First Aid Pharm

52
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

description

pharm board review

Transcript of First Aid Pharm

Page 1: First Aid Pharm

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

Page 2: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Bacteriostatic

Bactericidal

Penicillin G (IV)

Penicillin V (oral)

-Bactericidal for gram-positive

cocci, gram-positive rods,

gram-negative cocci, and

spirochetes.

1. Bind penicillin-binding proteins

2. Block transpeptidase cross-linking of cell wall

3. Activate autolytic enzymes

-Prototype β-lactam antibiotics

-Not penicillinase resistant

-SE: hypersensitivity reactions, hemolytic anemia

Penicillinase-resistant

penicillins

Methicillin

Nafcillin

Dicloxacillin

-S. aureus

(except MRSA; resistant

because of altered pencillin-

binding protein target site)

("Use naf (nafcillin) for staph")

-Same as penicillin

-Narrow spectrum

-Penicillinase-resistant

-Penicillinase resistant because of bulkier R group

-SE: hypersensitivity reactions;

methicillin - interstitial nephritis

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)

-Same as penicillin

-Wider spectrum

-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

Antipseudomonals

Ticarcillin

Carbenicillin

Piperacillin

(TCP: Takes Care of

Pseudomonas)

-Pseudomonas spp. and

gram-negative rods

-Same as penicillin

-Extended spectrum

-Susceptible to penicillinase; use with clavulanic acid

-SE: hypersensitivity reactions

ANTIBACTERIAL THERAPY (pp 176-183)

Bacteriostatic vs

bactericidal antibiotics

Erythromycin, Clindamycin, Sulfamethoxazole, Trimethoprim, Tetracyclines, Chloramphenicol

("We're ECSTaTiC about bacteriostatics")

Vancomycin, Fluoroquinolones, Penicillin, Aminoglycosides, Cephalosporins, Metronidazole

("Very Finely Proficient At Cell Murder")

Page 3: First Aid Pharm

Cephalosporins -β-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

-Gram-positive cocci,

Proteus mirabilis, E. coli,

Klebsiella pneumoniae

(PEcK)

2nd generation

Cefoxitin

Cefaclor

Cefuroxime

-Gram-positive cocci,

Haemophilus influenzae,

Enterobacter aerogenes,

Neisseria spp.,

Proteus mirabilis,

E. coli, Klebsiella pneumoniae,

Serratia marcescens

(HEN PEcKS)

3rd generation

Ceftriaxone

Cefotaxime

Ceftazidime

-Serious gram-negative infections

resistant to other β-lactams

-Meningitis (most penetrate the

blood-brain barrier)

-Examples

-ceftazidime for Pseudomonas

-ceftriaxone for gonorrhea

4th generation

Cefepime

- ↑ activity against Pseudomonas

and gram-positive organisms

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Aztreonam -Gram-negative rods:

Klebsiella spp.

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

-A monobactam resistant to β-lactamases

-Inhibits cell wall synthesis (binds to PBP3)

-Synergistic with aminoglycosides

-No cross-allergenicity with penicillins

-No cross-sensitivity with penicillins or cephalosporins

-SE: usually nontoxic; occasional GI upset

Imipenem / cilastatin,

Meropenem

-Gram-positive cocci,

gram-negative rods, and

anaerobes.

-Drug of choice for Enterobacter

-Imipenem is a broad-spectrum,

β-lactamase-resistant carbapenem

-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.

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

-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)

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Aminoglycosides

Gentamicin,

Neomycin,

Amikacin,

Tobramycin,

Streptomycin

("Mean" GNATS

canNOT kill anaerobes)

-Severe gram-negative rod

infections

-Synergistic with β-lactam

antibiotics

-Neomycin for bowel surgery

-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

Tetracyclines

Tetracycline,

Doxycycline,

Demeclocycline,

Minocycline

Vibrio cholerae, Acne, Chlamydia,

Ureaplasma Urealyticum,

Mycoplasma pneumoniae,

Tularemia, H. pylori, Borrelia

burgdorferi (Lyme disease),

Rickettsia

(VACCUUM THe BedRoom)

-Bind to 30S and prevent attachment of

aminoacyl-tRNA

-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

Macrolides

Erythromycin

Azithromycin

Clarithromycin

-URIs, pneumonias, STDs -

gram-positive cocci

(streptococcal infections in

patients allergic to penicillin),

Mycoplasma, Legionella,

Chlamydia, Neisseria

-Inhibit protein synthesis by blocking

translocation

-Bind to the 23S rRNA of the 50S ribosomal

subunit

-Bacteriostatic

-SE: GI discomfort (most common cause of

noncompliance), acute cholestatic hepatitis,

eosinophilia, skin rashes. Increases serum

concentration of theophyllines, oral anticoagulants.

Chloramphenicol -Meningitis

(Haemophilus influenzae,

Neisseria meningitidis,

Streptococcus pneumoniae)

-Inhibits 50S peptidyltransferase activity -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)

Clindamycin -Treat anaerobic infections

(e.g. Bacteroides fragilis,

Clostridium perfringens)

-Treats anaerobes above the

diaphragm

-Blocks peptide bond formation at 50S

ribosomal subunit

-Bacteriostatic

-SE: pseudomembranous colitis (C. difficile overgrowth),

fever, diarrhea

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Sulfonamides

Sulfamethoxazole

(SMX),

Sulfisoxazole,

Triple sulfas,

Sulfadiazine,

-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)

Trimethoprim -Used in combination with

sulfonamides (trimethoprim-

sulfamethoxazole (TMP-SMX)),

causing sequential block of

folate synthesis.

-Combination used for recurrent

UTIs, Shigella, Salmonella,

Pneumocystis jiroveci

pneumonia

-Inhibits bacterial dihydrofolate reductase -Bacteriostatic

-SE: Megaloblastic anemia, leukopenia,

granulocytopenia. (May alleviate with supplemental

folic acid)

( Trimethoprim = TMP : "Treats Marrow Poorly )

Sulfa drug allergies

Fluoroquinolones

Ciprofloxacin,

Norfloxacin,

Ofloxacin,

Sparfloxacin,

Moxifloxacin,

Gatifloxacin,

Enoxacin,

(fluoroquinolones),

Nalidixic acid (a

quinolone)

-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)

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

-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

Page 7: First Aid Pharm

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

M. tuberculosis

M. avium-intracellulare

M. leprae

Anti-TB drugs

Streptomycin,

Pyrazinamide,

Isoniazid (INH),

Rifampin,

Ethambutol

(INH-SPIRE (inspire))

Cycloserine (2nd-line

therapy)

-important SE of ethambutol is

optic neuropathy (red-green color blindness).

-for other drugs, hepatotoxicity

Isoniazid (INH) -Mycobacterium tuberculosis

-The only agent used as solo

prophylaxis against TB

- ↓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)

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 -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)

Antimycobacterial drugs -prophylaxis: Isoniazid

-treatment: Isoniazid, rifampin, ethambutol, pyrazinamide

-prophylaxis: Azithromycin

-treatment: Azithromycin, rifampin, ethambutol, streptomycin

-prophylaxis: N/A

-treatment: Dapsone, rifampin, clofazimine

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Penicillins / cephalosporins

Aminoglycosides

Vancomycin

Chloramphenicol

Macrolides

Tetracycline

Sulfonamides

Quinolones

Meningococcal infection

Gonorrhea

Syphilis

History of recurrent UTIs

Pneumocystis jiroveci pneumonia

Endocarditis with surgical or dental

procedures

MRSA

VRE

Treatment of highly

resistant bacteria

Vancomycin

Linezolid and streptogramins (quinupristin / dalfopristin)

Nonsurgical

antimicrobial prophylaxis

Rifampin (drug of choice), minocycline

Ceftriaxone

Benzathine penicillin G

TMP-SMX

TMP-SMX (drug of choice), aerosolized pentamidine

Penicillins

Resistance mechanisms

for various antibiotics

β-lactamase cleavage of β-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

Page 9: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Amphotericin B -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.

-Binds ergosterol (unique to fungi);

forms membrane pores that allow leakage of

electrolytes

-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 "Swish and swallow" for oral

candidiasis (thrush); topical for

diaper rash or vaginal

candidiasis.

-Binds to ergosterol, disrupting fungal

membranes.

Misc. notes: Too toxic for systemic use.

Azoles

Fluconazole,

Ketoconazole,

Clotrimazole,

Miconazole,

Itraconazole,

Voriconazole

-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.

-Inhibit fungal steroid (ergosterol) synthesis. -SE: Hormone synthesis inhibition (gynecomastia),

liver dysfunction (inhibits cytochrome P-450), fever,

chills.

Flucytosine -Used in systemic fungal

infections (e.g., Candida,

Cryptococcus ) in combination

with amphotericin B.

-Inhibits DNA synthesis by conversion to

fluorouracil, which competes with uracil.

-SE: Nausea, vomiting, diarrhea, bone marrow

suppression.

Caspofungin -Invasive aspergillosis -Inhibits cell wall synthesis. -SE: GI upset, flushing

Terbinafine -Used to treat dermatophytoses

(especially onychomycosis)

-Inhibits the fungal enzyme squalene

epoxidase.

Griseofulvin -Oral treatment of superficial

infections; inhibits growth of

dermatophytes (tinea,

ringworm).

-Interferes with microtubule function;

disrupts mitosis

-Deposits in keratin-containing tissues

(e.g., nails).

-SE: Teratogenic, carcinogenic, confusion, headaches,

↑ P-450 and warfarin metabolism.

ANTIFUNGAL THERAPY (p 184)

Page 10: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Amantadine -Prophylaxis and treatment for

influenza A

-Parkinson's disease

-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)

-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 -Rimantidine is a derivative of amantadine with fewer

CNS side effects. Does not cross the blood-brain barrier

Zanamivir

Oseltamivir

-Both influenza A and B -Inhibit influenza neuraminidase, decreasing

the release of progeny virus.

Ribavirin -RSV, chronic hepatitis C -Inhibits synthesis of guanine nucleotides by

competitively inhibiting IMP dehydrogenase.

-SE: Hemolytic anemia. Severe teratogen.

Acyclovir -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.

-Monophosphorylated by HSV/VZV thymidine

kinase.

-Triphosphate formed by cellular enzymes.

-Preferentially inhibits viral DNA polymerase by

chain termination.

-Mechanism of resistance:

Lack of thymidine kinase.

-SE: Generally well tolerated

Ganciclovir -CMV, especially in

immunocompromised.

-5`-monophosphate formed by CMV viral

kinase or HSV/VZV thyrmidine kinase.

-Triphosphate formed by cellular kinases.

-Preferentially inhibits viral DNA polymerase.

-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.

Foscarnet -CMV retinitis in

immunocompromised patients

when ganciclovir fails.

-Acyclovir resistant HSV.

-Viral DNA polymerase inhibitor that binds to

the pyrophosphate binding site of enzyme

-Does not require activation by viral kinase.

(FOScarnet=pyroFOSphate analog)

-Mechanism of resistance:

Mutated DNA polymerase

-SE: Nephrotoxicity

Interferons -IFN-α :

chronic hepatitis B, C,

Karposi's sarcoma

-IFN-β :

MS

-IFN-γ :

NADPH oxidase deficiency.

-Glycoproteins from human leukocytes that

block various stage of viral RNA and DNA

synthesis

-Induce ribonuclease that degrades viral

mRNA.

-SE: Neutropenia.

ANTIVIRAL THERAPY (pp 185-187)

Page 11: First Aid Pharm

Protease Inhibitors

Saqunavir,

Ritonavir,

Indinavir,

Nelfinavir,

Amprenavir

-all end in -navir

(NAVIR (never) TEASE

a proTEASE)

-HIV -Inhibit assembly of new virus by blocking

protease in progeny virions.

-SE: GI intolerance (nausea, diarrhea), hyperglycemia,

lipodystrophy, thrombocytopenia (indinavir)

Reverse

Transcriptase

Inhibitors

Nucleosides

Zidovudine (ZDV

formerly AZT),

Didanosine (ddI),

Zalcitabine (ddC),

Stavidine (d4T),

Lamivudine (3TC),

Abacavir

Non-Nucleosides

Nevirapine,

Efavirenz,

Delaviridine.

(Never Ever Deliver

nucleosides)

-HIV

-HAART (highly active

antiretroviral therapy) usually a

protease inhibitor + RT

inhibitor. Initiated when patients

have low CD4 (<500) or high

viral load.

-ZDV is used for general

prophylaxis and during

pregnancy to reduce risk of

fetal transmission.

-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.

Fusion Inhibitors

Enfuvirtide

-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

HIV THERAPY

Page 12: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Immunosuppressants

Cyclosporine -Suppresses organ rejection after

transplantation

-Selected autoimmune disorders

-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

-SE:

-predisposes patients to viral infections and lymphoma

-nephrotoxic (preventable with mannitol diuresis)

Tacrolimus (FK506) -Potent immunosuppressive used

in organ transplant recipients

-Similar to cyclosporine

-Binds to FK-binding protein,

inhibiting secretion of IL-2 and other

cytokines

-SE: Significant-nephrotoxicity, peripheral neuropathy,

hypertension, pleural effusion, hyperglycemia.

Azathioprine -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:

-Bone marrow suppression

-Active metabolite mercaptopurine is metabolized by

xanthine oxidase; thus, toxic effects may be ↑ by

allopurinol

Muromonab-CD3

(OKT3)

-Immunosuppression after kidney

transplantation

-Monoclonal Ab that binds to CD3 (epsilon

chain) on the surface of T cells.

Blocks cell interaction with CD3 protein

responsible for T cell signal transduction.

-SE: Cytokine release syndrome,

hypersensitivity reaction

Sirolimus (rapamycin) -Immunosuppression after kidney

transplantation in combo with

cyclosporine and corticosteroids

-Binds to mTOR (molecular target of

rapamycin).

-Inhibits T cell proliferation in response to IL-2

-SE: Hyperlipidemia, thrombocytopenia, leukopenia

Mycophenolate mofetil -Inhibits de novo guanine synthesis and

blocks lymphocyte production.

Daclizumab -Monoclonal Ab with high affinity for the

IL-2 receptor on activated T cells.

IMMUNOLOGY (pp 204-205)

Page 13: First Aid Pharm

Recombinant

cytokines

Aldesleukin (IL-2) -Renal cell carcinoma

-Metastatic melanoma

Erythropoietin (epoetin) -Anemias (esp in renal failure)

Filgrastim

(granulocyte colony-

stimulating factor)

-Recovery of bone marrow

Sargramostim

(granulocyte-

macrophage colony-

stimulating factor)

-Recovery of bone marrow

α-interferon -Hepatitis B and C

-Kaposi's sarcoma

-Leukemias

Malignant melanoma

β-interferon -Multiple sclerosis

γ-interferon -Chronic granulomatous disease

Oprelvekin (IL-11) -Thrombocytopenia

Thrombopoietin -Thrombocytopenia

Page 14: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Cholinergic agents(DIRECT, INDIRECT)

Direct agonists

Bethanechol -Postoperative and neurogenic

ileus and urinary retention

-Direct cholinergic agonist

-Activates Bowel and Bladder smooth muscle

-Resistant to AChE

(Beth Anne, call (bethanechol) me if you want to

activate your bowels and bladder)

Carbachol -Glaucoma

-Pupilary contraction

-↓ Intraocular pressure

-Direct cholinergic agonist

(muscarinic and nicotinic agonist)

Pilocarpine -Potent stimulator of

sweat, tears, saliva

-Emergency treatment for

open and narrow glaucoma

-Contracts ciliary muscle of eye

(open angle), pupillary

sphincter (narrow angle)

Direct cholinergic agonist -Resistant to AchE

(Pile on the sweat and tears)

Methacholine -Challenge test to diagnose

asthma

-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)

-(Indirect agonist (anticholinesterase)) =

-↑ endogenous Ach

-No CNS penetration (NEO CNS = NO CNS)

-Shorter acting than pyridostigmine

Pyridostigmine -Myasthenia gravis (long acting) -↑ endogenous Ach therefore

increases strength

-No CNS penetration

-Long acting

Edrophonium -Diagnosis of myasthenia gravis -↑ endogenous Ach -Extremely short acting

Physostigmine -Glaucoma (b/c crosses BBB)

-Atropine overdose

-↑ endogenous Ach

-Crosses the BBB to CNS

(PHYS is for EYES)

Ecothiophate -Glaucoma -↑ endogenous Ach

Cholinesterase inhibitor

poisoning

PHARMACOLOGY (pp 227-232)

-Causes: Parathion and other organophosphates. Irreversible inhibitors.

-Symptoms: (DUMBBELSS)

-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)

Page 15: First Aid Pharm

Muscarinic

antagonists

Atropine,

Homatropine,

Tropicamide

-Produce mydriasis and

cycloplegia

-(Organ system) =

-Eyes

Benztropine -Parkinson's disease

(PARK my BENZ)

-CNS

Scopolamine -Motion sickness -CNS

Ipratropium -Asthma, COPD -Respiratory

Methoscopolamine,

Oxybutynin,

Glycopyrrolate

-Reduce urgency in mild cystitis

and reduces bladder spasms

-Genitourinary

Pirenzepine,

Propantheline

-Peptic ulcer treatment -Gastrointestinal

Glaucoma drugs

Epinephrine -Glaucoma -α-agonist

-↓ aqueous humor synthesis due to

vasoconstriction

-SE: Mydriasis; stinging

-C/I: Do not use in closed angle glaucoma

Brimonidine -Glaucoma -α-agonist

-↓ aqueous humor synthesis

-No pupillary or vision changes

Timolol,

Betaxolol,

Carteolol

-Glaucoma -β-blockers

-↓ aqueous humor synthesis

-No pupillary or vision changes

Acetazolamide -Glaucoma -Diuretic

-↓ aqueous humor secretion due to

↓HCO3 (via inhibition of carbonic anhydrase)

-No pupillary or vision changes

Pilocarpine,

Carbachol,

Physostigmine,

Echothiophate

-Glaucoma -Cholinomimetics

-↑ outflow of aqueous humor

-Contract ciliary muscle and

opens trabecular meshwork

-Use pilocarpine in emergencies

-Very effective at opening the

canal of Schlemm

-SE: Miosis; cyclospasm

Latanoprost

(PGF 2-α)

-Glaucoma -Prostaglandin

-↑ outflow of aqueous humor

-SE: Darkens color of iris (browning)

Page 16: First Aid Pharm

Atropine (Blocks DUMBBELLS)

-Eye:

-pupil dilation, cycloplegia

-Airway

-↓ secretions

-Stomach

-↓ acid secretions

-Gut

-↓ motility

-Bladder

-↓ urgency in cystitis

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 -Ganglionic blocker - used in

experimental models to prevent

vagal reflex responses to

changes in blood pressure

(e.g. prevents reflex

bradycardia caused by NE)

Nicotinic antagonist -SE: Severe orthostatic hypotension, blurred vision,

constipation, sexual dysfunction

Page 17: First Aid Pharm

Sympathomimetics(DIRECT, INDIRECT,

SYMPATHOPLEGICS)

Direct

sympathomimetics

Epinephrine -Anaphylaxis, glaucoma (open

angle), asthma, hypotension

α1, α2, β1, β2, low doses selective for β1

NE -Hypotension (but ↓ renal

perfusion)

α1, α2 > β1

Isoproterenol -AV block (rare) β1 = β2

Dopamine -Shock (↑ renal perfusion),

heart failure

D1 = D2 > β > α -Inotropic and chronotropic

Dobutamine -Shock, heart failure, cardiac

stress testing

β1 > β2 -Inotropic but not chronotropic

Phenylephrine -Pupillary dilation,

vasoconstriction,

nasal decongestion

α1 > α2

Albuterol,

Terbutaline

-Albuterol for acute asthma

-Terbutaline reduces premature

uterine contractions

β2 > β1

Ritodrine -Reduces premature uterine

contractions

β2

Indirect

sympathomimetics

Amphetamine -Narcolepsy, obesity, attention

deficit disorder

-Indirect general agonist,

releases stored catecholamines

Ephedrine -Nasal decongestion, urinary

incontinence, hypotension

-Indirect general agonist,

releases stored catecholamines

Cocaine -Causes vasoconstriction and

local anesthesia

-Indirect general agonist,

uptake inhibitor

Sympathoplegics

Clonidine,

α-methyldopa

-Hypertension, especially with

renal disease (no ↓ in blood

flow to kidney)

-Centrally acting α2-agonist,

↓ central adrenergic outflow

Selective β2-agonists

Metaproterenol,

Albuterol,

Salmeterol,

Terbutaline

β2-agonist MAST: Metaproterenol, Albuterol, Salmeterol, Terbutaline

Page 18: First Aid Pharm

α-blockers(NONSELECTIVE,

α1 SELECTIVE,

α2 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)

Nonselective α-blocker -SE: Orthostatic hypotension, reflex tachycardia

α1-selective

Prazosin,

Terazosin,

Doxazosin

-Hypertension,

urinary retention in BPH

α1 selective α-blocker -SE: 1st-dose orthostatic hypotension, dizziness,

headache

α2-selective

Mirtazapine

-Depression α2 selective α-blocker -SE: Sedation, ↑ serum cholesterol, ↑ appetite

β-blockers

Propranolol,

Metoprolol,

Atenolol,

Nadolol,

Timolol,

Pindolol,

Esmolol,

Labetalol

-Hypertension

↓ cardiac output,

↓ renin secretion

-Angina pectoris

↓ heart rate and contractility,

resulting in ↓ O2 consumption

-MI

β-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 (β1 = β2)

propranolol, timolol, nadolol, pindolol, and

labetalol

-β1-selective antagonists (β1 > β2)

Acebutolol (partial agonist), Betaxolol,

Esmolol (short acting), Atenolol, Metoprolol

(A BEAM of β1-blockers)

-Nonselective α- and β- antagonists

carvedilol, labetalol

-Partial β-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

Page 19: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Antihypertensives

Hydrochlorothiazide

(HCTZ)

-Hypertension -Thiazide diuretic

(prevents NaCl resorption in early DCT)

-SE:

Hypokalemia, mild hyperlipidemia, hyperuricemia,

lassitude, hypercalcemia, hyperglycemia

Loop Diuretics -Hypertension -Loop diuretic

(blocks NKCC channel in TALH)

-SE:

Potassium wasting, metabolic alkalosis, hypotension,

ototoxicity

Clonidine -Hypertension -Sympathoplegic -SE:

Dry mouth, sedation, severe rebound HTN

Methyldopa -Hypertension -Sympathoplegic -SE:

Sedation, positive Coomb's test

Hexamethonium -Hypertension -Sympathoplegic -SE:

Severe orthostatic hypotension, blurred vision,

constipation, sexual dysfunction

Reserpine -Hypertension -Sympathoplegic -SE:

Sedation, depression, nasal stuffiness, diarrhea

Guanethidine -Hypertension -Sympathoplegic -SE:

Orthostatic and exercise hypotension, sexual

dysfunction, diarrhea

Prazosin -Hypertension -Sympathoplegic -SE:

1st dose orthostatic hypotension, dizziness,

headache

β Blockers -Hypertension -Sympathoplegic -SE:

Impotence, flushing,

Cardiovascular effects (bradycardia, CHF, AV block),

CNS effects (sedation, sleep alterations)

CARDIOVASCULAR (pp 266-272)

Page 20: First Aid Pharm

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 β blockers to prevent reflex tachycardia,

diuretic to block salt retention

Minoxidil -Severe hypertension -Vasodilator

-K+ channel opener - hyperpolarizes and

relaxes vascular smooth muscle

-SE: Hypertrichosis, pericardial effusion,

reflex tachycardia, angina, salt retention

-Use with β blockers to prevent reflex tachycardia,

diuretic to block salt retention

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

-SE:

Dizziness, nausea, flushing,

constipation (verapamil), AV Block (verapamil),

cardiac depression, peripheral edema

Nitroprusside -Hypertension

-Malignant HTN (see below)

-Vasodilator

-Short acting; ↑cGMP via direct release of NO

-SE:

Cyanide toxicity (releases CN)

Diazoxide -Hypertension

-Malignant HTN (see below)

-Vasodilator

-K+ channel opener - hyperpolarizes and

relaxes vascular smooth muscle

-SE: HypER*glycemia (reduces insulin release),

hypotension

*Annotate your FA- this is on the errata list

Captopril

Enalapril

Fosinopril

-Hypertension -ACE Inhibitor -SE:

Hyperkalemia, cough, angioedema, taste changes,

hypotension, pregnancy problems (fetal renal damage),

rash, ↑ renin

Losartan -Hypertension Angiotensin II Receptor Inhibitor (ARB) -SE:

Fetal renal toxicity, hyperkalemia

Nitroglycerin,

Isosorbide dinatrate

-Hypertension

-Angina

-Pulmonary edema

-Also used as an aphrodesiac

and erection enhancer

-Vasodilate by releasing nitric oxide in

smooth muscle, causing ↑ in cGMP and

smooth muscle relaxation.

-Vasodilates veins >> arteries; ↓preload

-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.

Page 21: First Aid Pharm

Malignant HTN

treatment

Nitroprusside Malignant HTN -Vasodilator

-Short acting; ↑cGMP via direct release of NO

-SE: Cyanide toxicity (releases CN)

Fenoldopam Malignant HTN -Vasodilator

-Dopamine D1 receptor agonist - relaxes renal

vasuclar smooth muscle

Diazoxide Malignant HTN -Vasodilator

-K+ channel opener - hyperpolarizes and

relaxes vascular smooth muscle

-SE: HypER*glycemia (reduces insulin release),

hypotension

*Annotate your FA- this is on the errata list

Antianginal therapy

Component Nitrates (affect preload) β Blockers (affect afterload) Nitrates + β Blockers

EDV ↓ ↑ No effect or ↓BP ↓ ↓ ↓

Contractility ↑ (Reflex response) ↓ Little/No Effect

HR ↑ (Reflex response) ↓ ↓Ejection time ↓ ↑ Little/No Effect

MVO2 ↓ ↓ ↓↓

-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 β blockers in effect.

-Labetalol, pindolol, and acebutolol are partial agonists- CONTRAINDICATED in angina

Page 22: First Aid Pharm

Lipid lowering agents -LDL "bad cholesterol"

-HDL "good cholesterol

-triglycerides = TG

HMG-CoA reductase

inhibitors

Lovastatin

Pravastatin

Simvastatin Atorvastatin

LDL HDL TG

↓↓↓ ↑ ↓

-Inhibit cholesterol precursor, mevalonate -SE: expensive, reversible ↑ LFTs, myositis

Niacin ↓↓ ↑↑ ↓ -Inhibits lipolysis in adipose tissue;

reduces hepatic VLDL secretion into

circulation

-SE: red, flushed face, which is reduced by aspirin or

long-term use

Bile acid resins

Cholestyramine

Colestipol

↓↓ slightly ↑ slightly ↑ -Prevent intestinal reabsorption of bile acids;

liver must use cholesterol to make more

-SE: pts hate it (tastes bad and causes GI discomfort),

↓ absorption of fat-soluble vitamins

Cholesterol absorption

blockers

Ezetimibe

↓↓ -- -- -Prevent cholesterol reabsorption at

small intestine brush border

-SE: rare, ↑LFTs

"Fibrates"

Gemfibrozil

Clofibrate

Bezafibrate

Fenofibrate

↓ ↑ ↓↓↓ -Upregulate LPL → ↑ TG clearance -SE: myositis, ↑LFTs

Cardiac glycosides

Digoxin -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+

Page 23: First Aid Pharm

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

-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)

-Affect both atrial and ventricular

arrhythmias, especially

reentrant and ectopic

supraventricular and ventricular

tachycardia

- ↑ AP duration

- ↑ effective refractory period (ERP)

- ↑QT interval

-SE:

-quinidine

-cinchonism (headache, tinnitus, thrombocytopenia)

-torsades de pointes due to ↑ QT interval;

-procainamide

-reversible SLE-like syndrome

Class IB

Lidocaine

Mexiletine

Tocainide

(I'd Buy Lidy's

Mexican Tacos)

-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

Class IC

Flecainide

Encainide

Propafenone

-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

ANTIARRHYTHMICS

Beta-blockers

(Class II)

Propanolol

Esmolol

Metoprolol

Atenolol

Timolol

-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

Page 24: First Aid Pharm

ANTIARRHYTHMICS

K+ channel blockers

(Class III)

-Used when other antiarrhythmics

fail

- ↑ AP duration,

- ↑ effective refractory period

- ↑QT interval

Sotalol -SE: torsades des pointes, excesssive β block

Ibutilide -SE: torsades des pointes

Bretylium -SE: new arrhythmias, hypotension

Amiodarone -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 -Drug of choice in

diagnosis/abolishment of

AV nodal arrhythmias

- ↑K+ out of cells → hyperpolarizing the cell -Very short acting (~15 sec)

-SE: Flushing, hypotension, chest pain

K+ -Depresses ectopic pacemakers

in hypokalemia

(e.g. digoxin toxicity)

Mg+ -Effective in torsades de pointes

and digoxin toxicity

Page 25: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Diabetic drugs

Insulins

Lispro (short-acting)

Aspart (short-acting)

NPH (intermediate)

Lente (long-acting)

Ultralente (long-acting)

-Type 1 DM

-Also:

life-threatening hyperkalemia &

stress-induced hyperglycemia

-Bind insulin receptor

(tyrosine kinase activity)

-Liver: ↑ glucose stored as glycogen

-Muscle: ↑ glycogen & protein synthesis,

K+ uptake

-Fat: aids TG storage

-SE: hypoglycemia, hypersensitivity reaction (very rare)

Sulfonylureas

First generation

Tolbutamide

Chlorpropamide

Second generation

Glyburide

Glimepiride

Glipizide

-Stimulate release of endogenous

insulin in type 2 DM.

-Require some islet function, so

useless in type 1 DM.

-Close K+ channel in β-cell membrane, so

cell depolarizes → triggering of insulin

release via ↑ Ca2+ intake

-SE:

-1st gen: disulfiram-like effects.

-2nd gen: hypoglycemia.

Biguanides

Metformin

-Used as oral hypoglycemic

-Can be used in patients without

islet function

-Exact mechanism is unknown

-Possibly:

↓ gluconeogenesis

↑ glycolysis

↓ serum glucose levels.

-SE: Most grave adverse effect is lactic acidosis.

Glitazone

Pioglitazone

Rosiglitazone

-Used as monotherapy in

type 2 DM or combined with

above agents.

- ↑ target cell response to insulin -SE: Weight gain, edema, hepatotoxicity, CV toxicity

α-glucosidase

inhibitors

Acarbose

Miglitol

-Used as monotherapy in

type 2 DM or combined with

above agents.

-Inhibit intestinal brush-border

α-glucosidases

-Delayed sugar hydrolysis & glucose

absorption lead to ↓ postprandial

hyperglycemia.

-SE: GI disturbances

ENDOCRINE (pp 287-288)

Page 26: First Aid Pharm

Misc endocrine drugs

Orlistat -Long-term obesity management

(in conjunction with modified diet)

-Alters fat metabolism by inhibiting pancreatic

lipases.

-SE: Steatorrhea, GI discomfort, reduced absorption of

fat-soluble vitamins, headache.

Sibutramine -Short-term & long-term obesity

management

-Sympathomimetic serotonin & norepinephrine

reupake inhibitor.

-SE: Hypertension, tachycardia.

Propylthiouracil,

Methimazole

-Hyperthyroidism -Inhibit organification and coupling of thyroid

hormone synthesis.

-Propylthiouracil also ↓ peripheral conversion

of T4 to T3

-SE: Skin rash, agranulocytosis (rare), aplastic anemia.

Levothyroxine,

Triiodothyronine

-Hypothyroidism, myxedema. -Thyroxine replacement. -SE: Tachycardia, heat intolerance, tremors, arrhythmias

Hypothalamic /

pituitary drugs

GH -GH deficiency

-Turner's syndrome

Somatostatin

(octreotide)

-Acromegaly

-Carcinoid

-Gastrinoma

-Glucagonoma

Oxytocin -Stimulates labor, uterine

contractions, milk let-down

-Controls uterine hemorrhage

ADH

(desmopressin)

-Pituitary DI

(central, not nephrogenic)

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).

Page 27: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

H2 blockers

Cimetidine

Ranitidine

Famotidine

Nizatidine

(take H2 blockers before

you DINE)

-Peptic ulcer

-Gastritis

-Mild esophageal reflux

-Reversible block of histamine H2 receptors

causing ↓secretion of H+ from parietal cells

-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

Proton pump

inhibitors

Omeprazole,

Lansoprazole

-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

-Triple therapy for H. Pylori ulcers :

Metronidazole, Amoxicillin (or Tetracycline), Bismuth.

-Can also use a PPI

(Please MAke Tummy Better)

Misoprotol -Prevention of NSAID-induced

peptic ulcers

-Maintenance of a patent ductus

arteriosus.

-Induction of labor

-a PGE1 analog

- ↑production and secretion of gastric

mucous barrier

- ↓acid production

-SE: Diarrhea

-C/I: contraindicated in women of childbearing potential

(abortifacient)

Muscarinic antagonist

Pirenzepine,

Propantheline

-Peptic ulcer -Block M1 receptors on ECL cells

(↓ histamine secretion)

-Block M3 receptors on parietal cells

(↓ H+ secretion)

-SE: Tachycardia, dry mouth, difficulty focusing eyes

Antacid use

Alumninum hydroxide

(AlOH3)

Magnesium hydroxide

Calcium carbonate -SE: Hypercalcemia, rebound acid ↑; can chelate and ↓ effectiveness of other drugs (e.g. tetracycline)

GASTROINTESTINAL (pp 317-318)

-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)

Page 28: First Aid Pharm

Infliximab -Crohn's disease

-Rheumatoid arthritis

-A monoclonal antibody to TNF, which is a

proinflammatory cytokine

(INFLIXimab INFLIX pain on TNF)

-SE: Respiratory infection, fever, hypotension

Sulfasalazine -Ulcerative colitis

-Crohn's disease

-A combination fo sulfapyridine (antibacterial)

and mesalamine (anti-inflammatory)

-Activated by colonic bacteria

-SE: Malaise, nausea, sulfonamide toxicity,

reversible oligospermia

Ondansetron -Control vomiting postoperatively

and in patients undergoing

cancer chemotherapy

-5-HT3 antagonist

-(Powerful central-acting antiemetic)

-SE: Headache, constipation

(You will not vomit with ONDANSetron, so you can go ON DANCing)

Prokinetic agents

Cisapride -Acts through 5HT receptors to ↑ACh release

at the myenteric plexus.

-↑ esophageal tone

-↑ gastric and duodenal contractility,

improving transit time (including through

the colon)

-No longer used

-SE: Serious interactions (torsades des pointes) with

Erythromycin, Ketoconazole, Nefazodone, Fluconazole

Metoclopramide -Diabetic and post-surgery

gastroparesis

-D2 receptor antagonist

-↑ resting tone, contractility, LES tone, motility

-Does not influence colon transport time

-SE:

-↑ Parksonian Effects.

-Restlessness, drowsiness, fatigue, depression,

nausea, diarrhea.

-Drug interaction with digoxin and diabetic agents

-C/I: pts with small bowel obstruction

Page 29: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Heparin -Immediate anticoagulation for

pulmonary embolism,

stroke, angina, MI, DVT

-Used during pregnancy

(does not cross placenta)

-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)

Lepirudin,

Bivalirudin

-Used as an alternative to

heparin for anticoagulating

patients with HIT

-Directly inhibit thrombin -Hirudin derivatives

Warfarin (Coumadin) -Chronic anticoagulant

-Not used in pregnant women

(because warfarin, unlike

heparin, can cross the

placenta)

-Interferes with normal synthesis and

γ-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

HEMATOLOGY AND ONCOLOGY (pp 336-340)

Page 30: First Aid Pharm

Heparin vs. warfarin Warfarin

Structure Small lipid-soluble molecule

Route of administration Oral

Site of action Liver

Onset of action Slow, limited by half-lives of normal clotting factors

Mechanism of action Impairs the synthesis of vitamin K-dependent clotting

factors II, VII, IX, and X (vitamin K antagonist)

Duration of action Chronic (days)

Inhibits coagulation in vitro No

Treatment of acute OD IV vitamin K and fresh frozen plasma

Monitoring PT/INR (extrinsic pathway)

Crosses placenta Yes (teratogenic)

Thrombolytics

Streptokinase,

Urokinase,

tPA (alteplase),

APSAC (anistreplase)

-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

-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

Yes

Protamine sulfate

PTT (intrinsic pathway)

No

Blood

Rapid (seconds)

Activates antithrombin III, which ↓ the action of IIa (thrombin) and Xa

Acute (hours

Heparin

Large anionic polymer, acidic

Parenteral (IV, SC)

Page 31: First Aid Pharm

Antiplatelet drugs

Aspirin (ASA) -Antipyretic

-Analgesic

-Anti-inflammatory

-Antiplatelet drug

-Acetylates and irreversibly inhibits

cyclooxygenase (both COX-1 and COX-2)

to prevent conversion of arachidonic acid to

thromboxane A2.

-↑ bleeding time.

-No effect on PT, PTT.

-SE: Gastric ulceration, bleeding, hyperventilation,

Reye's syndrome, tinnitus (CN VIII)

Clopidogrel,

Ticlopidine

-Acute coronary syndrome

-Coronary stenting

-↓ incidence or recurrence of

thrombotic stroke

-Inhibit platelet aggregation by

irreversibly blocking ADP receptors.

-Inhibit fibrinogen binding by

preventing glycoprotein IIb/IIIa expression.

-SE: Neutropenia (ticlopidine)

Abciximab -Acute coronary syndromes

-Percutaneous transluminal

coronary angioplasty

-Monoclonal antibody that binds to the

glycoprotein receptor IIb/IIIa on

activated platelets, preventing aggregation.

-SE: bleeding, thrombocytopenia

Page 32: First Aid Pharm

Cancer drugs

Methotrexate (MTX) -Leukemias

-Lymphomas

-Choriocarcinoma

-Sarcoma

-Abortion

-Ectopic pregnancy

-Rheumatoid arthritis

-Psoriasis

-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

5-Fluorouracil (5-FU) -Colon cancer and other solid

tumors

-Basal cell carcinoma (topical)

-Synergy with MTX

-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

-SE:

-Myelosuppression (NOT reversible with leucovorin).

Can "rescue" with thymidine

-Photosensitivity

6-mercaptopurine

(6-MP)

-Leukemias

-Lymphomas (not CLL or

Hodgkin's)

-Blocks de novo purine synthesis

-Activated by HGPRATase

-Metabolized by xanthine oxidase; thus ↑ toxicity with

allopurinol

-SE: Bone marrow, GI, liver

Cytarabine (ara-C) -AML -Inhibit DNA polymerase -SE: Leukopenia, thrombocytopenia, megaloblastic

anemia

Cyclophosphamide,

Ifosfamide

-Non-Hodgkin's lymphoma

-Breast and ovarian carcinoma

-Immunosuppressant

-Alkylating agent

'-Covalently cross-link (interstrand) DNA at

guanine N-7

-Requires bioactivation in liver

-SE: Myelosuppression; hemorrhagic cystitis.

Hemorrhagic cystitis can be partially prevented with

mesna

Nitrosoureas

Carmustine

Lomustine

Semustine

Streptozocin

-Brain tumors (including

glioblastoma multiforme)

-Alkylate DNA -Requires bioactivation

-Crosses blood-brain barrier → CNS

-SE: CNS toxicity (dizziness, ataxia)

Cisplatin,

Carboplatin

-Testicular, bladder, ovary, and

lung carcinomas

-Act like alkylating agent -SE: Nephrotoxicity, acoustic nerve damage

Busulfan -CML -Alkylates DNA -SE: Pulmonary fibrosis, hyperpigmentation

Doxorubicin

(adriamycin),

Daunorubicine

-Part of ABVD combo for

Hodgkin's and for myelomas,

sarcomas, solid tumors

(breast, ovary, lung)

-Generate free radicals and noncovalently

intercalate in DNA (creating breaks in

DNA strand to ↓ replication)

-SE: Cardiotoxic, myelosuppression,

marked alopecia, toxic extravasation

Dactinomycin

(actinomycin D)

-Wilm's tumor

-Ewing's sarcoma

-Rhabdomyosarcoma

(ACTinomycin D is used for

childhood tumors (children ACT

out)

-Intercalates in DNA -SE: Myelosuppression

Page 33: First Aid Pharm

Bleomycin -Testicular cancer

-Lymphoma (part of ABVD

regimen for Hodgkin's)

-Induces free radical formation, which causes

breaks in DNA strands

-SE: Pulmonary fibrosis, skin changes, but

minimal myelosuppression

Hydroxyurea -Melanoma

-CML

-Sickle cell disease

-Inhibits Ribonucleotide Reductase

→ ↓DNA Synthesis (S-phase specific)

-SE: Bone marrow suppression, GI upset

Etoposide (VP-16) -Small cell carcinoma of

lung and prostate

-Testicular carcinoma

-G2-phase-specific agent

-Inhibits topoisomerase II and

↑ DNA degradation

-SE: Myelosuppression, GI irritation, alopecia

Prednisone -Most commonly used

glucocorticoid in cancer therapy

-CLL

-Hodgkin's lymphoma (part of the

MOPP regimin)

-Immunosuppressant used in

autoimmune disease

-May trigger apoptosis

-May even work on dividing cells

-SE: Cushing-like symptoms, immunosuppression,

cataracts, acne, osteoporosis, hypertension,

peptic ulcers, hyperglycemia, psychosis

Tamoxifen,

Raloxifene

-Breast cancer

-Osteoporosis prevention

-Estrogen receptor antagonist in breast

-Agonist in bone

-Block the binding of estrogen to

estrogen receptor-positive cells

-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"

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

-SE: Cardiotoxic

Imatinib (Gleevec) -CML

-GI stromal tumors

-Philadelphia chromosome (bcr-abl) tyrosine

kinase inhibitor

-SE: Fluid retention

Vincristine,

Vinblastine

-Part of MOPP (Oncovin =

vincristine) regimen for

lymphoma

-Wilm's tumor

-Choriocarcinoma

-M-phase specific alkaloids

-Bind to tubulin and block polymerization of

microtubules so mitotic spindle cannot form

(Microtubules are the vines of your cells)

-SE:

-Vincristine :

-Neurotoxicity (areflexia, peripheral neuritis),

-Paralytic ileus

-VinBLASTine : BLASTs Bone marrow (suppression)

Paclitaxel,

other taxols

-Ovarian and breast carcinoma -M-phase specific agents

-Bind to tubulin and hyperstabilize polymerized

microtubules so mitotic spindle cannot break

down (anaphase cannot occur)

-SE: Myelosuppression and hypersensitivity

Page 34: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

NSAIDs

Ibuprofen

Naproxen

Indomethacin

Ketorolac

-Antipyretic

-Analgesic

-Anti-inflammatory

-Indomethacin: closure of PDA

-Reversibly inhibit cyclooxygenase

(both COX-1 & COX-2)

-Block prostaglandin synthesis

-SE: Renal damage, aplastic anemia, GI distress, ulcers

COX-2 inhibitor

Celecoxib

-Rheumatoid and osteoarthritis -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.

-SE:

-↑ risk of thrombosis

-Sulfa allergy.

-Less toxicity to GI mucosa (lower incidence of ulcers,

bleeding).

Gout drugs -Do not give salicylates

Colchicine -Acute gout -Depolymerizes microtubules, impairing

leukocyte chemotaxis & degranulation

-SE: GI side effects, especially if given orally.

(Indomethacin is less toxic, more commonly used in

acute gout).

Probenecid -Chronic gout -Inhibits reabsorption of uric acid in PCT

(also inhibits secretion of penicillin)

-C/I: should not be used to treat an acute episode of gout

Allopurinol -Chronic gout

-Also used in lymphoma &

leukemia to prevent

tumor lysis-associated urate

nephropathy

-Inhibits xanthine oxidase, ↓ conversion of

xanthine to uric acid.

-Interacts with azathioprine & 6-MP

-C/I: should not be used to treat an acute episode of gout

Misc drugs

Acetaminophen -Antipyretic

-Analgesic

-Lacks anti-inflammatory

properties

-Reversibly inhibits cyclooxygenase, mostly in

CNS.

-Inactivated peripherally.

-SE: Overdose produces hepatic necrosis;

acetaminophen metabolite depletes glutathione and

forms toxic tissue adducts in liver.

N-acetylcysteine is antidote - regenerates glutathione.

Etanercept -Rheumatoid arthritis

-Psoriasis

-Ankylosing spondylitis.

-Recombinant form of human TNF receptor

that binds TNF

(EtanerCEPT is a TNF decoy reCEPTor)

Infliximab -Crohn's disease

-Rheumatoid arthritis

-Ankylosing spondylitis

-Anti-TNF antibody

(INFLIXimab INFLIX pain on TNF)

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

MUSCULOSKELETAL (pp 358-359)

Page 35: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Opioid Analgesics

Morphine

Fentanyl

Codeine

Heroin

Methadone

Meperidine

Dextromethorphan

-Pain

-Cough suppression

(dextromethorphan)

-Diarrhea

(loperamide and diphenoxylate)

-Acute pulmonary edema,

-Maintenance programs for

addicts (methadone)

-Acts as agonist at opioid receptors

(mu=morphine, delta= enkephalin,

kappa=dynorphin) to modulate synaptic

transmission

-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).

Benzodiazepines

Diazepam

Lorazepam

Triazolam

Temazepan

Oxazepam

Midazolam

Chlordiazepoxide

Alprazolam

-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)

Carbamazepine -Epilepsy -SE: Diplopia, ataxia, blood dyscrasis (agranulocytocic,

aplastic anemia), liver toxicity, teratogenesis,

induction of cytochrome P-450

Ethosuximide -Epilepsy -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)

Barbiturates

Phenobarbital

Pentobarbital

Thiopental

Secobarbital

-Sedative for anxiety

-Epilepsy

-Seizures

-Insomnia

-Induction of anesthesia

(thiopental)

-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

NEUROLOGY (pp 394-399)

Note: There is a table on p. 395 of First Aid 2008 detailing the specific usage of epilepsy drugs

Page 36: First Aid Pharm

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).

Valproic acid -Epilepsy -SE:

-GI distress, tremor, weight gain

-Rare but fatal hepatotoxicity (measure LFTs)

-Neural tube defects in fetus (spina bifida)

-C/I: Pregnancy

Lamotrigine -Epilepsy -SE: Stevens-Johnson syndrome

Gabapentin -Epilepsy -SE: Sedation, ataxia.

Topiramate -Epilepsy -SE: Sedation, mental dulling, kidney stones, weight loss

Page 37: First Aid Pharm

Anesthetics -

general principles

Inhaled anesthetics

Halothane

Enflurane

Isoflurane

Sevoflurane

Methoxyflurane

Nitrous oxide

-Anesthesia:

myocardial depression,

respiratory depression,

nausea/emesis,

↑ cerebral blood flow

↓ cerebral metabolic demand

-Unknown -SE:

-malignant hyperthermia (rare)

-halothane: hepatotoxicity

-methoxyflurane: nephrotoxicity

-enflurane: proconvulsant

IV anesthetics B. B. King on Opiates Proposes Foolishly

Barbituates

(Thiopental)

-Induction of anesthesia

-Short surgical procedures.

-↓ cerebral blood flow

-High potency, high lipid solubility, rapid entry into brain.

-Effect terminated by redistribution from the brain.

Benzodiazepines

(Midazolam)

-Endoscopy

-used in adjunct with gaseous

anesthetics and narcotics

-SE:

-May cause severe postoperative respiratory

depression, ↓BP, and amnesia

-Treat overdose with flumazenil

Arylcyclohexylamines

(Ketamine)

-Act as dissociative anesthetics -PCP analogs -↑ cerebral blood flow

-SE:

-Cardiovascular stimulants

-Cause disorientation, hallucination, and bad dreams

Opiates

(Morphine,

Fentanyl)

-Used with other CNS

depressants during general

anesthesia

Propofol -Rapid anesthesia induction

-Short procedures

-SE: Less postoperative nausea then thiopental

-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

Page 38: First Aid Pharm

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

Used for muscle paralysis in

surgery or mechanical ventilation

Selective for motor (vs. autonomic) nicotinic

receptor

Depolarizing

Succinylcholine

-Phase 1 - prolonged depolarization

-No antidote

-Block potentiated by cholinesterase

inhibitors

-Phase 2 - repolarized but blocked

-Antidote is cholinesterase inhibitors

(e.g. neostigmine)

-SE: Hypercalemia and hyperkalemia

Nondepolarizing

Tubocurarine

Atracurium

Mivacurium

Pancuronium

Vecuronium

Rocuronium

-Competitive

-complete with Ach for receptors

-Reversal of blockade via:

-Neostigmine, edrophonium, and other

cholinesterase inhibitors

Dantrolene -Malignant hyperthermia

-Neuroleptic malignant

syndrome

-Prevents the release of Ca2+ from the

sarcoplasmic reticulum of skeletal muscle

-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

Page 39: First Aid Pharm

Parkinson's disease

drugs

Bromocriptine

Amantadine

Levodopa (with

carbidopa)

Selegiline (and

COMT inhibitors)

Antimuscarinics

(BALSA)

-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 β-blockers

Bromocriptine

Pramipexole

Ropinirole

-Parkinsons -Agonize dopamine receptors

-Bromocriptine is an ergot alkaloid and

partial dopamine agonist

Amantadine -Parkinsons

-Antiviral (influenza A and rubella)

-↑ dopamine release -SE: ataxia

L-dopa (levodopa) with

carbidopa

-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

-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

Selegiline -Parkinsons (is an adjunctive

agent to L-dopa for Parkinson's)

-Prevent dopamine breakdown

-Selectively inhibits MAO-B, thereby

↑ the availability of dopamine.

-SE: May enhance adverse effects of L-dopa

Entacarpone,

Tolcapone

-Parkinsons -Prevent dopamine breakdown

-COMT inhibitors

Benztropine -Improves tremor and rigidity

-Little effect on bradykinesia

-Antimuscarinic - curb excess cholinergic

activity

"↓ your tremor before you drive your Mercedes-BENZ"

Sumatriptan -Acute migraine

-Cluster headache attacks

-5-HT1D agonist

-Causes vasoconstriction

-Half-life < 2 hrs

-SE: Coronary vasospasm, mild tingling,

hypertensive emergencies.

-C/I: patients with CAD or Prinzmetal's angina

Page 40: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Psychiatric condition Drug used

Alcohol withdrawal BZD

Anorexia/bulimia SSRIs

Anxiety Barbiturates

BZD

Buspirone

MAOI

ADHD Methylphenidate (Ritalin)

Amphetamine

Atypical Depression MAOI

Bipolar Disorder Mood stabilizers:

Lithium

Valproic acid

Carbamazepine

Depression SSRI

TCA

Depression w/ insomnia Trazodone

Mirtazapine

OCD SSRIs

Panic D/O TCAs

Buspirone

Schizophrenia Antipsychotics

Tourette's Syndrome Antipsychotics (haloperidol)

PSYCHIATRY (pp 415-417)

Page 41: First Aid Pharm

Antipsychotics

(neuroleptics)

(Haloperidol + '-azine's)

-Schizophrenia

-Psychosis

-Acute mania

-Tourette's syndrome

-Block dopamine D2 receptors -Excess dopamine effects connected with schizophrenia

-DA = dopamine; DA-R = dopamine receptor

High potency

Haloperidol,

Trifluoperazine

-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)

Low potency

Thioridazine

Chlorpromazine

-SE: (Non-neurologic side effects)

-endocrine:

- DA-R antagonism → hyperPRL → galactorrhea

-muscarinic block: dry mouth, constipation

-α-block: hypotension

-histamine-R block: sedation

Unspecified

Fluphenazine

Page 42: First Aid Pharm

Atypical

antipsychotics

Clozapine

Olanzapine

Risperidone

Quetiapine

Aripiprazole

Ziprasidone

(It's not atypical for old

closets to risper)

-Schizophrenia, for positive and

negative symptoms

-Block 5-HT2 and dopamine receptors -SE: Fewer EPS and anticholinergic SE than other

antipsychotics

Olanzapine -Schizophrenia

-OCD

-Anxiety

-Depression

-Mania

-Tourette's syndrome

Clozapine -Schizophrenia -SE: agranulocytosis (requires weekly WBC monitoring)

Lithium -Mood stabilizer for

bipolar affective disorder

-Blocks relapse and

acute manic events

-Unknown

-Possibly related to inhibition of

phosphoinositol cascade

-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)

Buspirone -Anxiolytic for generalized

anxiety disorder (GAD)

-Stimulates 5-HT1A receptors -Does not cause addiction or sedation

-No interaction w/ EtOH

Page 43: First Aid Pharm

ANTIDEPRESSANTS -It normally takes 2-3 weeks for anti-dep to have an effect

SSRIs

Fluoxetine

Sertraline

Paroxetine

Citalopram

-Endogenous depression

-OCD

-Anorexia/bulimia

-Serotonin-specific reuptake inhibitors -SE: (Fewer than TCAs)

-GI distress

-sexual dysfunction (anorgasmia)

-"serotonin syndrome" w/ MAOI: hyperthermia,

muscle rigidity, cardiovascular collapse

Tricyclic

antidepressants (TCA)

Imipramine

Amitriptyline

Desipramine

Nortriptyline

Clomipramine

Doxepin

Amoxapine

-Major depression -Block reuptake of NE and serotonin -SE:

-sedation (desipramine is the least sedating)

-α-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)

Imipramine -Major depression

-Bedwetting

Clomipramine -Major depression

-OCD

Monoamine oxidase

inhibitors (MAOI)

Phenelzine

Tranylcypromine

-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 β-agonists

-CNS stimulation

-C/I: SSRIs or meperidine (prevent serotonin syndrome)

Page 44: First Aid Pharm

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

Venlafaxine -Depression

-Generalized anxiety disorder

-Inhibits serotonin, NE, DA reuptake -SE:

-stimulant effects

-increased BP

-sedation

-nausea, constipation

Mirtazapine -Depression -α2 antagonist (↑ release of NE and serotonin)

-Potent 5-HT2 and 5-HT3 receptor antagonist

-SE:

-sedation

-↑ appetite

-weight gain

-dry mouth

Maprotiline -Depression -Blocks NE reuptake -SE:

-sedation

-orthostatic hypotension

Trazodone -Depression -Inhibits serotonin reuptake -SE:

-sedation

-postural hypotension

-nausea

-priapism

Methylphenidate

(Ritalin)

-ADHD -↑ presynaptic NE vesicular release (like

amphetamines)

-Mechanism for relief of ADHD symptoms

is unknown

Page 45: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Mannitol -Shock

-Drug overdose

-↓intracranial/intraocular pressure

-Osmotic diuretic.

-↑ tubular fluid osmolarity,

producing ↑ urine flow

-SE: pulmonary edema, dehydration

-C/I: anuria, CHF

Acetazolamide -Glaucoma

-Urinary alkalinization

-Metabolic alkalosis

-Altitude sickness

-Carbonic anhydrase inhibitor.

-Causes self-limited NaHCO3 diuresis

and reduction in total-body HCO3 stores

(ACIDazolamide causes ACIDosis)

-SE: Hyperchloremic metabolic acidosis, neuropathy,

NH3 toxicity, sulfa allergy

Furosemide -Edematous states

(CHF, cirrhosis, nephrotic

syndrome, pulmonary edema)

-Hypertension

-Hypercalcemia

-Loop diuretic (Sulfonamide)

-Inhibits cotransport system (NKCC) of

thick ascending limb of loop of Henle.

-Abolishes hypertonicity of medulla,

preventing concentration of urine

- ↑Ca2+ excretion (Loops Lose calcium)

-SE: (OH DANG!)

Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa)

Nephritis (interstitial), Gout

Ethacrynic acid -Diuresis in patients allergic to

sulfa drugs

-Loop diuretic (NOT a sulfonamide)

-Essentially same action as furosemide

-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.

K+-sparing diuretics (the K+ STAys)

Spironolactone

Eplerenone

-Hyperaldosteronism

-K+ depletion

-CHF

-Competitive aldosterone receptor antagonist

in the cortical collecting tubule (CCT)

-SE:

Hyperkalemia,

endocrine effects (gynecomastia, antiandrogen effects)

Triamterene

Amiloride

-Hyperaldosteronism

-K+ depletion

-CHF

-Block Na+ channels in the CCT -SE:

hyperkalemia

RENAL (pp 435-436)

Page 46: First Aid Pharm

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

-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

Losartan -Angiotensin-II receptor antagonist -It is not an ACE inhibitor and does not cause cough

Page 47: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

Antiandrogens (5-alpha reductase)

- Testosterone -----------------------> DHT (more potent)

Finasteride (propecia) -Useful in BPH

-Promotes hair growth - used to

treat male pattern baldness

-5-alpha reductase inhibitor (↓ conversion of

testosterone to dihydrotestosterone)

-To prevent male-pattern hair loss, give a drug that will

encourage female breast growth)

Flutamide -Prostate carcinoma -Nonsteroidal competitive inhibitor of

androgens at the testosterone receptor

Ketoconazole -Used in the treatment of

polycystic ovarian syndrome to

prevent hirsutism

-Inhibits steroid synthesis -SE: gynecomastia and amenorrhea

Spironolactone -Used in the treatment of

polycystic ovarian syndrome to

prevent hirsutism

-Inhibits steroid binding -SE: gynecomastia and amenorrhea

Leuprolide -Infertility (pulsatile)

-Prostate cancer (continuous -

use with flutamide)

-Uterine fibroids

-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)

-SE: Antiandrogen, nausea, vomiting

Sildenafil,

Vardenafil

-Erectile dysfunction

(Sildenafil and vardenafil fill the

penis)

-Inhibits cGMP phosphodiestersase, causing

↑cGMP, smooth muscle relaxation in the

corpus cavernosum, ↑ blood flow, and

penile erection

-SE: headache, flushing, dyspepsia, impaired blue-green

color vision.

-C/I: Risk of life threatening hypotension in patients taking

nitrates

Mifepristone (RU-486) -Termination of pregnancy

-administered with

misoprostol (PGE1)

-Competitive inhibitor of progestins at

progesterone receptors

-SE:

-heavy bleeding

-GI effects (nausea, vomiting, anorexia)

-abdominal pain

REPRODUCTIVE (pp 453-454)

Page 48: First Aid Pharm

Oral contraception

(synthetic progestins,

estrogen)

Advantages

-Reliable (<1% failure)

-↓Risk of endometrial and

ovarian cancer

-↓Incidence of ectopic pregnancy

-↓Pelvic infections

-Regulation of menses

Disadvantages

-Taken daily

-No protection against STDs

-↑Triglycerides

-Depression, weight gain, nausea,

hypertension

-Hypercoagulable state

Hormone replacement

therapy (HRT)

-Used for relief or prevention of

menopausal symptoms

(eg. hot flashes, vaginal

atrophy)

-Osteoporosis (due to diminished

estrogen levels)

-SE:

-unopposed estrogen replacement therapy (ERT) ↑ the

risk of endometrial cancer, so progesterone is added

-possible ↑ CV risk

Dinoprostone -Cervical dilation and

uterine contraction to

induce labor

-PGE2 analog

Ritodrine,

Terbutaline

-Relax the uterus -β2 agonist

Anastrozole -Breast cancer in

postmenopausal women

-Aromatase inhibitor

Testosterone

(methyltestosterone)

-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)

-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

-Hypogonadism or ovarian failure

-Menstrual abnormalities

-HRT in postmenopausal women

-Use in men with androgen-

dependent prostate cancer

-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

Page 49: First Aid Pharm

Estrogen partial

agonists

(selective estrogen

receptor modulators-

SERMs)

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

-SE:

-hot flashes

-ovarian enlargement,

-multiple simultaneous pregnancies

-visual disturbances

Tamoxifen -Treat and prevent recurrence of

ER-positive breast cancer

-Antagonist on breast tissue

Raloxifene -Treat osteoporosis -Agonist on bone; ↓reabsorption of bone

Page 50: First Aid Pharm

CLASS/NAME CLINICAL USE MECHANISM SIDE EFFECTS / MISC

H1 Blockers

1st generation

Diphenhydramine,

Dimenhydrinate,

Chlorpheniramine

-Allergy

-Motion sickness

-Sleep aid

-Reversible inhibitors of

H1 histamine receptors-SE: Sedation, antimuscarinic, anti-α-adrenergic

2nd generation

Loratadine,

Fexofenadine,

Desloratadine,

Cetirizine

-Allergy relief, non-sedating -Reversible inhibitors of

H1 histamine receptors

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

↓entry into CNS

RESPIRATORY (pp 468-470)

Page 51: First Aid Pharm

Asthma drugs

Isoproterenol -non-specific β-agonist

-Relaxes bronchial smooth muscle (β2)

-SE: Tachycardia (β1)

Albuterol -Use during acute exacerbation

of asthma

-β2 agonist

-Relaxes bronchial smooth muscle (β2).

Salmeterol -β2 agonist

-Long acting agent for prophylaxis

-SE: Tremor, arrhythmia

Theophylline -Methylxanthine

-Likely causes bronchodilation by inhibiting

phosphodiesterase, thereby

↓ cAMP hydrolysis

-Metabolized by P450

-Usage is limited because of narrow therapeutic index.

-SE: Narrow therapeutic range (cardiotoxicity,

neurotoxicity)

Ipratropium -Asthma

-COPD

-Muscarinic antagonist

-Competitive block of muscarinic receptors,

preventing bronchoconstriction

-Also used for COPD

Cromolyn -Asthma prophylaxis -Prevents release of mediators from

mast cells

-Effective only for prophylaxis of asthma. Not effective

during acute asthma attack.

-SE: Rare

Corticosteroids

Prednisone

Beclomethasone

-1st line therapy for chronic

asthma

-Inhibit the synthesis of virtually all cytokines.

-Inactivate NF-κB, the transcription factor that

induces the production of TNF-α, among

other inflammatory agents.

Zileuton -Antileukotriene

-5-lipoxygenase pathway inhibitor.

-Blocks conversion of arachidonic acid to

leukotrienes

Zafirlukast -Especially good for

aspirin-induced asthma

-Antileukotriene

-Blocks leukotriene receptors

Montelukast -Especially good for

aspirin-induced asthma

-Antileukotriene

-Blocks leukotriene receptors

Page 52: First Aid Pharm

Expectorants

Guaifenesin (Robitussin) -Removes excess sputum but large doses

necessary; does not suppress cough reflex.

N-acetylcysteine -Mucolytic

-Acetaminophen overdose

-Can loosen mucous plugs in CF patients

-Also used as an antidote in

acetaminophen overdose.