PAIN MEDICATIONS

dr. Ave Olivia Rahman, MSc.

Bagian Farmakologi FKIK UNJA
Pain
 According to Duration
 Acute Pain

 Chronic Pain
 According to Type
 Nociceptive Pain

 Inflammatory Pain
 Neuropathic Pain
Pain Medications
 Non opioid analgesics
 Antipyretics
 Nonsteroidal anti-inflammatory
drugs (NSAIDs)
 Opioid analgesics
 Anesthetic drugs.
 Nonopioid Analgesics,
Antipyretics, and NSAIDs
The drug classes included in this group
are:
 Salicylates (especially aspirin), widely
used
 Para -aminophenol derivative
(acetaminophen)
 NSAIDS
 Phenazopyridine (urinary tract
analgesic).
Salicylates

common salicylates include:

 Aspirin
 Choline magnesium trisalicylate
 Choline salicylate
 Diflunisal
 Salsalate
 Sodium salicylate.
 Pharmacokinetics
 The pure and buffered forms of aspirin
are absorbed readily, sustained -release
and enteric-coated salicylate
preparations are absorbed more slowly.
 Food, antacids in the stomach  delay
absorption.
 Rectally : have a slower, more erratic
absorption.
 Salicylates are distributed widely.
 Pharmacodynamic
 Reduce pain and reduce inflammation
by Inhibiting the synthesis of
prostaglandin.
 Reduce fever by stimulating the
hypothalamus, producing dilation of
the peripheral blood vessels and
increased sweating.
 Aspirin, permanently inhibits platelet
aggregation by interfering the
production of thromboxane A2
 Pharmacotherapeutics
 Salicylates are used primarily to relieve
pain and reduce fever, not effective to
relieve visceral pain or severe pain from
trauma.
 Reduce inflammation in rheumatic fever,
rheumatoid arthritis, and osteoarthritis.
 Relieve headache and muscle ache
 Aspirin can be used to enhance blood flow
during myocardial infarction (MI) and to
prevent recurrence of MI (have Anticlotting
properties)
 Side Effects
 Gastric distress, Nausea, vomiting, and
bleeding tendencies.
 Hearing loss (when taken for prolonged
periods)
 Diarrhea, thirst, sweating, tinnitus,
confusion, dizziness, impaired vision,
and Hyperventilation (rapid breathing)
 Reye’s syndrome (when given to children
with chickenpox or flulike symptoms).
 Drug interactions
 Oral anticoagulants, heparin,
methotrexate, oral antidiabetic agents, and
insulin are may have increase toxicity
 Probenecid, sulfinpyrazone, and
spironolactone may have a decreased
effect
 Corticosteroids may decrease plasma
salicylate levels and increase the risk of
ulcers.
Continue...

 Alkalinizing drugs and antacids may

reduce salicylate levels.
 The antihypertensive effect of ACEI and
beta blockers may be reduced.
 NSAIDs may have a reduced therapeutic
effect and an increased risk of GI effects
Acetaminophen
 Member of para -aminophenol
derivatives
 Acetaminophen is absorbed rapidly
and completely from the GI tract, the
rectum.
 Acetaminophen is distributed widely,
readily crosses the placental barrier.
 Acetaminophen reduces pain and
fever, but it doesn’t affect
inflammation or platelet function
Pharmacotherapeutics

 Acetaminophen is used to reduce

fever and relieve headache, muscle
ache, and general pain.
 Effective pain reliever for some types
of arthritis
Drug interactions

 The effects of oral anticoagulants and

thrombolytic drugs may be slightly
increased.
 The risk of liver toxicity is increased
when combine with long-term alcohol
use, phenytoin, barbiturates,
carbamazepine, and isoniazid
 The effects of lamotrigine, loop diuretics,
and zidovudine may be reduced
Nonsteroidal anti-inflammatory
drugs

 Are typically used to combat

inflammation.
 Have analgesic and antipyretic effects.
 Effects of NSAIDs on platelet
aggregation are temporary.
Two Types of NSAIDs

 There are : selective and nonselective.

 The nonselective NSAIDs : diclofenac,
etodolac, fenoprofen, flurbiprofen,
ibuprofen, indomethacin, ketoprofen,
ketorolac, meloxicam, nabumetone,
naproxen, oxaprozin, piroxicam, and
sulindac.
 The selective NSAID : celecoxib
Pharmacodynamics

 Two isoenzymes of cyclooxygenase,

known as COX -1 and COX -2, convert
arachidonic acid into prostaglandins.
 The nonselective NSAIDs block both
COX -1 and COX -2.
 Selective NSAIDs block only the COX-2
enzyme.
Difference of Selective and Nonselective
NSAIDS
 The prostaglandins produced by COX-1
maintain the stomach lining, while those
produced by COX-2 cause inflammation.
 That’s why the nonselective NSAIDs (inhibit
COX -1and COX -2) commonly cause GI
adverse effects.
 Selective NSAIDs alleviate pain and
inflammation without causing significant GI
adverse effects because they inhibit only
COX-2.
Pharmacotherepeutics

 NSAIDs are used primarily to decrease

inflammation.
 They’re secondarily used to relieve
pain.
 Seldom prescribed to reduce fever.
 Particularly useful in the treatment of
osteoarthritis, rheumatoid arthritis,
acute pain, primary dysmenorrhea,
and familial adenomatous polyposis.
 Continue... favorably to treatment
 Ankylosing spondylitis
 Moderate to severe rheumatoid arthritis
 Osteoarthritis
 Acute gouty arthritis
 Dysmenorrhea (painful menstruation)
 Migraine headaches
 Bursitis and tendonitis
 Mild to moderate pain.
Side Effects

 Abdominal pain, bleeding, anorexia,

diarrhea, nausea, ulcers, and liver
toxicity
 Drowsiness, headache, dizziness,
confusion, tinnitus, vertigo, and
depression
 Bladder infection, blood in the urine, and
kidney necrosis
 Hypertension, heart failure, and pedal
edema.
Awareness

 Patients considering the use of

celecoxib should be carefully screened
for a history of cerebrovascular or
cardiovascular disease.
 Children: Some NSAIDs aren’t
recommended for use in children.
 Elderly patients: The risk of ulcers
increases with age.
Continue...

 Pregnant and breast -feeding women:

 Diclofenac, flurbiprofen, ketoprofen, and
naproxen are pregnancy risk category B
drugs.
 Etodolac, ketorolac, meloxicam,
nabumetone, oxaprozin, piroxicam ,
celecoxib are category C drugs.
 Because most NSAIDs appear in breast
milk, it’s best not to use these drugs in
breast -feeding women.
 Drug interactions
 A wide variety of drugs can interact with NSAIDs,
especially with indomethacin, piroxicam, and
sulindac.
 Such drugs as fluconazole, phenobarbital, rifampin,
ritonavir, and salicylates affect absorption of NSAIDs,
 NSAIDs affect the absorption of such drugs as oral
anticoagulants, aminoglycosides, ACE inhibitors,
beta-adrenergic blockers, digoxin, dilantin, and
many others.
 Decrease the clearance of lithium, which can result
in lithium toxicity.
 Reduce the antihypertensive effects of ACE inhibitors
and diuretics.
Phenazopyridine hydrochloride

 Produces a local analgesic effect on the urinary

tract  is used to relieve such symptoms as
pain, buring, urgency, and frequency associated
with urinary tract infections.
 Causing the patient’s urine to turn an orange or
red Color. The drug
 If the drug accumulates  the patient’s skin
and sclera may assume a yellow tinge stop
 Acute renal or hepatic failure may occur.
Opioid Analgesics

 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 also have
antitussive effects and antidiarrheal
actions.
Member of Opioids

 codeine  morphine sulfate

 fentanyl (including morphine
sulfate sustained -
 hydrocodone
release tablets and
 hydromorphone intensified oral
 levorphanol solution)
 Petidine/meperidine  oxycodone
 methadone  oxymorphone
 propoxyphene
 remifentanil
 sufentanil.
Pharmacokinetis
 Opioid agonists administered I.V.
provide the most rapid (almost
immediate) and reliable pain relief.
 The subcutaneous and I.M. routes may
result in delayed absorption, especially
in patients with poor circulation.
 It’s distributed widely throughout body
tissues.
 Have a relatively low plasma protein -
binding capacity (30% to 35%).
 Pharmacodynamics
 Opioid agonists reduce pain by binding to
opiate receptor sites (mu receptors and N-
methyl-D-aspartate receptors) in the
peripheral nervous system and the CNS.
 Drugs stimulate the opiate receptors 
mimic the effects of endorphins 
produces the therapeutic effects of
analgesia and cough suppression.
 It also produces respiratory depression .
Continue...
 Opioid agonists, especially morphine,
causes contraction of bladder and
ureter.
 Slowing intestinal peristalsis 
constipation
 Causing blood vessels to dilate,
especially in the face, head, and neck 
hypotension can occur.
 Causing constriction of the bronchial
muscles
Pharmacotherapeutics
 Opioid agonists are prescribed to relieve severe
pain in acute, chronic, and terminal illnesses.

 Reducing anxiety before a patient receives

anesthesia

 Sometimes prescribed to control diarrhea and

suppress coughing.

 Morphine relieves shortness of breath in

patients with pulmonary edema and left-sided
heart failure  by dilating peripheral blood
vessels and decreasing cardiac preload.
 Drug interactions
 increases respiratory depression when combine
with other drugs that also decrease respirations,
such as alcohol, sedatives, hypnotics, and
anesthetics,.
 Severe constipation and urine retention when
combine with tricyclic antidepressants,
phenothiazines, or anticholinergics.
 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.
Mixed opioid agonist-antagonists
 Have agonist and antagonist properties.
 The agonist component relieves pain, while the
antagonist component decreases the risk of
toxicity (respiratory depression) and drug
dependence.
 Member of this groups:
 Buprenorphine
 Butorphanol
 Nalbuphine
 Pentazocine hydrochloride (combined with
pentazocine lactate, naloxone, aspirin, or
Acetaminophen).
Awareness

 Patients who abuse opioids

shouldn’t receive mixed opioid
agonist-antagonists because these
drugs can cause symptoms of
withdrawal.
 Mixed opioid agonist-antagonists
are listed as pregnancy risk c
Anesthetic drugs

 Can be divided into three

groups’general anesthetics, local
anesthetics, and topical anesthetics.
 General anesthetic drugs are further
subdivided into two main types:
 those given by inhalation
 those given intravenously.
Inhalation Anesthetics
 Commonly used general anesthetics given by
inhalation include: desflurane, enflurane,
halothane, isoflurane, nitrous oxide,
sevoflurane.
Pharmacodynamics :
 Inhalation anesthetics work primarily by
depressing the CNS  producing loss of
consciousness, loss of responsiveness to
sensory stimulation (including pain), and
muscle relaxation.
Pharmacotherapeutics

 Inhalation anesthetics are used for

surgery because they offer more
precise and rapid control of depth of
anesthesia than injection anesthetics
do.
Intravenous anesthetics
Member of this groups :
 Barbiturates (methohexital, thiopental)
 Benzodiazepines (midazolam)
 Dissociatives (ketamine)
 Hypnotics (etomidate, propofol)
 Opiates (fentanyl, sufentanil).
 Pharmacotherapeutics
 It are typically used when the patient requires general
anesthesia for just a short period such as during
outpatient surgery.
 Also used to promote rapid induction of anesthesia or
to supplement inhalation anesthetics.
 Barbiturates are used alone in surgery that isn’t
expected to be painful and as adjuncts to other drugs
in more extensive procedures.
 Benzodiazepines produce sedation and amnesia, but
not pain relief.
 Etomidate is used to induce anesthesia and to
supplement low-potency inhalation anesthetics such
as nitrous oxide.
 The opiates provide pain relief and supplement other
anesthetics.
Local anesthetics
 Are administered to prevent or relieve pain
in a specific area of the body.
 In addition, these drugs are often used as
an alternative to general anesthesia for
elderly or debilitated patients.
 Amide anesthetics : bupivacaine,
lidocaine, mepivacaine, prilocaine,
ropivacaine.
 Ester anesthetics : chloroprocaine,
procaine, tetracaine.
Pharmacodynamics
 Local anesthetics block nerve impulses at the
point of contact in all kinds of nerves.
 They accumulate  causing the nerve cell
membrane to expand  the cell loses its
ability to depolarize (impulse transmission)

Pharmacotherapeutics
 Local anesthetics are used to prevent and
relieve pain from medical procedures, disease,
or injury.
 Also be used for severe pain that topical
anesthetics or analgesics can’t relieve.
Combined ....

 For some procedures, a local

anesthetic is combined with a drug
that constricts blood vessels, such as
epinephrine.
 Vasoconstriction helps control local
bleeding and reduces absorption of
the anesthetic.
 Reduced absorption prolongs the
anesthetic’s action at the site and
limits its distribution and CNS effects.
Topical anesthetics

 It are applied directly to intact skin or

mucous membranes.
 All topical anesthetics are used to
prevent or relieve minor pain.
 Some injectable local anesthetics,
such as lidocaine and tetracaine, are
also topically effective.
Pharmacodynamics

 Benzocaine, butacaine, cocaine,

dyclonine, and pramoxine produce
topical anesthesia by blocking nerve
impulse transmission.
 Dibucaine, lidocaine, and tetracaine
may also block impulse transmission
across the nerve cell membranes.
 continue...
 Topical anesthetics produce little systemic
absorption, except for the application of cocaine to
mucous membranes. Systemic absorption may
occur in frequent or high -dose applications
 Ethyl chloride spray superficially freezes the tissue,
stimulating the cold –sensation receptors and
blocking the nerve endings in the frozen area.
 Menthol selectively stimulates the sensory nerve
endings for cold, causing a cool sensation and
some local pain relief.
Pharmacotherapeutics
Topical anesthetics are used to:
 Relieve or prevent pain, especially minor burn
pain
 Relieve itching and irritation
 Anesthetize an area before an injection is given
 Numb mucosal surfaces before a tube/urinary
catheter, is inserted
 Alleviate sore throat or mouth pain when used
in a spray or solution.
 Tetracaine is also used as a topical anesthetic
for the eye.
 Benzocaine is used with other drugs in several
ear preparations.
WHO Analgesic step ladder

 Step 1: Non opioid (+ or-) adjuvant

.(VAS 2- 4/10).
 Step 2: Weak opioid (+) Non opioid (+
or-) adjuvant(VAS 4-6/10).
 Step 3: Strong opioid(+) Non opioid (+
or-) adjuvant (VAS>6/10).
 Step 4: Anesthetic/Neurosurgical
Interventions.
Hapalkan Dosis dan sediaan
berikut :
1. Parasetamol
2. Peroksikan
3. Na-diklofenak
4. Petidin
5. Morfin