Post on 22-Dec-2015
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PHARMACOLOGY IN INFLAMMATION, FEVER,
AND INFECTIOUS DISEASE
N402
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The physiology of inflammation (KP1) Response of vascular tissues to harmful stimuli
Pathogens Damaged cells Other irritants
The response is structured to eliminate Cause of cell injury Necrotic cells and tissues
Involves Host cells Blood vessels Proteins and mediators
Initiates process of repair Classic signs
Pain Heat Redness Swelling Loss of function
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Inflammation and infection (KP2)
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Role of prostaglandins (KP2)
Group of lipids created at site of injury or infections
Act as signals to control specific processes
Cause inflammation, pain, fever as part of healing process
Also involved in vasoconstriction, brochodilation/-constriction, gastric acid secretion, uterine contraction
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Nonpharmacologic treatment of inflammation (KP3)
Ω3 = (fish, grass-fed, walnuts, flaxseed) Ω6 (meat, dairy, grains)
Inflam-mation
Rest
Heat/
cold
H20
↑Ω3↓Ω6
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Primary classes of drugs used to treat inflammation (KP4)
NSAIDs
Salicylates
(ASA)
COX2 Inhib.
Ibu & Ibu-like
Gluco-corticoids
Various:
Cortisone
Dexamethasone
Methylprednisolone
Prednisone
Triamcinolone
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Function of NSAIDs (KP4)
Have multiple functions:AnalgesiaAnti-inflammatoryAnti-pyretic
Used for mild-moderate
inflammation ASA—antiplatelet, can cause GI bleeding Celecoxib (Celebrex)—increased risk of
thrombosis, MI, stroke Ibuprofen (Advil, etc.)—GI bleeding, heart
failure, blood dyscrasias
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Function of salicylates (KP4)
1897—scientists at Bayer
investigated aspirin as a less
irritating form of salicylates Binds to COX-1 and COX-2,
prevents from forming
prostaglandins May affect platelet for entire life-span (8-
11days (must d/c prior to surgery)
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Function of COX-2 inhibitors (KP4)
Do not have as many adverse effects on GI system because they do not inhibit COX-1 (protective of gastric lining)
Moderate to severe inflammation Early form (Vioxx) associated with
stroke and heart attack risk
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Function of Ibuprofen and Ibu-like NSAIDs (KP4)
Inhibit both COX-1 and COX-2 Ibu and Naproxen available OTC Variability of patient response to various
formats (e.g., ibuprofen, naproxen) Adverse GI effects, especially in the
elderly
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Function of glucocorticoids (KP4)
Drug form doses are much higher than levels occurring naturally in the body
Inhibit prostaglandins Serious adverse effects
Hyperglycemia Mood changesOsteoporosisCushing’s (↑cortisol →
rapid central obesity, polyuria, HTN) Short term treatment If long term required, low dose, alternate days Discontinue gradually (wean)
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General strategies: treatment of inflammation (KP5)
First concern is to identify and treat the cause Inflammation serves a healing purpose; use
nonpharmacologic approaches first Topical forms have fewer side effects Corticosteroids used only in severe cases Used only 1-3 weeks to control inflammation Patient then switched to
NSAIDs
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Treating fever (KP6)
Fever naturally occurring defense Elevated fever kills bacteria Prolonged fever can be problematic for
younger children Consider drugs as cause of fever if there
is no other cause evident:AntibioticsSSRIsAntipsychoticsAnaestheticsChemotherapy drugs
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Common medications to treat fever (KP6)
Aspirin Ibuprofen Acetaminophen
Can cause severe, fatal liver damageContraindicated in chronic alcoholism
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Terms you must know! (KP7)
Pathogenicity—ability of an organism to cause disease (qualitative)
Virulence—the degree of pathology or disease caused by an organism (quantitative)
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Methods of classifying bacteria (KP8)
Gram stain
• Gram +• Thick wall• Retain
color• Gram -• Thin wall• Don’t
retain color
Cellular shape
• Bacilli (rods)
• Cocci (spheres)
• Spirilla (spirals)
Use of oxygen
• Aerobic (live in O2-rich environ-ment)
• Anaerobic (live without O2)
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Broad classes of anti-infectives (KP8)
Abx
Anti-virals
Anti-TB
Anti-fungals
Anti-helminthics
Anti-virals
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Acquired resistance (KP9)
First line antibiotics selected based
on safety, availability, and cost Second line antibiotics are broader, greater
risk : benefit ratio (less safe), more costly Some forms of a microorganism are able
to survive exposure to a first or second line antiinfective
Antibiotic resistance is now a major threat to public health (WHO)
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Teaching points: preventing drug resistance (KP9&26)
Prevent infections from
occurring Use correct drug for the
infection Use antibiotics only when medically
necessary Instruct to complete full course of
therapy Prevent transmission of pathogen
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Selection of effective antibiotic (KP10)
Often selected “empirically” Laboratory testing prior
to initiating (not always
possible—see above!) C&S testing Start with broad spectrum, then… Switch to narrow spectrum after C&S
results obtained
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Host factors (KP11)
Host defenses Local Tissue Conditions
Allergy history Other variables
The patient’s natural immunity
Goal is to inter-fere with infec-tion enough so that natural body defenses can take over
Antibiotic must be able to cross any barriers:∙Blood-brain∙↓ Circulation∙Pus∙Hematomas∙Intracellular vs extracellular
Requires drug history
Be sure to ask what type of reaction occurred with suspected antibiotic use
AgePregnancyGenetics
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Classifications of antibacterial drugs (1) (KP12)
Drug class Mechanism of action Nursing considerations
Penicillins Disruption of bacterial cell wall
Generally safeAllergy is commonCross-allergy common
Cephalosporins(cefazolin)
Disrupt cell wall of gram-negative infections
Multiple generations10% PCN-allergic pts have Ceph-allergy
Tetracyclines Inhibit protein synthesis GI upset; take with food, not with milkPhotosensitivity Broad spectrum*Not for patients < 8 years
Macrolides(erythromycin)
Inhibit protein synthesisMost gram-positivesSome gram-negatives
Low-dose=bacteriostaticHigh-dose=bacteriocidalBroad spectrum*
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Classifications of antibacterial drugs (2) (KP12)
Drug class Mechanism of action Nursing considerations
Aminoglycosides(Gentamycin)
Inhibit protein synthesisBacteriocidalGram-negative
Used for serious systemic infectionsInner ear, renal toxicity
Fluoroquinolones(Cipro, levoflaxacin)
Affect DNA synthesisAll work against gm-negNewer against gm-pos
Well-absorbed orallyDo not take with MVIAssoc with tendon injury in pts > 60
Sulfonamides(sulfamethoxazole)
Gram-positive and gram-negative effectivenessInhibit folic acid synthesis
Overuse → resistanceUTIsUsed in MRSA
Other: Metronidazole Effective against anaerobes in abscesses and deep wounds; some parasites
Minor side effectsHigh doses may be neurotoxic
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Drug treatment of tuberculosis (KP 13)
Majority of cases are urban Half cases are Asian;
1/3 are Hispanic Increasing drug resistance Slow growing microorganism Therapy needs to continue for 6-12 months Requires treatment with 2-4 drugs Chemoprophylaxis for close contacts First line drug is isoniazid (INH)
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Fungal, protozoan, and helminthic infections (KP14)
Fungal
• Spores found in soil
• Lungs• Skin• Hair• Nails
Protozoan
• Found in water
• Poor sanitation and hygiene
Helminthic
• Parasitic worms
• Not common in North America
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Drugs for fungal, protozoan, and helminthic infections (KP15-16;18)
Drug class Mechanism of action Nursing considerations
Antifungals (amphotericin B)
Interfere with cell membrane synthesis, causing leaky membrane
Little-to-no antibacterial activity*Treatment may be monthsNephrotoxicity, blood dyscrasias
Antiprotozoan(chloroquine)
Especially malaria; inter-rupt protozoal life cycle
Rare in USPreventive treatment for high-risk travel
Antihelminthic(mebendazole)
Interrupt life cycle locally and systemically
Some are broad spectrumResistance not a factor
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Notes on superficial fungal infection (KP17)
Not exclusive to immune-suppressed patients
Examples:Vaginal candidiasisTinea pedis (athlete’s foot)Tinea cruris (jock itch)
Generally safe: poor penetration to deeper layers
Often available OTC Example: nystatin
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Characteristics of viruses (KP19)
Non-living Structurally simple Method of action
Enter target cellUse own viral enzymes, andReplicate using structural
components of target cell Many are self-limiting Rapid rate of mutation Drugs aimed at viral enzymes
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Simple pathophysiology of HIV (KP20)
Exposure to infected bodily fluids (“introduction”) HIV seeks out T-cell host (“viral attachment”) HIV injects own enzymes into cellular fluid (“viral
fusion”) Protective coating of RNA is dissolved (“uncoating”) RNA converts to DNA (“reverse transcription”) New DNA integrates into T-cell nucleus
(“integration”) Cells separate into new HIV (“final assembly”) HIV enters circulation, starts over (“budding”)
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Principles of HIV therapy (KP21)
Early treatment will delay progression to AIDSExpensiveLong-term treatment may cause resistance
Start if AIDS symptoms or when T-cell count is < 200 cells/mcl
Monitor viral load (amount HIV RNA in blood) regularly
Viral load goal is < 75
copies/ml
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Postexposure prophylaxis (PEP) after occupational HIV exposure (KP22)
If patient is known HIV-positive, start PEP within 24 to 36 hours
If HIV status unknown and exposure severe, PEP until patient is tested
If long-term treatment required, continue for 4 week period
Also monitor for hepatitis,
syphilis exposure
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Principles of Herpes virus pharmacotherapy (KP23)
Acquired through direct physical contact HSV resides in nerve ganglia May remain latent for many years Lesions may occur with physical or
emotional stress Virus stays with patient for lifetime Shingles vaccine recommended after
age 60 (Zostavax)
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Examples of shingles
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Principles of influenza pharmacotherapy (KP24)
Best approach is prevention—flu vaccineLTC residentsChronic cardiopulmonary diseaseChildren ages 5 years and youngerPregnant women in 2nd and 3rd trimestersAdults over age 65Health care workers
Antivirals should start within 48 hours
of symptoms startingWill shorten duration onlyAre not useful against common cold!
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Sidebar: cold or flu???
Cold
Begins with sore throat
Nasal symptoms follow
Cough 4th or 5th day
Fever uncommon; may be slight
Flu
More severe, comes on quickly
Sore throat, fever, cough
Muscle aches and pains, headache
May progress to pneumonia
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Principles of viral hepatitis pharmacotherapy (KP25)
Three primary types: A, B, CA spread by oral-fecal routeB spread through blood and body fluidsC spread through blood and body fluids
Best treatment is prevention Hep A and Hep B vaccines are available; not
for Hep C Non-A/non-B viruses include hepatitis C, D,
E, and G Interferon and antivirals are primary drugs