Transcript Analgesic

ANALGESICS
Pain Management
What is pain?
– A protective mechanism to warn of damage or
the presence of disease
– Part of the normal healing process
ANALGESICS
I.
Opioid (narcotic) analgesics
1. Agonists of opioid receptors – morphine hydrochloride, promedol,
omnopon, fentanyl, codeine;
2. Agonists – antagonists and partial agonists of opioid receptors –
pentazocin, buprenorphine.
II.
Non-opioid analgesics and non steroidal antiinflammatory drugs - NSAIDs
acetylsalicylic acid, paracetamol, analgin, indometacin, butadion,
ibuprofen, pyroxicam, diclofenac-sodium, ketorolac, ketoprofen.
III. Substances with mixed mechanism
(opioid and non-oioid components)
tramadole
of action
The structures that take part in perception of pain:
thalamus, hypothalamus, reticular formation,
limbic system, occipital and frontal areas of
cortex
System which conducts and perceives pain -
nociceptive
System which protects organism
from pain – antinociceptive
 Acute pain
Classification of Pain
By Onset and Duration
 Sudden in onset
 Usually subsides once treated
 Chronic pain
 Persistent or recurring
 Often difficult to treat
Major Sources of Pain
Source
Area Involved
Characteristics
Treatment
Somatic
body
framework
throbbing,
stabbing
narcotics,
NSAIDS
Visceral
kidneys,
intestines,
liver
aching,
throbbing,
sharp, crampy
narcotics,
NSAIDS
Neuropathic
Nerves
burning,
numbing,
tingling
narcotics,
NSAIDS,
antidepressants,
anticonvulsants
OPIOID
ANALGESICS
History of Opioids
• Opium is extracted from poppy seeds
(Papaver somniforum)
• Used for thousands of years to produce:
– Euphoria
– Analgesia
– Sedation
– Relief from diarrhea
– Cough suppression
History cont’d
• Used medicinally and recreationally from
early Greek and Roman times
• Opium and laudanum (opium combined
with alcohol) were used to treat almost
all known diseases
Morpheus
is the Greek god of
dreams and sleep.
Friedrich Wilhelm Adam
Sertürner, a German
pharmacist, isolated
Morphine from opium,
in 1805.
History and Background
• Invention of the hypodermic needle in 1856
produced drug abusers who self administered
opioids by injection
• Controlling the widespread use of opioids has
been unsuccessful because of the euphoria,
tolerance and physiological dependence that
opioids produce
Opioid receptors
• group of G-protein coupled receptors with
opioids as ligands.
• The endogenous opioids are dynorphins,
enkephalins, endorphins, endomorphins and
nociceptin.
Subtypes of opiod receptors:
mu, delta, kappa, epsilon, sigma
Opiod Receptor Activation
Response
Analgesia
Respiratory
depression
Euphoria
Dysphoria
Decrease GI
motility
Physical
Dependence
Mania,
hallucination
Mu-1
Mu-2
Kappa
Delta
Sigma
Morphine CNS
Depressant effects
• Analgesia
• Indifference to surroundings
• Mood and subjective effects
• Depression of respiration
• Cough centre
• Temperature regulating
centre
• Vasomotor centre
Stimulate effects
• CTZ (nausea, vimiting)
• Edinger Wesphal nucleus
(III nerve –producing miosis)
• Vagal centre (bradycardia)
• Certain cortical areas and
hippocampal
Morphine can be used as an
analgesic to relieve:
pain in myocardial infarction
pain associated with surgical conditions, pre- and
postoperatively (pre-anesthetic medication, balanced
anesthesia, surgical analgesia)
pain associated with trauma, burns
severe chronic pain, e.g., cancer
pain from kidney stones, renal colic, ureterolithiasis, etc
(pain may be valuable for diagnosis: should not be relived by
analgesic unless proper assessment of the patient has been done)
traumas of thorax accompanied by cough (morphine depresses
central links of coughing reflexes)
Acute left-ventricular cardiac failure
(cardiac asthma)
 Reduce preload on heard due to
vasodilatation
 Tending to shift blood from pulmonary
to systemic circuit; relieves pulmonary
congestion and edema
 Allays air hunger by depressing
respiratory centre
 Cuts down sympathetic stimulation by
calming the patient
Applications in Dentistry
• Narcotic (opioid) analgesics are extremely
effective in reducing acute dental and
postoperative pain.
• The narcotic analgesics have established a
niche for the treatment of pain in those
situations where the NSAIDs are less effective.
• Hydrocodone, oxycodone, codeine, and
occasionally meperidine are the narcotics used
to treat dental pain.
MORPHINE HYDROCHLORIDE
routes of administration
 subcutaneously and intramuscularly
(analgesic action after 10-15 min)
 oral administration – presystemic elimination
( 20-60 % enters general blood circulation)
 sublingually – quick absorption
 i.v. is indicated even in emergency
 Epidural or intrathecal ( into the spinal canal ) injection
produces segmental analgesia lasting 12 hours without
affecting other sensory, motor or autonomic modalities
Duration of analgesic action – 4-6 hours
Maximum single dose of morphine is 0,02 g,
maximum daily dose – 0,05 g
Side effects of morphine
 Respiratory depression
 Vomiting (excitation of starting zone of vomiting
center)
 bradycardia (increasing of tone of n. vagus nuclei)
 spasm of sphincters of gastro-intestinal tract
accompanied by constipations
 increasing of tone of smooth musculature of
urinary and bile-excreting tracts (retentions of
urination, bile stasis)
 Decreasing of BP
CONTRAINDICATIONS FOR ADMINISTRATION
OF MORPHINE
 acute respiratory depression
 renal failure (due to accumulation of the metabolites morphine-3glucuronide and morphine-6-glucuronide)
 chemical toxicity (potentially lethal in low tolerance subjects)
 raised intracranial pressure, including head injury (risk of worsening
respiratory depression)
 Biliary colic
Precauntation
 pain that accompanies chronic inflammatory pain
 children before the age of 2 years
Tolerance
• Tolerance is a diminished responsiveness to the drug’s action
that is seen with many compounds
• Tolerance can be demonstrated by a decreased effect from a
constant dose of drug or by an increase in the minimum drug
dose required to produce a given level of effect
• Physiological tolerance involves changes in the binding of a
drug to receptors or changes in receptor transductional
processes related to the drug of action
• This type of tolerance occurs in opioids
Addiction
• Physical dependence
• Physiological dependence
• Withdrawal reactions
Tolerance and Dependence
Withdrawl Reactions
Acute Action
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Analgesia
Respiratory Depression
Euphoria
Relaxation and sleep
Tranquilization
Decreased blood pressure
Constipation
Pupillary constriction
Hypothermia
Drying of secretions
Reduced sex drive
Flushed and warm skin
Withdrawl Sign
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Pain and irritability
Hyperventilation
Dysphoria and depression
Restlessness and insomnia
Fearfulness and hostility
Increased blood pressure
Diarrhea
Pupillary dilation
Hyperthermia
Lacrimation, runny nose
Spontaneous ejaculation
Chilliness and “gooseflesh”
OMNOPON
• contains mixture if opium alkaloids
(48-50% morphine)
• does not cause spasms of smooth
musculature, as it contains alkaloids of
isoquinoline raw
• is used for analgesia according to all the
indications of morphine hydrochloride, for
example, colics
Promedol (trimeperidine)
• produces similar effects to other opioids, such
as analgesia and sedation, along with side
effects such as nausea, itching, vomiting and
respiratory depression which may be harmful
or fatal.
• duration of analgesic action - 3-4 hours
• moderate spasmolytic influence on smooth
musculature of internal organs
• stimulation of rhythmic contractions of uterus
• can be used for analgesia
• in case of pain syndrome connected with
spasms of smooth musculature
Fentanyl
• synthetic opioid analgesic of short action
• analgesic activity is 300 times higher
than of morphine
• analgesic
effect
after
intravenous
introduction – after 1-3 min, lasts for
15-30 min
• used
with
neuroleptic
droperidol
(complex drug – “talamonal”) for
neuroleptanalgesia
fentanyl transdermal system
• should be used for longterm (chronic) pain
requiring continuous
narcotic pain
• Is designed to release the
drug into the skin at a
constant rate ranging
from 25 to 100
micrograms/h,
Codeine
 opium alkaloid
 analgesic action is not strong, but
anticough effect is considerable
 administered as an anticough drug of
central action
 combination with non opiod analgesics
(eg. Paracetamol) is supra-additive
Pentazocin
 agonist-antagonist of opioid receptors
 comparatively with morphine, it is a bit less dangerous in
the aspect of addiction development
 indicated in case of pain of medium intensity in such
conditions like other opioid analgesics. In case of strong
pain its administration is limited as in case of increasing
of dose of the drug excitation appears
 it can cause increasing of blood pressure and tachycardia
that’s why it’s not advised to use in case of acute
myocardium infarction
 if it is administered for people with narcotic addiction
manifestations of abstinence develop
Buprenorphine
• Partly agonist of mu-opioid receptors
• Acts longer than morphine (approximately 6 hours)
• Analgesic activity is higher than of morphine, that’s why it’s
used in doses of 0,3-0,6 mg
• In case of breathing depression, which it causes, naloxon is
less effective since buprenorphine is slowly released from the
connection with mu-receptors
• Indicated for pain decreasing in the same situations as other
narcotic analgesics
• May be used for detoxication and supporting treatment of
individuals who is addicted to heroine
Acute poisoning with opioid analgesics
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Respiratory Depression
Euphoria
Relaxation and sleep
Tranquilization
Decreased blood pressure
Constipation
Pupillary constriction
Hypothermia
Drying of secretions
Flushed and warm skin
Triad in case
poisoning with
morphine
Acute miosis
(Pinpoint
pupils)
Cheyne Stokes
respiration
deep tendon
reflexes
increased
Treatment of acute poisoning
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Naloxon
(antagonist of opioid receptors)
intravenously - 0,4-1,2 mg
general dose of naloxon should not overcome 10 mg
stomach lavage (for morphine enterohepatic circulation
is typical) with 0,05-0,1% solution of potassium
permanganate and 0,5 % tannin solution
suspension of 20-30 g of activated charcoal
salt laxative agents (sodium sulfate)
forced diuresis
atropine sulfate
inhalation of carbogen (5-7 % СО2 and 93-95 % O2)
NON-OPIOID
ANALGESICS
Pharmacodynamic Effects
• Analgesic
• Antipyretic
• Anti-inflammatory
(except paracetamol)
Mechanism of action of non-opioid analgesics
• depression of cyclooxygenases activity
• decreasing
of
prostaglandins
synthesis
in
peripheral tissues and in central nervous system
• decreasing of sensitivity of nervous endings and
depression of transmission of nociceptive impulses
on the level of CNS structures
• pain-relieving action of non-opioid analgesics is
partly connected with their anti-inflammatory
activity
Effects of COX Inhibition
by Most NSAIDS
COX-1
Gastric ulcers
COX-2
Reduce inflammation
Bleeding
Reduce pain
Acute renal failure
Reduce fever
NSAIDs : anti-platelet—decreases ability of blood to clot
COX Enzyme:Prostaglandin Effects
COX-1: beneficial COX-2: harmful
Peripheral injury
site
Brain
Inflammation
Modulate pain
perception
Promote fever
(hypothalamus)
Stomach
protect mucosa
Platelets
aggregation
Kidney
vasodilation
Indications for administration of nonnarcotic analgesics
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headache
toothache
backache
neuralgias
pulled muscles
joint pain
dysmenorrhea
for potentiating of their action – combinations
paracetamol with codeine,
metamizol with dimedrol, metamizol with codeine
Applications in Dentistry
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Toothache
Post extraction pain
Periodontitis
Neuritis
Stomatitis
Arthritis
Local usage as keratoplatic agents for
hyperkeratosis, hyperesthesia
Paracetamol
(Acetaminophen)
• analgesic and antipyretic drug
• maximal effect if the drug is introduced
orally – after 2 hours, lasts approximately
for 4 hours
• in case of durable administration of big
doses – damaging of liver and kidneys,
production of met-hemoglobin
Paracetamol (Acetaminophen)
N-Acetyl-P-Aminophenol
Classification: analgesic, antipyretic, misc.
not an NSAID
Mechanism: inhibits prostaglandin synthesis
via CNS inhibition of COX (not peripheral)doesn’t promote ulcers, bleeding or renal failure;
peripherally blocks generation of pain impulses,
inhibits hypothalamic heat-regulation center
Paracetamol
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Tablets
Suppositories
Syrups
Soluble tablets
Capsules
PARACETAMOL
Pharmacokinetics: paracetamol
Metabolism: major and minor pathways
Half-life: 1-3 hours
Time to peak concentration: 10-60 min
Treatment for overdose: Acetylcysteine
Paracetamol Liver Metabolism
1. Major pathway —Majority of drug is
metabolized to produce a non-toxic metabolite
2. Minor pathway —Produces a highly reactive
intermediate (acetylimidoquinone) that
conjugates with glutathione and is inactivated.
• At toxic paracetamol levels, minor pathway
metabolism cannot keep up (liver’s supply of
glutathione is limited), causing an increase in the
reactive intermediate which leads to hepatic toxicity
and necrosis
Acetylsalicylic acid
 Blocks irreversibly COX
 As antipyretic and analgesic
drug – 0,25 and 0,5 g per time
 As an anti-inflammatory – 3-4 g
per
day
(for
arthritis,
myocarditis, pleuritis, bronchitis
etc.
 As platelets inhibitor - for
prophylaxis
of
thrombusformation (in case of ischemic
heart disease, thrombophlebitis
etc.) – daily dose – 80-100 mg
Pharmacokinetics: ASA
Absorption: from stomach and intestine
Distribution: readily, into most fluids/tissues
Metabolism : primarily hepatic
• ASA contraindicated for use in children with viral
fever –can lead to Reye’s Syndrome
• Fatal overdose is possible
Similar pharmacokinetics for ibuprofen and related NSAIDs
Analgin
(metamizol-sodium)
Baralgin (maxigan, spazgan,
spazmalgon, trigan)
metamizol-sodium +pitophenon
hydrochloride+pheniverinium bromide
Ampoules
tablets
suppositories
Analgesic and
spasmolytic
activity
Traditional and selective COX-2
inhibitors
Ketorolak (ketanov)
• according to analgesic activity it
prevails over effect of acetylsalicylic
acid, indometacin and equals to
opioid analgesics
• moderate
anti-inflammatory,
antipyretic and anti-aggregate effects
• high effectiveness in case of pain in
postoperative period, in oncology,
during child delivery, traumas, colic
• i/m, i/v, orally
NOT indicated
for chronic pain syndrome
Ketoprophen (ketonal)
• strong analgesic, anti-inflammatory and
antipyretic agent
• administered in case of arthroses and
arthritis, ancilizing spondilitis, pain of
different genesis (after surgeries, in case
of traumas, painful menstruations etc.)
• administered orally, intramuscularly, in
forms of suppositories and ointments
TRAMADOL
Analgesic activity is similar to the activity
of morphine
Abuse potential is low
Less respiratory depression
Hemodynamic effects are minimal
In case of intravenous administration effect
develops after 5-10 min, if administered
orally – after 30-40 min, action lasts for
3-5 hours.
Tramadol possesses agonist actions at the μ-opioid receptor
and affects reuptake at the noradrenergic and serotonergic systems
ADMINISTRATION OF TRAMADOL
surgery, traumatology, gynecology,
neurology, urology, oncology
For all kinds of acute and chronic pain of
moderate and considerable intensity,
including
neuralgias, postoperative, traumatic pain
diagnostic and therapeutic interventions
oncologic pathology
Thank you!
QUESTIONS?!