Transcript Pharmacology in Inflammation, Fever, and Infectious Disease

N402
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The physiology of inflammation (KP1)
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Response of vascular tissues to harmful stimuli
 Pathogens
 Damaged cells
 Other irritants
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The response is structured to eliminate
 Cause of cell injury
 Necrotic cells and tissues
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Involves
 Host cells
 Blood vessels
 Proteins and mediators
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Initiates process of repair
Classic signs
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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)
Rest
↑Ω3
↓Ω6
Inflammation
Heat/
cold
H20
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Ω3 = (fish, grass-fed, walnuts, flaxseed)
Ω6 (meat, dairy, grains)
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Primary classes of drugs used to
treat inflammation (KP4)
NSAIDs
Salicylates
(ASA)
COX2 Inhib.
Ibu & Ibu-like
Glucocorticoids
Various:
Cortisone
Dexamethasone
Methylprednisolone
Prednisone
Triamcinolone
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Function of NSAIDs (KP4)
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Have multiple functions:
 Analgesia
 Anti-inflammatory
 Anti-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 (811days (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)
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Drug form doses are much higher than levels
occurring naturally in the body
Inhibit prostaglandins
Serious adverse effects
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Hyperglycemia
Mood changes
Osteoporosis
Cushing’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:
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Antibiotics
SSRIs
Antipsychotics
Anaesthetics
Chemotherapy drugs
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Common medications to treat
fever (KP6)
Aspirin
 Ibuprofen
 Acetaminophen
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 Can cause severe, fatal liver damage
 Contraindicated in chronic alcoholism
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Terms you must know! (KP7)
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Pathogenicity—ability of an organism to
cause disease (qualitative)
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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 O2rich
environment)
• Anaerobic
(live without
O2)
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Broad classes of anti-infectives
(KP8)
Abx
Anti-virals
Anti-virals
Antihelminthics
Anti-TB
Antifungals
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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
The patient’s
Antibiotic must
natural immunity be able to cross
any barriers:
Goal is to inter- ∙Blood-brain
∙↓ Circulation
fere with infec∙Pus
tion enough so
∙Hematomas
that natural
∙Intracellular vs
body defenses
can take over
extracellular
Allergy history
Other variables
Requires drug
history
Age
Pregnancy
Genetics
Be sure to ask
what type of
reaction
occurred with
suspected
antibiotic use
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Classifications of antibacterial
drugs (1) (KP12)
Drug class
Mechanism of action
Nursing considerations
Penicillins
Disruption of bacterial cell Generally safe
wall
Allergy is common
Cross-allergy common
Cephalosporins
(cefazolin)
Disrupt cell wall of gramnegative infections
Multiple generations
10% PCN-allergic pts
have Ceph-allergy
Tetracyclines
Inhibit protein synthesis
GI upset; take with food,
not with milk
Photosensitivity
Broad spectrum*
Not for patients < 8 years
Macrolides
(erythromycin)
Inhibit protein synthesis
Most gram-positives
Some gram-negatives
Low-dose=bacteriostatic
High-dose=bacteriocidal
Broad spectrum*
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Classifications of antibacterial
drugs (2) (KP12)
Drug class
Mechanism of action
Nursing considerations
Aminoglycosides
(Gentamycin)
Inhibit protein synthesis
Bacteriocidal
Gram-negative
Used for serious
systemic infections
Inner ear, renal toxicity
Fluoroquinolones
(Cipro, levoflaxacin)
Affect DNA synthesis
All work against gm-neg
Newer against gm-pos
Well-absorbed orally
Do not take with MVI
Assoc with tendon injury
in pts > 60
Sulfonamides
(sulfamethoxazole)
Gram-positive and gram- Overuse → resistance
negative effectiveness
UTIs
Inhibit folic acid synthesis Used in MRSA
Other: Metronidazole
Effective against
anaerobes in abscesses
and deep wounds; some
parasites
Minor side effects
High doses may be
neurotoxic
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Drug treatment of tuberculosis (KP
13)
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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
Protozoan
• Spores
found in
soil
• Lungs
• Skin
• Hair
• Nails
• 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
months
Nephrotoxicity, blood
dyscrasias
Antiprotozoan
(chloroquine)
Especially malaria; interrupt protozoal life cycle
Rare in US
Preventive treatment for
high-risk travel
Antihelminthic
(mebendazole)
Interrupt life cycle locally
and systemically
Some are broad spectrum
Resistance not a factor
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Notes on superficial fungal
infection (KP17)
Not exclusive to immune-suppressed
patients
 Examples:
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 Vaginal candidiasis
 Tinea 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
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 Enter target cell
 Use own viral enzymes, and
 Replicate 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)
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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)
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Early treatment will delay progression to
AIDS
 Expensive
 Long-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)
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Best approach is prevention—flu vaccine
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LTC residents
Chronic cardiopulmonary disease
Children ages 5 years and younger
Pregnant women in 2nd and 3rd trimesters
Adults over age 65
Health care workers
Antivirals should start within 48 hours
of symptoms starting
 Will shorten duration only
 Are not useful against common cold!
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Sidebar: cold or flu???
Cold
Flu
Begins with sore throat
More severe, comes on quickly
Nasal symptoms follow
Sore throat, fever, cough
Cough 4th or 5th day
Muscle aches and pains,
headache
Fever uncommon; may be slight
May progress to pneumonia
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Principles of viral hepatitis
pharmacotherapy (KP25)
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Three primary types: A, B, C
 A spread by oral-fecal route
 B spread through blood and body fluids
 C 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
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