Drugs used to control
pain
Drugs used to control pain range from mild,
over-the-counter(OTC) preparations such as
acetaminophen to potent general anesthetics.
They include:
• nonopioid analgesics, antipyretics, and
nonsteroidal antiinflammatory drugs (NSAIDs)
• opioid agonist and antagonist drugs
• anesthetic drugs.
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Nonopioid analgesics, antipyretics, and
NSAIDs are a broad group of pain
medications.
in addition to pain control, they produce
antipyretic and anti-inflammatory effects.
They have a ceiling (upper limit or
maximum)effect (maximum dose above which
there’s no added benefit) and don’t cause
physical dependence.
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The drug classes included in this group are:
• salicylates (especially aspirin).
Aspirin is the most commonly used salicylate.
• para-aminophenol derivative
acetaminophen.
• NSAIDs.
• the urinary tract analgesic phenazopyridine.
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salicylates are absorbed partly in the stomach,
but primarily in the upper part of the small
intestine.
Food or antacids in the stomach also delay
absorption.
Salicylates are distributed widely throughout
body tissues and fluids, including breast milk. In
addition, they easily cross the placental barrier.
The liver extensively metabolizes salicylates into
several metabolites.
The kidneys excrete the metabolites.
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They relieve pain primarily by inhibiting the
synthesis of prostaglandin. (Recall that
prostaglandin is a chemical mediator that
sensitizes nerve cells to pain.)
In addition, they may also reduce
inflammation by inhibiting the prostaglandin
synthesis and release that occurs during
inflammation.
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Salicylates reduce fever by stimulating the
hypothalamus,producing dilation of the
peripheral blood vessels and increased sweating.
 Also, because prostaglandin E increases body
temperature, inhibiting its production lowers a
fever.
 aspirin, permanently inhibits platelet aggregation
by interfering with the production of a substance
called thromboxane A2, necessary for platelet
aggregation.
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Salicylates are used primarily to relieve pain
and reduce fever.
they don’t effectively relieve visceral pain or
severe pain from trauma.
Salicylates won’t reduce a normal body
temperature.
They can reduce an elevated body
temperature, and will relieve headache and
muscle ache at the same time.
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Salicylates can provide considerable relief in
24 hours when they’re used to reduce
inflammation in rheumatic fever, rheumatoid
arthritis, and osteoarthritis.
As a result of its anticlotting properties,
aspirin can be used to enhance blood flow
during myocardial infarction (MI) and to
prevent recurrence of MI.
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the main guideline of salicylate therapy is to
use the lowest dose that provides relief.
This reduces the likelihood of adverse
reactions.
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• Oral anticoagulants, heparin, methotrexate,
oral antidiabetic agents, and insulin are
among the drugs that have an increased
effect or risk of toxicity when taken with
salicylates.
• Corticosteroids may decrease plasma
salicylate levels and increase the risk of
ulcers.
• NSAIDs may have a reduced therapeutic
effect and an increased risk of GI effects
when taken with salicylates.
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The most common adverse reactions to
salicylates include gastric distress, nausea,
vomiting,and bleeding tendencies.
Other adverse reactions include:
• hearing loss (when taken for prolonged
periods)
• diarrhea, thirst, sweating,tinnitus,
confusion,dizziness, impaired vision,and
hyperventilation.
• Reye’s syndrome(when given to children with
chickenpox or flulike symptoms
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Children and teenagers: Don’t use aspirin or
salicylates to treat flulike symptoms or
chickenpox because of the risk of triggering
Reye’s syndrome.
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Pregnant women: Aspirin is classified as
pregnancy risk category D,and salicylates are
classified as category C. Salicylates appear in
breast milk.
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Surgical patients: Discontinue aspirin, if
possible,one week before surgery .
Asthmatics: These patients have an increased risk
of sensitivity to aspirin, leading to
bronchospasm, urticaria, angioedema, or shock.
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Although the class of para-aminophenol
derivatives includes two drugs—phenacetin
and cetaminophen—only acetaminophen is
available in the United States.
Acetaminophen is an OTC drug that
produces analgesic and antipyretic effects.
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Acetaminophen is absorbed rapidly and
completely from the GI tract. It’s also
absorbed well from the mucous membranes
of the rectum.
Acetaminophen is distributed widely in body
fluids and readily crosses the placental
barrier.
After acetaminophen is metabolized by the
liver, it’s excreted by the kidneys and, in
small amounts, in breast milk.
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Acetaminophen reduces pain and fever, but
unlike salicylates, it doesn’t affect
inflammation or platelet function.
The pain-control effects of acetaminophen
aren’t well understood.
It reduces fever by acting directly on the
heat-regulating center in the hypothalamus.
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Acetaminophen is used to reduce fever and
relieve headache,muscle ache, and general
pain.
Acetaminophen is the drug of choice to treat
fever and flulike symptoms in children.
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• The effects of oral anticoagulants and
thrombolytic drugs may be slightly increased.
• The risk of liver toxicity is increased when
long-term alcohol use, phenytoin,
barbiturates, carbamazepine, and isoniazid
are combined with acetaminophen.
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- Most patients tolerate acetaminophen well.
- Unlike the salicylates,acetaminophen rarely
causes gastric irritation or bleeding tendencies.
- Acetaminophen may cause severe liver toxicity,
and the total daily dose should be monitored.
- (The total daily dose shouldn’t exceed 4,000
mg/day.)
- Other adverse reactions include:
• skin rash
• hypoglycemia
Acetyl systein
• neutropenia.
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The word opioid refers to derivatives of the opium
plant or to synthetic drugs that imitate natural
narcotics.
Opioid agonists (also called narcotic agonists)
include opium derivatives and synthetic drugs
with similar properties.
They’re used to relieve or decrease pain without
causing the person to lose consciousness.
Some opioid agonists may also have antitussive
effects that suppress coughing and antidiarrheal
actions that can control diarrhea.
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- Opioid antagonists aren’t pain medications.
- Instead, they block the effects of opioid
agonists and are used to reverse adverse
drug reactions, such as respiratory and CNS
depression, produced by those drugs.
- Unfortunately, by reversing the analgesic
effect, they also cause the patient’s pain to
recur.
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codeine
fentanyl
hydrocodone
hydromorphone
levorphanol
meperidine
methadone
morphine sulfate
oxycodone
oxymorphone
propoxyphene
remifentanil
sufentanil.
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A person may receive an opioid agonist by
any administration route, although inhalation
administration is uncommon.
Oral doses are absorbed readily from the GI
tract; however, transmucosal and intrathecal
opiates are faster-acting.
Opioid agonists administered I.V. provide the
most rapid (almost immediate) and reliable
pain relief.
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Distribution
- Opioid agonists are distributed widely
throughout body tissues.
- They have a relatively low plasma proteinbinding capacity (30% to 35%).
Metabolism
Opioid agonists are metabolized extensively in the
liver.
Excretion
Metabolites are excreted by the kidneys. A small
amount is excreted in stool through the biliary
tract.
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Opioid agonists reduce pain by binding to opiate
receptor sites (mu receptors and N-methyl-Daspartate receptors) in the peripheral nervous
system and the CNS.
When these drugs stimulate the opiate
receptors, they mimic the effects of endorphins
(naturally occurring opiates that are part of the
body’s own pain relief system).
This receptor-site binding produces the
therapeutic effects of analgesia and cough
suppression.
It also produces adverse reactions such as
respiratory depression and constipation.
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- Opioid agonists, especially morphine, affect
the smooth muscle of the GI and
genitourinary tracts (the organs of the
reproductive and urinary systems).
- This causes contraction of the bladder and
ureters. It also slows intestinal peristalsis
(rhythmic contractions
- that move food along the digestive tract),
resulting in constipation,a common adverse
effect of opiates.
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These drugs also cause blood vessels to
dilate, especially in the face, head, and neck.
In addition, they suppress the cough center in
the brain, producing antitussive effects and
causing constriction of the bronchial muscles.
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- Opioid agonists are prescribed to relieve severe
pain in acute, chronic, and terminal illnesses.
- They also reduce anxiety before a patient
receives anesthesia and are sometimes
prescribed to control diarrhea and suppress
coughing.
- Morphine relieves shortness of breath in patients
with pulmonary edema and heart failure .
- It does this by dilating peripheral blood vessels,
and decreasing cardiac preload.
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• The use of opioid agonists with other drugs that
also decrease respirations, such as alcohol,
sedatives, hypnotics, and anesthetics,increases
the patient’s risk of severe respiratory
depression.
• Taking tricyclic antidepressants, phenothiazines,
or anticholinergics with opioid agonists may
cause severe constipation and urine retention.
• Drugs that may affect opioid analgesic activity
include amitriptyline, diazepam, phenytoin,
protease inhibitors, and rifampin.
• Drugs that may be affected by opioid analgesics
include carbamazepine,warfarin, beta-adrenergic
blockers, and calcium channel blockers
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One of the most common adverse reactions to opioid agonists
is decreased rate and depth of breathing that worsens as the
dose of opioid is increased.
- Other adverse reactions include:
• flushing
• orthostatic hypotension
• pupil constriction.
- Adverse reactions to meperidine include:
• tremors
• palpitations
• tachycardia
• delirium
• seizures.
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Opioid antagonists have a greater attraction
for opiate receptors than opioids do;
however, they don’t stimulate those
receptors.
As a result, opioid antagonists block the
effects of opioid drugs,enkephalins, and
endorphins.
Opioid antagonists include:
• naloxone
• naltrexone
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Pharmacokinetics
Naloxone is administered I.M., subQ, or I.V.
Naltrexone is administered orally in tablet or
liquid form.
Both drugs are metabolized by the liver and
excreted by the kidneys.
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Pharmacotherapeutics
Naloxone is the drug of choice for managing an
opioid overdose.
It reverses respiratory depression and sedation and
helps stabilize the patient’s vital signs within
seconds after administration.
Naloxone also reverses the analgesic effects of
opioids. Therefore,after naloxone administration,
the patient may complain of pain or even
experience withdrawal symptoms.
Naltrexone is used along with psychotherapy or
counseling to treat drug abuse;
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