Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

Headache, Fever, and Musculoskeletal Pain

Learning Objectives

1. Describe the basic pathophysiology behind various sources of pain and fever
2. List exclusions to self-treatment and know when to refer patients to a physician for
further assessment
3. Recommend appropriate non-pharmacologic and pharmacologic treatment options
4. Counsel patients on the selection and proper use of pain and fever products

Pain
1. Unpleasant sensory and/or emotional experience
a. Defined as an unpleasant sensation signaling actual or possible injury
b. Physical, affective, and learned components
2. Self-treatment is common in pain
a. $75+ million spent on OTC analgesics
b. Nearly half of patients dont read labeling
3. Acute or Chronic Pain
a. Acute pain: begins suddenly and usually does not last long
i. Symptoms:
b. Chronic pain: lasts for weeks or months; associated with a chronic disorder (such as
cancer, arthritis, diabetes, or fibromyalgia) or an injury that does not heal
i. Effects: depression, disturbed sleep, decreased energy, a poor appetite,
weight loss, decreased sex drive, and loss of interest in activities
ii. Breakthrough pain: pain that occurs during treatment for chronic pain
1. Begins suddenly, lasts up to 1 hour, and feels like the original pain but
more severe
4. Pain Pathways
a. Pain due to injury begins at special pain
receptors
b. Transmit signals along nerves to the
spinal cord and then upward to the
brain
c. Signal sent backwards to original site of
pain, triggering muscles to contract
d. Pain signal also sent to the brain
e. Only when the brain processes the
signal and interprets it, do people
become conscious of the pain

Headaches
1. Classified as primary or secondary
a. Primary headaches: not associated with an underlying illness
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Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

i. Accounts for ~90% of headaches

ii. Examples: episodic and chronic tension-type headaches, migraine
headache with and without aura, cluster headaches, and medicationoveruse headaches
b. Secondary headaches: symptoms of an underlying condition such as head trauma,
stroke, substance abuse or withdrawal, bacterial and viral diseases, and disorders of
craniofacial structures
2. Pathophysiology of Headache
a. Sinus Headache:
b. Tension-type Headaches:
c. Migraine:
3. Clinical Presentation
a. Chronic tension-type headaches occurring 15 days/month for at least six months
may be a manifestation of psychological conflict, depression, or anxiety
i. May be associated with sleep disturbances, shortness of breath, constipation,
weight loss, fatigue, decreased sexual drive, palpitations, and menstrual
changes

Sinus Headache

Tension-type Headaches

Migraine

4. Treatment of Headache
a. Goals
i.
ii.
iii.
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Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

iv.
v.
b. Non-Pharmacologic Treatment
i. Avoidance of possible food triggers (nitrates, tyramine, phenylalanine,
caffeine, MSG
ii. Avoidance of hunger and low blood glucose
iii. Relaxation exercises, stress coping methods
iv. PT, acupuncture
v. Regular sleep and eating schedule
vi. Ice/cold packs
Exclusion Criteria for Self-Treatment
Primary Headaches
Symptoms > 10 days
Severe symptoms
3rd trimester
Children <8 years old
Symptoms of migraine without diagnosis
Diagnosed migraines with moderate to severe
symptoms

Secondary Headaches
High fever or sign of infection
Associated with a stiff neck and vomiting
Onset follows bending, lifting, or coughing
Sleep is disturbed
Headache is present upon awakening
Recent head or neck (e.g. whiplash) injury
Numbness, tingling, weakness of arms or legs

5. Self-Care of Headache
Asthma & nasal polyps, chronic/recurrent GI
ulcers, gout, coagulation disorders or
anticoagulant therapy, HBP, CHF, kidney
disease, or aspirin allergy?

Yes

Avoid salicylates & NSAIDS

No
Yes

< 12 years of age?

Avoid Naproxen

No
Yes

< 15 years of age?

No

Avoid salicylates if symptoms of

viral illness are present

For tension-type headaches, recommend

APAP, NSAID, or salicylate as appropriate.
For migraine, recommend NSAID or salicylate
as appropriate

Chronic Headache

Severe Headache

Episodic Headache

Severe Headache

Medical Referral

Follow up after 6-12 weeks

Follow up after 4-6 weeks

Follow up within 10 days

No

Adequate analgesia?

Yes

Intermittent use < 3x/week

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Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

6. Pharmacologic Treatments

Indication

Products

Mechanism of
Action

Non-Prescription Analgesic/Antipyretic Treatments

Salicylates
NSAIDs
Mild to moderate pain, fever,
Mild to moderate pain, fever,
inflammation
and inflammation

Acetylated: aspirin (ASA)

Non-acetylated: magnesium,
choline, sodium
Irreversibly inhibit prostaglandin
synthesis by inhibiting COX-1
and COX-2
Decrease prostaglandins =
decrease sensitivity to pain

Adverse Effects

Contraindications/P
recautions

Nausea, dyspepsia, heartburn,

bruising, prolonged bleeding
time, rash, angioedema (rare)
Pre-existing conditions: asthma,
nasal polyps, h/o ulcers or GI
bleeding, blood-clotting
disorders, gout, heart failure
Allergy: hypersensitivity to drug

Ibuprofen, Naproxen,
Ketoprofen
Reversible inhibition of
prostaglandin synthesis by
inhibiting COX-1 and COX-2
(peripheral sites)
Decrease prostaglandins =
decrease sensitivity to pain
Abdominal pain, heartburn,
nausea, vomiting, constipation,
flatulance
Asthma, allergy to ASA, ulcers,
gout, heart failure, high blood
pressure

APAP
Mild to moderate
pain, fever
No anti-inflammatory
effects
Tylenol

Central (CNS)
inhibition of
prostaglandins

Well tolerated
Skin rash, jaundice,
thrombocytopenia
Active Liver Disease
Alcoholics

Avoid in pregnancy (especially

3rd trimester)

Not recommended in children

with recent viral infection
(Reyes Syndrome)

Drug Interactions

Formulations

Avoid in pregnancy (especially

3rd trimester)
Valproic Acid
NSAIDs, including COX-2
inhibitors
Anticoagulants
Alcohol
Methotrexate
Sulfonylureas
Enteric Coated
Buffered
Effervescent
Sustained Release

Anticoagulants
Alcohol
Digoxin
Methotrexate
Sulfonylureas
Phenytoin (ibuprofen)

Alcohol
Warfarin

Ibuprofen: immediate-release,
chewable, capsules,
suspension, liquid drops
Naproxen: tablets

All forms

a. Recommended Dosages
Agent

Usual Adult Dose (Maximum Daily Dosage)

Pediatric Dosing
Dose by body weight (mg/kg)

Acetaminophen
Ibuprofen
Naproxen
Aspirin

Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

b. Combination Products
i. ASA (250mg) +/- APAP (250mg) + Caffeine (30-65mg)
1. Synergistic analgesic effects-addition of caffeine causes
vasoconstriction of blood vessels in the brain
2. Indicated in mild to moderate pain, fever, and inflammation; often
used in migraines
7. Herbals and Supplements
Agent
Feverfew

Peppermint oil

Risks
Possible rebound headache
with chronic use; mouth
ulceration with direct contact
with leaves; possible
anticoagulation effect
Skin irritation, avoid during
pregnancy and lactation

Coenzyme Q10

Avoid during pregnancy and

lactation; minor GI disturbances

Magnesium

Diarrhea; GI upset

Use/Effectiveness
Treatment and prevention of migraine
headaches; mixed results from clinical trials
(difference in formulations?)

Topical treatment of tension headache;

preliminary evidence suggests peppermint oil
applied to forehead and temples may relieve
tension headaches
Prevention of migraine headaches; small, open
label trial demonstrated that 150mg/day
reduced frequency by 33%
Treatment and prevention of migraine
headache; mixed results for prevention

8. Patient Education
Tension-Type Headache

Migraine Headache

Precautions for Nonprescritpion Analgesics

Salicylates & NSAIDs

APAP

Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

Musculoskeletal Pain
1. Musculoskeletal pain arises from the muscles, bones, joints, and connective tissue
a. Can be idiopathic, iatrogenic, or related to injury
b. Acute: result of minor injuries, strains, or sprains; self-limiting
c. Chronic: ongoing, persistent, or repetitive pain (arthritis, gout)
Types/Causes

Goals of Treatment

Myalgias: acute overuse of muscle

Tendonitis and bursitis: chronic overuse of
joint
Sprains, strains: twisting, excessive
stretching, tearing
Cramps: exercise-induced, menstrual
Lower back pain: muscle or disc
Joint pains: arthritis

2. Self-Care of Musculoskeletal Injuries and Disorders

Exclusions for Self-Treatment

Patient with complaint of pain

Pain duration > 10-14 days

Patient < 7 years old
High fever or other signs of infection
Nausea or severe vomiting
Weakness, numbness in any limb
Accompanied by redness, warmth,
swelling (joint/muscle)
Suspected fracture
Pelvic or abdominal pain (not
associated w/ menses)
Pregnancy or breast-feeding
Severe or worsening pain
Signs of neurological problems

Perform initial assessment

Yes

Exclusions for self-treatment?

No
Contraindications/
intolerances to OTC
analgesics?

Yes

Medical Referral

No
Pain from overexertion, or
muscle/joint injury?

No

Osteoarthritis?

No

Yes

Yes

Initiate nondrug
therapies & APAP.
F/U in 1 month

RICE therapy & oral or topical

analgesic. F/U in 7 days

Pain relief
satisfactory
or complete?

No

Maximize
therapy or
add topical.
F/U in 1 month

Yes
Pain improved or resolved?
No
Medical Referral

Yes

Continue therapy
PRN < 2 weeks. F/U to
assess for ADRs

Continue
therapy
Yes

Pain improved or resolved

No
6

Titrate dose to max dose.

Consider referral

Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

3. Treatment Options
Non-Pharmacologic
a. Acute Therapies: use immediately (first 48-72
hours)
R
I
i. Systemic agents: APAP, ASA, NSAIDs
(see tables above for dosing
C
information)
E
b. Topical Agents: applied to intact skin to relieve
(REFERAL to health care provider/rehab)
pain
i. Analgesics/Anesthetics/Antipruritics
1. Inhibit cutaneous sensation of pain, burning, itching
ii. Counterirritants
1. Principle of paradoxical pain relief producing a less severe pain
counters a more intense one
a. Produce mild, local inflammatory effect thought to provide
relief at adjacent or underlying site
b. Many have analgesic/anesthetic properties as well
2. Applied not more than 3-4 times/day for up to 7 days
3. OK for use in children 2+ years old
Allyl isothicynate, ammonia
water, methyl salicylate,
turpentine oil
Menthol & camphor
Histamine dihydrochloride &
methyl nicotinate
Capsicum, capsicum
oleoresin, capsaicin

Rubefacients; promote redness & irritation via

capillary dilation
Promote cooling sensations, depress nerves
that perceive pain
Cause vasodilatation
Incite irritation without rubefacients (no
vasodilation)

c. Sub-acute & Chronic Therapies: use 72 hours after injury or long-term

i. Non-Pharmacological
1. Once inflammation resolved, replace ice with HEAT
a. 15-20 min intervals x 4 times/day
b. Promotes healing, minimizes muscle spasms
2. Reinstate exercise SLOWLY
Electronic heating pad
d. Complementary Therapies
-Pros: Reusable / Cons: $$$
i. Massage
Temporary heat products
-E.g.
Thermal
wraps, patches
ii. Acupuncture, acupressure
-Provide low-level heat for up to 12 hours
iii. Stress reduction
-Pros: Inexpensive / Cons: One-time use
iv. Physical therapy
1. Stretching, strengthening, range-of-motion exercises
v. Herbals/Supplements
1. Glucosamine + Chondroitin
a. MOA: anti-inflammatory properties, protect/rebuild cartilage
matrix & synovial fluid
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Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

2.
3.

4.
5.

b. Evidence grade A (strong) for osteoarthritis pain

i. Most evidence for knee joint
ii. Reduces subjective pain, NSAID dose
c. Glucosamine1500mg + Chondroitin 800-1200mg daily
d. Likely safe, well-tolerated
e. Cons:
i. $$$
ii. Slow onset of efficacy
Turmeric plenty of pain relief benefits
a. Evidence grade: C arthritis
Ginger relieves arthritis, headaches, menstrual cramps and
muscle soreness
a. Evidence grade: C dysmenorrhea, migraine, arthritis
Valerian Root natures tranquilizernatural pain reliever
a. Evidence grade: NOT studied for pain
Eucommia for your aching back and joints
a. Evidence grade: NO human studies available

Fever
1. Introduction
a. Body Temperature
i. Normal body temperature: 97.5-98.9F
ii. Regulated by a feedback system (physiological and behavioral adaptations
keep temperature in range)
1. Varies depending on: age, sex, ambient temperature, activity level
2. Time of day: 2am and 6am (lowest); 4pm and 10pm (highest)
b. Fever (pyrexia): regulated rise in body temperature in response to a pyrogen (sign of
increase in core set point)
i. Generally considered temp > 98.9F
ii. More common in children
iii. Majority self-limiting, nonthreatening; major reason for treating: alleviate
discomfort
iv. Causes: viral/bacterial pathogens, tissue damage, malignancy, CNS
inflammation, medications, idiopathic
c. Fever pathway
Release of
Pyrogens

Activation of
arachidonic
acid pathway

Release of
prostaglandin E2

FEVER

Body temp
reaches new set
point

Rise in set point

of hypothalamus

Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

d. Types of fever
Hyperthermia

Hyperpyrexia

Unregulated increae incore

temperature without elevation of
hypothalamic set point
Temperature: 99.5-100.9F
Inadequate heat dissipation in response
to a warm enviornment (heat stroke)
Can be rapid and fatal
Antipyretic agents are ineffective

Temperature >106.7F
Extreme elevation of body temperature
(emergency situation)
Requires immediate and aggressive
body cooling
Usually associated with CNS
hemorrhage (thyroid storm, NMS,
kawasaki syndrome)

2. Signs/Symptoms and Complications

a. Fever itself is a symptom
i. Often accompanied by headache, diaphoresis, malaise, chills, arthralgia
b. Complications
i. Serious complications are rare: seizures, delirium, brain damage
ii. Increased risk of neural tube defects in pregnancy
iii. Febrile seizures
3. Detection of fever
a. When monitoring, always measure with same type of thermometer at same site
Body Site

Normal Range (F)

Fever
(F)

Thermometer

Comments

Rectal

Mercury, digital

Oral
Axillary
Tympanic

Mercury, digital
Mercury, digital
Infrared thermometer

Closest to core temp (Gold Standard)

1st line in infants/children
1st line in adults
Do not use for infants <6 mo

b. Thermometers
i. Mercury-in-glass: Rarely used in the US
1. ~5 minutes to obtain reading
2. Pros: Inexpensive, Compact size
3. Cons: breakable, slow, difficult to read, contents hazardous
ii. Digital electronic thermometer
1. 30-60 seconds to obtain reading
2. Pros: durable, easy to read, available in pen or pacifier shape, disposable
probe covers
3. Cons: require batteries, need to be calibrated
iii. Infrared: used for temporal & tympanic measurement
1. < 5 seconds to obtain reading
2. Detects heat from the arterial blood supply
3. Pros: fasting reading, relatively non-invasive
4. Cons: $$$, require batteries, require routine recalibration, inaccurate if
placed improperly
iv. Adhesive temperature strips: placed on forehead-changes color at various
temperature gradients
1. Pros: non-invasive
2. Cons: very inaccurate use NOT recommended; track trends in
temperature over time

Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

4. Treatment
a. Goal: alleviate the discomfort by reducing temperature
Assess how temperature was
measured. Was it accurate?

No

Yes

Offer to take temp. Explain

proper methods. If fever
present go to next box

Obtain symptom
information, medical history,
allergy information

Exclusions for self-treatment?

Yes

Medical referral

No
Oral temp >101F or
equivalent?

Yes

No

Nondrug measures
antipyretic agent based on
patient factors

Exclusions for Self-Treatment

>6 mo. old with rectal temp
>104F
<6 mo. old with rectal temp
>100F
Severe symptoms of infection
that are not self-limiting
Risk for hyperthermia
Impaired oxygen utilization
Impaired immune function
CNS damage
Children with history of febrile
seizures or seizures
Child who develops spots or
rash
Child who refuses to drink fluids
Child who is very sleepy,
irritable, or hard to wake up
Child who is vomiting and
cannot keep down fluids

Nondrug measures
antipyretic agent if patient
has discomfort or if
patient/caregiver requests

Fever resolved after 3 days?

No

Medical referral

Yes
D/C therapy

b. Non-pharmacologic treatment
i. Adjunctive therapy if temp > 102
ii. Options: reduce clothing, remove blankets; keep room comfortably cool;
increase fluid intake; cold compress (armpits, groin, forehead)
c. Pharmacologic treatments
i. Antipyretics: aspirin, APAP, NSAIDs
1. Work to lower set point, NOT body temperature; bodys own adaptive
mechanisms facilitate drop in body temp
2. Dosing: see earlier charts
Pediatrics
Ibuprofen approved for use in children >6 mo.
APAP products do not have dosing listed for children <2
Alternating use of APAP and NSAIDs not recommended
Potential for overdose: risk dosing too frequently,
confusing with varying doseages/concentrations
No proof of increased efficacy

Pregnancy and Lactation

APAP is drug of choice
NSAIDs/ASA not recommended (especially in 3rd
trimester)
ASA not recommended during breast feeding

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Amber Lanae Smith, PharmD, MS, BCPS

PHA 4010 Principles of Pharmacotherapy 1: Self-care and Alternative Health Care

5. Fever Phobia: displayed by parents with young children who present with fever
a. Characterized by:
i. Unnecessary or aggressive treatment of fever
ii. Checking temperature every hour
iii. Administering antipyretic agents for temperatures <100F
iv. Administering antipyretic agents more frequently than directed
v. Awakening children to administer antipyretic
b. Reassure parents
i. Educate on when to self-treat, appropriate dosing, how to monitor progress, and
when to call pediatrician
6. Counseling points
a. Generic vs. Brand name

b. Picking a specific product

c. Use caution with combination products

d. Importance of non-pharmacologic measures first

e. Reading labeling carefully before taking or administering

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