Pathopharmacology

Exam 2 Inflammation
Inflammation: an immunologic defense against tissue injury, infection, or allergy
Acute, chronic or repair/restorative
Normal and expected physiologic response to cellular injury
Immunologic defense against injury, infection, or allergy
Pathophysiology: a tissue reaction resulting in the release of chemical mediators
o Involves both a vascular response and the migration of fluid and cells (WBCs)
to the injured site (good sign)
o Chemical mediators:
Histamine: causes dilation of arterioles and increase capillary
permeability
Kinins (cytokines): increase capillary permeability & contributes to
pain sensation
Cause of swelling
Prostaglandins: increase arterial vasodilation, capillary permeability,
pain & fever
Affect vasodilation, relax smooth muscle, increase capillary
permeability and sensitize cells to pain
o COX (cyclooxygenase) is the enzyme responsible for
converting arachiodonic acid into prostaglandins
o COX-1: protects the stomach lining, regulates platelets;
regulate normal cell activity
o COX-2: triggers inflammation and pain
Anti-Inflammatory Drugs = act by inhibiting chemical mediators thus decrease
the inflammatory response; they lessen loss of function by reducing fluid migration
and pain
o Cardinal signs of Inflammation:
Redness
Swelling
Pain
Heat
Loss of function
Inflammatory Response
o Release of Chemical Mediators Vasodilation & Capillary Permeability
Heat, Redness, Fever & Swelling
o Release of Chemical Mediators Pain Loss of function & Mobility
Causes of Inflammation
o Infection (may or may not be)
o Trauma
o Surgical intervention
o Extreme heat (burn)
o Extreme cold (frostbite)
o Caustic chemical agents
o Autoimmune (rheumatoid arthritis)
Pain: an unpleasant sensory and emotional experience associated with actual or
potential tissue damage, or described in terms of such damage

Pain is whatever the patient says it is = SUBJECTIVE EXPERIENCE

o Perception of pain influenced by: previous pain experience and emotional,
physical, psychological, spiritual status
Can be a warning something is wrong
Pain may be a major indication for drug therapy = pain relieved by drugs,
dependence can occur
Related to [perceived] tissue injury
A significant component of nursing care: the fifth vital sign
Nurses Role in Pain Management:
o To assess and thoroughly document pain
o To alleviate pain through medical (medication) and complementary
interventions
o To teach patient techniques for pain management and control
Acute Pain: mild to severe pain lasting less than 6 months; involves SNS
o The immediate phase of response to an insult or injury, results from tissue
damage
o Symptoms: increased HR, RR, BP, glucose level; decreased urine output and
peristalsis
Chronic Pain: mild to severe pain lasting longer than 6 months; associated with
PSN
o May persist well beyond actual tissue injury and healing
o May lead to decreased functional status and depression
Acute Pain: Manifestations
Heart rate
Respiratory rate
Blood pressure
Diaphoresis/pallor
Anxiety, agitation, confusion
Urine retention
Goal: pain control with
eventual elimination

Acute Pain: Manifestations

Flat affect (psychosocial issues)
Physical movement/activity
Fatigue
Withdrawal from others and
social interaction
Depression
Goal: pain control to the extent
possible; focus on enhancing
function and quality of life

Sympathetic Nervous System

Nociceptive Pain: the physiologic process by which information about tissue is

communicated to the central nervous system (CNS)
o Caused by the activation of the delta and C nociceptors in response to
painful stimuli, such as an injury
Delta nociceptors = fast traveling; sense sharp, stinging, cutting,
pinching pain
C nociceptors = slow traveling; sense dull, burning, aching pain
o Normal processing of stimulus that damages normal tissue or has the
potential to do so if prolonged
Usually responsive to non-opioid and/or opioid drug
o Nociception involves four processes: ROUTE OF PAIN
1. Transduction: describes phenomena associated with initiation of a
pain signal

Pain receptors found on the peripheral end plates of afferent

neurons
Sensation of peripheral pain begins in afferent neurons called
nociceptors, which are found in skin, muscle, CT, circulatory
system and viscera
1. Noxious stimuli causes cell damage with the release of
sensitizing chemicals
o Sensitizing chemicals: Prostaglandins, bradykinin,
serotonin, substance P, histamine
2. These substances activate nociceptors and lead to generation
of action potential
2. Transmission: action potential continues from ...
Site of injury spinal cord brainstem & thalamus cortex for
processing
3. Perception: conscious experience of pain
4. Modulation: neurons originating in the brainstem descend to the
spinal cord and release substances (endogenous opioids) that inhibit
nociceptive impulses
Neuropathic Pain: abnormal processing of sensory input by the peripheral or
central NS
o Represents pain in which the underlying pathology is abnormal processing of
stimuli in the peripheral or central nervous system
o Symptoms: numbing, hot, burning, shooting, stabbing, sharp or electric
shock-like
o Common causes: trauma, inflammation, metabolic disease, alcoholism,
infections of the nervous system, tumors
Multidimensional Nature of Pain
o Physiologic
o Affective: anger, fear, depression, and anxiety
o Cognitive: suffering
o Behavioral: observable actions used to express pain
o Sociocultural influences: demographics, support systems, social roles, and
culture
Unrelieved Pain: can lead to ...
o Prolonged stress response
o Reduced immune competence
o Cardiovascular instability
o Respiratory dysfunction
o Genitourinary disturbances
o Decreased GI motility
o Metabolic imbalance
o Developmental issues
o Increased chronic post-surgical pain syndromes
Pain Assessment
o Pain Characteristics:
Pattern of pain: onset, duration
Area of pain
Intensity

 Pain quality
Associated symptoms
Management strategies
Rheumatoid Arthritis and Juvenile Idiopathic Arthritis: immune system response
against bodys cells
Inflammation of CT, joints
Disability and shortened life expectancy
Symmetric involvement of multiple peripheral joints (remission and exacerbation)
RA: adults between 20-50 years
o Women are 3x more likely than men to have disease
o Children (peak 1-3 years)
Chronic pain, altered body image, modified tools to perform ADL
Holistic approach, physical, psychosocial, and safety needs
Drug classes used to manage RA: non-steroidal anti-inflammatory drugs (NSAIDS),
glucocorticoid steroids, and disease modifying anti-rheumatic drugs (DMARDs)
Etiology and Risk Factors:
o Worldwide, more women, onset 20-50 years, increases with age
o Genetic (major factor in susceptibility and severity of RA), environmental,
hormonal, reproductive factors, infectious agents (Epstein-Barr virus)
o Family history, heavy smokers
Clinical Manifestations:
o Chronic, symmetric inflammation of peripheral joints
o Tenderness, limitation of movement, morning stiffness, redness, swelling,
and warmth of soft tissues
o Symptoms can cause sleep disturbances
o Deformities of extremities due to pannus (
Pannus = long term, severe proliferation of the synovial intimal layer
o Remission and exacerbations
o Focus on maintaining functional status for older adult
Joint and Other Manifestations:
o Coronary heart disease (C-reactive proteins, inflammation)
o Low-high-density lipoproteins level
o High cholesterol and triglyceride levels
o High BP
o High homocysteine levels
Treatment/Collaboration:
o Goal: relieve pain, reduce inflammation, slow or stop joint damage, and
improve well-being and ability to function
o No cure, goal is to relieve manifestations
o Interdisciplinary approach is used, with a balance of rest, exercise, physical
therapy, and suppression of the inflammatory response
o Labs:
Rheumatoid factor (+)
CBC: RBC, WBC (leukocytes), hemoglobin, hematocrit
Erythrocyte sedimentation rate
Synovial fluid including increased turbidity, decreased viscosity, and
increased protein and WBC levels (X-rays of affected joints)
o Treatment:

Physical therapy, hot/cold compress

Aspirin: good because it is nonsteroid but 1. Helps pain, 2. Antiinflammatory, 3. Anti-platelet (helps prevent platelets from coming
together
Do not give children aspirin if they have flu symptoms because of
Reyes Syndrome
Reye syndrome: a potentially fatal disease characterized by
swelling in the brain, increased intracranial pressure, and
seizures
o Rheumatoid factor (RF): test that measures the amount of rheumatoid factor in
your blood, which are proteins produced by your immune system that can attack
healthy tissue in your body
Juvenile Idiopathic Arthritis: formerly known as juvenile rheumatoid arthritis
NO definitive diagnostic tests, elevated sedimentation rate in some cases
o Antinuclear antibodies common, but not specific for juvenile idiopathic
arthritis
o Leukocytosis during exacerbations
o Diagnosis based on criteria of American College of Rheumatology
Possible causes: immunogenic susceptibility, environmental trigger
Peak onset: 1-3 years of age
Often undiagnosed
Actually a heterogeneous group of diseases:
o Systemic onset
High fever, rash
Hepatosplenomegaly = enlargement of liver and spleen
Pericarditis = inflammation of pericardium
Pleuritis = inflammation of tissues that line lung cavity
Lymphadenopathy = lymph nodes that are abnormal size, number or
consistency
o Oligoarthritic (involves <= 4 joints)
o Polyarthritic (involves >= 5 joints)
o Psoriatic enthesitis and undifferentiated
Affected children: 90% have negative rheumatic factor
Symptoms: may burn out and become inactive
o Chronic inflammation of synovia with joint effusion, destruction of cartilage,
and ankylosis [stiffness] of joints as disease progresses
Therapeutic Management of Juvenile Idiopathic Arthritis:
o No specific cure
o Goals: preserve function, prevent deformities, and relieve symptoms
o Primarily outpatient care
o Physical therapy, occupational therapy to keep joint in functional position
o Relief of pain
o Promotion of general health
o Encouraging the use of heat and exercise
When trying to keep child in remission phase, we want to keep child
moving - swimming, riding bicycles helps with mobility
o Support child and family

Drug Classifications
Drugs normally used for pain management are the opioid (narcotic) analgesics and
the non-steroidal anti-inflammatory drugs (NSAIDs)
By giving different pain meds and individualizing pain control for each pt, we can
manage pain
Narcotic Analgesics: act on the CNS to interfere with the pain experience
Required for conditions, disorders, or treatments that are accompanied by
MODERATE-TO-SEVERE PAIN
Include: opiate agonists, mixed agonist-antagonists, and antagonists based on
their activity at opioid receptors
Narcotics have important role in pain management and control
Controlled substance = can be addicting, can build up tolerance
Tolerance: means the body has become accustomed to the effects of a substance
and that the pt must increase dose to achieve the desired effect
Breakthrough pain: term used to describe transitory flare-ups of pain over
baseline in a patient receiving opioid therapy; generally graded as moderate to
severe in intensity
o May last a few seconds or a few hours
o Rescue dose: the dose of an analgesic required for the relief of
breakthrough pain
Adjunct analgesics: drugs that are used secondarily for pain relief
o An additional substance, treatment, or procedure used for increasing the
efficacy or safety of the primary substance, treatment, or procedure or for
facilitating its performance
o Usually outcome is more effective than one drug alone
MORPHINE: strong narcotic agonist
Pharmacotherapeutics: SEVERE acute and chronic pain; anti-anxiety
Pharmacokinetics:
o A: oral, SC, IM, IV, patch
o D: systemic
o E: active metabolite excreted, urine unchanged
o M: liver, gut wall
o HL: 1.5h
o Dur: 3-7h
o Onset: 15-30min
Pharmacodynamics: agonist at the mu opioid receptor; reduces release of
neurotransmitters in the presynaptic space and prevents transmission of
nociceptive pain
Contraindications: decreased respirations altering ventilation, pt with low fluids,
premature infants, pt in labor
Adverse Effects: respiratory depression, orthostatic hypotension, CNS sedation,
bradycardia; later urinary retention, constipation
Interactions: illicit drugs, alcohol, CNS depressants
Labs: pancreatic labs: lipase, amylase; kidney, liver
Patient Teaching: know sedative effects, how to manage breakthrough pain
Lifespan Issues: infants

Pregnancy: C

CODEINE: mild narcotic agonist

**Combined with NSAID for increased pain control
Pharmacotherapeutics: MILD to MODERATE pain; cough suppressant
Pharmacokinetics:
o A: GI tract; oral
o D: stomach
o E: kidneys
o M: liver through P-450
o HL: 3 hours
o Peak: 1-2 hours
Pharmacodynamics: acts on opioid receptors in CNS (analgesia, euphoria, and
sedation); less respiratory depression than morphine
Contraindications: pt with asthma or emphysema, other CNS drugs, post-op
thoracic and ab
Adverse Effects: dry mouth, nausea/vomiting, constipation
Interactions: other CNS drugs, histamine-2 antagonists (cimetidine)
Labs: Kidney, liver
Patient Teaching: sedation effects; monitor tolerance, dependence, addiction
Lifespan Issues: infants
Pregnancy: C
ASPIRIN: salicylates
Pharmacotherapeutics: fever and inflammation
Pharmacokinetics:
o A: GI tract; oral (highly protein bound- 30 min: depends on dosage form,
food, gastric pH)
o E: kidneys
o M: 99% liver, highly bound to plasma albumin
o HL: 15 min
Pharmacodynamics: antipyretic, anti-inflammatory, analgesic, and antiplatelet
Contraindications: black box warning; peptic ulcer disease, bleeding disorders,
renal or hepatic impairment, children with flu-like symptoms (Reyes syndrome),
confusion, drowsiness
o Methotrexate may decrease renal clearance and plasma protein binding of
this drug, leading to toxicity
Adverse Effects: GI upset, renal failure, bleeding, false urine testing for glucose in
diabetics
Interactions: drugs that alter bleeding, highly-protein bound drugs,
anticoagulants
Labs: CBC (platelets), kidney, liver
Patient Teaching: OTC drugs, herbal supplements; dont take more than 4g
Lifespan Issues:
Pregnancy: not in third trimester

Salicylate poisoning: life-threatening event in which there is no antidote;

characterized by respiratory alterations; fluid, electrolyte, and acid-base
imbalances; seizures; high temps; and shock leading to coma or death
o Treatment includes gastric lavage; administration of activated charcoal, life
support
o Lethal dose is 5-8grams for child, 10-30 grams for adult

ACETAMINOPHEN: para-aminophenol derivatives

Pharmacotherapeutics: mild or moderate pain, fever hypersensitivity to aspirin
Pharmacokinetics:
o A: GI tract; oral, IV
o D:
o E: kidney
o M: liver
o HL: 1-3.5h
o Peak: 60 min
Pharmacodynamics: primarily centrally acting; inhibits prostaglandin synthesis
in the CNS
Contraindications: black box warning; liver problems, hepatic disease, viral
hepatitis, alcoholism (for all- metabolism decreased, risk of hepatotoxicity)
Adverse Effects: generally well tolerated risk for toxicity; rash, urticaria, nausea
Interactions: activated charcoal, antacids, warfarin
o ANTIDOTE = acetylcysteine (mucomyst)
Labs: CBC, kidney, liver
Patient Teaching: diabetic- check glucose (hypo), s/s toxicity, OTC drugs
Lifespan Issues: fever, children (metabolize less), elderly
Pregnancy: B
NSAIDs: act on the peripheral nervous system, interfering with prostaglandin synthesis
and preventing the transmission of pain impulses
Inhibit COX and prostaglandin synthesis
Therapeutic efficacy of an NSAID is based on clinical response
Carry Black Box warning: risk MI and stroke
IBUPROFEN: NSAIDs prostaglandin synthetase inhibitors
Pharmacotherapeutics: anti-inflammatory, analgesic, antipyretic effects
Pharmacokinetics:
o A: 80% GI, food affects absorption; oral
o D:
o E: kidney, within 24 hours
o Peak: 1-2h
Pharmacodynamics:
Contraindications: pregnancy, blood dyscrasia, hemophilia, liver disease, active
GI disease
Adverse Effects: nausea/vomit, diarrhea, constipation, liver/renal toxicity,
abdominal pain
Interactions: highly protein bound, salicylates

Labs: CBC (platelets), kidney, liver

Patient Teaching: s/s adverse effects (black, tarry stools; dark urine; rashes;
wheezing)
Lifespan Issues: pregnancy, older adult
Pregnancy: B until third trimester, and then D

Disease-Modifying Anti-rheumatic Drugs (DMARDs)

Used in conjunction with salicylates and NSAIDs, or as monotherapy
They are named because they are capable of arresting the progression of RA and
can induce remission in some patients
Therapeutic class of DMARDs is a combination of several different pharmacologic
classes of drugs
METHOTREXATE: DMARDs
Pharmacotherapeutics: immunosuppressive effects RA, cirrhosis
Pharmacokinetics:
o A: oral; may be influenced in stomach
o D:
o E: urine, unchanged
o M: small amount in liver
o HL: 2-4h
o Symptom Relief: 3-6 weeks
Pharmacodynamics: exerts immunosuppressive effects and results production of
cytokines; may result in folate depression (pt may need folic acid)
Contraindications: immunosuppression, blood dyscrasia, pregnancy
Adverse Effects: stomatitis, alopecia, GI upset, fatigue, hepatic cirrhosis,
intestinal pneumonitis, myelosuppression (suppression of bone marrow)
Interactions: drugs that potentiate same effects, illicit drugs, alcohol
Labs: kidney, liver, CBC; bilirubin, GFR, liver biopsy (later on)
Patient Teaching: takes 3-6 weeks, come in for lab, photosensitivity, caffeine,
encourage fluids
Lifespan Issues: young, elderly
Pregnancy: X
Tumor Necrosis Factor Inhibitor
Etanercept produced by recombinant DNA technology
In the past, TNF inhibitors were used in pt who did not respond to MTX
Combination therapy with TNF inhibitors and MTX has exceptional results and is
now considered gold standard of RA treatment
ETANERCEPT: tumor necrosis factor (TNF) inhibitor
Pharmacotherapeutics: RA to decrease s/s; delays structural damage; plaque
psoriasis
Pharmacokinetics:
o A: SC WEEKLY
o HL: 115h
o Therapeutic Effects: 12 weeks

Pharmacodynamics: RA, T cells release inflammatory mediators (cytokines TNF); inflammation of synovial membrane and joint destruction. Drug binds
specifically to circulating TNF, prevents it from binding to TNF receptors on cell
membranes, and prevents the response
Contraindications: hypersensitivity, current active infections,
immunosuppression,
Adverse Effects: injection site reactions, URI, diabetes
Interactions:
Labs: CBC, liver, kidney, CRP, ESR, chest x-ray, TB skin test
Patient Teaching: avoid live vaccinations, SC injection technique, weekly shot
Lifespan Issues: not approved for children <4
Pregnancy: B

NALOXONE: narcotic antagonist (antidote for morphine overdose)

Pharmacotherapeutics: respiratory depression, morphine overdose
Pharmacokinetics:
o A: IM, SC, IV
Pharmacodynamics: antagonize the effects of narcotics by competing for opioid
binding sites. Used to reverse the effects of opiates (analgesic, respiratory
depression, OD)
Contraindications: hepatic impairment, children, pregnancy, abrupt withdrawal
of narcotic
Adverse Effects: tremors, drowsiness, sweating, tachycardia, hypertension,
relapse into respiratory depression or arrest
Interactions: hypersensitivity

MORPHINE: strong narcotic agonist

Pharmacotherapeutics:
Pharmacokinetics:
o A:
o D:
o E:
o M:
o HL:
o Dur:
o Onset:
Pharmacodynamics:
Contraindications:
Adverse Effects:
Interactions:
Labs:

Patient Teaching:
Lifespan Issues:
Pregnancy: