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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