLIX pain on TNF)

-SE: Overdose produces hepatic necrosis; acetaminophen metabolite depletes glutathione and forms toxic tissue adducts in liver. N-acetylcysteine is antidote - regenerates glutathione.

Etanercept

Infliximab

-SE: Predisposes to infections (reactivation of latent TB)

CLASS/NAME Opioid Analgesics Morphine Fentanyl Codeine Heroin Methadone Meperidine Dextromethorphan

CLINICAL USE -Pain -Cough suppression (dextromethorphan) -Diarrhea (loperamide and diphenoxylate) -Acute pulmonary edema, -Maintenance programs for addicts (methadone)

NEUROLOGY (pp 394-399) MECHANISM -Acts as agonist at opioid receptors (mu=morphine, delta= enkephalin, kappa=dynorphin) to modulate synaptic transmission

SIDE EFFECTS / MISC -SE: -Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs -Tolerance does not develop to miosis and constipation. -Toxicity treated with naloxone (opioid receptor antagonist).

Note: There is a table on p. 395 of First Aid 2008 detailing the specific usage of epilepsy drugs Benzodiazepines Diazepam Lorazepam Triazolam Temazepan Oxazepam Midazolam Chlordiazepoxide Alprazolam Carbamazepine -Anxiety -Spasticity -Status epilepticus (lorazepam and diazepam) -Detoxification (esp. alocohol withdraw- DTs) -Night tremors -Sleepwalking -Facilitate GABAA action by frequency of Cl- channel opening (FREnzodiazepines= FREquency) -Most have long half-lives and active metabolites -Short acting= TOM Thumb (Triazolam, Oxazepam, Midazolam) -SE: -Sedation, tolerance, dependence, addictive CNS depression effects with alcohol -Less risk of respiratory depression and coma than with barbiturates -Treat overdose with flumazenil (competitive antagonist at GABA receptor) -SE: Diplopia, ataxia, blood dyscrasis (agranulocytocic, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P-450 -SE: -GI distress, fatigue, headache, urticaria -Stevens-Johnson syndrome -Prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital). Skin lesions progress to epidermal necrosis and sloughing. (EFGH- Ethosuximide, Fatigue, GI, Headache) -Facilitate GABAA action by duration of Cl- channel opening, thus neuron firing (BarbiDURATe ( DURATion)) -SE: -Sedation, tolerance, dependence -Induction of cytochrome P-450; -Addictive CNS effects with alcohol, -Respiratory or cardiovascular depression (can lead to death) -Treat overdose with symptom management (assist respiration, BP) -C/I: Porphyria

-Epilepsy

Ethosuximide

-Epilepsy

Barbiturates Phenobarbital Pentobarbital Thiopental Secobarbital

-Sedative for anxiety -Epilepsy -Seizures -Insomnia -Induction of anesthesia (thiopental)

Phenytoin

-Epilepsy -Tonic-clonic seizures -Also a class IB antiarrhythmic

-Use-dependent blockade of Na+ channels -Inhibition of glutamate release from excitatory presynaptic neuron

-SE: -Nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, megablastic anemia, teratogenesis, SLE-like syndrome, induction of cytochrome P-450 -Chronic use produced gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia ( folate absorption), and malignant hyperthermia (rare) -Teratogenic (fetal hydantoin syndrome). -SE: -GI distress, tremor, weight gain -Rare but fatal hepatotoxicity (measure LFTs) -Neural tube defects in fetus (spina bifida) -C/I: Pregnancy -SE: Stevens-Johnson syndrome -SE: Sedation, ataxia. -SE: Sedation, mental dulling, kidney stones, weight loss

Valproic acid

-Epilepsy

Lamotrigine Gabapentin Topiramate

-Epilepsy -Epilepsy -Epilepsy

Anesthetics general principles

-CNS drugs must be lipid soluble (cross blood-brain barrier) or actively transported -Drugs with solubility in blood = rapid induction and recovery times -Drugs with solubility in lipids = potency = 1/MAC (minimal alveolar concentration) -Examples: -N2O has low blood and lipid soluble, and thus fast induction and low potency -Halothane, in contrast, has lipid and blood solubility and thus slow induction and high potency -Anesthesia: myocardial depression, respiratory depression, nausea/emesis, cerebral blood flow cerebral metabolic demand -Unknown -SE: -malignant hyperthermia (rare) -halothane: hepatotoxicity -methoxyflurane: nephrotoxicity -enflurane: proconvulsant

Inhaled anesthetics Halothane Enflurane Isoflurane Sevoflurane Methoxyflurane Nitrous oxide IV anesthetics Barbituates (Thiopental) Benzodiazepines (Midazolam)

B. B. King on Opiates Proposes Foolishly -Induction of anesthesia -Short surgical procedures. -Endoscopy -used in adjunct with gaseous anesthetics and narcotics -Act as dissociative anesthetics -PCP analogs - cerebral blood flow -High potency, high lipid solubility, rapid entry into brain. -Effect terminated by redistribution from the brain. -SE: -May cause severe postoperative respiratory depression, BP, and amnesia -Treat overdose with flumazenil - cerebral blood flow -SE: -Cardiovascular stimulants -Cause disorientation, hallucination, and bad dreams

Arylcyclohexylamines (Ketamine)

Opiates (Morphine, Fentanyl) Propofol

-Used with other CNS depressants during general anesthesia -Rapid anesthesia induction -Short procedures

-SE: Less postoperative nausea then thiopental

Local anesthetics Esters Procaine Cocaine Tetracaine Amides Lidocaine Mepivacaine Bupivacaine (AmIdes have 2 letter I's in the name)

-Minor surgical procedures -Spinal anesthesia -Give amides if allergic to esters

-Block Na channels by binding to specific receptors on inner portion of channel. -Preferentially bind to active Na channels, so most effective in rapidly firing neurons. -3 amine local anesthetics penetrate the membrane in uncharged form, then bind to ion channels as charged form.

-Principles: -In infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate membrane effectively. Therefore, more anesthetic is needed in these cases. -Order of nerve block: - small-diameter fibers > large diameter - myelinated fibers > unmyelinated fibers - Overall, size factor predominates over myelination such that small myelinated > small unmyelinated > > large myelinated > large unmyelinated -Order of loss: - pain (first) > temperature > touch > pressure (last) -Except with cocaine, given with vasoconstrictors (epinepherine) to enhance local action bleeding, anesthesia by systemic concentration -SE: -CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine)

Neuromuscular blocking drugs Depolarizing Succinylcholine

Used for muscle paralysis in surgery or mechanical ventilation

Selective for motor (vs. autonomic) nicotinic receptor -Phase 1 - prolonged depolarization -No antidote -Block potentiated by cholinesterase inhibitors -Phase 2 - repolarized but blocked -Antidote is cholinesterase inhibitors (e.g. neostigmine) -Competitive -complete with Ach for receptors -Reversal of blockade via: -Neostigmine, edrophonium, and other cholinesterase inhibitors -SE: Hypercalemia and hyperkalemia

Nondepolarizing Tubocurarine Atracurium Mivacurium Pancuronium Vecuronium Rocuronium Dantrolene -Malignant hyperthermia

-Prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle

-Neuroleptic malignant syndrome

-Malignant hyperthermia is caused by concomitant use of inhalation anesthetic (except nitrous oxide (N2O)) and succinylcholine. -Neuroleptic malignant syndrome is a toxicity of antipsychotic drugs

Parkinson's disease drugs Bromocriptine Amantadine Levodopa (with carbidopa) Selegiline (and COMT inhibitors) Antimuscarinics (BALSA) Bromocriptine Pramipexole Ropinirole Amantadine L-dopa (levodopa) with carbidopa

-Strategies to treat Parkinson's are to -Agonize dopamine receptors - dopamine -Prevent dopamine breakdown -Curb excess cholinergic activity

-Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity -For essential or familial tremors, use -blockers

-Parkinsons

-Agonize dopamine receptors -Bromocriptine is an ergot alkaloid and partial dopamine agonist -SE: ataxia -Carbidopa is given with L-dopa in order to the bioavailability of L-dopa and limit peripheral side effects -SE: -Arrhythmias from peripheral conversion to dopamine -Long-term use dyskinesia following administration and akinesia between doses -SE: May enhance adverse effects of L-dopa

-Parkinsons - dopamine release -Antiviral (influenza A and rubella) -Parkinsonism -Carbidopa increases bioavailability of L-dopa and limits peripheral side effects - level of dopamine in the brain -L-dopa, unlike dopamine, can cross the blood brain barrier and is converted into dopamine in the CNS by dopa decarboxylase -Carbidopa is a peripheral decarboxylase inhibitor -Prevent dopamine breakdown -Selectively inhibits MAO-B, thereby the availability of dopamine. -Prevent dopamine breakdown -COMT inhibitors -Antimuscarinic - curb excess cholinergic activity -5-HT1D agonist -Causes vasoconstriction

Selegiline

-Parkinsons (is an adjunctive agent to L-dopa for Parkinson's) -Parkinsons -Improves tremor and rigidity -Little effect on bradykinesia -Acute migraine -Cluster headache attacks

Entacarpone, Tolcapone Benztropine Sumatriptan

" your tremor before you drive your Mercedes-BENZ" -Half-life < 2 hrs -SE: Coronary vasospasm, mild tingling, hypertensive emergencies. -C/I: patients with CAD or Prinzmetal's angina

CLASS/NAME Psychiatric condition Alcohol withdrawal Anorexia/bulimia Anxiety

CLINICAL USE Drug used BZD SSRIs Barbiturates BZD Buspirone MAOI Methylphenidate (Ritalin) Amphetamine MAOI Mood stabilizers: Lithium Valproic acid Carbamazepine

PSYCHIATRY (pp 415-417) MECHANISM

SIDE EFFECTS / MISC

ADHD Atypical Depression Bipolar Disorder

Depression

SSRI TCA Depression w/ insomnia Trazodone Mirtazapine OCD SSRIs Panic D/O Schizophrenia Tourette's Syndrome TCAs Buspirone Antipsychotics Antipsychotics (haloperidol)

-Schizophrenia -Psychosis -Acute mania (Haloperidol + '-azine's) -Tourette's syndrome Antipsychotics (neuroleptics) High potency Haloperidol, Trifluoperazine

-Block dopamine D2 receptors

-Excess dopamine effects connected with schizophrenia -DA = dopamine; DA-R = dopamine receptor

-SE: (Neurologic side effects) -Extrapyramidal system (EPS) effects: -dystonia (muscle spasm, stiffness) -akinesia (parkinsonian sx) -akathisia (restlessness) -tardive dyskinesia (stereotypic oral-facial movements due to DA-R sensitization; due to long-term antipsychotic use) -Evolution of EPS SEs: -4 h acute dystonia -4 d akinesia -4 wk akathisia -4 mo tardive dyskinesia (often irreversible) -Neuroleptic malignant syndrome: -rigidity -myoglobinuria -autonomic instability -hyperpyrexia -(treat w/ dantrolene and DA agonists) -SE: (Non-neurologic side effects) -endocrine: - DA-R antagonism hyperPRL galactorrhea -muscarinic block: dry mouth, constipation --block: hypotension -histamine-R block: sedation

Low potency Thioridazine Chlorpromazine

Unspecified Fluphenazine

Atypical antipsychotics Clozapine Olanzapine Risperidone Quetiapine Aripiprazole Ziprasidone

-Schizophrenia, for positive and negative symptoms

-Block 5-HT2 and dopamine receptors

-SE: Fewer EPS and anticholinergic SE than other antipsychotics

(It's not atypical for old closets to risper) Olanzapine -Schizophrenia -OCD -Anxiety -Depression -Mania -Tourette's syndrome Clozapine Lithium -Schizophrenia -Mood stabilizer for bipolar affective disorder -Blocks relapse and acute manic events -Unknown -Possibly related to inhibition of phosphoinositol cascade -SE: agranulocytosis (requires weekly WBC monitoring) -narrow therapeutic window, so requires close monitoring of serum lvls -SE: -tremor -polyuria (ADH antagonist => nephrogenic diabetes insipidus) -hypothyroidism -teratogenesis (LMNOP: Lithium side effects - Movement (tremor), Nephrogenic DI, HypOthyroidism, Pregnancy problems) -Does not cause addiction or sedation -No interaction w/ EtOH

Buspirone

-Anxiolytic for generalized anxiety disorder (GAD)

-Stimulates 5-HT1A receptors

ANTIDEPRESSANTS SSRIs Fluoxetine Sertraline Paroxetine Citalopram -Endogenous depression -OCD -Anorexia/bulimia -Serotonin-specific reuptake inhibitors

-It normally takes 2-3 weeks for anti-dep to have an effect -SE: (Fewer than TCAs) -GI distress -sexual dysfunction (anorgasmia) -"serotonin syndrome" w/ MAOI: hyperthermia, muscle rigidity, cardiovascular collapse -SE: -sedation (desipramine is the least sedating) --blocking effects -atropine-like (anticholinergic) side effects (tachycardia, urinary retention) -3 (amitriptyline) have more anticholinergic effects than 2 (nortriptyline) -at toxic levels, Tri-C's: Convulsions, Coma, Cardiotoxicity (arrhythmias); respiratory depression, hyperpyrexia. In elderly, confusion and hallucinations due to anticholinergic side effects (use nortriptyline)

-Major depression Tricyclic antidepressants (TCA) Imipramine Amitriptyline Desipramine Nortriptyline Clomipramine Doxepin Amoxapine

-Block reuptake of NE and serotonin

Imipramine Clomipramine Monoamine oxidase inhibitors (MAOI) Phenelzine Tranylcypromine

-Major depression -Bedwetting -Major depression -OCD -Atypical depression (i.e. w/ mood reactivity, sensitivity to rejection, hypersomnia) -Anxiety -Hypochondriasis

-Nonselective MAO inhibition => levels of amine neurotransmitters

-SE: -hypertensive crisis w/ tyramine ingestion (in many foods, e.g. cheese) and -agonists -CNS stimulation -C/I: SSRIs or meperidine (prevent serotonin syndrome)

OTHER ANTIDEPRESSANTS You need Butane in your VEINs to MURder for a MAP of AlcaTRAZ. Bupropion (Wellbutrin) -Depression -Smoking cessation -Not well known - SE: -stimulant effects (tachycardia, insomnia) -headache -seizure in bulimic patients -does not cause sexual SE -SE: -stimulant effects -increased BP -sedation -nausea, constipation -SE: -sedation - appetite -weight gain -dry mouth -SE: -sedation -orthostatic hypotension -SE: -sedation -postural hypotension -nausea -priapism

Venlafaxine

-Depression -Generalized anxiety disorder

-Inhibits serotonin, NE, DA reuptake

Mirtazapine

-Depression

-2 antagonist ( release of NE and serotonin) -Potent 5-HT2 and 5-HT3 receptor antagonist

Maprotiline

-Depression

-Blocks NE reuptake

Trazodone

-Depression

-Inhibits serotonin reuptake

Methylphenidate (Ritalin)

-ADHD

- presynaptic NE vesicular release (like amphetamines) -Mechanism for relief of ADHD symptoms is unknown

CLASS/NAME Mannitol

CLINICAL USE

RENAL (pp 435-436) MECHANISM

SIDE EFFECTS / MISC -SE: pulmonary edema, dehydration -C/I: anuria, CHF (ACIDazolamide causes ACIDosis) -SE: Hyperchloremic metabolic acidosis, neuropathy, NH3 toxicity, sulfa allergy - Ca2+ excretion (Loops Lose calcium) -SE: (OH DANG!) Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa) Nephritis (interstitial), Gout

-Shock -Osmotic diuretic. -Drug overdose - tubular fluid osmolarity, -intracranial/intraocular pressure producing urine flow -Glaucoma -Urinary alkalinization -Metabolic alkalosis -Altitude sickness -Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema) -Hypertension -Hypercalcemia -Diuresis in patients allergic to sulfa drugs -Carbonic anhydrase inhibitor. -Causes self-limited NaHCO3 diuresis and reduction in total-body HCO3 stores -Loop diuretic (Sulfonamide) -Inhibits cotransport system (NKCC) of thick ascending limb of loop of Henle. -Abolishes hypertonicity of medulla, preventing concentration of urine -Loop diuretic (NOT a sulfonamide) -Essentially same action as furosemide

Acetazolamide

Furosemide

Ethacrynic acid

-Phenoxyacetic acid derivative -SE: similar to furosemide, can be used in hyperuricemia, acute gout (never used to treat gout)

Hydrochlorothiazide (HCTZ)

-Hypertension -CHF -Idiopathic hypercalciuria -Nephrogenic diabetes insipidus

-Thiazide diuretic -Inhibits NaCl reabsorption in the early distal tubule, reducing diluting capacity of nephron

-Ca2+ excretion -SE: (hyperGLUC) Sulfa allergy. Hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia. (the K+ STAys)

K+-sparing diuretics Spironolactone Eplerenone Triamterene Amiloride -Hyperaldosteronism -K+ depletion -CHF -Hyperaldosteronism -K+ depletion -CHF -Competitive aldosterone receptor antagonist in the cortical collecting tubule (CCT) -Block Na+ channels in the CCT

-SE: Hyperkalemia, endocrine effects (gynecomastia, antiandrogen effects) -SE: hyperkalemia

ACE inhibitors Captopril Enalapril Lisinopril

-Hypertension -CHF -diabetic renal disease

-Inhibit angiotensin-converting enzyme, reducing levels of angiotensin-II and preventing inactivation of bradykinin, which is a potent vasodilator

Losartan

-Angiotensin-II receptor antagonist

-Renin release is due to loss of feedback inhibition -SE: (CAPTOPRIL) Cough, Angioedema, Proteinuria, Taste changes, hypOtension, Pregnancy problems (fetal renal damage), Rash, Increased renin, Lower angiotensin II. Hyperkalemia. -C/I: bilateral renal artery stenosis -It is not an ACE inhibitor and does not cause cough

CLASS/NAME Antiandrogens Finasteride (propecia)

CLINICAL USE

REPRODUCTIVE (pp 453-454) MECHANISM

SIDE EFFECTS / MISC

(5-alpha reductase)

- Testosterone -----------------------> DHT (more potent) -Useful in BPH -Promotes hair growth - used to treat male pattern baldness -Prostate carcinoma -Used in the treatment of polycystic ovarian syndrome to prevent hirsutism -Used in the treatment of polycystic ovarian syndrome to prevent hirsutism -Infertility (pulsatile) -Prostate cancer (continuous use with flutamide) -Uterine fibroids -5-alpha reductase inhibitor ( conversion of testosterone to dihydrotestosterone) -Nonsteroidal competitive inhibitor of androgens at the testosterone receptor -Inhibits steroid synthesis -To prevent male-pattern hair loss, give a drug that will encourage female breast growth)

Flutamide Ketoconazole

-SE: gynecomastia and amenorrhea

Spironolactone

-Inhibits steroid binding

-SE: gynecomastia and amenorrhea

Leuprolide

-GnRH analog with -agonist properties when used in pulsatile fashion -antagonist properties when used in continuous fashion. (Leuprolide can be used in lieu of GnRH) -Inhibits cGMP phosphodiestersase, causing cGMP, smooth muscle relaxation in the corpus cavernosum, blood flow, and penile erection -Competitive inhibitor of progestins at progesterone receptors

-SE: Antiandrogen, nausea, vomiting

Sildenafil, Vardenafil

-Erectile dysfunction (Sildenafil and vardenafil fill the penis)

-SE: headache, flushing, dyspepsia, impaired blue-green color vision. -C/I: Risk of life threatening hypotension in patients taking nitrates -SE: -heavy bleeding -GI effects (nausea, vomiting, anorexia) -abdominal pain

Mifepristone (RU-486)

-Termination of pregnancy -administered with misoprostol (PGE1)

Oral contraception (synthetic progestins, estrogen)

Advantages -Reliable (<1% failure) -Risk of endometrial and ovarian cancer -Incidence of ectopic pregnancy -Pelvic infections -Regulation of menses -Used for relief or prevention of menopausal symptoms (eg. hot flashes, vaginal atrophy) -Osteoporosis (due to diminished estrogen levels) -Cervical dilation and uterine contraction to induce labor -Relax the uterus -Breast cancer in postmenopausal women -Treat hypogonadism and promote development of secondary sex characteristics -Stimulation of anabolism to promote recovery after burn or injury -Treat ER-positive breast cancer (exemestane) -Hypogonadism or ovarian failure -Menstrual abnormalities -HRT in postmenopausal women -Use in men with androgendependent prostate cancer

Disadvantages -Taken daily -No protection against STDs -Triglycerides -Depression, weight gain, nausea, hypertension -Hypercoagulable state -SE: -unopposed estrogen replacement therapy (ERT) the risk of endometrial cancer, so progesterone is added -possible CV risk

Hormone replacement therapy (HRT)

Dinoprostone

-PGE2 analog

Ritodrine, Terbutaline Anastrozole Testosterone (methyltestosterone)

-2 agonist -Aromatase inhibitor -Agonist at androgen receptors -SE: -masculinization in females -reduces intratesticular testosterone in males by inhibiting Leydig cells; leads to gonadal atrophy -premature closure of epiphyseal plates - LDL, HDL.

Estrogens Ethinyl estradiol DES Mestranol

-Bind estrogen receptors

-SE: - risk of endometrial cancer -bleeding in postmenopausal women -clear cell adenocarcinoma of vagina in females exposed to DES in utero - risk of thrombi. '-C/I: ER-positive breast cancer

Progestins

-Used in oral contraceptives -Endometrial cancer -Abnormal uterine bleeding

-Bind progesterone receptors, reduce growth, and vascularization of endometrium

Estrogen partial agonists (selective estrogen receptor modulatorsSERMs) Clomiphene

-Treat infertility and PCOS

-Partial agonist at estrogen receptors in pituitary gland -Prevents normal feedback inhibition, and release of LH and FSH from pituitary, which stimulates ovulation -Antagonist on breast tissue -Agonist on bone; reabsorption of bone

-SE: -hot flashes -ovarian enlargement, -multiple simultaneous pregnancies -visual disturbances

Tamoxifen Raloxifene

-Treat and prevent recurrence of ER-positive breast cancer -Treat osteoporosis

CLASS/NAME H1 Blockers 1st generation Diphenhydramine, Dimenhydrinate, Chlorpheniramine 2nd generation Loratadine, Fexofenadine, Desloratadine, Cetirizine

CLINICAL USE -Allergy -Motion sickness -Sleep aid -Allergy relief, non-sedating

RESPIRATORY (pp 468-470) MECHANISM -Reversible inhibitors of H1 histamine receptors

SIDE EFFECTS / MISC -SE: Sedation, antimuscarinic, anti--adrenergic

-Reversible inhibitors of H1 histamine receptors

-SE: Far less sedating than 1st generation because of entry into CNS

Asthma drugs Isoproterenol Albuterol Salmeterol Theophylline -Use during acute exacerbation of asthma -non-specific -agonist -Relaxes bronchial smooth muscle (2) -2 agonist -Relaxes bronchial smooth muscle (2). -2 agonist -Long acting agent for prophylaxis -Methylxanthine -Likely causes bronchodilation by inhibiting phosphodiesterase, thereby cAMP hydrolysis -Asthma -COPD -Muscarinic antagonist -Competitive block of muscarinic receptors, preventing bronchoconstriction -SE: Tremor, arrhythmia -Metabolized by P450 -Usage is limited because of narrow therapeutic index. -SE: Narrow therapeutic range (cardiotoxicity, neurotoxicity) -Also used for COPD -SE: Tachycardia (1)

Ipratropium

Cromolyn

-Asthma prophylaxis

-Prevents release of mediators from mast cells -Inhibit the synthesis of virtually all cytokines. -Inactivate NF-B, the transcription factor that induces the production of TNF-, among other inflammatory agents. -Antileukotriene -5-lipoxygenase pathway inhibitor. -Blocks conversion of arachidonic acid to leukotrienes

-Effective only for prophylaxis of asthma. Not effective during acute asthma attack. -SE: Rare

Corticosteroids Prednisone Beclomethasone Zileuton

-1st line therapy for chronic asthma

Zafirlukast Montelukast

-Especially good for aspirin-induced asthma -Especially good for aspirin-induced asthma

-Antileukotriene -Blocks leukotriene receptors -Antileukotriene -Blocks leukotriene receptors

Expectorants Guaifenesin (Robitussin) N-acetylcysteine -Mucolytic -Acetaminophen overdose

-Removes excess sputum but large doses necessary; does not suppress cough reflex. -Can loosen mucous plugs in CF patients -Also used as an antidote in acetaminophen overdose.