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76 Cards in this Set

  • Front
  • Back
Types of Antimicrobial Therapy
Prophylaxis
>Primary – surgical, HIV, transplant
>Secondary
>Post-exposure
Types of Antimicrobial Therapy
Empiric therapy
Obtain appropriate cultures first – only 1 opportunity
Use early appropriate therapy (broad)
>Choose antibiotics based on:
>Likely bugs, local susceptibility and patient-specific factors
>Usually up to 72 hours
Types of Antimicrobial Therapy
Definitive therapy
>Narrowest, most effective, least toxic, most pharmacoeconomic agent possible
The Targeted Approach to Antimicrobial Therapy
Optimize antimicrobial effectiveness
>Early, appropriate therapy (be broad)
>Use local susceptibility data and risk for resistance

Limit unnecessary antimicrobial use
>Reassess diagnosis and therapy w/in 72 hours
>De-escalate based on culture/susceptibility data
>Use shortest duration needed
Susceptibility Testing
-the susceptibility of an organism is determined by the MIC (minimum inhibitory concentration) of a drug.
>this is determined by: mixing a standard conc. of bug the pt has grown with increasing conc, of Abx in a plate, incubated for a day, then inspected for signs of cloudiness.
>the mixture with the lowest conc. of Abx where there is no visible growth is deemd to be the MIC. (called the breakpoint) for "Sensitive/Intermediate/Resistance".
>note: just b/c an Abx has the lowest MIC for a bug, does not mean it is the best choice.
Static V. Cidal
static = keep org from growing any more.
cidal = kill the bacteria
>cidal isn't important in uncomplicated infx w functioning immune system.
>PK/PD maximization, host immunity and source control are more important.
cidal drugs are preferred for:
>Endocarditis, osteomylitis, meningitis, febrile neutropenia
Mechanisms of Bacterial Resistance
-enzymatic inactivation
-drug target modification
-reduced cell permeability
-drug removal/efflux
mechanisms of resistance:
examples of enzymatic inactivation
Organism: Haemophilus influenzae, E. coli.

Ex of resistance: Beta lactamase, Aminoglycoside inactivating enzymes.
mechanisms of resistance:
examples of drug target modification
Organism: E. coli, Staph aureus

Ex of resistance: DNA gyrase mutations, PBP2a in MRSA
mechanisms of resistance:
examples of reduced cell permeability
Organism: Pseudomonas aeruginosa

Ex of resistance: alteration of porin channels with imipenem
mechanisms of resistance:
examples of drug removal/efflux
Organism: E. coli

Ex of resistance: Tetracycline resistance
Beta Lactams
the pied piper picked a pack around noon
>all betalactams can cause hypersensitivity rxns from mild rashes to drug fever and acute interstitial nephritis/anaphylaxis.
>seizures can result from very hi dose of any beta-lactm.
>all inhibit transpeptidases in the bacterial cell wall
>all lack activity agaist atypical organisms like Mycoplasma pneumoniae & Chlamdophila pneumponiae
>all lack activity against MRSA
Ticarcillin
Piperacilin
Penicillin VK
Penicillin G
Ampicillin
Penicillin G benzathine
Amoxicillin +/- Clavulanic acid
Nafcillin
Other Beta lactams:
Cephalosporins
Cephalexin (Keflex)
Cefotaxime
Cefuroxime
Cetriaxone
>>Wide spectrum of activity, but resistance…
Enterococcus species
Gram (-): Extended-spectrum -lactamase, Amp-C -lactamase
Generally good oral absorption
Short half-life/renal elimination (except ceftriaxone)
CSF penetration for 3rd/4th generation
Other Beta lactams:
Carbapenems
Impenem
Carbapenem
Monobactams
Azetreonam
Glycopeptides
&
Other cell wall types
glycoprotein: Vancomycin

other cell wall: Daptomycin
Macrolides
Azithromycin
Erythromycin
Clarithromycin
Tetracyclines
Doxycycline
Clindamycin
Fluoroquinolones
Ciprofloxacin
Levfloxacin (levaquin)
Moxifloxacin
Aminoglycosides
Gentamicin
Amikacin
Antifolates
Sulfamethoxazole +/- trimethoprim (Bactrim)
Nafcillin
-inhibits transpeptidases in bacterial cell wall
-antistaph penicillin (Beta lactam)
-basic structure of penicillin was altered to resist bact enzymes
-Stable against penicillinase (methicillin)
-Hepatic metabolism; nafcillin for CNS
-Less active vs. streptococci; MRSA in 1960’s
-Can use continuous infusion
USES: Skin/soft tissue infections, endocarditis, osteomyelitis
Staphylococcus and streptococcus sp.
NO activity against gram-negative species
Penicillin G
Penicillin G benziathine
Penicillin VK
-natural penicillins
-inhibits transpeptidases in bacterial cell wall
-have a very short half life, but long acting depot formuations (penicillin g benziathine) are available IM inj.
-penicillin G = drug of choice for syphillis
-peniclin V is oral form of penicillin G
-penicillin VK is potassium salt of penicillin V
-do not give benziathine IV->fatal
A: Gastric acid; most on empty stomach
D: Wide distribution; variable protein binding
M/E: Short half-life (0.5 – 1 hour)
Glomerular filtration + tubular secretion
Common Uses: Neurosyphilis
S pneumoniae, viridans streptococci, GAS, GBS, meningococci
>Early/latent syphilis, rheumatic fever prophylaxis
Amoxicillin
Ampicillin
-aminopenicillins
-inhibits transpeptidases in bacterial cell wall
-for cidal effect combine with aminoglycoside
-Some activity vs. Gram negative pathogens
-Some E. coli, Klebsiella, Proteus, H. influenzae
-Some Salmonella and Shigella strains
-Greater activity vs. Enterococci
Listeria monocytogenes
>Amoxicillin PO; Ampicillin IV; not stable for 24 hours
>Common Uses: Community-acquired RTIs, prophylaxis in dental procedures
Amoxicillin + Clavulanic Acid

(beta lactams with lactamase inhibitor cominations
-aminopenicliin + lactamase inhibitor - just restore activity of original drug, not add to it.
-available orally, hi dose assoc w/ diarrhea.
Spectrum: good: MSSA, streptococci, enterococci, many anaerobes, enteric GNRs,
moderate: GNRs with advanced beta-lactamases
Poor: MRSA, extended spectrum beta lactamase producing GNRs.
>>Effective against β-lactamases produced by:
S. aureus, H. influenzae, M. catarrhalis, Bacteroides spp., and some Enterobacteriaceae
Uses:
Mixed infections, intra-abdominal, HAP/VAP
piperacillin
ticarcillin
-antipseudomonal penicillins/extended spectrum penicillin
>Extends to GNR, including P. aeruginosa
Piperacillin > Pseudomonas and enterococcal activity
Ticarcillin > Stenotrophomonas activity
Similar Gram-positive activity as aminopenicillins
E:Renal elimination
>Ticarcillin not available alone
Common Uses:
Nosocomial pathogens, including susceptible
P. aeruginosa
other beta lactams: cephalosporins

1st generation:
Cephalexin (Keflex)
Gram (+): Staphylococcus and Streptococcus
Some Gram (-): M. catarrhalis, E. coli, K. pneumoniae
Agents
IV & PO: (good absorption)
Clinical Use: Susceptible skin and soft tissue infections, surgical prophylaxis, streptococcal pharyngitis, osteomyelitis
>>No CSF penetration
other beta lactams: cephalosporins

2nd generation: Cefuroxime
Improved Gram (-) activity vs. 1st generation against:
E. coli, K. pneumoniae, H. influenzae, M. catarrhalis, and N. meningitidis
Certain will cover Anaerobes (cephamycins-cefoxitin/cefotetan)
Clinical Use: >> Skin/soft tissue infections, UTI
Mild CAP (3rd gen preferred), sinusitis, AECB
Surgical prophylaxis (GI/GU)
other beta lactams: cephalosporins

3rd generation:
Cefotaxime
Ceftriaxone
Improved gram-negative coverage:
E. coli, Klebsiella spp., P. mirabilis
S. pneumoniae (variable), S. aureus (variable)
Watch Enterobacter species (Amp-C) and ESBLs
Agents:
Ceftriaxone IV(better Gram (+))
Cefotaxime IV(better Gram (+))
Ceftazidime IV(better Gram (-), P. aeruginosa)
Cefdinir, cefpodoxime, cefixime (PO)
Clinical Use:
Upper/lower RTIs, UTIs, STDs, meningitis, cellulitis, osteomyelitis
other beta lactams: carbapenems

Imipenem
>product of Streptomyces cattleya (New Jersey swamp)
Spectrum:
Most Gram-positives (no MRSA) + anaerobes
Gram-negative: including P. aeruginosa
Stable in presence of ESBLs and Amp-C; No S. maltophilia activity
Resistance: Carbapenemases, porin channel/efflux mutants
>Induce production of Amp-C
>Adverse effects:
Seizures (more with imipenem?)
>>Clinical utility/Common Uses:
Nosocomial pneumonia, UTIs, ESBL infections
Intra-abdominal infections, neutropenic fever
CNS infections (meropenem); nocardia
>Empiric treatment of multi-drug resistant organisms
Monobactams:
Aztreonam
>>Gram-negative activity only (includes P. aeruginosa)
>>No cross reactivity in PCN allergy
Normal adult dose: 1-2 g IV q 8 h
>>is a type of betalactam, avoid giving another to avoid redundancy
Glycopeptides:
Vancomycin
-Glycopeptide
>Blocks the formation of cross-linked peptides
>Binds to D-Ala-D-Ala carboxy-terminus
>Weakened cell wall and eventual osmotic lysis
Spectrum: Gram-positive organisms
--Including anaerobics
Bacteriostatic vs. enterococci
>Virtually no activity vs. gram negatives
>>NOT absorbed orally (< 5%)
>>With IV use, measure vancomycin troughs:
Good trough 10 – 20 (sometimes 15 – 20).
Toxicity: "red man's neck syndrome" Thrombophlebitis, neutropenia, thrombocytopenia, rash >>Nephrotoxicity
>Early reports were confounded by other toxins
>True incidence of 5 – 7% and reversible
>Ototoxicity
>Rare case reports in humans
***Consider a loading dose for severely ill:
cyclic lipopeptides (other cell wall):

Daptomycin:
MOA: the drug kills bacteria in a concentration-dependent manner by binding preferentially to gram-positive bacterial membranes, inserting into the membrane, and causing rapid membrane depolarization and bacterial cell death due to disruption of critical metabolic functions, such as protein, DNA, and RNA synthesis. (sweet!)
>>Cyclic lipopeptide antibiotic
Rapid depolarization due to membrane attachment (potassium out) Calcium-dependent
>Rapid, bactericidal activity
Gram-positive activity only (includes anaerobes)
>No Gram-negative activity
>Active vs. resistant Staphylococci, Streptococci, and Enterococci
Clinical Use: Skin and soft tissue infections
*Bacteremia/endocarditis
*Non-inferior to vancomycin or nafcillin
Vancomycin failures/intolerance
*MRSA with vancomycin MIC=2 ug/mL
*Severe infections due to VRE
*Safety: CPK elevation - monitor weekly
Vancoymycin:
Monitoring & Place in Therapy
>>For patients with serious MRSA infections, target trough concentrations of 15-20 ug/mL
Pneumonia, endocarditis, osteomyelitis, meningitis
>>Check trough just prior to the next dose at steady state conditions (before 4th to 5th dose)
>If therapeutic, re-check every 5-7 days or with change in renal function
>>Severe S. aureus infections
>Less effective than anti-staph PCNs for MSSA
>Severe β-lactam allergy
>Severe coagulase-negative staph infections
>>Community-acquired meningitis
Vancomycin + 3rd gen cephalosporin empiric
C. difficile associated diarrhea
>>Drug of choice for severe infection
Anti-Folates:
Linezolid (Zyvox)
MOA: Inhibits protein synthesis (binds at 50s ribosomal subunit)
>>Gram-positive bacteriostatic activity :Stahphylococci, Streptococci, and Enterococci
>Nocardia, atypical mycobacteria
>No Gram-negative activity
>Oral formulation is 100% bioavailable
>Wide distribution, including lung and CSF
>Metabolized via hepatic oxidation (no CYP450)
>Decreased conc. with rifampin (p-glycoprotein)
>Both renal (30%)/non-renal elimination (70%)
>No adjustment for renal/mild hepatic dysfunction
Clinical Use: Serious infections caused by VRE
Infections caused by MRSA:
Vancomycin intolerance/failure/elevated MICs
>Skin and soft tissue infections
>Hospital-acquired pneumonia
>Meningitis
>>Limitations
>Drug Interactions (No use with many antidepressants, etc)
>Toxicity and emergence of resistance with prolonged therapy (Low platelets, need weekly CBC)
$$High cost of therapy $$
aminoglycosides:

Gentamicin
Amikacin
MOA: Inhibits protein synthesis (irreversible binding at 30s ribosomal subunit)
>>Spectrum of activity:
Gram-negative rods: P. aeruginosa (tobra/amikacin)
Staph, strep, enterococi: synergy dosing (gent only)
Others: non-TB mycobacteria, nocardia
>Available (parenteral) agents
Gentamicin, tobramycin, amikacin, streptomycin
>Other agents Paromomycin, neomycin
>Absorption: PO < 1%
IM/IV: All rapidly absorbed, peak 30-90 minutes
>Distribution Good penetration: bone, urine, peritoneal fluid
Poor penetration: lung, CNS, abscess
>Elimination No metabolism
85-95% excreted unchanged in urine (by GFR)
Toxicity: Proximal renal tubule uptake (saturable)
Acute tubular necrosis (ATN)
Non-oliguric renal failure, ↑ in SCr/BUN after 7-10 days
Risk factors: Length of therapy, concomitant nephrotoxins
Age, pre-existing renal disease, liver disease, volume depletion
Ototoxicity/vestibulotoxicity (2 - 25%) Bilateral, high-frequency hearing loss
AminoGlycosides
Concentration-dependent killing
>>Rate and extent of bacterial killing is maximized at high exposure (AUC or peak)
>>This usually occurs when the drug peak is approximately 10X the MIC
>Prolonged post-antibiotic effect (PAE) of 0.5 to 7.5 hrs
Macrolides/Ketolides:

Azithromycin
Erythromycin
Clarithromycin
MOA: Reversible binding to 50s ribosomal subunit Inhibit protein chain elongation (static generally)
>>Immunomodulatory effects (doubtful)
*Gram positive: Staphylococci and streptococci (no MRSA)
*Group A strep, some S. pneumoniae Gram negative:
H. influenzae, H. pylori
Others: Treponema spp., non-TB Mycobacteria spp.
Legionella spp., Mycoplasma and Chlamydophila spp.
Salmonella and campylobacter diarrhea
Absorption:
PO absorption: 40 to 60% (variable)
Distribution: *Wide, especially ELF, alveolar macrophages; no CSF
>Metabolism/elimination:
*Hepatic with variable CYP450 involvement
*Variable half-life; up to 68 hours with azithromycin; some renal (clari)
Macrolides/Ketolides:

Azithromycin
Erythromycin
Clarithromycin
More on absorption/Clinical Usage
Azithromycin: Long tissue half-life, 37% PO absorption
Erythromycin: 25% PO absorp
Clarithryomycin: Higher serum concentrations, PO absorption 50%
Clinical Usage:
**Azithromycin: Mild CAP, AECB, pharyngitis, otitis media, STDs, MAC (Well-tolerated, easy to use and abuse, category B in pregnancy)
**Erythromycin: Pharyngitis (PCN allergy)
Gastric paresis (>>Largely replaced by newer, improved agents<<)
**Clarithromycin: CAP, AECB, pharyngitis, sinusitis, otitis media, H. pylori, MAC
(>>Increased GI upset and drug interactions vs. azithro, but greater potency vs. S. pneumoniae<<)
Lincosamides:
Clindamycin
MOA: Inhibits protein synthesis (binds to 50s ribosomal subunit)
May diminish exotoxin production
>>Spectrum
No Gram negative activity, No Enterococus. >>Gram positive aerobes/anaerobes
S. aureus (including MRSA), Streptococci
Clostridia spp., Peptococci, Peptostreptococci spp.
Protozoa/fungal – Toxoplasma, Pneumocystis, Plasmodium spp.
>>Absorption/distribution
Oral/IV (90% absorbed)
Excellent tissue penetration (not CNS); good bone
Metabolism/elimination
Metabolized in the liver; half-life = 3 hrs
>>Adjust in severe hepatic failure
**Adverse effects (GI)
Antibiotic-associated diarrhea
C. difficile diarrhea
Clinical Use; Skin/soft tissue infections >Mild community-acquired
>Severe: necrotizing fasciitis (not primary therapy)
>Osteomyelitis
Alternative for PCN allergic patients
>Intra-abdominal/pelvic infections
>Aspiration pneumonia/lung abscess
>Others: odontogenic infections, endocarditis prophylaxis, acne vulgaris
Glycyclyines/tetracyclines:

Doxycyline
Inhibit protein synthesis at 30s subunit
Bacteriostatic
Spectrum
Gram positive and Gram negative pathogens (limited)
Community-acquired pathogens
Vibrio, Brucella, Bartonella, Pasteurella, Yersinia spp.
Ehrilichia, Spirochetes, Rickettsia, Plasmodium spp.
Agents:
Tetracyline,Doxycycline, Minocycline
>>Absorption/distribution
80 to 100% PO absorption
>High volume of distribution; low serum levels
>Metabolism/elimination
TCN is renal, doxy/mino mainly hepatic
>Adverse effects / contraindc:
-GI effects, esophageal ulceration, Photosensitivity, vestibular (minocycline)
>Teeth and bone (pregnancy or children < 9 yrs)
>>Clinical use: Community-acquired infections
CAP (outpatient, mild disease without risk factors)
Cellulitis (CA-MRSA)
*Sexually-transmitted diseases
*Nongonococcal urethritis and alternative for syphilis
Tick-born infections (doxycycline)
Other: >Vibrio, brucellosis, tularemia, bartonellosis, etc.
Malaria prophylaxis/treatment
>Minocycline for MDR-Ab infections
Anti Folates

Sulfamethoxazole +/- Bactrim
MOA: Inhibits microbial synthesis of tetahydrofolic acid from PABA (DHFR and DHF synthetase)
Essential for thymidine…inhibits DNA synthesis (cidal)
Resistance: Decreased cell permeability, Overproduction of DHFR, Altered enzymatic binding sites
>Spectrum: Community-acquired gram (-) and gram (+)
E. coli, S. aureus (including MRSA)
>>Pharmacokinetics:
70-90% PO absorption
>Liver metabolized and excreted via the kidney
T1/2 ranges from 5-15 hours
>>Adverse effects: GI, rash, hematologic, hepatitis, fluid load
Rifampin
MOA: Inhibits DNA-dependent RNA polymerase
Spectrum: Bacteria (mainly gram-positive)
Mycobacteria
Pharmacokinetics:
PO/IV (90% bioavailable)
>Penetrates most tissue compartments
>Hepatic metabolism/biliary elimination
Adverse effects :>Hepatotoxicity
>Red-orange coloring of body fluids
Clinical Use: (mostly in combination) >TB
>Prophylaxis of bacterial meningitis (alone)
>Combination tx for gram-positive infections
>Prosthetic-valve endocarditis
>Osteomyelitis (implant infections)
>Legionella infections
Watch CYP450 induction!
Metronidazole
(Flagyl)
MOA: Inhibits DNA synthesis (bactericidal)
Spectrum: Gram-negative anaerobes (Bacteroides spp.)
Gram-positive anaerobes (Clostridium spp.)
Parasites
Pharmacokinetics:
>Completely absorbed PO
>High penetration to most sites
>Hepatic metabolism/renal elimination (T1/2 = 8hrs)
Adverse effects: ETOH intolerance (disulfiram-like) >Peripheral neuropathy with prolonged duration
Metallic taste, rare pancreatitis
Clinical Role:
C. difficile-associated diarrhea
>Mixed aerobic/anaerobic soft tissue or intra-abdominal/pelvic infections
>Brain abscess in combination
>Trichomoniasis/bacterial vaginosis
Fluoroquinolones

Ciprofloxacin
Levofloxacin
Moxifloxacin
MOA: Inhibit DNA gyrase and topoisomerase IV
Regulate supercoiling of genomic DNA
Inhibition results in rapid cell death
SpectruM: Gram-negatives
Enterobacteriaceae, P. aeruginosa, H. influenzae
Gram-positives : S. pneumoniae, S. aureus (poor vs. MRSA) -Mycobacteria
>“Atypical organisms”
Legionella, Chlamydia, Mycoplasma, Anaerobes
Absorption: All well absorbed PO (oral = IV)
Distribution: Lung, prostate, skin, urinary tract, bone
Elimination: >Mostly renal (moxifloxacin 50% hepatic)
Antihistamines: in general
MOA: >Competes with H1 histamine receptors
>Acts as a decongestant as well as an anticholinergic
>Adverse Effects = demonstrated by central nervous system depression or agitation, hyperactivity or psychosis, blurred vision, or abdominal discomfort
>Well absorbed orally
>Therapeutic effects begin within 15-30 minutes with peak effects in 1 hour
>Drug Interactions = sedatives, anti-depressants, muscle relaxants, tramadol
>Avoid use = BPH, Glaucoma, COPD/Asthma (poorly controlled)
First-Generation OTC Antihistamine:

Benadryl (Diphenhydramine)
MOA:>Sedation and Impairment
Crosses blood-brain barrier
CNS effects in 20%
>Anticholinergic effects
>Dry mouth and eyes
>Impotence
>Urinary hesitancy
>Glaucoma
>Confusion, especially in older adults
>Young children: Paradoxical agitation
Second-Generation OTC Antihistamines:

-Loratadine (Alavert, Claritin)
-Cetirizine (Zyrtec)
Second-Generation
-Less sedative effects
-No evidence of tolerance
Decongestants:
In general
>Narrow blood vessels in the lining of the nose
Decreases blood flow
>Decreases inflammation and swelling of nasal tissue
>>Nasal sprays should not be used for more than 3 days, can lead to “rebound” effect
>Increases air flow through nasal passage ways
>Adverse Effects = minimal with short term use
>Nervousness, dizziness, sleeping disorders
>CV effects = tachycardia, palpitations, increasing blood pressure
>Available as pills or as a nasal spray
>Acts within 15-30 minutes; Lasts up to 4-6 hours; 12 hours for extended release products
>Drug Interaction = Asthma medications or anti-hypertensives
>Avoid in patients with hypertension, glaucoma, thyroid disorders, prostate problems, cardiovascular disease
Nasal Decongestants:
Pseudoepedrine
(Sudafed)
>Pseudoephedrine (Sudafed)
>Limited to be sold behind the pharmacy counter
>Limited to a 1 month supply
>Need photo ID
>Retailers have to keep records of consumers purchases for 2 years
Antitissives:
Dextromethorphan
Coughs typically do not require treatment – resolve on own
>Some coughs should not be treated
>Smoking, emphysema, COPD, asthma, pneumonia, bronchitis
>Antitussives = Block cough reflex (cough suppressants)
>Dextromethorphan (brand names: Triaminic Cold and Cough, Robitussin Cough, Vicks 44 Cough and Cold) is a commonly used antitussive.
Expectorants:
Guiafenisen
Expectorants = Thin mucus, helping to clear the mucus from out of the airways
Onset in 30 minutes and lasts 4 – 6 hours
Adverse effects = irritability, sleepiness, or dizziness
Avoid chronic use in elderly
>The only expectorant available in OTC products is guaifenesin (brand names: Mucinex, Robitussin Chest Congestion)
OTC Pain med:
Acetaminophen
(Tylenol)
>Analgesic and antipyretic
>Inhibits the nitric oxide pathway mediated by a variety of neurotransmitter receptors including substance P
>Endogenous pyrogens produced by leukocytes cause an elevation of prostaglandin E (PGE) in the cerebrospinal fluid. >Fever results when the elevated PGE acts on the pre-optic area of the anterior hypothalamus to decrease heat loss and increase heat gain; inhibit the action of endogenous pyrogens on the heat-regulating centers in the brain by blocking the formation and release of prostaglandins in the central nervous system
Rapidly absorbed; 85 – 98% oral bioavailability
Adverse Effect:
Liver Toxicity = doses > than 3 grams per day
>From 1998 to 2003, acetaminophen was the leading cause of acute liver failure in the United States, with 48% of acetaminophen-related cases (131 of 275) associated with accidental overdose.
>A 2007 CDC population-based report estimates that, nationally, there are 1600 cases of ALF each year (all causes). >Acetaminophen-related ALF was the most common etiology.
>>Summarizing data from five different surveillance systems, there were an estimated 56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths related to acetaminophen-associated overdoses per year during the 1990-1998 period.
FDA: Black box warnings of liver toxicity
OTC Pain med:
Non-steroidal anti-inflammatory agents (NSAIDs)
(Motrin)
>Aspirin, Naproxen (Aleve), Ibuprofen (Motrin, Advil)
>Inhibit cyclooxygenase, decreasing prostaglandin synthesis
>2 types: Non-selective
Inhibit the enzymes found in the stomach, blood platelets, and blood vessels (COX-1) as well as those at sites of inflammation >(COX-2) to a similar degree – >All OTC products
>>Selective COX-2 inhibitors – Celecoxib (Celebrex)
**Avoid in patients with aspirin allergy, h/o ulcers, liver or kidney disease, hypertension, blood thinner**
Ophthalmic Products:
Artificial Tears
>1st line tx
>Diluting the allergens and lubricating the eye
2-4 times daily
>Contain preservatives and inorganic electrolytes to achieve tonicity and sustain pH
Contain:carboxymethylcellulose, glycerin, polyethylene glycol 400
>Can be refrigerated to provide additional soothing and comfort upon use
>Several forms:
>H20 based solution
>Ointment = Lacri-Lube, Moisture Eyes PM, Refresh PM
>Eye washes = contain boric acid (AK Rinse, Dacriose, Eye Stream)
Ophthalmic Products:
Phenylephrine
>2nd line Tx:
>Topical antihistamines or Topical antihistamine-decongestants
>Alpha-adrenergic receptors of the ophthalmic vasculature to constrict conjunctival vessels, thereby decreasing eye redness
>Naphazoline has demonstrated efficacy in decreasing tearing and pain associated with superficial inflammation of the ocular area.
>Oxymetazoline has been shown to improve the symptoms of burning, itching, and tearing associated with allergic conjunctivitis.15
ophthalimic products:
antihistamine/mast-cell stabilizer

Ketotofen
In 2006, the FDA approved ketotifen 0.025% ophthalmic solution from prescription to OTC status
>Relieves ocular itching without the use of a decongestant
>Ketotifen is a benzocycloheptathiophene derivative. It is classified as a noncompetitive H1-receptor antagonist and mast cell stabilizer that inhibits release of mediators from cells involved in hypersensitivity reactions
>Use in 3 years of age and older
1 drop every 12 hours
>Onset of action: Minutes
Ophthalmic products
How to properly instill drops
Wash hands and face
Do not touch dropper tip against the eye or anything else to avoid contamination
Tilt head back, pull down lower lid
After drop, close eye for 2-3 minutes and tip the head down
Instill 1 drop at a time; wait 5 minutes
If using a suspension, instill that drop last
Nasal Decongestants:
Nasalcrom
(Cromolyn Sodium)
Cromolyn = Approved in ages 5 and older; use 3 to 6 times a day
Narrow blood vessels in the lining of the nose
Decreases blood flow
Decreases inflammation and swelling of nasal tissue
Increases air flow through nasal passage ways
Adverse Effects = minimal with short term use
Nervousness, dizziness, sleeping disorders
CV effects = tachycardia, palpitations, increasing blood pressure
Available as pills or as a nasal spray
Acts within 15-30 minutes; Lasts up to 4-6 hours; 12 hours for extended release products
Drug Interaction = Asthma medications or anti-hypertensives
Avoid in patients with hypertension, glaucoma, thyroid disorders, prostate problems, cardiovascular disease
Ophthalmic products:
Ketotifen
>Use: Ophthalmic: Temporary relief of eye itching due to allergic conjunctivitis
>MOA: Exhibits noncompetitive H1-receptor antagonist and mast cell stabilizer properties.
>Onset of action: Minutes
Duration: 8-12 hours
AR: Ophthalmic: 1% to 10%: Allergic reactions, burning or stinging, conjunctivitis, discharge, dry eyes, eye pain,
Contraind: hypersensitivity
otic products
water logged ear:
Swim-ear
External otitis media “Swimmer’s Ear”: Isopropyl alcohol 95% in anhydrous glycerin 5% is the only FDA-approved "ear-drying" agent that has been proven to be safe and effective.
> Boric acid has been added to some products to increase acidity and acts as a weak germicide.
>For use in individuals 12 years of age and older.
Examples:
Auro Dri Ear
Star Otic
Swim-Ear
Otic products: cerumen impaction:

Debrox
Indication: Excessive/Impacted Cerumen
>Carbamide peroxide 6.5% in anhydrous glycerin is the only FDA-approved nonprescription cerumen-softening agent for the softening and removal of excessive earwax in individuals 12 years of age and older
>Use twice daily for up to 4 days only
Examples:
Auro Earwax
Debrox Earwax
Murine Earwax
Angina:
Beta Blockers:
Metroprolol ER/XL
Caredilol
Labetalol
Indication: HTN, (often used w/ vasodilator/diuretic), arrhythmias, ischemic heart disease,
MOA:Negative inotrop/chronotrop
Decreases “double product”
(HR X SBP= cardiac O2 demand)
Contraindications: Asthma and other bronchospastic conditions
Severe bradycardia/atrioventricular blockade
Severe unstable left ventricular failure/decompensated CHF
Fatigue, impaired exercise tolerance, insomnia, unpleasant dreams, worsening of claudication, and erectile dysfunction.
Depression
Angina:
Ca2+ Channel Blockers
Dihydropyridines: **amlodipine,**
felodipine
Nifedipine,
Mechanism – blocks voltage-gated calcium channels in vascular smooth muscle; decreases calcium entry
Pharmacological Effect – arterial vasodilation; decrease in BP; mild reflex sympathetic activation
Therapeutic Uses – hypertension (a mainstay); angina
Adverse Effects – excessive vasodilation (hypotension, etc.); edema, constipation
Angina:
Ca2+ Channel Blockers
Non-dihydropyridine:
verapamil, diltiazem
Mechanisms – block voltage-gated calcium channels in vascular smooth muscle; decreases calcium entry; modest slowing of calcium channel reactivation in the heart
Pharmacological Effect – arterial vasodilation (less potent than nifedipine); decrease in BP; cardiac actions block reflex sympathetic activation of heart; modest decrease in HR with diltiazem
Adverse Effects – excessive vasodilation (hypotension, etc.); bradycardia, transient asystole in patients with A-V conduction problems
Therapeutic Uses – hypertension (a mainstay); angina; tachycardias
angina:
Nitroglycerin
Isosorbide dinitrate or mononitrate
MOA: Releases nitric oxide in smooth muscle, which activates guanylyl cyclase and increases cGMP
Effects: Smooth muscle relaxation, especially in vessels other smooth muscle is relaxed but not as markedly vasodilation decreases venous return and heart size may increase coronary flow in some areas and in variant angina
Clinical: Angina: Sublingual form for acute episodes oral and transdermal forms for prophylaxis IV form for acute coronary syndrome
Pharm/Tox/Interx: Very high first-pass effect, so sublingual dose is much smaller than oral high lipid solubility ensures rapid absorption Toxicity: Orthostatic hypotension, tachycardia, headache Interactions: Synergistic hypotension with phosphodiesterase type 5 inhibitors (sildenafil, etc)
pFOX inhibitors:
Ranolozine
MOA: Inhibits late sodium current in heart also may modify fatty acid oxidation
Effects: Reduces cardiac oxygen demand fatty acid oxidation modification may improve efficiency of cardiac oxygen utilization
Clinical: Prophylaxis of angina Oral, duration 6–8 h Toxicity: QT interval prolongation, nausea, constipation, dizziness Interactions: Inhibitors of CYP3A increase ranolazine concentration and duration of action
angina:
beta blockers:
propanalol
MOA: Nonselective competitive antagonist at adrenoceptors Effect: Decreased heart rate, cardiac output, and blood pressure decreases myocardial oxygen demand
Clinical: Prophylaxis of angina
Oral and parenteral, 4–6 h duration of action
Toxicity: Asthma, atrioventricular block, acute heart failure, sedation Interactions: Additive with all cardiac depressants
Class IA: Antiarrhythmic
Quinidine (more toxic)
Procainamide
MOA: INa (primary) and IKr (secondary) blockade
Effect: Slows conduction velocity and pacemaker rate prolongs action potential duration and dissociates from INa channel with intermediate kinetics direct depressant effects on sinoatrial (SA) and atrioventricular (AV) nodes
Clinical: Most atrial and ventricular arrhythmias drug of second choice for most sustained ventricular arrhythmias associated with acute myocardial infarction Pharm: Oral, IV, IM eliminated by hepatic metabolism to N-acetylprocainamide (NAPA; see text) and renal elimination NAPA implicated in torsade de pointes in patients with renal failure
Toxicity: Hypotension long-term therapy produces reversible lupus-related symptoms
Class IB: Antiarryhthmic
Lidocaine
Mexilitine
MOA:Sodium channel (INa) blockade
Effect: Blocks activated and inactivated channels with fast kinetics does not prolong and may shorten action potential Clinical: Terminate ventricular tachycardias and prevent ventricular fibrillation after cardioversion
Pharm: IV first-pass hepatic metabolism reduce dose in patients with heart failure or liver disease
Toxicity: Neurologic symptoms
Mexiletine: Orally active congener of lidocaine; used in ventricular arrhythmias, chronic pain syndromes
Class IC: Antiarrhythmic
Flecainide
MOA:Sodium channel (INa) blockade
Effect: Dissociates from channel with slow kinetics no change in action potential duration Supraventricular arrhythmias in patients with normal heart do not use in ischemic conditions (post-myocardial infarction)
Pharm: Oral hepatic, and kidney metabolism half life ~ 20 h
Toxicity: Proarrhythmic
Class II: Antiarrhythmic
Propanalol
MOA: B-Adrenoceptor blockade
Effect: Direct membrane effects (sodium channel block) and prolongation of action potential duration slows SA node automaticity and AV nodal conduction velocity
Clinical: Atrial arrhythmias and prevention of recurrent infarction and sudden death
Pharm: Oral, parenteral duration 4–6 h
Toxicity: Asthma, AV blockade, acute heart failure Interactions: With other cardiac depressants and hypotensive drugs
Class III: Antiarrhythmic
Amiodarone
MOA: Blocks IKr, INa, ICa-L channels, adrenoceptors
Effect: Prolongs action potential duration and QT interval slows heart rate and AV node conduction low incidence of torsade de pointes
Effect: Serious ventricular arrhythmias and supraventricular arrhythmias Pharm: Oral, IV variable absorption and tissue accumulation hepatic metabolism, elimination complex and slow
Toxicity: Bradycardia and heart block in diseased heart, peripheral vasodilation, pulmonary and hepatic toxicity hyper- or hypothyroidism. Interactions: Many, based on CYP metabolism
Class III: Antiarrhythmic
Dofetilide
Sotalol
MOA: IKr block
Effect: Prolongs action potential, effective refractory period Clinical: Maintenance or restoration of sinus rhythm in atrial fibrillation
Pharm: Oral renal excretion Toxicity: Torsade de pointes (initiate in hospital) Interactions: Additive with other QT-prolonging drugs
*Sotalol: B-Adrenergic blocker, direct action potential prolongation properties, use for ventricular arrhythmias, atrial fibrillation
Class IV: Antiarrhythmic
Verapamil
Diltiazem
MOA: Calcium channel (ICa-L type) blockade
Effect: Slows SA node automaticity and AV nodal conduction velocity decreases cardiac contractility reduces blood pressure
Clinical: Supraventricular tachycardias
Pharm: Oral, IV hepatic metabolism caution in patients with hepatic dysfunction
Toxicity: see other card on same
Other Antiarrhythmic Agents
Adenosine
MOA: Activates inward rectifier IK blocks ICa
Effect: Very brief, usually complete AV blockade Clinical: Paroxysmal supraventricular tachycardias
Pharm: IV only duration 10–15 Toxicity: Flushing, chest tightness, dizziness Interactions: Minimal