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Definition of a FEVER.
REGULATED rise in CORE body temperature.
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What ORGAN maintains body temperature?
HYPOTHALAMUS
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The hypothalamus raises body temperature in RESPONSE to what?
PYROGEN
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Define CORE temperature.
The temperature of the BLOOD that surrounds the HYPOTHALAMUS
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NORMAL core temperature?
100 F
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A FEVER is ________________ & ________________.
CONTROLLED & ON PURPOSE
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An INCREASE in body temperatre due to:
MALFUNCTIONING of normal thermoregulatory process (Internal) OR
INSUFFICIENT heat disspiation (External)
HYPERTHERMIA
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Body temperature GREATER than 106 F?
HYPERPYREXIA
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Body temperature where internal DAMAGE begins?
106 F (Hyperpyrexia)
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RECTAL fever temperature?
102 F
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ORAL fever temperature?
101 F
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AXILLARY fever temperature?
100 F
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TYMPANIC fever temperature?
101 F
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Order of site of measurements from GREATEST to LEAST accurate?
Rectal (~+1), Tympanic (~+.5), Temporal (~+.25), Oral (BASE), Axillary (~-1)
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Farenheit TO Celsius Equation?
C = 5/9 x (F-32)
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Celsius TO Farenheit Equation?
F = (9/5 x C) + 32
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Fever Etiology:
INFECTIOUS ORIGIN
- Most Common
- Higher with BACTERIAL than VIRAL infections
- Elderly and Immunocompromised
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Fever in the IMMUNOCOMPROMISED?
100.4 F
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Fever Etiology:
NON-INFECTIOUS ORIGIN
- Malignancies
- Tissue Damage (surgery)
- Antigen-antibody rxn
- Inflammation
- Metabolic Disorders
- Dehydration
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Cause of fever from MALIGNANCIES, TISSUE DAMAGE or ANTIGEN-ANTIBODY RXN?
Increase in the release of PYROGENS
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Cause of fever from METABOLIC DISORDERS (hyperthyroidism)?
Increase in the bodies METABOLIC RATE and the body increases temperature
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Cause of fever in DEHYDRATION?
Decrease in HEAT DISSIPATION because cannot release sweat
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Fever Etiology:
DRUG-INDUCED
- 3-5%
- Hypersensitivity most common
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Factors to identify DRUG FEVER?
- TEMPORAL relationships
- Fever PERSISTS after improvement of 1st condition
- Other SYMPTOMS are present
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Similarities between DRUG fever and INFECTION fever?
HIGH fever and CHILLS
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Idiosyncratic drug reactions:
GENERAL ANESTHETICS (succinylcholine)
MALIGNANT HYPERTHERMIA
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Malignant Hyperthermia SYMPTOMS?
- Rapid ONSET- w/in hours
- Temp GREATER than 104 F
- Muscle RIGIDITY
- Metabolic ACIDOSIS (low serum pH, Inc CO2)
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Idiosyncratic drug reactions:
ANTI-PSYCHOTIC MEDS
(phenothiazines, butyrophenones, thioxathenes)
- NEUROLEPTIC MALIGNANT SYNDROME
- (dopamine receptor blockers)
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Neuroleptic Malignant Syndrome (NMS) SYMPTOMS?
- GRADUAL onset- w/in 2 weeks or any time
- HIGH fever, muscle RIGIDITY, ABNORMAL body movements, SWEATING, TACHYCARDIA, hyper OR hypo TENSION, INCONTINENCE, & altered CONSCIOUSNESS
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THERAPEUTICS for NMS?
- ICE bath if temp GREATER than 106
- Muscle RELAXANTS
- IV Fluids
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Thermoregulation:
Heat LOSS & Heat GENERATION are EQUAL
NORMAL Thermoregulation
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Thermoregulation:
INC Heat LOSS & DEC Heat GENERATION
HYPOTHERMIA
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Thermoregulation:
DEC Heat LOSS & INC Heat GENERATION
FEVER
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The ______________________ is the __________ & determines the SET-POINT for body temp.
HYPOTHALAMUS & FULCRUM
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How heat is LOST from the body?
- CONDUCTION
- EVAPORATION- sweat
- RADIATION
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How heat is GENERATED in the body?
(at the cellular level)
- LIVER
- Skeletal MUSCLE contraction
- METABOLIC Activity (thyroid & adrenal gland)
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Thermoregulation MECHANISM for INCREASE body temp stimulus?
Stimulus-- Hypothalamus-- Capillaries DILATE & Sweat glands ACTIVATE-- DEC. Body Temp
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Thermoregulation MECHANISM for DECREASE body temp stimulus?
Stimulus-- Hypothalamus-- Capillaries CONSTRICT & Skeletal Muscles ACTIVATE-- INC. Body Temp
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How do ANTICHOLINERGICS increase body temperature?
Block SWEATING
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What are BEHAVIORAL compensatory mechanism to temeprature change?
- ADD Clothing
- RUBBING Hands
- ADJUSTING AC
- SEEKING Shade
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What re PHYSIOLOGIC compensatory mechanism to temperature change?
- Sweating
- Vasodilation
- Shivering
- Vasoconstriction
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The RELEASING of Hormones at different TIMES in a day? (change in body temp thru-out day?
CIRCADIAN RHYTHM
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The NORMAL variation in temperaure thru-out the day?
~ 2 degrees
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Body temp PEAKS in __________ & ____________ and is LOWEST in ________________________.
- Late AFTERNOON & Early EVENING
- Early hours of MORNING
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PYROGENS _________________ the thermoregulatory set-point.
INCREASE
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How does Fever EFFECT the pyrogen?
IMPAIRS the pathogens REPLICATION and METABOLIC processes
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Pyrogen and Fever MECHANISM?
Exogenous pyrogen-- Phagocytic Cell (cytokine)-- Endogenous pyrogen--Hypothalamus (prostaglandin derivatives)-- Elevated Temp
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EXOGENOUS Pyrogens
MICROORGANISM or TOXIN (which stimulates release of endo pyrogens--cytokines)
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ENDOGENOUS Pyrogens
- Interleukin- 1
- Interleukin- 6
- Tumor Necrosis Factor alpha
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Endogenous pyrogens trigger the SYNTHESIS & RELEASE of _______________________.
PROSTAGLANDIN E (the agent that directly adjusts set-point)
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MERCURY Thermometer ADVANTAGES:
- Patient Familiarity
- Low cost
- Light Weight
- Compact
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MECURY Thermometer DISADVANTAGES:
- Break
- Difficult to read
- Takes up to 5 min
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ELECTRONIC Thermometer ADVANTAGES
- Quick- 30 to 60 sec
- Durable
- Easy to Read
- Probe Covers
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ELECTRONIC Thermometer DISADVANTAGES
- Batteries
- Calibration
- Higher Cost
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INFRARED Thermometer ADVANTAGES:
- Fast (5 sec)
- Accurate
- Non-invasive
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INFRARED Thermometer DISADVANTAGES:
- Incorrect placement
- Expensive
- Batteries
- Calibration
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When to NOT use ORAL route to take temeprature?
- Mouth breathers
- Recent oral surgery
- Not fully alert
- Patient LESS than 3 yrs
- W/in 20 mins SMOKED or drank HOT/COLD beverage
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When to NOT use RECTAL route to take temperature?
- Patient LESS than 6 mos
- Neutropenic
- Recent rectal injury
- Diarrhea
- Impacted stool
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When to NOT use TYMPANIC route to tkae temperature?
- Patient LESS than 6 mos
- Wax impaction
- Otitis media
- Sleeping on side (on ear)
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When to NOT use AXILLARY route to take temperature?
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When to NOT use TEMPORAL route to take temperature?
- Sweating
- Hot/Cold compress
- Open scars/sores
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Complications of fever:
A SEIZURE with a FEVER and no other CAUSE?
- FEBRILE SEIZURE
- In Children 6mos to 5ys
- Last LESS than 15 min
- Antiepileptic/Antipyretic drugs not recommended
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Drug-induced fever:
HYPERSENSITIVITY
ANY DRUG
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Drug-induced fever:
INTERFERES W/ HEAT DISSIPATION
- Antichoilnergics
- TCA (tricyclic antidepressants)
- Phenothiazines
- Amphetamines
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Drug-induced fever:
INCREASED METABOLIC RATE
Thyroid Hormones
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Drug-induced fever:
MODIFIED BEHAVIORAL RESPONSE
Sedatives
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Drug-induced fever:
RELEASE OF ENDOTOXINS or ENDO PYRO CELL DEATH
- Antibiotics
- Chemotherapies
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Drug-induce fever:
DRUG ADMIN or VEHICLE or VENOUS IRRITATION
Chemotherapies
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Drug-induced fever:
ANTIBODY-ANTIGENIC COMPLEXES
- Biological drugs
- Cardiovascular
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Drug-induced fever:
STRUCTUALLY MIMICS ENDO PYROGENS
Interferons (INF)
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Exclusions to Self-Care:
CHILDREN
- Less than 6mos w/ rectal >101 F
- History of seizures
- Rash or spots
- Refuse to drink
- Very sleepy, irritable, hard to wake up
- Vomitting
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Exclusiond to Self-Care:
EVERYONE
- Rectal temp >104 F
- Symptoms of infection
- Risk for hyperthermia
- Imapired oxygen use
- Impaired immune system
- CNS damage
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NON-PHARMACOLOGIC Treatments of fever:
- Increase fluid (Child: 1oz/hr Adult: 2-4oz/hr)
- Light Clothing
- Remove blankets
- Keep room at 78 F
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What non-pharmacological treatments NOT to use?
- Body Sponging
- Alcohol use
- Ice baths
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PROSTAGLANDINS are synthesized from__________________.
ARACHIDONIC ACID
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ARACHIDONIC ACID is derived from _______________________________ via ________________________________.
PHOSPHATIDLINOSITOL & PHOSPHOLIPASE A2
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The TWO pathways Arachidonic acid is a PRECURSOR to?
- Cyclic (cyclooxygenase/PGH2 Synthase)
- Linear (lipoxygenase)
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What TWO catalytic activities does PGH2 SYNTHASE (COX)exhibit?
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State of COX-1?
CONSTITUTIVE-- active all the time/every day processes
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State of COX-2?
INDUCIBLE-- activated by cytokines, growth factors, and endotoxins
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COX forms PGH2 as an ____________________________ which is then converted to other __________________________.
- TRANSIENT INTERMEDIATE
- PROSTAGLANDIN TYPES
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Where is COX ENZYME bound?
Plasma MEMBRANE of ER.
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What does COX ENZYME utilize as a substrate?
ARACHIDONIC ACID
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Arachidonic Acid enters the enzyme thru the _______________________ & approaches the _____________________.
- HYDROPHOBIC CHANNEL
- HEME GROUPS
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Site of Synthesis & Biological Activity of:
PGD2
- Mast Cells (Allergic Rxn)
- Vasodilation
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Site of Synthesis & Biological Activity of:
PGE2
- Kidney, Spleen, Heart
- Vasodilation, Enhance platlet aggregation, Enhance bardkinin and histamine, GI protection, ELEVATION OF THERMREG SET-POINT
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Site of Synthesis & Biological Activity of:
PGF2
- Kidney, Spleen, Heart
- Decrease in introcular pressure
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Site of Synthesis & Biological Activity of:
PGH2
Intermediate Precursor
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Site of Synthesis & Biological Activity of:
PGI2
- Heart, Vasc. Endothelial
- Vasodilation, enhance bradykinin and histamine, GI protection
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Site of Synthesis & Biological Activity of:
TXA2
- Platelets
- Enhance platelet aggregation
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Site of Synthesis & Biological Activity of:
TXB2
- Platelets
- Vasoconstriction
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General Characteristics of NSAIDs
- Inhibit Cyclooxygenase activity of PGH2 synthase
- Inhibit formation of prostaglandins
- Inhibit blood clotting by blocking thromboxane
- Inhibit GI protective effects of PGs
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Aspirin MECHANISM?
- Non-specific COX-1/COX-2 Inhibitor
- Acetlylates SERINE
- Prevents BINDING of AA to active COX enzyme
- IRREVERSIBLE (cells can re-synthesize PGH2 synthase)
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Aspirin DOSE?
- 325-650mg q 4-6hrs
- 1000mg q 4-6hrs
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Aspirin OVERDOSE?
- Chronic (accumulation over time)
- Acute (mild <150mg/kg, moderate 150-300mg/kg, >300mg/kg)
- USUALLY 100mg/kg x 2days
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Aspirin OVERDOSE MANAGEMENT?
- Ipecac (not recommended)
- Charcoal (must use w/in 2 hrs of ingestion)
- Gastric Lavage
- NO Supportive Care
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Aspirin ADVERSE EFFECTS?
- Decreased platelet agg
- GI upset/ulcers
- Tinnitus
- Increased BP
- Edema
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Aspirin CONTRAINDICATIONS?
- Allergy (asthma, chronic urticaria, nasal polyps, cross-sensitivity w/ NSAIDs the tartrazine)
- Children <16yrs (Reyes syndrome)
- Pregnancy (C/D)
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Aspirin PRECAUTIONS?
- Bleeding disorders
- Peptic ulcer disorder (PCD)
- Gout
- Renal Failure
- Sever liver disease
- Edema/Fluid retention (CHF, HTN)
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Drug Interaction:
ASA & ALCOHOL
Increased Risk if GI ULCERS and prolonged BLEEDING TIME
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Drug Interaction:
ASA & NSAIDs
- 1. Increased risk of BLEEDING and ULCERS
- 2. ASA and IBU compete--- IBU wins= no cardio protection [take ASA 30min before IBU or 8hrs after]
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Drug Interaction:
ASA & METHOTREXATE (MTX)
Increased levels can cause MTX TOXICITY (goes thru kidneys..competition)
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Drug Interaction:
ASA & ANTICOAGULANTS
Increased BLEEDING risk
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Drug Interaction:
ASA & ANTI-HYPERTENSIVES
- ANTAGONIZED causing fluid retention which decreases effectiveness
- RENAL effects
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Drug Interaction:
ASA & SULFONYLUREAS
ASA knocks SAs of protein binding site----more free drug---RAPID REDUCTION OF SUGAR
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Drug Interaction:
ASA & VALPROIC ACID
ASA knocks it off protein binding site---more free drug---INCREASED LEVELS OF DRUG
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Drug Interaction:
ASA & ANTIDEPRESSANTS (SSRIs)
Increased risk of BLEEDING
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Acetaminophen MECHANISM?
- Competively blocks HYDROPHOBIC channel (AA cannot enter COXase active site)
- EQUAL antipyretic, but NOT anti-inflammatory ("peroxide tone")
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Why does APAP not have an ANIT-INFLAMMATORY response?
- Weakly inhibits BOTH COX enzymes
- PEROXIDE TONE-- inflammation has leukocytes--generates peroxides--decrease blockage of enzymes
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THREE differences of APAP and ASPIRIN?
- APAP has NO effect on THROMBOXANE synthesis in platelets
- MORE ACTIVE in central tissues
- LACKS anti-inflammatory, blood thinning and GI side effects
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Acetaminophen OVERDOSE?
- Chronic-- > 4g/day (hepatotoxicity and kidney damage)
- Acute-- > 7.5g (140mg/kg...w/in 2-3hrs---nausea, vomitting, abdominal pain, guarding, excitation then stupor, liver failure 2-6 days)
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Acetaminophen OVERDOSE MANAGEMENT?
- N-ACETYLCYSTEINE
- 140mg/kg x1 dose, then 70mg/kg x17 doses
- TOTAL= 18 doses
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Acetaminophen DOSAGE?
- 325-650mg q 4-6hrs
- 1000mg q 4-6hrs
- 1300mg q 8hrs
- Child: 10-15 mg/kg q 4-6hrs (Max 5 doses OTC)
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Acetaminophen ADEVERSE EFFECTS?
- GI Upset
- Jaundice-- in toxicity
- Bleeding-- in presence of alcoholism/liver disease
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Acetaminophen CONTRAINDICATIONS?
SEVERE active liver disease
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Acetaminophen DRUG INTERACTIONS?
- Alcohol- increased hepatocity--increase bleeding--increase liver toxicity
- Wafarin-- in high doses or long duration can increase effect of warfarin
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Acetaminophen CLINICAL PEARLS?
- DRUG OF CHOICE (< 2 alcoholic drinks/day, pregnancy, anti-coag therapy)
- Dosing OTC label is 2yrs but safe at ANY age
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Traditional NSAID MECHANISM?
- Non-specific COX-1/COX-2 inhibitors
- Competively blocks HYDROPHOBIC channel
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Ibuprofen DOSAGE?
- 200-400mg q 4-6hrs
- Child > 6mos: 5-10 mg/kg q 6-8hrs
- REVERSIBLE
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Naproxen DOSAGE?
220-440mg q 8-12hrs (for 1 dose w/in 1 hour can take ONE other 220mg tablet)
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Ketoprofen DOSAGE?
12.5-25mg q 6-8hrs
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Traditional NSAID OVERDOSE
- NOT toxic
- CNS and GI symptoms
- NO antidote--SUPPORTIVE CARE
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Traditional NSAID ADVERSE EFFECTS?
- GI
- Edema/Fluid Retention
- Platelet aggregation
- Photosensitivity
- Increase BP
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Traditional NSAID CONTRAINDICATIONS?
- Allergy to other NSAIDs or ASA
- Caution with CHF, EDEMA, HIGH BP
- Pregnancy (C/D)
- Renal Insufficiency
- Sever Liver Disease
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NSAIDs are associated with ______________ risk of ____________________.
INCREASED & CV EVENTS
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Patients who SHOULD NOT self care with NSAIDs?
- > 60yrs
- History of GI problems
- Taking a blood thinner or steroid
- Taking other NSAIDs
- Drinks > 3 drinks/day
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Drug Interactions:
NSAIDS & BLOOD THINNERS
Increased risk of BLEEDING
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Druf Interactions:
NSAIDS & DIGOXIN
Increased levels of DRUG (CHF)
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Drug Interactions:
NSAIDS & MTX
Increased MTX levels
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Drug Interactions:
NSAIDS & BISPHOSPHATE
Increased GI UPSET
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Drug Interactions:
NSAIDS & ANTIHYPERTENSIVES
Antaogonized
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Drug Interactions:
NSAIDS & CYCLOSPORINE
Increased drug LEVELS, concerning effects on kidneys
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Drug Interactions:
NSAIDS & LITHIUM
Increased Drug LEVELS
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Drug Interactions:
NSAIDS & ANTI-DEPRESSANTS
Increased BLEEDING
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Drug Interactions:
IBUPROFEN & PHENYTOIN
Increased LEVELS of Phenytoin
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Recommended NSAID AGES?
- Ibuprofen: < 6 mos
- Naproxen: < 12 yrs
- Ketoprofen: < 16 yrs
- Aspirin: < 16 yrs
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DRUG THERAPY may take up to ______________, but may have results in ____________________.
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DRUG THERAPY would decrease temperature ~_______________.
2-3 DEGREES
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TEMPERATURE should be checked _______________________.
2-3 TIMES PER DAY.
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REFER to MD is symptoms do NOT improve/worsen in ________.
3 DAYS
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