First Aid Pharm
description
Transcript of 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
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")
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
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)
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
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
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
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
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)
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)
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
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)
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
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)
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)
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
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
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
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)
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.
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
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+
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
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
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)
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).
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)
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
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)
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)
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
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
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
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)
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
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
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
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
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
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)
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
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
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)
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
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)
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
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)
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
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
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)
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
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.