Analgesics

What are Analgesics?

Analgesics are medicines that are used to relieve pain (provide analgesia). They are also known as painkillers. Technically, the term analgesic refers to a medication that relieves pain without loss of consciousness, as opposed to an anesthetic, which is a substance that induces insensitivity to pain via a loss of consciousness and an absence of sensory perception.

A large number of medicines have pain-relieving properties, and analgesics with similar mechanisms of action are usually grouped together; for example, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids (narcotics). Analgesics can also be grouped depending on the severity of pain they are indicated for, for example, acetaminophen and NSAIDs are indicated for mild-to-moderate pain, and weak opioids, such as codeine, dihydrocodeine or tramadol are indicated for moderate-to-severe pain.

Central nervous system analgesics act in the brain or spinal cord to produce their effects; examples include opioids such as morphine and oxycodone. Peripherally acting analgesics act outside of the brain and spinal cord and include NSAIDs and COX-2 inhibitors.

Miscellaneous analgesics

Miscellaneous analgesics are drugs that work by different mechanisms to relieve pain. They are used to treat mild to moderate, acute and chronic pain.

• Acetaminophen

Acetaminophen is a pain reliever and a fever reducer.

Acetaminophen is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers.

Acetaminophen may also be used for purposes not listed in this medication guide.

Usual Adult Dose for Fever

Doses may be given as a single or repeated dose as follows:
Parenteral:
Weight 50 kg or greater: 1000 mg IV every 6 hours OR 650 mg IV every 4 hours
Maximum Single Dose: 1000 mg
Minimum Dosing Interval: every 4 hours
Maximum Dose: 4000 mg per 24 hours
Weight less than 50 kg: 15 mg/kg IV every 6 hours OR 12.5 mg/kg IV every 4 hours
Maximum Single Dose: 15 mg/kg
Minimum Dosing Interval: every 4 hours
Maximum Dose: 75 mg/kg per 24 hours
Oral:
Immediate-release: 325 mg to 1 g orally every 4 to 6 hours
Minimum Dosing Interval: every 4 hours
Maximum Single Dose: 1000 mg
Maximum Dose: 4 g per 24 hours
Extended-Release: 1300 mg orally every 8 hours
Maximum dose: 3900 mg per 24 hours
Rectal:
650 mg rectally every 4 to 6 hours
Maximum dose: 3900 mg per 24 hours

Usual Pediatric Dose for Fever

Doses may be given as a single or repeated dose as follows:
PARENTERAL:
Neonates (premature neonates born at least 32 weeks gestational age up to 28 days chronological age): 12.5 mg/kg IV every 6 hours
Minimum Dosing Interval: 6 hours
Maximum Daily Dose: 50 mg/kg/day
Infants (29 days to 2 years old): 15 mg/kg every 6 hours
Minimum Dosing Interval: 6 hours
Maximum Daily Dose: 60 mg/kg/day
2 to 12 years: 12.5 mg/kg IV every 4 hours OR 15 mg/kg IV every 6 hours
Maximum Single Dose: 15 mg/kg; not to exceed 750 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 75 mg/kg in 24 hours; not to exceed 3750 mg
13 years or older; weight less than 50 kg: 12.5 mg/kg IV every 4 hours OR 15 mg/kg IV every 6 hours
Maximum Single Dose: 15 mg/kg; not to exceed 750 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 75 mg/kg in 24 hours; not to exceed 3750 mg
13 years or older; weight 50 kg or greater: 650 mg IV every 4 hours OR 1000 mg IV every 6 hours
Maximum Single Dose: 1000 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 4000 mg in 24 hours
ORAL:
10 to 15 mg/kg orally every 4 to 6 hours as needed not to exceed 5 doses in 24 hours
-Alternatively, use weight first, then age:
2.7 to 5.3 kg (0 to 3 months): 40 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
5.4 to 8.1 kg (4 to 11 months): 80 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
8.2 to 10.8 kg (12 to 23 months): 120 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
10.9 to 16.3 kg (2 to 3 years): 160 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
16.4 to 21.7 kg (4 to 5 years): 240 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
21.8 to 27.2 kg (6 to 8 years): 320 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
27.3 to 32.6 kg (9 to 10 years): 400 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
32.7 to 43.2 kg (11 to 12 years): 480 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
12 years or older:
Immediate-release: 325 mg to 1 g orally every 4 to 6 hours
Minimum Dosing Interval: every 4 hours
Maximum Single Dose: 1000 mg
Maximum Dose: 4 g per 24 hours
RECTAL:
6 to 11 months: 80 mg rectally every 6 hours up to a maximum of 4 doses in 24 hours
12 to 36 months: 80 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
3 to 6 years: 120 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
6 to 12 years: 325 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
12 years or older: 650 mg rectally every 4 to 6 hours up to a maximum of 6 doses in 24 hours

Salicylates

A salicylate is a salt or ester of salicylic acid. Salicylates are found naturally in some plants (such as white willow bark and wintergreen leaves) and are thought to protect the plant against insect damage and disease. 

Aspirin is a derivative of salicylic acid - and is also known as acetylsalicylic acid.

Salicylates are used as food preservatives and antiseptics and have bacteriostatic, fungicidal and keratolytic (skin peeling) properties. 

Salicylic acid and acetylsalicylic acid have analgesic (pain relieving), anti-inflammatory, and antipyretic (temperature-lowering) effects. 

The main risk of acetylsalicylic acid at therapeutic dosages is gastrointestinal irritation; however, it can be toxic if ingested in large quantities.

Most people have no problem with salicylate-containing foods or medicines; however, some people are extremely sensitive to them. In addition to aspirin, other common salicylate-containing medicines include bismuth subsalicylate, choline salicylate, diflunisal, magnesium salicylate, and salsalate.

Aspirin:

Aspirin is a salicylate (sa-LIS-il-ate). It works by reducing substances in the body that cause pain, fever, and inflammation.

Aspirin is used to treat pain, and reduce fever or inflammation. It is sometimes used to treat or prevent heart attacks, strokes, and chest pain (angina).

Aspirin should be used for cardiovascular conditions only under the supervision of a doctor.

Usual Adult Dose for Osteoarthritis

Initial dose: 3 g orally per day in divided doses
Maintenance: Adjust dose as needed for anti-inflammatory efficacy
Comments:
-Dosing should be individualized.
-Target plasma salicylate levels of 150 to 300 mcg/mL are associated with anti-inflammatory response while plasma salicylate levels greater than 200 mcg/mL are associated with a higher incidence of toxicity.
Uses: For the relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and arthritis and pleurisy associated with systemic lupus erythematous. 

Usual Adult Dose for Rheumatoid Arthritis 

Initial dose: 3 g orally per day in divided doses
Maintenance: Adjust dose as needed for anti-inflammatory efficacy
Comments:
-Dosing should be individualized.
-Target plasma salicylate levels of 150 to 300 mcg/mL are associated with anti-inflammatory response while plasma salicylate levels greater than 200 mcg/mL are associated with a higher incidence of toxicity.
Uses: For the relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and arthritis and pleurisy associated with systemic lupus erythematous. 

Usual Adult Dose for Systemic Lupus Erythematosus 

Initial dose: 3 g orally per day in divided doses
Maintenance: Adjust dose as needed for anti-inflammatory efficacy
Comments:
-Dosing should be individualized.
-Target plasma salicylate levels of 150 to 300 mcg/mL are associated with anti-inflammatory response while plasma salicylate levels greater than 200 mcg/mL are associated with a higher incidence of toxicity.
Uses: For the relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and arthritis and pleurisy associated with systemic lupus erythematous.

          Usual Adult Dose for Fever

Oral:
300 to 650 mg orally every 4 to 6 hours as needed
Maximum dose: 4 g in 24 hours
Rectal:
300 to 600 mg rectally every 4 hours
Uses: As a temporary fever reducer or for the temporary relief of minor pain due to headache, menstrual pain, arthritis, muscle pain, or toothache.

Usual Adult Dose for Pain

Oral:
300 to 650 mg orally every 4 to 6 hours as needed
Maximum dose: 4 g in 24 hours

Rectal:
300 to 600 mg rectally every 4 hours

Uses: As a temporary fever reducer or for the temporary relief of minor pain due to headache, menstrual pain, arthritis, muscle pain, or toothache.

Usual Adult Dose for Myocardial Infarction

Immediate-Release:
Initial dose: 160 to 162.5 mg orally once as soon as myocardial infarction is suspected
Maintenance dose: 160 to 162.5 mg orally once a day for 30 days post-infarction
Comments:
-Extended-release products should not be used when a rapid onset of action is desired such as suspected MI; non-enteric tablet may be chewed or crushed for immediate-action.
-This drug has been shown to reduce the risk of vascular mortality in patients with a suspected acute MI.
-After 30 days, secondary prophylaxis for prevention of recurrent MI should be considered.
Use: For treatment of a suspected myocardial infarction.

 

Usual Adult Dose for Ischemic Stroke
Immediate-release: 50 to 325 mg orally once a day
Extended-release (ER): 162.5 mg orally once a day
Comments:
-Therapy should be continued indefinately.
-ER capsules are designed to slowly release drug from encapsulated microparticles thereby prolonging the absorption across the gastrointestinal tract; the pharmacodynamic effect of ER 162.5 mg is similar to that attained with IR aspirin 81 mg..
Uses: To reduce the risk of death and recurrent stroke in patients who have had ischemic stroke or transient ischemia attack.

Nonsteroidal anti-inflammatory agents

Nonsteroidal anti-inflammatory agents (usually abbreviated to NSAIDs) are a group of medicines that have anti-inflammatory (reduce inflammation), analgesic (relieve pain) and antipyretic (lower temperature) effects.

Although different NSAIDs have different structures, they all work by blocking cyclo-oxygenase (COX) enzymes. There are two main types of COX enzymes: COX-1 and COX-2. Both types produce prostaglandins; however, the main function of COX-1 enzymes is to produce baseline levels of prostaglandins that activate platelets and protect the lining of the gastrointestinal tract, whereas COX-2 enzymes are responsible for releasing prostaglandins after infection or injury. Prostaglandins have a number of different effects, one of which is to regulate inflammation.

Most NSAIDs inhibit both enzymes, although a few are available that mainly inhibit COX-2. The pain-relieving and anti-inflammatory effects of NSAIDs are mainly due to inhibition of COX-2, and their unwanted side effects are largely due to inhibition of COX-1.

1. diclofenac
2. ibuprofen
3. mefenamic acid
4. ketoprofen
5. fenoprofen
6. naproxen

         Cox-2 inhibitors

    Cyclo-oxygenase-2 (COX-2) inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that specifically blocks COX-2 enzymes.

There are two main types of COX enzymes: COX-1 and COX-2. Both types produce prostaglandins; however, the main function of COX-1 enzymes is to produce baseline levels of prostaglandins that activate platelets and protect the lining of the gastrointestinal tract, whereas COX-2 enzymes are responsible for releasing prostaglandins after infection or injury. Prostaglandins have a number of different effects, one of which is to regulate inflammation.

By specifically only blocking COX-2 enzymes, COX-2 inhibitors relieve inflammation and pain with less adverse gastrointestinal effects than NSAIDs that inhibit both COX-1 and COX-2 enzymes. However, they are not devoid of gastrointestinal effects entirely, and their use (like all NSAIDs) has been associated with a higher risk of stroke and heart attack.

examles:

 valdecoxib

 celecoxib

Narcotic analgesics

Narcotic analgesics (also called opiates, opioid analgesics, or narcotics) are a group of medicines that relieve acute and chronic severe pain by binding to opioid receptors. 

There are at least four opioid receptors: mu, delta, kappa and opioid receptor like-1 (ORL1) receptor. These influence the opioid system which controls pain, reward and addictive behaviors. 

Opioid receptors are most abundant in the brain but are also found elsewhere in the body, including the digestive tract, respiratory tract and spinal cord.

Pleasurable activities (such as laughing and loving) release natural endorphins, dynorphins, and enkephalins which activate opioid receptors, improving our mood. Opioid receptors can also be activated by exogenous compounds, for example narcotic analgesics. Most narcotic analgesics act on the mu receptor and are very effective at relieving pain, but unfortunately, also activate reward pathways meaning that narcotic analgesics have a tendency to cause addiction, dependence and tolerance (where increasing dosages are needed to provide the same pain-relieving effect). Morphine and codeine are alkaloid opiates because they occur naturally. Heroin, hydrocodone, hydromorphone, oxycodone and oxymorphone are semi-synthetic because they are made by modifying morphine.

Common side effects of opiates include constipation, itch, low blood pressure, miosis (excessive constriction of the pupil of the eye), nausea, sedation, urinary retention, and respiratory depression. Most are also effective at suppressing the urge to cough. Different narcotic analgesics have different potencies, based on how strongly they bind to the opioid receptor, meaning dosages vary considerably from one narcotic to the next (for example, fentanyl is 80 to 100 times stronger than morphine).

Morphine

Morphine is an opioid pain medication. An opioid is sometimes called a narcotic.

Morphine is used to treat moderate to severe pain. Short-acting formulations are taken as needed for pain.

The extended-release form of this medicine is for around-the-clock treatment of pain. This form of morphine is not for use on an as-needed basis for pain.

Morphine is not for treating short-term pain just after surgery unless you were already taking morphine before the surgery.

 You should not take morphine if you have severe asthma or breathing problems, a blockage in your stomach or intestines, or a bowel obstruction called paralytic ileus.

Morphine can slow or stop your breathing. Never use this medicine in larger amounts, or for longer than prescribed. Do not crush, break, or open an extended-release pill. Swallow it whole to avoid exposure to a potentially fatal dose.

 Morphine may be habit-forming, even at regular doses. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

MISUSE OF NARCOTIC MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription.Tell your doctor if you are pregnant. Morphine may cause life-threatening withdrawal symptoms in a newborn if the mother has taken this medicine during pregnancy.Do not drink alcohol. Dangerous side effects or death could occur.

 

Usual Adult Dose for Pain
The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.
Immediate release tablets:
Opioid naive:
Initial dose: 15 to 30 mg orally every 4 hours as needed
Oral solution:
Opioid naive:
Initial dose: 10 to 20 mg orally every 4 hours as needed
Comments:
-Oral solution: Opioid naive patients should be initiated on 10 mg per 5 mL or 20 mg per 5 mL strengths. Opioid-tolerant patients that have already been titrated to a stable analgesic regimen using lower strengths of morphine may be initiated on the 100 mg per 5 mL (20 mg/mL).
Extended-release oral:
Different extended-release products are not bioequivalent. Conversion from one extended-release product to the same total daily dose of another extended-release product may lead to either excessive sedation at peak or inadequate analgesia at trough. Individual product information should be consulted before prescribing and the dosage should be adjusted to the individual patient.
Opioid naive:
Initial dose: 30 mg orally every 24 hours
Opioid tolerant:
Dose should be taken 1 to 2 times daily depending upon the product prescribed.
Suppository:
10 to 20 mg rectally every 4 hours needed
Subcutaneous/IM:
Initial dose: 10 mg every 4 hours as needed
Dose range: 5 to 20 mg every 4 hours as needed
IV:
-For relief of pain and as preanesthetic:
Initial dose: 4 to 10 mg every 4 hours administered slowly over 4 to 5 minutes
Dose range: 5 to 15 mg
Daily dose range: 12 to 120 mg
Alternate dose: 2 to 10 mg/70 kg of body weight
-Acute myocardial infarction:
Initial dose: 4 to 8 mg
Maintenance dose: 2 to 8 mg every 4 to 15 minutes as needed
Severe chronic pain associated with terminal cancer:
-Continuous IV Infusion: Prior to initiation of the infusion (in concentrations between 0.2 to 1 mg/mL), a loading dose of 15 mg or higher of morphine sulfate may be administered by IV push to alleviate pain.
-IV patient controlled analgesia or subcutaneous patient controlled analgesia:
1 to 2 mg injected 30 minutes after a standard IV dose of 5 to 20 mg. The lockout period is 6 to 15 minutes.
Epidural:
Initial dose: 5 mg in the lumbar region may provide satisfactory pain relief for up to 24 hours. If adequate pain relief is not achieved within one hour, careful administration of incremental doses of 1 to 2 mg at intervals sufficient to assess effectiveness may be given.
Maximum dose: 10 mg per 24 hr
Intrathecal:
-Dosage is usually one-tenth that of epidural dosage
-Initial dose: 0.2 to 1 mg may provide satisfactory pain relief for up to 24 hours. Repeated intrathecal injections are not recommended.
Usual Pediatric Dose for Pain
-The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.
-Safety and efficacy of this drug in neonates have not been established. Opiate agonists should not be used in premature neonates since the drugs cross the immature blood-brain barrier more readily than in the mature barrier producing disproportionate respiratory depression. Opiates should be administered with caution and in monitored dosages to infants and small children since they may be relatively more sensitive to opiates on a body weight basis.
-Subcutaneous: 0.1 to 0.2 mg per kg as needed. Not to exceed 15 mg per dose.
-IV: 50 to 100 mcg (0.05 to 0.1 mg) per kg, administered very slowly. Not to exceed 10 mg per dose.

Oxycodone

Oxycodone is an opioid pain medication. An opioid is sometimes called a narcotic.

Oxycodone is used to treat moderate to severe pain.

The extended-release form of this medicine is for around-the-clock treatment of pain. This form of oxycodone is not for use on an as-needed basis for pain.

 Usual Adult Dose for Pain

The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time
Immediate-release:
As First Opioid Analgesic: 5 to 15 mg orally every 4 to 6 hours
-Oral solution: To avoid dosing errors include total dose in mg and mL
CONVERSION from Other Oral Opioids: There is great inter-patient variability in the potency of opioid drugs and their formulations; when converting patients to this drug from other opioids or when switching from controlled-release products, it is best to underestimate the oxycodone requirement and provide rescue medication than to overestimate and manage an overdose.
Comments:
-Doses should be individually titrated to provide adequate analgesia while minimizing adverse reactions.
-Because of the risks of addiction, abuse and misuse, the lowest effective dose for the shortest duration consistent with individual patient treatment goals should be used.
-Monitor patients closely for respiratory depression within the first 24 to 72 hours of initiating therapy and following any increase in dose.
Use: For the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate
Usual Adult Dose for Chronic Pain
The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time
60 and 80 mg extended-release (ER) tablets, a single dose greater than 40 mg (36 mg oxycodone base), a total daily dose greater than 80 mg (72 mg oxycodone base), or use of the 100 mg/5 mL (20 mg/mL) oral solution should be restricted to use in opioid-tolerant patients only
Extended-release (ER):
Initial dose for OPIOID-NAIVE and OPIOID NON-TOLERANT patients:
-Oxycodone hydrochloride ER tablets: 10 mg orally every 12 hours
-Oxycodone (base) ER capsules: 9 mg orally every 12 hours with food
Immediate-release (IR):
-Initial dose for OPIOID-NAIVE patients: 5 to 15 mg orally every 4 to 6 hours on an around-the-clock basis
-Oral solution: To avoid dosing errors total dose should be included in both mg and mL
MAINTENANCE: Adjust dose every 1 to 2 days as needed to obtain an appropriate balance between pain management and opioid-related adverse reactions; goal should be to find the lowest effective dosage for the shortest duration consistent with individual patient treatment goals
Maximum daily dose: Oxycodone (base) ER capsules: 288 mg as the safety of the excipients has not been established; maximum dose of oxycodone hydrochloride tablets has not been established
EQUIVALENCE OF OXYCODONE HYDROCHLORIDE TO OXYCODONE BASE:
-Oxycodone hydrochloride 10 mg = Oxycodone base 9 mg
-Oxycodone hydrochloride 15 mg = Oxycodone base 13.5 mg
-Oxycodone hydrochloride 20 mg = Oxycodone base 18 mg
-Oxycodone hydrochloride 30 mg = Oxycodone base 27 mg
-Oxycodone hydrochloride 40 mg = Oxycodone base 36 mg
Comments:
-Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression with first dose; selection of initial dose should take into account degree of opioid tolerance, patient's general condition, medical status, concurrent medications, type and severity of pain, and risk factors for abuse, addiction, or diversion.
-Opioid tolerant patients are those who have received for 1 week or longer: oral morphine 60 mg/day; transdermal fentanyl 25 mcg/hr; oral oxycodone 30 mg/day; oral hydromorphone 8 mg/day; oral oxymorphone 25 mg/day or an equianalgesic dose of another opioid.
-Extended-release products are reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; these products are not intended to be used as as-needed (prn) analgesics.
-DOSE CONVERSIONS from other opioids should be done carefully and with close monitoring due to large patient variability in regards to opioid analgesic response; consult dose adjustment section for recommendations.
Use: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

fentanyl

methadone

opium

tramadol

Antimigraine agents

Antimigraine agents are used to treat migraine headaches. 

Migraines are different from other headaches because they occur with symptoms such as nausea, vomiting, or sensitivity to light. 

Some people who get migraines have warning symptoms, called an aura, before the actual headache begins. 

Pain relieving drugs can be taken as soon as the pain begins and include agents in the drug classes such as 

ergots, triptans and NSAID's.

exampels:

1. sumatriptan

Sumatriptan Injection

      2. caffeine/ergotamine

• Very bad and sometimes deadly poor blood flow to the hands, feet, or brain has happened when this medicine (ergotamine and caffeine suppositories) was taken with certain other drugs like clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, nelfinavir, ritonavir, and troleandomycin. Do not take this medicine if you are taking any of these drugs. There are many drugs that can do this. Check to make sure that it is safe for you to take this medicine (ergotamine and caffeine suppositories) with all of your drugs.

      3. acetaminophen/dichloralphenazone/isometheptene mucate

• This medicine has acetaminophen in it. Very bad and sometimes deadly liver problems like the need for a liver transplant have happened with acetaminophen use. Most of the time, liver problems have happened in people taking more than 4,000 milligrams of acetaminophen in a day. Also, people who had liver problems were often using more than 1 drug that had acetaminophen in it. Talk with your doctor.
• Avoid drinking alcohol while taking acetaminophen, isometheptene, and dichloralphenazone.