PAIN
Ms. Jehan Hadjiusman, RPh, RChT
INSTRUCTOR
Section 2 1
WEEK 1

PAIN
Pain is classified into two main categories:
1. Nociceptive pain: occurs when sensory nerves (nociceptors) identify tissue
damage. Injured tissue releases substances (such as prostaglandins (PGs),
substance P, histamine. which stimulate the nociceptors to send impulses to the
brain that result in feeling pain.
2. Neuropathic pain: it does not result from tissue injury or damage, but from
damage or malfunction of the nervous system. Such as fibromyalgia, diabetic
neuropathy
Background and Types of Pain

Acute and Chronic Pain
• Acute Pain
• Begins suddenly
• Never prescribe ER/LA opioids for acute pain
• Chronic Pain
• Persists beyond normal healing time
• Cancer pain and non cancer pain
N.B Pain is subjective and assessed by using pain scale where the
choice of drug depends on the patient’s self-reported pain severity.

NSAIDS
• NSAIDs are most commonly used or mild pain but can be
added to an opioid-based regimen to reduce the total opioid
dose required and provide better pain relief
• Acetaminophen (Tylenol)
• MOA:
• Reduces pain and fever (is an antipyretic) but does not provide an anti-
inflammatory effect.
• Inhibition of PG synthesis in the central
• BW:
• Severe hepatotoxicity (can require liver transplant or result in death),
associated with doses> 4 grams/day or use of multiple acetaminophen-
containing products.

• Acetaminophen (Tylenol)
• Dose:
• 10-15 mg/kg Q4-6H Pediatric dose.
• Conc of infant and children suspension product is 160mg/5ml
• Combination products
• Exist in combination with hydrocodone-oxycodone-caffeine-
diphenhydramine.
• Antidote
• Antidote for Tylenol is NAC that restores hepatic glutathione. It is
administered IV or orally using Rumac*-Matthew nomogram.

• The COX-1 and 2 enzymes catalyze the conversion of arachidonic acid to PGs
and thromboxane A2 (TA2). All NSAIDs decrease the formation of PGs which
results in decreased inflammation.
• Non-selective NSAIDs block the synthesis of both COX enzymes. COX-2
selective NSAIDs block the synthesis of COX-2 only, which decreases Gl risk
because COX-1 protects the gastric mucosa
• Aspirin is an irreversible COX- 1 and 2 inhibitor and is an effective antiplatelet
agent that provides cardiovascular benefit.

• Non-Aspirin Boxed Warnings
• All prescription, non-aspirin NSAIDs require a MedGuide due to
these risks.
• GI Risk: NSAIDs can increase the risk of serious Gl adverse events
including bleeding and ulceration.
• CV Risk: NSAIDs can increase the risk of MI and stroke. Avoid use
in patients with CV disease or risk factors. This warning includes all
OTC non-selective NSAIDs except aspirin.
• Coronary Artery Bypass Graft ( CABG) Surgery: NSAID use is
contraindicated after CABG surgery. Antiplatelet therapy (commonly
aspirin) is recommended after CABG surgery.

• Side Effects of all NSAIDS
• Used cautiously ( or avoided) in renal failure because they can
decrease renal clearance
• Avoid in patients with uncontrolled hypertension. Can increase
blood pressure
• Can cause premature closure of the ductus arteriosus. Do not use
NSAIDs in the third trimester of pregnancy(> 30 weeks).
• Take with food
• Can cause photosensitivity
Non-Aspirin NSAIDs
Non-selective Increased COX-2
selectivity
Ibuprofen (lower risk of GI complications)
Indomethacin Celecoxib
Naproxen Diclofencac
Ketorolac Meloxicam and Etodolac
Others Nabumetone

Non-Aspirin NSAIDS
1. IBUPROFEN
• OTC strength is 200 mg
• Pediatric dose is 5-10mg/kg/dose Q6-8 hours
• SE: dyspepsia, abdominal pain, nausea
2. INDOMETHACIN
• Has high risk CNS side effects. Avoid in psych patients.
• Preferred in Gout
3. NAPROXEN
• Dosed BID. Preferred by les compliant patients
• Used in combination medications for migraines with sumatriptan.
4. KETOROLAC
• BW: max combined duration for IV/IM and PO is five days.
• Warning. Not used in renal failure and liver failure
5. PIROXICAM AND SULINDAC

Juanito Carlo M. Deita VI, RPh
Doctor of Pharmacy, Centro Escolar University – Makati
Over the Counter Drugs and Self-Care

Headache
• Headache – cephalgia; A painful and disabling pain in the head
• Headaches include migraine, tension headache and trigeminal
neuralgia such as cluster headaches.
• According to GBD 2019, headache disorders are fifth cause of
disability-adjusted life years (DALYs) for both adolescent and
adult men and women .
• 46% suffers from general headache in a year, and 64% suffered
in a lifetime.

Fever
• Fever – pyrexia; a body temperature that is higher than normal
• NOT classified as a disease but, a symptom.
• Usually caused by an underlying condition (for most cases, it is
caused by an infection)
• COMMON clinical manifestation of COVID-19 infection.
• It can also be caused by medications, external factors such as
heat exhaustion or heat stroke due to too much exposure to the
sun and inability to regulate temperature by sweating.

What about self-care?
• Management of headache and fever can be done through the
use of OTC analgesics and antipyretics to relieve mild-to-
moderate pain and also reduces inflammation and fever.
• Analgesics are effective in treating pain of visceral origin.
• According to survey of 325 parents of children, majority of them
purchase OTC medicines if recommended by a physician and
of the medicines were effective previously.

Common OTC products for Self-Care

What causes headache?
• Tension-type headaches – caused by stress, anxiety,
depression, emotional conflicts and other stimuli
• Migraine headache
• Oversleeping, missing a meal or vasoactive substances
• Menstrual cycle for women
• Dysfunction of trigemin0vascular system and consequent, magnesium deficiency to
produce aura symptoms
• Sinus headache – Infection or blockages of the paranasal sinuses
• MOH Headache – Related to the overuse which causes rebound effects of analgesics.

What causes fever?
• Pyrogens (fever-producing substances) activates the host’s
defenses, resulting in an increase hypothalamic heat regulatory
set point.
• Pyrogens can be exogenous or endogenous.
• Prostaglandins, speficically PGE2, are produced in response to
circulating pyrogens which affects the thermoregulatory set
point in hypothalamus resulting to a new set point and fever
occurs.

Clinical Manifestation of Headache
Characteristics of Tension-Type, Migraine and Sinus Headaches
(Handbook of Nonprescription Drugs, 16th Edition)
Tension-Type Headache Migraine Headache Sinus Headache
Location Bilateral
Over the top of head, extending to
base of skull
Usually unilateral Face, forehead or
periorbital area
Nature Varies from diffuse ache to tight,
pressing constricting pain
Throbbing
May be preceded by an aura*
Pressure behind eyes or
face
Dull, bilateral pain
Worse in the morning
Onset Gradual Sudden Simultaneous with sinus
symptoms, including
purulent nasal discharge
Duration Minutes to days
(If chronic – occurs at least 15 days
per month for at least 6 months)
Hours to 2 days Days (resolves with sinus
symptoms)

Clinical manifestations of Headache
www.drshehadi.com/4-common-types-of-headaches-symptoms-duration/

Migraine Aura
migrainecanada.org/posts/the-migraine-tree/roots/migraine-categories/migraine-with-aura-an-overview
Aura – Series of neurologic symptoms (shimmering or flashing areas
or blind spots, visual and auditory hallucinations and usually, one-
sided muscle weakness) that may last for up to 30 minutes and the
throbbing headache that follows may last from hours to 2 days

Exclusions for Self-Care for Headache
• Chronic headache – headaches that persist for 10 days with or without treatment
• Severe head pain
• Last trimester of pregnancy
• Younger than 8 years of age
• High grade fever or signs of serious infection
• Persistent nasal discharge (for sinus headache)
• History of liver disease or consumption of ≥3 alcoholic drinks per day
• Secondary headache – headache associated with underlying pathology such as cerebrovascular
accidents
• Symptoms consistent with migraine but no formal diagnosis of migraine headache

Clinical Manifestation Fever
• The most important sign of fever is an elevated temperature.
Fever is a symptom of a larger underlying process, whether it is
an infection, abnormal metabolism or drug induced.
• Symptoms that accompany fever and cause a great discomfort
include:
 Headache
 Diaphoresis
 Generalized Malaise
 Chills
 Tachycardia
 Arthralgia
 Anorexia
 Myalgia
 Irritability

Exclusion for Self-Care for Fever
• Infants > 6 months with rectal temperature of ≥ 40 ºC or equivalent
• Children < 6 months with rectal temperature ≥ 38 ºC
• Severe symptoms of infection that are not self-limiting
• Risk for hyperthermia
• Impaired oxygen utilization (e.g., severe COPD, ARDS, heart failure)
• Impaired immune function (e.g., cancer, HIV)
• History of CNS damage (e.g., head trauma, stroke)
• Children with history of febrile seizures or seizures
• Fever that persists >3 days with or without treatment
• Child who develops spots or rash, refuses to drink any fluids, very sleep, irritable or hard to wake up
or vomiting and cannot keep down fluids

Self-Care Approaches
Medicines, Interventions, Practices, Dosing and Drug
Selection

Treatment Goals
• For headache: 1. Alleviate acute pain; 2. Restore normal
functioning; 3. Prevent relapse; 4. Minimize side effects; For
chronic pain: reduction of frequency of headaches is an
additional goal
• For fever: the major goal is to alleviate the discomfort of fever
by reducing the body temperature to normal range.

Non Pharmacologic Interventions
(Headache)
• Chronic tension-type headache often respond to relaxation
exercise and physical therapy that emphasizes stretching and
strengthening of head and neck muscle
• For migraines, interventions includes regular sleeping and
eating schedule and create methods for coping stress.
Moreover, nutritional strategies such as dietary restrictions of
food containing triggers should be generally avoided.
• Ice bags/ cold packs can applied to forehead or temporal areas
to reduce pain.

Non Pharmacologic Interventions
(Fever)
• Increase fluid intake to prevent dehydration unless fluid is
contraindicated.
• Sponging or baths is not routinely recommended for febrile
patients with less than 40 ºC since it induces shivering leading
to increase body temperature
• Sponging with hydroalcoholic solutions is not recommended,
especially to pediatric patients.
• Wearing light apparels, removal of blankets and maintain a
room temperature are proven to be beneficial.

Pharmacologic Interventions
• Available non-Rx for management of headache
and fever includes Paracetamol/Acetaminophen,
NSAIDs and Salicylates

Pharmacologic Interventions
Drug Mechanism of Action
Acetaminophen/ Paracetamol Central inhibition of PG synthesis
(including PGE2 to produce analgesia
and decreases feedback between the
thermoregulatory neurons and the
hypothalamus, thereby reducing the
hypothalamic set point during fever.
NSAIDs (Ibuprofen and
Naproxen)
Peripheral inhibition of COX and
subsequent inhibition of PG synthesis.
Salicylates Irreversible inhibition of COX
enzymes and subsequently, inhibits
PG synthesis. (Primarily peripheral
mechanism)

Dosing Guidelines
Drug Usual Adult Dose Usual Pediatric Dose
Acetaminophen 325 – 1000 mg Q4-6 hours
(MAX: 4 g)
Neonate: 10 – 15 mg/kg/dose
PO/PR Q6-8 hours
Pediatric; 10 – 15 mg/kg/dose
PO/PR Q4-6 hours
(MAX: 90 mg/kg/24 hours)
Ibuprofen 200 – 400 mg Q4-6 hours
(MAX: 1.2 g)
For infant and child ≥6 months
for analgesia and antipyretic:
5-10 mg/kg/dose Q6-8hr
(MAX: 40mg/kg/24 hours)
Naproxen Sodium 220 mg Q8 – 12 hours
(MAX: 660 mg)
Child of at least >2 years:
5-7 mg/kg/dose Q8-12 hours
PO
(MAX: 1000 mg/ 24 hours)
Child of at least 12 years:
200 mg Q8-12 PRN PO
(MAX: 600 mg/ 24hr)
Aspirin 650 – 1000 mg Q4 – 6 hours
(MAX: 4 g)
CI to children due to Reye’s
Syndrome
Magnesium
Salicylate
650 mg Q4 hours or 1000 mg
Q6 hours
(MAX: 4 g)

Combination Products
Combination Products
Caffeine + Analgesic
combinations (APAP,
Paracetamol)
Effective treatment for variety
of conditions, including
tension-type and migraine
headaches but may cause
MOH with frequent use.
NSAID/Paracetamol + Nasal
decongestants
Effective for sinus headache
or other indications for which
both analgesia and
decongestion are needed.
Analgesics + Antihistamine Enhanced analgesia;
Effective for acute pain
compared to acetaminophen
alone but limited use due to
sedating effects
Orphenadrine/Phenyltoloxami
ne + Acetaminophen

Alternative Medicines For Headache

Special Population Considerations
(Age)
• It is an important consideration in the selection of an
appropriate OTC medication for both fever and headache.
• Parents of children younger than 8 years old should seek the
advice of their pediatrician before doing self-treatment.
• Aspirin is contraindicated for children ages 15 years and below
• Elderly patients are at high risk for many adverse effects of
salicylates and NSAIDS. Moreover, impaired systems such as
comorbidities, impaired renal function and use of other
medications may contribute to the increased risk

Special Population Considerations
(Pregnancy)
• Acetaminophen can cross the placenta, but it is considered safe
during pregnancy and also, compatible with breast feeding.
• NSAIDs are CI during the third trimester of pregnancy due to
delay parturition, prolonged labor, increases postpartum
bleeding and can cause fetal cardiovascular effects such as
premature closure of ductus arteriosus. Although, both
Ibuprofen and Naproxen are compatible with breastfeeding
• Avoidance to aspirin is strictly advised.

Patient Factors
(Physiologic)
• Effectiveness and safety vary among age groups.
• Constantly changing physiology of pediatric patients including
different pharmacokinetics and pharmacodynamics.

Patient Factors
(Psychological)
• Cognitive ability of the patient, or with caregiver in the context of
pediatrics.

Patient Factors
(Psychosocial)
• Living environment can affect self-care.
• Multiple caregivers can increase risk of miscommunication for
drug administration to pediatric patients.

Patient Factors
(Compliance)
• Ensure that the product is safe for use to increase adherence.
• Intolerances to drug therapy necessitates withdrawal to the drug
product, especially if the patient experiences hypersensitivity or
rebound effects
• Ensure that there is a need for medicines and whether the drug
related need were met
• Consider preferences for all ages (palatability, dosing frequency
and etc.) and take note on the past medication experience.

Patient Education
Specific recommendations for Headache and Fever Self-Care
Treatment Algorithms

Aims of Patient Education
• The objectives of self-treatment are to (1) relieve the symptoms
of headache pain and discomfort of fever by returning the body
temperature to normal, (2) prevent the symptoms of headaches
and prevent complications associated with fever, (3) Prevent
medication overuse, misuse or duplication of therapy.

Episodic Headaches
• Instruct the patient to take appropriate dose of analgesic in the
early course of headache.
• Patients who experiences frequent episodic headaches should
be advised to keep a log of their headaches to document
triggers; how frequent they experience them, the intensity and
the duration of episodes and their response to treatment.

Tension-Type Headaches
• Non-prescription are usually effective for this condition.
However, consult a medical provider before using them for
chronic tension-type headache.
• Keep records (how often they appear and how often they
medications) and share them with their primary care physician.
• Do not use products containing caffeine because of the risk of
caffeine-withdrawal effects

Migraine Headaches
• Avoid triggers
• Follow dietary restrictions
• Eat regularly to avoid hunger and low sugar
• Consider taking magnesium supplements
• If onset of migraines are predictable (e.g., headache occurs during
menstruation), take NSAIDs to prevent headache. Start taking the
analgesic 2 days before you expect the headache and continue
regular use during the time the headache might start.
• Try to abort migraine by taking an NSAID at the onset of headache
pain
• If desired, use an ice bag or cold pack applied with pressure to
forehead or temple to reduce the pain.

Fever
• Do not rely on feeling the body for fever. Take a temperature
reading with an appropriate thermometer.
• RECTAL measurement is preferred for children up to 6 months
of age. Tympanic thermometer is not recommended in this age
group due to the size and shape of the infant’s ear canal.
• For 6 months to 5 years, the rectal methods is still preferred;
however, the tympanic, temporal or oral method may be used if
proper technique is followed
• Ages 5 years and above, the oral, temporal or tympanic method
is appropriate.

Fever
• Do not use isopropyl or ethyl alcohol for body sponging.
• For all levels of fever, wear lightweight clothing, remove
blankets and maintain room temperature.
• Unless unadvised, drink or provide sufficient fluids to replenish
body fluid loss

Fever
• Monitor fever and level of discomfort using the same
thermometer two or three times per day.
• Use OTC antipyretics/analgesics for up to 3 days only, unless
you have an exclusion to self-care
• Avoid alternating antipyretics because of the complexity of the
dosing regimens, increased medication errors and adverse
effects.
• Dosing of either ibuprofen or acetaminophen in children should
be based on weight.
• Use appropriate measuring device

Headache Treatment Algorithm

Headache Treatment Algorithm

Fever Treatment Algorithm

Evaluation of Outcomes
Fever
• Primary monitoring
parameters include
temperature and experienced
discomfort.
• If symptoms did not improve
during the 3-day self-care
antipyretic treatment,
regardless of a drop of
temperature, medical
consultation either by phone
or appointment is needed for
evaluation
Headache
• Follow-up will depend on the
headache frequency and
severity and patient factors
• For all cases, the patient
should seek medical attention
if headaches persists longer
than 10 days or become
worse despite self-treatment.

References
• MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 Jun 24]. Heart attack; [updated 2022
Feb 2; reviewed 2016 Dec 15; cited 2022 Mar 17]; Available from: https://medlineplus.gov/fever.html
• Cann, S. A. H. (2021, January 9). Fever: Could a cardinal sign of COVID-19 infection reduce mortality? The American Journal of
the Medical Sciences. Retrieved March 17, 2022, from https://www.sciencedirect.com/science/article/pii/S0002962921000045
• Islam, M. A., Kundu, S., Alam, S. S., Hossan, T., Kamal, M. A., & Hassan, R. (2021). Prevalence and characteristics of fever in
adult and paediatric patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of 17515
patients. PLOS ONE, 16(4). https://doi.org/10.1371/journal.pone.0249788
• Kristoffersen, E. S., & Christofer, L. (2014). Medication-overuse headache: Epidemiology, diagnosis and treatment. Therapeutic
Advances in Drug Safety, 5(2), 87-99. doi: http://dx.doi.org/10.1177/2042098614522683
• Trajanovska, M., Manias, E., Cranswick, N., & Johnston, L. (2010). Use of over-the-counter medicines for young children in
Australia. Journal of Paediatrics and Child Health, 46(1-2), 5–9. https://doi.org/10.1111/j.1440-1754.2009.01609.x
• Vos, T., Lim T. S., Abbafati C., et al. (2020).Global burden of 369 diseases and injuries in 204 countries and territories, 1990–
2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet. https://doi.org/10.1016/S0140-
6736(20)30925-9
• Trajanovska, M., Manias, E., Cranswick, N., & Johnston, L. (2010). Parental management of childhood complaints: over-the-
counter medicine use and advice-seeking behaviours. Journal of clinical nursing, 19 (13-14), 2065–2075.
https://doi.org/10.1111/j.1365-2702.2009.03092.x
• Trajanovska, M., Manias, E., Cranswick, N., & Johnston, L. (2010). Use of over-the-counter medicines for young children in
Australia. Journal of Paediatrics and Child Health, 46(1-2), 5–9. https://doi.org/10.1111/j.1440-1754.2009.01609.x
• Handbook of Nonprescription Drugs: An Interactive Approach, 16th Edition
• The Harriet Lane Handbook: A Manual of Pediatric House Officers, 20th Edition