CYTOTOXIC AGENTS

ALKYLATING AGENTS

MECHLORETHAMINE (Nitrogen mustard)

-IV; half life is very short

ma: 1. Alk of 7-guanine= mispairing, ring openings, excision of guanine

       2. binfunctional interstrand crosslinking= cytotoxic

r: -decreased permeability

   -increased production of nucleophiles

    -increased DNA repair

tu: Hodgkins (MOPP)

tox: Nausea, vomit, marrow depression, phlebitis, amenorrhea

CYCLOPHOSPHAMIDE (Nitrogen mustard)

-oral or IV, must be metabolized by liver before active

tu:1.Hodgkins and ALL

    2. Autoimmune dz

    3. bone marrow transplant, cheap alt for renal transplant

tox: nausea, vomit, marrow depression, hemorrhagic cystitis

BUSULFAN

ma: bifunctional alky. crosslinker

tu: CML

tox: dose limiting marrow depression, pulm. fibrosis at high doses

BCNU (nitrosourea)

-IV, very lipophilic

ma: similar to nitrogen mustards

tu: HD, CNS leukemia and tumors, solid tumors (lung,gi,breast)

tox: thrombocytopenia, leukopenia, nausea, vomit, phlebitis, HoTN, tachycardia, pulm. fibrosis, renal damage, reversible hepato tox, CNS tox, leukemia

CCNU

-oral, very lipophilic, active metabolite

tox: thrombocytopenia, leukopenia, nausea, vomit, pulm fibrosis, renal, CNS, leukemia

CISPLATIN

-IV, intraperitoneal, rapidly nephrotoxic

ma: intra and interstrand crosslinking of DNA

tu: testicular, ovarian, lung CA

tox: Nephrotoxic, severe nausea and vomit, anaphylactic rxn, ototox, peripheral neuropathy, marrow depression

CARBOPLATIN

tox: mod nausea, vomiting, marrow depression, low potential for ototox and peripheral neuropathy

NONCOVALENT DNA BINDING

ACTINOMYCIN D

-can cause severe local necrosis

ma: 1. Intercalates into DNA

       2. inhibits DDRNA pol

r: increased efflux

tu: 1. Pediatric tumors

      2. choriocarcinoma

tox: marrow depr, dermatologic, radiation recall

DAUNORUBICIN (anthracycline antibiotic)

-IV, extensive metabolism by liver

ma:1. Intercalation

      2. topo II inhib = DNA breaks

r: MDR

tu: ALL & AML

tox: marrow depr, cardiotox, radiation recall

DOXORUBICIN

TU: 1. Solid tumors (BREAST, ovary, bladder, lung)

ETOPOSIDE

-iv or oral

ma: topoII inhib = DNA breaks

r: decr. Topi II and MDR

tu:testicular, lung CA

tox: marrow depr, +

TOPOTECAN

ma: topo I

tu: ovarian, lung CA

tox: myelosuppression, diarrhea

BLEOMYCIN

-iv or im, RENAL excretion

ma: bind Fe and DNA = oxygen free radicals = DNA cleavage

R: high levels of hydrolase enzyme

Tu: squamous cell CA, testicular CA, HD

Tox: skin and mucous, pulm tox (NOT immunosuppressive!)

ANTIMETABOLITES

METHOTREXATE (antifolate)

-oral, iv, intrathecal; 50% protein bound, renal elim

ma: inhibits DHFR = blocks formation of thymidylate and purines during s phase

r: 1. Decr. Uptake

    2. incr. DHFR gene

    3. decr. MTX polyglutamate formation (needed to retain drug in cell)

tu:1. Choriocarcinomas

    2. ALL maintenance in children to prevent CNS relapse

    3. breast CA

    4. RA and GvH dz

tox: marrow depr, mucositis, gi bleeding

HIGH DOSE MTX RESCUE THERAPY

-given with folinic acid to protect normal tissues

tu: protections against leukemic meningitis, osteosarcoma

tox: renal

6-MERCAPTOPURINE AND 6-THIOGUANINE

ma: first must be converted to nucleotide thru PRTase

1.      inhib de novo purine synthesis (PRPP & IMP)

2.       inhib purine interconversion

3.       incorp into DNA and RNA as a triphosphate

r: altered PRTase, increased alkaline phosphatase

tu: 6MP=ALL maintenance in children

     6TG= AML

tox: marrow depr, nausea, vomit, anorexia, hyperuricemia, hyperuricosuria

5-FLUOROURACIL

-IV, liver metabolism, enters CNS

ma: must be converted to nucleotide

1.      inhib thymidylate synthetase (TMP)

2.       incorp into DNA and RNA

r: 1. Decr. Conversion to nucleotide

2.       changes in TMP

tu: gi  &  basal cell CA

tox: bone marrow depr, mucositis, diarrhea, nausea, vomit, alopecia, cerebellar, dermopathy, jaundice

CYTOSINE ARABINOSIDE

-iv, liver is major site of deamination

ma: must be converted to a nucleotide

      -potent inhib of DNA elongation

r: depends on balances of kinases and deaminases

tu:ALL & AML

tox: marrow depr, neurotox at high doses

GEMCITABINE

Ma: once converted, incorp into DNA, it promotes its own intracellular accumulation

Tu: metastatic breast cancer, non-small cell lung, ovarian, bladder, PANCREATIC

Tox: marrow depr

MICROTUBULE INHIBITORS

VINCRISTINE

-iv, very irritating to tissues, caution with decr. Liver function!

Ma: inhib aggregation of microtubules = metaphase arrest

R: decr. Drug accumulation and MDR

Tu: ALL, HD, NHD

Tox: peripheral neuropathy

VINBLASTINE

Tu: metastatic testicular ca, HD, NHD

Tox: marrow depr

PACLITAXEL (Taxol)

-ma: increases microtubule aggregation

r: MDR

tu: ovarian, lung, breast

tox: bone marrow depr

MISCELLANEOUS

ASPARAGINASE

Ma: asparaginase hydrolysis

Tu: ALL

HYDROXYUREA:

Ma: ribonucleotide reductase inhib

Tu: CML

Tox: marrow depr

NONCYTOTOXIC AGENTS

TAMOXIFEN (antiestrogen)

Ma: competitive inhib of estrogen receptor = decr. Autocrine stimulation

Tu: breast ca (ER+ and PR+) and chemoprevention of breast ca

Tox: menopausal symptoms, ocular tox, thromboemolic events, gynecologic (endometrial CA, polyps, cysts)

ANASTROZOLE

-nonsteroidal, reversible

ma: aromatase inhib

tu: metastatic breast ca

tox: gi

EXEMESTANE

-steroidal, nonreversible

-otherwise same as anastrozole

BEXAROTENE

Ma: activate retinoid x receptor = increased cellular differentiation and proliferation

Tu: cutaneous T cell lymphoma

Tox: lipid abnormalities, hypothyroidism

RUTUXIMAB

Ma: 1. Mouse/ human IgG to CD20 = lysis

             2.does not affect stem cells

    3. sensitizes lymphoma cells to cytotoxic effects of drugs

tu: NHD

tox: flu-like

IMMUNOTHERAPY

ALPHA INTERFERON

Ma:stimulates host defense

Tu: 1. Hematologic malignancies

       2. solid tumors (renal, Kaposis, melanoma)

       3. immunomodulation (chronic gran. Dz, MS)

tox: flu like

AZATHIOPRINE (imuran)

Ma: prodrug of 6-MP

Tu: 1. Renal transplant

       2. autoimmune dz

tox: marrow depr, gi, hepatotox

MYCOPHENOLATE MOFETIL

Ma: 1. Inhib IMP (de novo purine syn)

       2. inhib lymphocyte prolif and Ab production

       3. inhib lymphocyte recruitment

tu: renal and liver transplant

tox: gi and marrow depr

MUROMONAB-CD3

Ma: monoclonal Ab to CD3 of  T cells (not humanize)

Tu: renal, liver, and heart transplants

Tox: 1. Cytoki ne release syndrome

         2. anaphylaxis

         3. CNS

              4. immunosuppression

BASILIXIMAB

Ma: mouse/human Ab that blocks IL2 receptor on T cells

Tu: renal transplants (with cyclosporine and corticosteroids)

Tox: gi

CYCOSPORINE

-cytochrome P450 metabol, very lipophilic and hydrophobic

ma: 1. Binds to cyclophilin and inhibits calcineurin leading to down regualtion of IL2 and other cytokines

        2. stimulates TGF-beta (immunosuppressive and may stimulate tumor growth)

tu: 1. Organ transplants

     2. autoimmune dz (psoriasis)

tox: nephrotox, neurotox, HTN, opportunistic infections, increased risk of lymphoma

TACROLIMUS

-cytochrome P450

ma: like cyclosporine (except binds to FK506) and more potent

tu: organ transplants

tox: nephrotox, neurotox, metabolic tox

SIROLIMUS

-cytochrome P450

ma: antiproliferative by blocking cytokine pathways, binds to FKBP12 in a calcium independent pathway

tu: organ transplants

tox: gi, thrombocytopenia, lipid abnormalities

ANTICOAGULANTS

HEPARIN

-iv and subcutaneous, does NOT cross placenta

ma: needs ATIII to be active, inhibits thrombin and Xa (also Ixa,Xia,XII, kallikrein)

se: bleeding, thrombocytopenia, rare allergic rxns, liver tox, aldosterone inhib, nausea, vomit, HA, lacrimation, fever

PROTAMINE SULFATE

-inhibits heparin by preventing its binding with ATIII

ENOXAPARIN & DALTEPARIN               

-low molecular weight heparin, longer half life

ma: inhib Xa when ATIII present (NOT thrombin)

tu: following hip replacement to prevent DVT

HIRUDIN

-direct inhib of thrombin, can activate fibrin bound thrombin

-no interaction with platelets

WARFARIN

-given ORALLY; activity is delayed 36-72 hrs

-99% protein bound, excreted in urine and stool

ma: prevents activation of vit K dependent factors (2,7,9,10, protein C&S)

-can be reversed with VitK or fresh frozen plasma transfusion

tox: bleeding and many drug interactions

THROMBOLYTIC AGENTS

STREPTOKINASE

- complexes with plasminogen which activates serine protease and converts other plasminogens to plasmin systemically

ANTISTREPLASE

-streptokinase linked to lys-plasminogen which is anisoylated at the active serine site

-more localized, but must be given in large amounts

t-PA

-physiologic bound plasminogen activator with serine protease activity

UROKINASE

-serine protease that converts plasminogen to plasmin

-also facilitates migration of cells

ANTIPLATELET DRUGS

ASPIRIN

Ma: irreversibly inhib COX = decr. Thromboxane A2= decr. Platelet aggregation

Tu: prevents secondary MI

Se: gi bleeding

TICLOPIDINE

Ma: inhibits action of ADP on platelets

Tu: used in pts who can’t tolerate asp

Se: severe neutropenia, bleeding, nausea, diarrhea

DIPYRIDAMOLE

Ma: inhib platelet phosphodiesterase = incr. cAMP

Tu: prophylaxis of thromboemboli in pts with prosthetic heart valves

Se: HA, dizziness, nausea

FOLIC ACID INHIBITORS

Sulfonamides (Sulfisoxazole, Sulfacetamide, Silver Sulf)

-inhibits dihydropteroate sumtjetase

-acetylation in liver, can crystalize in kidney

-SE: Photosensativity

-TU: simple UTIs, Norcardiosis

Cotrimoxazole = Trimeth + Sulfa

-inhibits dihydropteroate reductase

TU: UTIs, Resp, Pneumo. Carinii, gi

SE: gi, rashes, thrombocytopenia, megaloblastosis (reversed by folinic acid)

CELL WALL    

Penicillins

Pen G; procaine; benzathine- IV/IM

-Strep, Meningococcal, Syphilis, some Anaerobes

-Prophylaxis of Strep Rhem. Fever, Syphilis, Surgery with valvular dz

Pen. V – oral, prophylaxis of RF

Dicloxacillin

-oral, penicillinase R

-moderately sever infections for prolonged time (osteomyelitis)

-serious Staph infections

Nafcillin

-NOT oral ; penicillinase R

Amoxicillin

-oral, incr. gram neg activity (gets thru porins)

-RT, UTI, meningitis

Ticarcillin

-Antipsuedomonal carboxypenicillin, IV/IM

Piperacillin

-antipsuedomonal ureidopenicillin, IV

-substantial biliary excretion, less effect on platelets

Augmentin

-Amox + clavulonic acid; oral or IV

-more diarrhea than others

Cephalosporins

Ceftriaxone

-drug of choice for severe gm – inf: CAP, UTI, bacteremia, meningitis, GC

SE: nephro and hema tox

Fosfomycin

-inhibits enolpyruvyl transferase

TU: uncomplicated UTIs

Vancomycin IV

TU: serious Staph inf, Strep endocard, AAPC

SE: oto & nephro tox ; Red man syndrome

NUCLEIC ACID

Metronidazole (Flagyl)

MA: inhibits na synthesis

TU: doc for trichomonas, amebiasis, giardias, ANAEROBIC inf (esp. endocarditis or meningits by B. fragilis), AAPC

SE: peripheral neuropathy, HA, gi, increases warfarin

CI: in pregnancy and with alcohol

Quinolones :Cipro  and Sparfloxacin

MA: inhib DNA gyrase (topoII), newer also topoIV

TU: UTIs, prostatitis, bone, joint, soft tissue, RT, STDs, gi, MDR Tb

SE: gi, CNS, Photosens, prolonged QT, do NOT use in children due to effects on cartilage!

50S

Erythromycin (estolate for absorption)

-macrolide, excereted by the liver

TU: doc for Mycoplasma, Legionaires, Chlamydia, MAC

SE: gi, oto tox, hepatitis (due to estolate), interferes with cyto p450

Azithromycin (Zithromax) & Clarithromycin (biaxin)

-macrolides, lack of gi effects

Clindamycin

-enterohepatic recirc.

TU: Bacteroides fragilis

SE: causes AAPC, skin rashes

Linezolid

Ma: distorts tRNA fmet

TU: MRSA and VRE                     

SE:gi

Chloramphenicol

Ma: inhibits peptidyl transferase

-excreted by kidney

TU: Typhoid, Rickettsial, meningitis, anaerobic

SE: Idiosyncratic aplastic anemia!

Streptogramins

-quinuprisin= stops aa addition

-dalfopristin= blocks peptidyl transferase

TU: bacteremia, pneumonia, skin & soft tissue (vano R staph & strep)

SE: inflamm of veins arthralgia, myalgia, diarrhea, drug interactions

30S

Aminoglycosides

-need oxygen! For transport

SE: oto & nephro tox, neuro musc block

-Streptomycin= vacterial endocard, Tb

-Gentamycin, Tobramycin, Amikacin = gm – esp. Psuedo, Enterobacter, Klebsiella, Serratia

Tetracyclins = Doxycycline

Ma: prevent access to aminoacyl tRNA

-excreted by liver and kidney

-Mg and Ca interfere with absorbtion

TU: Rickettsial, Mycoplasma, Chlamydial, Bacillary inf, Lyme dz, H. pylori, Malaria

SE: gi, photosens, hep and nephro tox, discolors teeth

(minocycline – oto tox)

ANTI-FUNGALS

Amphotericin B

MA: alters membrane, binds to ergosterol = leaks

TU: sys. Fungal inf, neutropenic and transplant pts

-lipid prep is less nephrotox

SE: infusion se, nephrotox, rev. normo anemia, neurotox

Flucytosine

MA: inhibits na syn, 5-FdUMP inhib TMP synthetase

TU: candida and cryptococcus

SE: gi,  bone marrow suppression, hepatotox

Ketoconazole

MA: alters membrane, binds to p450 and inhib lanosterol to ergosterol

TU: dermatophytes, some systemic inf when oral

SE: gi, endocrine effects

CI: preg

Itraconazole

MA: inhib ergosterol syn

TU: blasto, histo, paracocc (non-life threatening); aspergillous, Cryptococcus, Coccidio

SE: gi +

Griseofulvin

MA: inhib cellular mitosis thru microtubules

TU: dermatophytes

SE: HA, gi, induces p450-CYP3A4

CI: preg

ANTI-TUBERCULOSIS

Streptomycin (aminoglycoside)

MA: binds 30S, blocks initiation and causes misreads

TU: extracellular TB

SE: oto and nephro tox

Isoniazid

MA: inhibits mycolic acid syn

-prodrug converted by katG-catalase

TU: extracellular, intracellular, and caseous TB

SE: peripheral neuritis (if no vit B6), hepatotox, hypersensitivity

Ethambutol

MA: may affect mycolic acid (arbinogalactan syn) &/or RNA synthesis

TU: where TB  resistance is increasing & MAC

SE: optic nuritis and red-green discrimination problems

Rifampin

MA: inhibits nuc. Acid syn (DDRNA pol B)

-induces microsomal enzyme and its own metabolism

TU: extracellular, intracellular, and caseous lesions

SE: gi, hepatotox, orange-pink secretions, with high dose flu like

Pyrazinamide

MA: inhib FA synthetase1 (early step in mycolic acid syn)

TU: short term against slowly growing TB

SE: hepatotox and non-gouty arthralgia

ANTIVIRALS

Amantadine and Rimantadine

MA: reduces viral uncoating by blocking M2 ion channel

TU: RNA viruses esp. Influenza A

SE: nausea, anorexia, CNS with amantadine

CI: preg

Zanamivir (relenza)

MA: inhibits influ A and B neuraminidase

-intranasaly or inhalation

TU: influ A & B

SE: upper resp irritation and gi

Osestamivir (tamiflu)

MA: inhib influ A&B neuraminidase

-orally

TU: influ A&B

SE: nausea and vomiting

Trifluridine

MA: inhib nuc acid syn (nucleotide analog)

TU: herpes OCULAR infections

SE: hematological tox

Acyclovir

MA: inhibits na syn, (DNA pol & chain term)

-requires viral thyamidine to be present!

TU: HSV encephalitis, VZV, HSV keratitis

SE: nephro tox, gi , lcal irritation, neurotox, HA, rash

CI: preg

Valacyclovir

MA: prodrug of acyclovir with incr. oral bioavailability

TU: recurrent genital HSV, prevent CMV in transplant pts

SE: similar to acyclovir, esp. HA; thrombocytopenia and HUS in immunosuppressed

Famciclovir

MA: nucleoside analog (chain term and some DNA pol)

TU: VZV and genital HSV

SE: HA, fatigue, gi

Ganciclovir

MA: analog of acyclovir but not and absolute chain term

-much longer half life

TU: CMV retinitis, colitis, esophagitis, transplant pts

SE: granulocytopenia and thrombocytopenia!,  renaltox, fever, phlebitis, dec. visual acuity

CI: preg

Foscarnet

MA: inhibits DNA pol (pyrophosphate analog)

-give with lots of fluids

TU: CMV retinitis, acylclovir-R HSV and VZV

SE: renal dysfunction, electrolyte imbalance

Ribavirin

MA: nucleoside analog (interferes with mRNA formation, RNApol, and dec. the nucleotide pool)

TU: broad spectrum for RNA and DNA viruses, RSV, hepC, hemorrhagic viruses

SE: anemia                    CI: preg

Interferons

MA: stimulates immune sys

TU: HPV, HepC, HepB, Kaposki’s sarcoma

SE: flulike syndrome, gi effects, CNS, many others

HIV

Zidovudine (AZT)

MA: inhib RT(competitively inhib and chain term)

SE: bone marrow suppression, lactic acidosis, gi, HA, myalgia, insomnia, dizziness, myopathy

Didanosine

MA: inhibits RT

-only once daily on empty stomach

SE: painful neuropathy, pancreatitis

Lamivudine

MA: inhibits RT

-also used in chronic hepB

SE: painful neuropathy and pancreatitis

Nevirapine

MA: non-nucleoside RT inhib

SE: liver tox and skin rash

Saquinavir

MA: protease inhib (late step in Hiv replication)

SE: gi, hepatotox, hypertriglycidemia, bleeding, hyperglycemia, diabetes, fat wasting, fat redistribution (mitochondrial tox)

ANTIHISTAMINES

Diphenhydramine (benedryl. Dramamine)

-1^st generation

TU: allergic rhinitis, sleep aid, motion sickness, itching

SE: sedation, topical allergic rxns

Chlorpheniramine

-1^st generation

TU: allergies, OTC cold meds

SE: less sedation

Loratidine (claritin)

-2^nd generation H1 blocker

-prodrug, but NO cardiac K channel problems

TU: allergic rhinitis, utricaria

Fexofenadine (allegra)

-2^nd generation H1 blocker

-metabolite of tertenodine, so NO cardiac problems

TU: allergic rhinitis, utricaria

ASTHMA

Epinephrine

MA: nonselective beta agonist

-rapid and short lived

SE: anxiety, tremors, tachycardia

Albuterol (4hrs)

Ma: beta 2 agonist and some mast cell inhib

TU: acute constriction and prevention of exercise induced

SE: fine finger tremor, palpitations, tachycardia, hypokalemia

Salmeterol (12hrs)

Ma: beta2 agonist

TU: maintenance and nocturnal

SE: same as above

Ipratropium Bromide (atrovert)

MA: derv. of atropine, blocks muscarinic receptors- vagal bronchoconstriction

TU: used in tolerant pts and elderly

SE: dry mouth, throat irritation, incr. ocular pressure

Theophylline

MA: weak bronchodilator, inhib adenosine recep, phosphodiesterase, and inflamm

TU: persistant and nocturnal

SE: TOXIC! CNS, vomiting, arrhythmias, seizures

Cromolyn Sodium and Nedocromil

MA: stabilizes mast cells and hyperresponsiveness (no bronchodilation!)

TU: only prophylaxis

SE: some wheezing, bad taste

Zafirlukast

MA: leukotriene receptor antagonist

TU: maintenance

SE: mild HA, gi, incr. serum aminotransferase

Zileuton

MA: leukotriene syn. Inhib

Tu: maintenance

SE: hepatotox (must monitor)

Budesonide & Fluticasone

MA: corticosteroid

TU: prevent inflamm damage

SE: weight gain, incr. BP, osteoporosis, etc.

THYROID

Levothyroxine Sodium

-pure t4, slow (10X protein bound), long half life

TU: Hashimotos

-careful use in pt has heart dz

Liothyronine Sodium

-pure t3, rapid and shor , 5X more potent

ANTITHYROID

Propyithiouracil (PTU)

MA:throamide, inhib peroxidase, iodination, coupling, and the peripheral conversion of t4 to t3, slow onset

TU: hyperthyroid symptoms, thyroid strom

SE: agranulocytosis, rash

Methimazole

MA: thioamide, 10X more potent, slow onset

TU: used in young pts

Potassium Iodide

MA: inhib release of preformed TH (fast onset), uptake and  syn of iodide, decreases the size and vascularity of gland (before surgery), also used in radiation emergency

SE: sore throat, burning mouth, rash, diarrhea

Radioactive Iodine (I131)

-local destruction of gland

-used in old

CI: in preg/ breast feeding

PITUITARY AND HYPOTHALAMIC

Somatrem

TU: GH deficiency (IM)

MA: human sequence GH + methionine

Somatropin

TU: same

MA: human sequence GH

Sermorelin: GHRH

Octreotide

MA: somatostatin analog (inhibits GH release)

TU: acromegaly, carcinoid, secreting adenomas

SE: decr. gi motility and secretions, nausea, malabsorption, flatulence

Bromocriptine

MA: dopamine analog , D1 & D2(inhibits prolactin release)

TU: hyperprolactenemia

SE: HA, dizziness, gi

Cabergoline

-dopamine agonist, D1

TU: hyperprolactemia

SE: fewer

Arginine Vasopressin

-synthetic VP, V1 receptor – vasoconstriction

Desmopressin Acetate (DDAVP)
MA: VP analog (first oral peptide)

TU: DOC for diabetes insipidus &

        V2 (noctural eneursis, hemophilia, vonWillebrand)

DIABETES

Glyburide

MA: sulfonylurea, long acting

      -binds to ATP/K channel in beta cell = Ca++ influx = incr. insulin secretion

SE: hypoglycemia, gi, skin, liver, blood problems, weight gain

Glipizide : short acting  sulfonylurea

Metformin (glucophage)

MA: decr. glucose production, incr. glucose  uptake by liver

SE: lactic acidosis, gi, do NOT use in renal ds

Acarbose

MA: decr. glucose absorption ( inhib alpha- glucosidase)

SE: flatulence, cramps, diarrhea

Pioglitazone and Rosiglitazone

MA: thiasolidinedione- binds to PPAR (nuclear trans. Factor) to decr. gluconeogenesis and trigly. syn. in liver, incr. glucose uptake by muscle and adipose, decr, FA syn by adipose

SE: hepatotox, cardiovasc. Complications, check LFTs q 2 mo.

ADRENAL

Hydrocortisone (cortisol)

MA: short acting, not  selective

TU: replacement in adrenal insufficiency

SE: some mineralocorticoid effects

Prednisolone

MA: intermediate, relatively selective

SE: less mineralocorticoid effects

Prednisone: prodrug of Prednisone

Triamcinolone

MA: intermediate

Dexamethasone

MA: long acting (less protein bound), highly selective

TU:  after neuro surgery to reduce edema

Betamethasone

MA: long acting (less protein bound)

TU: stimulate surfactant in premies

Fludrocortisone

MA: meneralocorticoid selectivity

TU: 21-hydroxylase def. (primary adrenal insuff.)

Spironolactone

MA: aldosterone antangonis

TU: K+ sparing diuretic, also used for aldo secreting tumors and hisutism

Metyrapone

MA: adrenocortical inhibitor (inhibits 11-hydroxylase)

TU: to diagnose adreanal insuff and Cushings, to treat adrenal cancer or ectopic ACTH production

Aminoglutethimide

MA: adrenocortical inhib, stops first step in corticosteroid syn. (ALL)

TU: Cushing s and hormone dependent tumors

Ketoconazole

MA: adrenocortical inhib, blocks heme site in p450 of 11-hydroxylase and others

TU: some use in Cushings from a malignacy

MA of glucocorticoids (anti-inflamm)

-decr. arachidonic acid metabolism, vasoconstriction and decr. perm, decr. # of inflamm cells at site, decr. cytokines and response.

SE of glucocorticoids:

-immunosuppression, muscle wasting, thinning skin, osteoporosis, Decr. growth, diabetes, weight gain, ulcers, CNS effects, cataracts, glaucoma, decr. response to stress

-edema, hypernatremia, hypokalemia, alkalosis, HTN

BENZODIAZEPINES

MA: pos. allosteric modulators = incr. affinity of GABA-A for GABA rec.

SE: drowsiness, impaired coordination, confusion, short term memory loss, blurred vision, hallucinations, paradoxical rage, FATAL with ETOH, tolerance, dependence, withdrawl, cross dependence

CI: during preg, sleep apnea, drug abuse

Long acting (phase 1oxi & 2 conj):

-Clorazepate:  (prodrug) anxiety, sedative, add on for partial seizures

-Diazepam: anxiety, withdrawl, muscle relax, panic, status epi

-Flurazepam: insomnia

Short acting (phase 1 alpha hydrox &2 conj):

-Alprazolam (Xanax): anxiety, agoraphobia, pani, sedative

-Midazolam: pre-anesthetic

Triazolam: insomnia

Short acting (phase 2 conj):

-Lorazepam: anxiety, antiemetic, panic, muscle relax, st. epi, withdrawl, tremor

-Temazepam: insomnia

Flumaxemil

MA: Benzo antagonist

TU: reverse sedative effect of benzo after anesthesia or od

Buspirone

MA: partial 5HT agonist

TU: generalized anxiety

SE: tachycardia, palpitations, nervousness, gi, paresthsias

BARBITURATES

MA: prolongs the action of GABA, general membrane depressant, decr reticular activating systme, alters sleep patterns, inhibits excitatory neurotransmitter receptors (AMPA glut)

SE: decr. vasomotor, resp, and thermo center; tolerance, cross tol, dependence, withdrawl

CI: acute intermittent porphyria, sever liver ds, sleep apnea, drug abuse, morbilliform rash, uncontrolled pain

Thiopental*: ultra short, IV anesthetic

Secobarbital: short, hypnotic

Pentobarbital: intermed, hypnotic

Phenobarbital*: long, sedative and anticonvulsant

*: incr. excretion by alkalating urine

HYPNOTICS

Flurazepam (benzo)

MA: decr. delta and REM sleep. May be more effective on 2^nd night

SE: daytime drowsiness (long acting)

Temazepam (benzo)

MA: prolonged onset of action

SE: REM and insomnia rebound after chronic use discontinuation

Triazolam (benzo)

MA: ultra short

SE: REM and insomnia rebound can occur in one night, ncr. anterograde amnesia, hyperexcitability, anxiety, agitation, affective disturbances, somnambulism

Zolipidem (Ambien)

MA: acts on benzo site of GABA-A, ultra short (does not decr REM or delta )

SE: drowsiness, drugged feeling, mild rebound insomnia

Pentobarbital and Secobarbital also

ANTICONVULSANTS

Phenytoin

MA: blocks voltage gated Na channels

TU: partial and general tonic clonic, st epi

SE: nystagmus, diplopia, ataxia, lethargy, gingival hyperplasia, hirsutism, coarsening of facial features, rash, lympadenopathy, mild peripheral neuropathy

Fosphenytoin

MA: prodrug of phenytoin, no propyleneglycol or ethanol so can be given IM

Phenobarbital

MA: inc. GABA mediated Cl-

TU: partial and tonic clonic (esp. infants), st. epi, febrile sz

SE: sedation, mental dulling, paradoxical excitement, dependence, rash, decr. resp drive

Carbamazepine (tegretol)

MA: blocks voltage Na; epoxide metabolite

TU: partial and tonic-clonic

SE:  nausea, diplopia, ataxia, rashes, decr. bone marrow, hyponatremia

Oxcarbazepine

MA: prodrug for 10-hydroxy-carbazepine, so no bad metabolite or autoinduction

SE: very expensive

Valproic Acid

MA: blocks voltage Na, possible incr. GABA and decr. Cl-

MA: broad spectrum

SE: inhibits metabolism of phenobarb and lamotrigine; gi, tremor, hair loss, weight gain, rash, thrombocytopenia, hepatotox esp under 2 yo

Ethosuximide

MA: blocks voltage Ca (not protein bound)

TU: absence sz

SE: gi, HA,  behavior, rash, rare hematologic dyscrasnias

Felbate

MA: blocks NMDA receptors, voltage Ca, Na, and incr. GABA

TU: broad  spectrum

SE: anaplastic anemia, hepatic  failure esp. in adults

Lamotrigine

MA: blocks voltage Na and Ca

TU: partial, possibly tonic-clonic and L-G

SE: rash (esp with valproate), dizziness, HA, diplopia, somnolence

Gabapentin

MA: incr GABA release, blocks Na and Ca (not protein bound, no hepatic metabolism, no drug interactions)

TU: partial and tonic-clonic, mainly add-on

SE: somnlence, dizzy, HA

Topiramate

MA: blocks voltage Na, Incr. GABA, decr. glut

TU: add on for partial and tonic-clonic, possibly L-G

SE: somnolence, cognitive slowing, renal stones

Tiagabaine

MA: incr. GABA

TU: partial and tonic clonic

SE: CNS and weakness

Zonisamide

MA: blocks Na and Ca; incr GABA

TU: broad spectrum

SE: renal stones and drowsiness

Vigabatrin

MA: incr GABA

TU: partial and infantile

SE: cognitive and decr. visual field

Benzos

MA: incr GABA

-Diazepam  and Lorazepam- st epi

-Clonazepam- infantile, myclonic, occ. Absence

-Clorazepate- add-on for partial

SE: sedation, tolerance, decr resp drive

PARKINSON’S DISEASE

Levodopa

MA: bypasses rate limiting step in dopamine synthesis, converted by dopa decarboxylase

TU: used with carbidopa to decr metabolism in perphery

SE: nausea, vomiting, anorexia, peak dose dyskinesia, cariovasc, psychiatric, sleep disturbances, on –off effect phenom, loss of effect over time, interaction with vit b6 and MAOIs

CI: psychotics, angle closure glaucoma, arrythmias, melanoma

Carbidopa

MA: aromatic aa decarboxylase inhib in periphery

TU: decr SE of levodopa by decr necessary dose

Sinemet= fixed dose of Levo & carbi

Bromocriptine

MA: D2 agonist, ergot

SE: similar to levodopa + ergot assoc ( angina, digital vasospasm, erythromelagia, edema)

DI: macrolides, caffiene, ETOH

Pergolide

MA: D1 &D2 agonist, ergot

TU: longer half life, used with levodopa

Pramipexole

MA: nonergot dopamine agonist with antidepressant effects

TU: can be used alone

Ropinirole

MA: nonergot dopa agonist

SE: sudden sleep

Selegeline

MA: MAOI type B = decr metabolis of levodopa  and dopamine without tyramine syndrome

TU: may slow progress of PD (neuroprotective)

SE: insomnia, buzz, AF, incr. SE of levodopa

DI: meperidene, tricyclics

Entacapone

MA: COMT inhibitor = decr metabolism of levodpa in periphery

SE: dyskinesia, diarrhea, may incr SE of levodopa

Tolcapone

MA: similar to Entacapone

SE: liver toxictiy

Trihexyphenidyl  & Benztropine

MA: antichol (help balance Ach with dopa)

TU: reduces tremor and rigidity ( not bradykinesia)

SE: dry mouth, blurred vision, constipation, urinary retention, memory

Amantadine

MA: unknown, ? glutamate antago nist?

TU: decr tremor, bradykinesia, effects disappear over time

ANTIPSYCHOTICS

Traditional

MA: blocks all D2 receptors

TU: treats + symptp,s

-Chlorpromazine                            antichol, histamine, adrenergic SE

-Iozapine

-Haloperidol                                       EPSE

SE: incr. seizures, antichol, antihistamine, antiadrenergic, EPSE, cardio tox, sen to sun and temp, weight gain, neuroleptic malignancy syndrome

Atypical

MA: dopamine selective, 5HT2 blocker

TU: treats + & - symptoms with little EPSE

-Clozapine: A10 D1 blocker, 5HT2 blocker

SE: antichol, hist, adr, weight gain, drooling, incr. temp, tachycardia, rare agranulocytosis

-Risperidone: A9 &A10 D blocker, 5HT2 blocker, alpha-1 blocker

                        SE: dizzy, sedation, agitation; less common- EPSE, mod hyperprolactemia, incr. weight

-Olanzapine: A10 D1-4, alpha1&2, hist

                        SE: dizzy, daytime sedation, weight gain; less common- agitation, mild               hyperprolactemia, EPSE at high doses

ANTIDEPRESSANTS

Nortriptyline (palmelor)

MA: tricyclic; inhibits NE and 5HT reuptake (minor DA); also blocks hist, adr, chol

SE: antihist, adr, chol, switching,seizures

Withdrawl= Sialorrhea, Lacrimation, Urination, Diarrhea, Diaphoresis (SLUDD)

Phenelzine (Nardil)

MA: MAOi type A & B

SE: orthostatic HoTN, nausea, constipation, dry mouth, sedation, weight gain, edema, impotence, ejaculation problems, SIADH, photosens, switching, parasthesias, tyramine crisis

DI: sympathomimetics, asthma inhalants, merperidine, dopamine, ssRIs

Fluoxetine (prozac)

MA: inhib 5HT reuptake, minor NE (ssRI)

SE: 5HT2= anxiety, akathisia, agitation, insomnia, panic, sexual; 5HT3= nausea, gi, diarrheaHA;   photo sens, switching, seizures,  weight gain

Serotonin syndrome= confusion, hypomania, hyperreflexia, myoclonus, diaphoresis, shiver, tremor, diarrhea, incoordination

Buproprion (wellbutrin and zyban)

MA: inhib NE and DA reuptake

SE: overstimulation, HA, insomnia, nausea, agitation, HTN, rash; but little sexual dysfunction

Mirtazepine (remeron)

Ma: alpha2 antagonist (= incr. NE & 5HT), 5HT2 &3 blocker

SE: sedation and weight gain, photosens, switching

Venlafaxine (effexor)

MA: blocks 5HT, NE, DA reuptake

SE: 5HT2 and 3, photosens, switching, HTn

Nefazodone (serzone)

MA: inhib 5HT and NE reuptake; blocks 5Ht2 and alpha1

SE: 5HT3 with little sexual SE; photosens, switching

PEPTIC ULCER TREATMENT

Aluminum Hydroxid and Magnesium Hydroxide

MA: weak bases neutralize acid, reduce pepsin activity, protective effects

TU: duodenal ulcers

SE: inpleasant tast, large volume needes\d, Mg – laxative & ALOH – constipating, cation absroption problems, systemic alkalosis, Na content prob in CHF, may alter absroption of other drugs

Cimetidine (tagamet)

MA: H2 receptor antagonist

TU: duodenal and gastric ulcers, Z-E syndrome, GERD

SE: diarrhea, confusion esp in elderly, reversible gynecomastia, dose dependent incr prolactin, alters estrogen metabolism in men, in hibits CYP450

Ranitidine (zantac)

MA & TU: same

SE: HA in 34%

Omeprazole (prilosec)

Ma: proton pump inhib (prodrug)

TU: gastric & duodenal ulcers, GERD, hypersecretory conditions

SE: gi, gastrin dependent hyperplasia, inhib of drug metabolism

Misoprostol

MA: prostaglandin E agonist,  decr. acid secretion

TU: prophylaxis for extendend NSAID use

SE: dose dependent diarrhea, nausea

CI: in pregnancy

Sucralfate

MA:  gels at ph<4 and binds to necrotic tissue

SE: constipation ( aluminum), dry mouth, binds some drugs

Bismuth Subsalicylate (pepto bismol)

MA:  antimicrobial., binds to ulcers, inhibits pepsin, stimulates mucous secretion

SE: staining of oral and anal tissues, tinnitus

Clarithromycin + Amoxicillin + Lansoprazol (ppi)

TU: H. pylori

SE: nausea, diarrhea, dizzy

GI MOTILITY DRUGS

Diphenoxylate plus Atropine

MA: synthetic opiod;  (penetrates CNS poorly)

TU: diarrhea

SE: some abuse potential ( so atropine added to discourage abuse)

Loperamide

MA: synthetic opiod, highly specific fo gi receptors; antisecretory at low doses

TU: diarrhea

SE:

Octreotide

MA: peptide analog of Somatostain; antisecretory

TU: some hypersecretory tumors and AIDS diarrhea

SE: nausea, gi upset with short term use

Psyllium (metamucil)

MA: incr fecal mass to stimulate stretch receptors; promotes fluid retention in feces

TU: constipation

SE: allergic rxns, flatulence, obstruction, impaction (drink full glass of H2O)

Magnesium salts

MA: osmotic laxative

TU: constipation

SE: avoid us in CHF, renal impairment, elderly; excessive evacuation possible

Lactulose

Ma: osmotic; safe

Docusate salts

MA: detergent that favors fluid retention

Phenolphythalein (stimulant)

MA:  promote accumulation of water, stimulates peristalsis,  complex mechanisms

SE: cramping, vomiting, electrolyte disturbances, fat malabsorption, dependence, allergic rxns, carcinogenicity

Senna, Casacara, Bisacodyl

MA:  stimulant laxatives

Mesalamine and Sulfasalazine

MA: inhibit prostaglandin and leukotriene syn (COX)

TU: I nflamm bowel dz

SE: gi upset, malaise, allergic rxns, immune suppression

Prednisone

MA: antiinflamm

TU: IBD

SE: lots!

Infliximab

MA: monoclonal ab to TNF

TU: IBD

SE: allergic rxn, immune suppression

ANTIEMETICS

Odansetron

MA: 5HT3 antagonist

TU: during chemo and radiation

SE: transient- HA, gi, constipation, lightheadness, sedation, dizziness

Metoclopramide

MA: D2 antagonist, prokinetic, at high doses blocks 5HT3 receptor

TU: antiemetic

SE: antidopaminergic (extrapyramidal, anxiety, depression)

PARASITIC DRUGS

Chloroquine

MA: accum. In food vacuole & interferes with polymerization of heme and detox of reactive oxygen

TU:  erythrocytic forms & entaemoba histolytica

SE: if given IV- HoTN, vasodilation, EKG abnormalities ; gi, mild HA, utricaria, pruritis, visual disturbances; prolonged doses- severe visual and cardiac rxns

CI:  liver dz, gi, neurologic or blood disorders, G6-PDH def, preg

Quinine and Quinidine

MA: similar to above

TU: blood schixonticide; esp for chloroquine R faciparum

SE: gi, cinchonism (tinnitus, HA, nausea, hearing and visual disturb), hyperinsulinemia, severe HoTN (IV), hemolysis in G6-PDH def

CI: preg, G6-PDH def, hypersens, cardiac arrhythmias, tinnitus, optic neuritis

Fansidar

MA: inhib. Dihydropteroate syn (sulfadoxine) and  inhib dihydrofolate reductase (pyrimethamine)

TU: blood schixonticide for chloroquine R in one dose self tz

SE: rashes, decr. hematopoiesis, megaloblastic anemia, erythema multiforme & S-J rash

Primaquine

MA: converted to electrophiles that  interfere with ETC in parasite

TU: late HEPATIC stage

SE: large doses- gi, nausea, HA; hemolyic anemia, cyanosis, leukocytosis

CI: preg and G6-PDH def

Mefloquine

MA: similar to quinine

TU: blood schizonticide  and prophylaxis of choloroquine R and MDR falciparium

SE: gi upset, CNS tox, rare  neuropsychiatric disturbances

Artemisinin

MA: may produce free radicals

TU: blood schizonticide for all types

SE: abd pain, diarrhea, emrytox

Doxycycline

TU: used in conjunction with other antimalarial agent s for tx in MDR regions and prophylaxis

Iodoquinol

MA: unknown ? direct amebicide

TU: luminal amebicide for asymptomatic cyst passers

SE: subacute myelo-optic neuropathy

Metronidazole

MA: chemical reduction of nitro gp within parasite by ferredoxin produces reactive metabolite which damaged DNA

TU: DOC for all symptomatic cases (must be given with luminal agent)

SE: mild gi, occ neuro tox, disulfiram –like effect (ETOH)

Mebendazole

MA: inhib of microtubule polymerization by binding tubulin (poorly absorbed)

TU: broad  spectrum antihelmintic, esp for mixed inf

SE: transient abd pain and cramping, teratogenic

Thiabendazole

MA: inhib of microtubule polymerization

TU: cutaneous laval migrans (canine hookworm); alternative for Strongyliodes

SE: gi, CNS, fever, rash, potential hepatotox

Praziquantel

MA: interferes with Ca homeostasis, spastic paralysis, tegument damage and activation of host defenses

TU: DOC for shistosomiasis, trematodes, cestodes

SE: gi, CNS

Ivermectin

MA: potentiation of glutamate Cl- channels in  invertebrates

TU: onchocercisis, filariasis, nematodes

SE: mazotti-like rxn (fever, pruritis, dz, edema); minimal ocular inflamm

GOUT

Allopurinol

MA: allopurinol & active metabolite (oxypurinol) inhib xanthine oxidase = decr. uric acid

TU: hyperuricemia; ihib perfusion injury of transplants

SE: gi, drowsiness, HA, metallic taste, allopurinol hypersens synd (rash, pruritis, gi, fever, hep-renal tox), incr. freq of acute attacks, drug interactions

Probenecid

MA: uricosuric agent (blocks tubular reabsorption of uric acid )

SE: gi (no effect if taken with aspirin!), incr. frequency of acute attacks, drug interaction

CI: if history of renal lithiasis, >800mg of uric acid excreted per day, GFR<55 ml/min

Sulfinpyrazone

MA: uricosuric agent

SE: gi, ulcers, inhib thrombaxane syn and platelet formation, no effects if taken with aspirin, displaces warfarin, asp, and oral  hypoglycemics

CI: same

Colchicine

MA: prevents formation of microtubules for leukocytes to migrate along,  inhib release of chemotactic factors

TU: diagnositic aid, acute attack IF NSAIDS CI, to prevent recurrence

SE: gi (stop if you see this), if OD- liver tox, kidney tox, bone marrow depr, allopecia; if IV- tissue necrosis; hypersens. Rxn

Indomethacin

TU: actue attack and inflamm

SE: HA, gi

MUSCLE RELAXANTS

Baclofen

MA: GABA-B agonist

TU: decr. spasticity from MS &  spinal cord injury; hiccups; neuropathic pain

SE: drowsiness, insomnia, dizzy, weakness, ataxia, mental confusion, gi, withdrawl (hallucinations, anxiety, tachycardia, rebound flexor spasms); toxic ( coma, resp depr, seizures)

Diazepam

MA: GABA-A  Cl- channels (decr. excitatory neurotrans)

TU: decr. spasticity esp for spinal cord injuries; occ for cerebral palsy; muscle spasms

SE: more sedation, impaired coordination, weakness, dz, confusion, ataxia; withdrawl ( dysphoria, irritability, sweating, unpleasant dreams, tremors, anorexia); toxic (drowsiness, ataxia, dysarthria, areflexia)

Dantrolene sodium

MA: decr Ca+ release from sarcoplasmic reticulum; little effect on cardiac and smooth muscle; decr. reflex rather than voluntary contraction

TU: decr  spasticity in UMN lesions including stroke; prevent or tx malignant hypterthermia and neuroleptic malignant syndrome

SE:  will developtolerance to : drowsiness, dz, malaise, fatigue, diarrhea ; WEAKNESS; hepatotox

Cyclobenzaprine

MA: decr polysynaptic feflexes and facilitative and inhib neurol activity affecting  stretch reflexes

TU: short term tx of muscle spasms and pain

SE: drowsiness, dryness of the mouth, dz; other antichol; large doses- areflexia, flaccid paralysis, resp depr, tachycardia, HoTN

CI: acute MI, arrhythmias, CHF

Methocarbamol

MA: same

TU: discomfort caused by spasms

SE: drowsiness, incoordination, dz, discoloration of urinem gi, hypersens, blurred vision,; if IV- syncope, HoTN, bradycardia, ataxia, vertigo, seizures, hemolysis; large doses- CNS and resp depr

NSAIDS also used for muscle spasms

NEUROMUSCULAR BLOCKING AGENTS

TU: muscle paralysis for surgery, during ECT, artificial ventilation

CI: muscle dz (ALS, myasthenia gravis), burns

DI: all of the following increase NMB: antibiotics, anesthetics, barbs, quinidine, Ca channel blockers

d-Tubocurarine

MA: competitive blocker at nicotinic Ach receptor

SE: HoTN caused by: histamine release and blockade of ganglionic receptors

Pancuronium

MA: same

SE: blocks muscarinic receptors in the heart = tachycardia and slight HTN; minor effect of blocking NE reuptake

Succinylcholine

MA: phase I block= nicotinic receptor agonist (not metabolized by AchE)- accomodation= flaccid; phase II block = after large dose Ach receptor is desensitized

SE: in low dose (children): stimulates muscarinic rec in heart= neg. inotropic and chronotropic , can be prevented with atropine; in high dose (adults): stimulates nicotinic rec in autonomic ganglia = arrhythmias and HTN; may cause malignant hyperthermic crisis; do not use if atypical plasma choinesterase

LOCAL ANESTHETICS

MA: block Na+ channels along axon (ioniozed form is active; can be given with Epinephrine to reduce uptake)

SE: vasodilation (except cocaine), bradycardia, CNS effects, hypersensitivity

Benzocaine: Paraaminobenzoic acid ester, no hydrophilic gp = topical

Procaine: para aminobenzoic acid ester

Cocaine: benzoic acid ester

Lidodaine: amide

GENERAL ANESTHETICS

Thiopental

MA: barb

TU: induction (30-60 sec; duration 5min, half life=11.5 hrs)

SE: HoTN, decr myocardium, TPR, resp; antianalgesic

Propofol

MA: pot. GABA, GABA agonist at high conc

TU: induction, maintenance, sedation in ICU (11sec, duration- 8 min; half life- 1hr)

SE: HoTN, decr TPR, resp

Midazolam

MA short acting benzo

TU: calm patient; decr amt of anesthetic needed

SE: decr resp in elderly

Fentanyl

MA: opiod analgesic

TU: general anesthesia (neurolepthanesthesia)

Nitrous Oxide

MA: Least lipid soluble (incr. MAC); least aqueaous sol (fastest)

TU: good analgesic with very little effect on resp and heart

SE: degree of CNS depression  and muscle relax is limited

Halothane (most potent)

MA: very lipid sol (decr MAC), very aquesous sol (slow induction); can be given with N2O for second gas effect

SE: resp depr, decr cardiac output (sensitizates the heart), poor analgesic and muscle relax, malignant hyperthermia, autoimmune hepatitis

Isoflurane

MA: les aq and lipid sol than halothane

TU: adequate muscle relax and some analgesia

SE: dec BP, TPR, resp;  incr HR; malignant hyperthermia

Sevoflurane

TU: adequate muscle relax

SE: decr TPR, BP, CO, resp, malignant hyperthermia, release offree Fl-

HERBAL MEDS

Aloe

TU: skin ulcerations, burns, frostbite, preserving circ, dieter’s tea

MA: antimicrobial, antineoplastic, antiiinflamm, and bradykinase

SE: ARF, derm rxns, hypokalemia with prolonged use

Garlic

TU: decr chol and BP; antiCA

MA: cardiovasc, antimicrobial, antineoplastic effects

SE: heartburn, flatulence, malodorou breath and skin, possible antiplatelet effects

Ginseng

TU: tonic, performance enhancer, aphrodisiac, adaptogen, antiCA

MA: incr neurotrans, potentiates 5HT, may pot. GABA, inhib cAMP phosphodiesterase

SE: weak estrogenic (vaginal bleeding, mastalgia), ginseng abuse syn, CNS stim  and HTN in high does, hypoglycemia

DI: with digoxin and warfarin, caution with psychiatric, estrogenic, hypoglycemic drugs

CI: in preg,

Chamomile

TU: sedative, spasmolytic, antiinflamm, wound healing

MA: antineoplastic, decr inflamm, binds benzo receptors

SE: allergies

DI: avoid other sedatives

Valerian

TU: mild sedative, sleep aid, anxiolytic

MA: inhib GABA breakdown, binds to GABA-A, may bind benzo receptor, direct smooth muscle relzx, antiarrhythmic and coronary art dilation, cytotoxic to granulocyts, macrophages, lymphs, RBCs

SE: liver damage, rare HA, rare palpitations

CI: in preg and with other sedatives

St. John’s Wort

TU: mood disorders, weight loss

MA: MAOi, ssRI, NERi, DARi, antiviral, antiCA

SE: allergic rxns, photosens, gi, hypomania, mania, dizziness, confusion

CI: in preg, with other psychoactive drugs; induces CYP3A4 and glutathion-S transferase (= decr. warfarin, clozapin, olanzapine, etc.)

Kava

TU: anxiety, stress, sedative, centrally acting muscle relaxant

MA: alters limbic modulation, MAOi (b), antiplatelet effects

SE: tingling in mouth, gi upset, CNS effects (euphoria, visual, auditory), dermopathy

CI: with other depressants,  dopamine agonists/antagonists, benzos, in preg

Milk Thistle

TU: liver dz and cirrhosis

Echinacea

TU: prophylaxis of viral URI, wound healant

MA: immune modulation, inhibs COX and 5-lipoxygenase

SE: mild allergic rxns, flu-like, unpleasant taste, gi upset

Black Cohosh

TU: perimenopausal and postmenopausal symptoms

MA: may suppress LH levels and bind to estrogen receptors

SE: occ gi

CI: in preg and lactation

Phytoestrogens

TU: HRT and decr breast and endometrial CA

MA: high affinity for estrogen receptors with low activity

SE: none reported

Saw  Palmetto

TU: BPH and to improve reproductive functioning

MA: antiandrogenic, -estrogenic, -inflamm, -androgen; 5alpha reductase inhib, COX and 5-lipooxygenase inhib

SE: mild HA, gi upset, HTN, impotence, decr libido

Ginkgo

TU: dementia and diabetes circulatory problems

MA: incr blood flow, decr blood viscosity, incr NO, superoxide dismutase-like activity, blocks chemotactic factors, modifies CNS neurotrans, PAF antagonist

SE: nauseau, HA, allergy, anxiety, insomnia, hemorrhage,  ingestion of seeds can cause death

DI: antiplatelet and anticoag meds

Feverfew

TU: migranes, antiarthritic

MA: inhib 5HT release from platelets and WBCs, vasodilation, decr inflamm, inhib phagocytosis, platelet agg, and inflamm mediators

SE: gi, dz, oral ulcers, rebound HA with discontinuation

CI: in preg and coag problems

ESTROGENS

TU: Ocs, hypogonadism, hypopit, HRT (vasomotor disturbances, urogenital atropy, psychological, osteoporosis, heart dz (dec LDL, incr HDL), alzheimers), given with progestins to decr endometrial ca risk

SE: nausea, edema, breast enderness, hyperpig, HA, HTN, cholestasis, gall bladder dz, thrombophlebitis at high doses, endometrial hyperplasia and CA if given alone, gynecomastia and feminization in men

Estradiol: oral (rapid first pas metabolism), depot, topical

Conjugated Es (Premarin): oral, IV, Vaginal; major use in HRT

Ethinyl Estradiol: ethinyl gp greatly slows metabolism; used in Oral Contraceptives

Mestranol: prodrug of ethinyl estradiol,  used in Ocs

Alendronate (fosamax) (NOT AN ESTROGEN)

MA: nonsteroidal bisphosphonate that decr bone resoption

TU: postmenopausal osteoporosis

ANTI-ESTROGENS

Tamoxifen

MA: nonsteroidal mixed agonist/ antagonist

TU: breast CA, breast CA prophylaxis, beneficial effects on osteoporosis & lipids

SE: incr endometrial CA risk, incr thrombosis risk

Raloxifen (Evista)

MA: SERM

TU: beneficial effects on breast , uterus, bone, lipids

SE: ? agonist for clotting

Clomiphene (Clomid)

TU: stimulate ovulation

MA: blocks feedback receptors and incr. gonadotropin release

SE: mult births, ovarian cysts and enlargement, hot flashes

Danazol

TU: endometriosis, fibrocystic breast changes

MA: inhib gonadotropin  secretion and steroid syn, weak androgen and progestin activity

Leuprolide

TU: breast CA, endometriosis, uterine fibroids, PCO; prostate CA, hirsutism, precocious puberty

MA: GnRH agonist ( initially stimulates gonadotropin release but then desensitizes the GnRH receptors and decr. gonadotropins)

PROGESTINS

TU:alone or with E for contraception, with E for HRT, DUB due to endometrial hyperplasia, endometriosis, pallation in metastatic endometrial and breast ca, diagnosis of strogen secretion and endometrial responsiveness

SE: mentral changes, nausea, bloating, teratogenesis, androgenic (acne, weight gain, masculinization, decr. HDL and inc LDL)

Progesterone: IM, cream, suppositories, IUD, oral

Medroxyprogesterone acetate:  Provera= replacement; Depro-Provera= contraception (can have delayed recovery of fertility); chemical castration  in males

Norgestrel & Norethindrone Acetate: structurally related to testosterone; used in Ocs; lack of regular menstration, still have ovulation but affects implantation when used alone

Levonorgestrel (Norplant)

TU: birth control for 5-6 yrs, fertility returns to normal

SE: visible under skin, irregular bleeding

RU486- Mifepristone

MA: progesterone ANTAGONIST; disrupts endometrium maintence; stimulates prostaglandin levels slightly

SE: vaginal bleeding, cramps, nausea, vomiting, diarrhea, HA

“Emergency Contraceptive Kit”

-4 tablets with mod high doses of Ethinyl estradiol and levonorgestrel (2ASAP, 2 12 hrs later) ; OR 2 pills of levonorgestrel within 72 hrs

OVULATION

Clomiphene: see antiEs

Bromocriptine

TU: infertility due to excess prolactin

MA: dopamine agaonist (inhib prolactin secretion)

Human Chorionic Gonadotropin (hCG)

TU: induce ovulation and hypogonadism

MA: very similar to LH (not orally effective)

Menotropins (hMG)

TU: with hCG to induce ovulation

MA: LH and FSH activity

SE: ovaria hyperstimulation, mult births, cyst enlargement

Gonadorelin

TU: induce ovulation when defect in hypothalamus

MA: pulsatile synthetic GnRH (like leuporlide, but pulsatile)

UTERINE MOTILITY

Oxytocin

TU: induce and augment labor, restore uterine tone after delivery, enduce milk let down

MA: stimulates smooth muscle contraction, elicits milk ejection, constricts umbilical arteries and veins (but high doses relax – HoTN), stimulates prostaglandins – contraction

Prostaglandins

TU: 2^nd trimester abortions with RU486, cervical ripening at low conc

MA: stimulates uterine contractions

SE: diarrhea, vomiting, vasoconstriction, fever

Ergot Alkaloids

TU: post partum to control bleeding and maintain uterine contractions

MA: incr frequency and force of uterine contractions, constrict vascular smooth musc

SE: forceful contractions

CI: in HTN

TOCOLYTICS

Ritodrine

MA: beta-2 adrenergic receptor agonist (IV & oral)

TU: delay delivery

SE: reflex tachycardia, incr cardiac output, can induce hyperglycemia,  bronchodilation

Magnesium salts

MA: blocks Ca++ effects

TU: m. sulfate- IV to inhibit uterine motility and control eclamptic seizures; m. gluconate- orally for tocolysis maintenance

SE: high conc= resp depression and cardiac arrest

ANROGENS

TU: hypogonadism, hypopit, muscle wasting dz, antiestrogen in breast CA, promote erythropoiesis

SE: hirsutism, deep voice, clitoral enlargment, decr breast size, baldness, feminization in men, testicular atrophy, oligospermia, prostate enlargement, in cr risk of prostate CA, acne, liver dz, liver tumors (esp 17-alkyl), salt and H20 retention, HTN, psychosis, androgen rage

Testosterone- transdermal patches, pellets, gel

Testosterone esters- IM

Methyltestosterone- (17-alkyl); oral, HEPATOTOXIC

ANTI-ANDROGENS

Leuprolide

MA: GnRH analog (initially stimulates gonadotropin release but then desens receptors)

TU: prostate CA; breast CA, endometriosis, fibroids, PCO

Flutamide

MA: nonsteroidal androgen receptor antagonist

TU: prostate CA, hirsutism in women

Spironolactone

MA: antagonist at mineralocorticoid and androgen receptor

TU: alone or with Ocs for hirsutism in women; diuretic

Finasteride (propecia)

MA:  5 alpha reductase inhib (blocks Ts conversion to DHT)

TU: BPH and male pattern baldness

HYPERLIPOPROTEINEMIA

Lovastatin

MA: HMG CoA reductase inhib = incr hepatic LDL receptors, also may decr inflamm at plaque site

TU: decr LDL, TGs, inc HDL (often used with BABR)

SE: gi, HA, rash, liver problems, myopathy; CI in preg

Gemfibrozil (fibric acid)

MA: binds PPAR- gamma =incr lipoprotein lipase= incr VLDL catabolis  & decr Apo C II  may also decr FA incorp into TGs

TU: decr VLDL and incr HDL (types III, IV, V)

SE: gi, rash

CI with statins -  may incr myopathy

Cholestyramine

MA: bile acid binding resin = decr reabsorption of bile acids leads to decr feedback inhib of the enzyme converting chol to bile acid =  incr breakdown of hepatic chol = incr HMG CoA reductase and  incr LDL receptors

TU:  decr LDL, incr HDL (type Iia)

SE: constipation, mild steatorrhea, will bind other drugs

Nicotinic Acid (niacin)

MA: decr VLDL  synthesis via lipolysis inhib in adipose; decr esterification of TGs in liver, incr lipoprotein lipase = decr IDL, LDL,  and  incr HDL

TU: rapidly decr VLDL, slowly decr LDL, incr HDL = decr TGs

SE: intense cutaneous flush and pruritus, gi, hepatic, peptic ulcers, hyperglycemia, hyperuricemia

CI: preg, hepatic dz, ulcers, gout

ANTIARRHYTHMICS

Class I = Na+ channel blockers (“fast  tissue”)

                        Ia=  Na+ and Ca++ (uinidine, Procainamide, Disopyramide)

                        Ib = Na+ (Lidocaine)

                        Ic: potent Na+ and variable beta (Propafenone)

Class II = Beta blockers (“slow tissue”)  (Propranolol)

Class III = K+ channel blockers (“fast”) (Amiodarone, Bretylium, Sotalol)

Class IV = Ca++ channel blockers (“slow”) (Verapamil)

Quinidine

MA: class Ia, antimuscarinic, alpha NE blocking

TU: supravent and vent arr

SE: SA block, torsade de pointes, in AF paradox. Incr in vent rate, asystole or arr if QRS >30% wider; conchonism (tinnitus, dz, blurry, HA), gi, incr digoxin, if IV HoTN

Procainamide

MA: class Ia, proarrhythmic metabolte NAPA

TU: supravent and vent arr

SE: similar to quinine but less tdp, HoTN with rapid IV, drug induced lupus (esp in slow acetylators)

Discopyramide

MA: class Ia, antimuscarinic, Ca++ channel blocker

TU: supra vent and vent arr

SE: same as quinidine but incr antimuscarinic, negative inotropic

Lidocaine

MA: class Ib (little effect on normal tissue and atria, does NOT widen QRS)

TU: vent tachy/ arr following MI, surgery, or cardiov ersion

SE: CNS (paresthesis, drowsiness), toxic levels = convulsions, hearing disturbances, resp arrest

Propafenone

MA: class Ic, variable beta blocker

TU: life threatening vent arr (AF, SVT)

SE: proarrhythmic

Propranolol

MA: class II, at high conc direct effect on Na & K, affects regulation of Ca &K channels

TU: vent arr due to exercise/ emotions, after MI, supravent arr (AV nodal reentry)

SE: may incr CHF due to decr contraction BUT decr mortality in mild CHF; SA and AV block, sudden withdrawl may incr angina and arr

Bretylium

MA: class III (incr vent, transient incr NE followed by decr NE)

TU: drug R VF or sustained VT (chemical defib)

SE: HoTN

Amiodarone

MA: class III, Na block, Ca block, beta block

TU: prevent recurrent VF/VT (half life is 1-2 months!)

SE: pulmonary fibrosis, hepatic tox, photosens,neuro, thyroid, (? Blue discoloration of face?)

CI: with many other antiarr drugs esp beta blockers and Ca blockers

Sotalol

MA: class III and beta blocker

TU: supra vent and  vent arr

SE: tdp

Verampamil

MA: class III & beta blocker

TU: COD for supra vent tachycardia  due to AV nodal reentry; also for AF

SE: CI in severe heart failure, HoTN, sick sinus syndrome, AV block, VT , WPW synd;

Constipation, nausea, peripheral edema, if given with beta blockers or digitalis- bradycardia or AV block

Adenosine

ME: opens K+ channels and hypopolarizes AV nodal tissue

TU: paroxysmal  supravent tachy

SE: very short time of action (seconds)

Digonxin

MA: direct positive inotropic effect (inhibits Na/K/ ATPase = incr Ca++); indirect incr in parasymp

TU: CHF & AF

SE: vent extrasystoles (DAD), SA & AV block, A V junctional rhythum (triggered activity), toxic levels -  stim sympathetics; gi, neuro

ANTIHYPERTENSIVE

Hydrochlorothiazide

MA: thiazide diuretic, inhibits NaCL reabsorption

Captopril

MA: ACEi

SE: dry cough, ARF

Enalapril

MA: ACEi (prodrug & longer acting)

Losartan

MA: AT receptor antagonist

SE: HoTN, gi

Valsartan

MA: similar to losartan

SE: dizziness

Nifedipine

MA: Ca++ channel blocker

- less cardiac depression

Propranolol

MA: nonselective beta antagonist

Pindolol

MA: beta 1 , beta 2, and  sympathomimetic activity

Labetalol

MA: blockade of alpha1, beta 1, beta 2

Terazosin

MA: alpha  adrenergic receptor blocker

Clonidine

MA: CNS alpha 2 adrenergic receptors = decr symp & incr parasym

SE: dry mouth, sedation, impotence, withdrawl

Methyldopa

MA: acts on medulla oblongata = decr sympathetic = NaCl and H2O retention

SE: sedation, CNS effects, + Coombs test

Hydralazine

MA: arteriolar dilation (?unknown mech)

SE: HA, sweating, reflex tachycardia

Sodium Nitroprusside

MA: dilates arteries and veins

SE: cyanide accumulation (arrhythmias, HoTN)

Diazoxide

MA: dilates arteries, opens K+ channels

TU: HTN  emergency

SE: HoTN

ANTIANGINALS

Nitroglycerin

MA: incr NO = incr cGMP = myosin light chain dephosphorylation =  relaxation of veins = decr VR = decr preload; & dilation of coronary arteries

SE: reflex tachycardia, relax of other smooth muscles, tolerance can develop

DI: dildenafil (viagra) = severe HoTN

Isosorbide Dinitrate

MA: longer acting

Nifedipine

MA: Ca++ channel blocker = arterial relax = decr afterload; & dilation of coronaries

SE: reflex tachycarida (could aggrevate angina at high doses, HA, HoTN, dizziness, rash, somnolence, gi

Verapamil

MA: Ca++ channel blocker & negative inotropic, chronotropic, dromotropic (therefore no reflex tachycardia)

SE: cardiac depression, constipation

Propranolo, Metoprolol (beta1), Timolol, Atenolol (beta1), Nadolol

MA: beta adrenergic receptor antagonists (neg inotrope and chronotrope)

STIMULATES  M                                                     BLOCKS  M

-Bethanechol (bladder)                                     -Atropine (CNS)

                                                                                                -Scopolamine

                                                                                                -Ipratropium (bronchioles)

                                                                                                -Tropicamide (iris)

STIMULATES M &N                                              BLOCKS  M&N

-Ach                                                                                    -Botulism toxin

-Pilocarpine (ciliary)

AchE INHIB AT M                         

-Physostigmine (CNS)

-Donepezil (Alsheimers)

-Rivastigmine (Alzheimers)

AchE INHIB AT M&N                                           AchE REACTIVATOR AT N

-Neostigmine (also stimulates N)             -Pralidoxime

-Edrophonium

-Echothiophate

-Parathion

-Isoflurophate

STIMULATES ALPHA1                                    BLOCKS ALPHA1

-Phenylephrine                                                        -Prazosin

-Phenylpropanolamine

STIMULATES ALHPA2                                     BLOCKS ALPHA2

-Clonidine

STIMULATES BETA1                                       BLOCKS BETA1

-Dobutamine                                                                -Metoprolol

STIMULATES BETA2                                        BLOCKS BETA2

-Terbutaline              

-Ritodrine (uterus)

STIMULATES BETA1&2                                 BLOCKS BETA1&2

-Isoproterenol                                                          -Propranolo

                                                                                                -Timolol

BLOCKS UPTAKE OF NE                                BLOCKS DA UPTAKE

-Cocaine                                                                         = decr NE

-Imipramine                                                                 -alpha methyldopa

-Reserpine

RELEASES NE

-Tyramine

-Amphetamine