Opioid Analgesic Agents Leah Nabirye

Opioid Analgesic Agents
Leah Nabirye
Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

some important terms
• Analgesics: Are the Drugs which selectively relieves pain by
acting in the CNS or on peripheral pain mechanisms, without
significantly altering the consciousness – Opioids and
NSAIDS
• Opioids: Any drug which binds to the opioid receptors
(Pharmacologically related) in the CNS and antagonized by
Naloxone . They may be – Natural, Synthetic and semi-
synthetic
• Opiates: Drugs derived from opium – Natural or semi-
synthetic
• Narcotics: Drugs derived from opium or opium like
compounds, with potent analgesic effects associated with
significant alteration of mood and behavior, and with the
potential for dependence and tolerance following repeated
administration.
Some important terms
Nociception; mechanism whereby noxious peripheral stimuli
are transmitted to the central nervous system.
Pain is a subjective experience and difficult to quantify,
is very important protective phenomenon that
accompanies many pathological conditions and is not
always associated with nociception (or) an unpleasant
sensory and emotional experience with actual or
potential tissue damage.
Superficial: Stimulation of skin & mucous membranes
- Fast response
Deep: Arises from muscles, joints, tendons, heart ..etc.
- Slow response
Analgesia – absence of pain
Pain receptors in our bodies are nerves that transmit
pain. These are free nerve endings located in various
body tissues that respond to thermal, mechanical and
chemical stimuli.
When stimulated, these pain receptors generate an
impulse. The pain results of various impulses
arriving at the spinal cord and the brain.
When tissues become injured, they release
chemicals called prostaglandins and
leukotrienes that make the pain receptors more
sensitive and thus causing pain.
Analgesics
• Medications that relieve pain without causing

loss of consciousness
• Painkillers

Types of Pain
Classification of Pain
By Onset and Duration
• Acute pain
– Sudden in onset
– Usually subsides once treated
• Chronic pain
– Persistent or recurring
– Often difficult to treat

Acute Vs chronic
Acute pain Chronic pain
 Sudden onset  Persistent – usually lasting
Temporary (disappears more than six months

once stimulus is Cause unknown – may be
removed) due to neural stimulation or

can be somatic, a decrease in endorphins
visceral, referred Physiological responses are
 Associated anxiety less obvious especially with

Physiological responses
adaptation.
 Psychological responses
to acute pain include
increased RR, HR, BP may include depression
and reduction in gastric
motility – sympathetic
response)
Types of Pain – contd.
Classification of Pain
• Somatic
• Visceral
• Superficial
• Vascular
• Referred
• Neuropathic
• Phantom
• Cancer
• Psychogenic
• Central
Classification of Pain By Source
Vascular pain
• Possibly originates from vascular or
perivascular tissues
Neuropathic pain
• Results from injury to peripheral nerve fibers or
damage to the CNS
Superficial pain
• Originates from skin or mucous membranes
Pain Transmission Gate Theory
• Most common and well-described

• Uses the analogy of a gate to describe how
impulses from damaged tissues are
sensed in the brain

Pain Transmission
Tissue injury causes the release of:

• Bradykinin
• Histamine
• Potassium
• Prostaglandins
• Serotonin
These substances stimulate nerve endings,
starting the pain process.
Pain Transmission
There are two types of nerves stimulated:

• “A” fibers
and
• “C”
fibers

Pain Transmission
“A” Fibers “C” Fibers

Myelin sheath No myelin sheath
Large fiber size Small fiber size
Conduct fast Conduct slowly
Inhibit pain Facilitate pain
transmission transmission
Sharp and Dull and
well-localized nonlocalized

Pain Transmission
• Types of pain related to proportion of

“A” to “C” fibers in the damaged areas

Pain Transmission
• These pain fibers enter the spinal cord

and travel up to the brain.
• The point of spinal cord entry is the
DORSAL HORN.
• The DORSAL HORN is the location
of the “GATE.”

Pain Transmission
• This gate regulates the flow of sensory

impulses to the brain.
• Closing the gate stops the impulses.
• If no impulses are transmitted to higher
centers in the brain, there is NO pain
perception.

Pain Transmission
• Activation of large “A” fibers CLOSES gate

• Inhibits transmission to brain
– Limits perception of pain

Pain Transmission
• Activation of small “B” fibers OPENS gate

• Allows impulse transmission to brain
– Pain perception

Pain Transmission
• Gate innervated by nerve fibers from brain,

allowing the brain some control over gate
• Allows brain to:
– Evaluate, identify, and localize the pain
– Control the gate before the gate is open

Pain Transmission
“T” cells
• Cells that control the gate have a threshold
• Impulses must overcome threshold to be sent
to the brain

Pain Transmission
• Body has endogenous neurotransmitters

– Enkephalins
– Endorphins
• Produced by body to fight pain

• Bind to opioid receptors
• Inhibit transmission of pain by closing gate

Pain Transmission
Rubbing a painful area with massage or

liniment stimulates large sensory fibers
• Result:
– GATE closed, recognition of pain
REDUCED
– Same pathway used by opiates

Narcotic Analgesics / Opioid analgesics
Naturally occurring, semi-synthetic and synthetic drugs, which have
morphine like action (i. e) relief from pain and depression of CNS
associated with drug dependence (Mental and Physical) and withdrawal
side effects.
Therapeutic Uses
- Management of pain (Acute / Chronic / Severe)
- Cough Suppression
- Treatment of Diaarhoea.
- Management of acute pulmonary oedema & acute MI
- Pre-operative medication & Intra-operative adjunctive agents in
anaesthesia
Side effects
- Respiratory depression
- Physical dependency & addiction
- Nausea, Vomiting & Constipation
Opioids - Opium
• A dark brown, resinous material
obtained from poppy (Papaver
somniferum) Capsules.
OPIUM
PHENANTHRENE BENZYLISOQUINOLINE
•Morphine 9-14% •Papaverine 0.8-1%
•Codeine 0.5-2% •Noscapine 3-10%
•Thebaine 0.2-1% •Narcine 0.2-0.4%
Poppy Plant - image
Poppy to Opioids
Opium - History
• Friedrich Wilhelm Serturner
– A German Pharmacist
– Isolated Morphine in 1803 and named it
after the Greek god of Dreams
“MORPHEUS”
Opioid Analgesics
• Pain relievers that contain opium,

derived from the opium poppy
or
• chemically related to opium
Narcotics: very
strong pain relievers

Classification
I) Morphine analogs
Name R R’
Morphine H H
Ethyl morphine C2H5 H
Codeine CH3 H
Heroine COCH3 COCH3

Ia) Hydromorphone derivatives
Name R R’
Hydromorphone OH H
Oxymorphone H OH
Hydrocodone -OCH3 H
Oxycodone -OCH3 OH
Ib) Dihydromorphine derivatives

Name R
Dihydromorphine H
Dihydrocodeine -CH3
Ic) Morphinan derivatives
Name R R’ R’’
Levorphanol H H -CH3
Levallorphan H H -CH2-CH=CH2
Buterphanol H OH
Dextromethorphan -CH3 H -CH3

II) Meperidine / Phenyl (ethyl) Piperidines
Name R1 R2 R3 R4
Meperidine CH3 COOC2H5 H
Bemidone CH3 COOC2H5 H
Properidone CH3 COOCH(CH3)2 H
Ketobemidone CH3 COC2H5 H
Alphaprodine CH3 COOC2H5 CH3
Anileridine COOC2H5 H
Fentanyl H H
Name R1 R2 R3 R4
Lofentanil COOCH3 CH3
Sufentanil CH2OCH3 H
Alfentanil CH2OCH3 H
Diphenoxylate COOC2H5 H
Loperamide OH H
III) Methadone / Diphenyl heptanones
Name R2 R3 R4
Methadone C6H5 COC2H5 -CH2-CH(CH3)N(CH3)2
Isomethadone C6H5 COC2H5 -CH(CH3)CH2N(CH3)2
Normethadone C6H5 COC2H5 -CH2-CH2N(CH3)2
Dipanone C6H5 COC2H5
α-Acetyl Methdone C6H5 -CH2-CH(CH3)N(CH3)2
Dextromoramide C6H5
Phenadoxone C6H5 COC2H5
Propoxyphene or CH2 C6H5 OCOC2H5 -CH(CH3)-CH2N(CH3)2

Dextropropoxyphene
IV) Benzazocine / Benzomorphan analogs
Name R R1
Pentazocine CH2-CH=C(CH3)2 CH3
Phenazocine CH2-CH2-C6H5 CH3
Cyclazocine CH3
Ketazocine C=O
Metazocine CH3 CH3

Opioid Analgesics
• codeine sulfate
• meperidine HCl (Demerol)
• methadone HCl (Dolophine)
• morphine sulfate
• propoxyphene HCl

Opioid Analgesics
Three classifications based on their actions:

• Agonist
• Antagonist
• Partial agonist

Opioid Analgesics: Site of action
• Large “A” fibers

• Dorsal horn of spinal cord

Opioid Analgesics:
Mechanism of Action
• Bind to receptors on inhibitory fibers,
stimulating them
• Prevent stimulation of the GATE
• Prevent pain impulse transmission
to the brain

Opioid Analgesics:
Mechanism of Action
Three types of opioid receptors:
• Mu
• Kappa
• Delta

Opioid Analgesics: Therapeutic Uses
Main use: to alleviate moderate to severe pain

• Opioids are also used for:
– Cough center suppression
– Treatment of constipation

Opioid Analgesics: Side Effects
• Euphoria
• Nausea and vomiting
• Respiratory depression
• Urinary retention
• Diaphoresis and flushing
• Pupil constriction (miosis)
• Constipation
Opiate Antagonists
naloxone (Narcan)
naltrexone
•(Revia)
Opiate antagonists
• Bind to opiate receptors and prevent a response
Used for complete or partial reversal of

opioid-induced respiratory
depression

Opiates: Opioid Tolerance
• A common physiologic result of chronic

opioid treatment
• Result: larger dose of opioids are required
to maintain the same level of
analgesia

Opiates: Physical Dependence
• The physiologic adaptation of the body to

the presence of an opioid

Opiates: Psychological Dependence
(addiction)
• A pattern of compulsive drug use
characterized by a continued craving for
an opioid and the need to use the
opioid for effects other than pain relief

Opiates
• Opioid tolerance and physical dependence

are expected with long-term opioid treatment
and should not be confused with
psychological dependence (addiction).

Opiates
• Misunderstanding of these terms leads to

ineffective pain management and contributes
to the problem of undertreatment.

Opiates
• Physical dependence on opioids is seen

when the opioid is abruptly discontinued or
when an opioid antagonist is
administered.
– Narcotic withdrawal
– Opioid abstinence syndrome

Opiates
Narcotic Withdrawal Opioid Abstinence

Syndrome
• Manifested as:
– anxiety, irritability, chills and hot flashes, joint
pain, lacrimation, rhinorrhea, diaphoresis,
nausea, vomiting, abdominal cramps, diarrhea

Opioid Analgesics:
• Before beginning therapy, perform a

thorough history regarding allergies, use of
other medications,health history, and
medical history.
• Obtain baseline vital signs and I & O.
• Assess for potential contraindications and
drug interactions.

Opioid Analgesics:
• Perform a thorough pain assessment,

including nature and type of pain,
precipitating and relieving factors, remedies,
and other pain treatments.
– Assessment of pain is now being considered
a “fifth vital sign.”

Opioid Analgesics:
• Be sure to medicate patients before the pain

becomes severe as to provide adequate
analgesia and pain control.
• Pain management includes pharmacologic
and nonpharmacologic approaches. Be sure
to include other interventions as indicated.

Opioid Analgesics:
• Oral forms should be taken with food to

minimize gastric upset.
• Ensure safety measures, such as keeping
side rails up, to prevent injury.
• Withhold dose and contact physician if there
is a decline in the patient’s condition or if
VS are abnormal—especially if respiratory
rate is below 12 breaths/minute.

Opioid Analgesics:
• Follow proper administration guidelines for

IM injections, including site rotation.
• Follow proper guidelines for IV
administration, including dilution, rate of
administration, and so forth.
CHECK DOSAGES CAREFULLY

Opioid Analgesics:
• Constipation is a common side effect and

may be prevented with adequate fluid and
fiber intake.
• Instruct patients to follow directions for
administration carefully, and to keep a
record of their pain experience and
response to treatments.
• Patients should be instructed to change
positions slowly to prevent possible
orthostatic hypotension.
Opioid Analgesics:
• Patients should not take other medications

or OTC preparations without checking
with their physician.
• Instruct patients to notify physician for signs
of allergic reaction or adverse effects.

Opioid Analgesics:
Monitor for side effects:

• Should VS change, patient’s condition decline,
or pain continue, contact physician immediately.
• Respiratory depression may be manifested by
respiratory rate of less than 12/min, dyspnea,
diminished breath sounds, or shallow breathing.

Opioid Analgesics:
Monitor for therapeutic effects:

• Decreased complaints of pain
• Increased periods of comfort
• With improved activities of daily living, appetite,
and sense of well-being

MORPHINE (Pharmacological actions) - CNS
• Analgesia:
• Strong analgesic
• Visceral pain is relieved better than somatic
pain
• Degree of analgesia increases with dose
• Nociceptive pain is better relieved than
Neuretic pain
• Associated reactions to pain are also
relieved
– apprehension, fear and autonomic
effects
• Tolerance to pain is better
MORPHINE – Analgesia action
• Two components – spinal and supraspinal
• Inhibits release of excitatory transmitters
from primary afferents – at Substantia
gelatinosa of dorsal horn
• Exerted through Interneurones – gating of
pain
• At supraspinal level in cortex, meidbrain and
medulla - alter processing and
interpretation and send inhibitory impulses
through descending pthway
Morphine -The Gate Theory
Pharmacological actions of Morphine (CNS) –
contd.
• Sedation:
– Drowsiness and indifference to surroundings
– Inability to concentrate and extravagant imagination –
colorful day dream
– Apparent excitement
– Larger doses produce sleep – EEG resembles normal
sleep
• Mood effects:
– In Normal persons calming effect, mental clouding,
feeling of detachment, lack of initiative etc. -
unpleasant in absence of pain
– Sometimes DYSHORIA
– But in persons with pain & addicts sense of wellbeing,
pleasurable floating feelings – kick
– EUPHORIA
Pharmacological actions of Morphine.
• Depression: • Stimulation:
1. Respiratory centre 1. CTZ – sensitize CTZ
depression – Both rate and to vestibular and
depth of respiration are other impulses
diminished
• Dangerous in Head injury 2. Edinger Westphal
and asthmatics Nucleus – miosis
1. Cough Centre – 3. Vagal centre –
Depressed
Bradycardia
2. Temperature regulating
centre – depressed 4. Hippocampal
3. Vasomotor centre – high cells –
doses cause fall in BP convulsions (inhibition of
GABA release)
Morphine - Effects
Pharmacological actions of
Morphine – contd.
• Neuro-endocrine:
• GnRH and CRH are inhibited – FSH, LH and ACTH levels
are lowered – only short term – tolerance develops
• Decrease in levels of Sex hormone and corticosteroids, but
no infertility
• Increases ADH release – oliguria
• CVS: NO DIRECT EFFECT ON HEART
• Vasodilatation – histamine release, depression of vasomotor
centre and directly on blood vessels decreasing the tone
• Cardiac work reduction due to consistent vasodilatation
Pharmacological actions of
Morphine – contd.
• GIT: CONSTIPATION
• Due to direct action on intestine reducing
propulsive movement, spasm of sphincters,
decrease in all GIT secretions
• Smooth Muscles:
• Billiary Tract: Billiary colic – closure of sph.
Of Oddi
• Bladder: Urinary urgency but difficulty
• Bronchi - Bronchospasm
Morphine -
Pharmacokinetics
• Absorption and Distribution:
• Variable orally (usually not given orally – 1st pass metabolism,
given IM or IV)
• Widely distributed – liver, spleen, kidney etc.
• Enters Brain slowly
• Readily crosses placental barrier – dependence in fetus
• Metaboloism:
• In Liver by glucoronidation – water soluble metabolites
• Morphine-6- Glucoronide – analgesic – in renal failure
prolong analgesia
• Morphine-3-glucoronide – No analgesia –
neuroexcitatory
• Excretion:
• Via Urine, Plasma t1/2 = 2-3 Hrs
• Action lasts for 4-6 Hrs
• Completely eliminated in 24 Hrs
• Preparation: 10, 15, and 20 mg. (IV: 2 – 10 mg)
Morphine -
Pharmacokinetics
Morphine – Adverse
Effects
1. Respiratory Depression: Infant and Old
2. Vomiting
3. Sedation, Mental Clouding – sometimes dysphoria
4. Hypotensive effect
5. Rise in Intracranial Pressure
6. Apnoea: Newborn
7. Urinary retention
8. Idiosyncrasy and allergy
9. Acute Morphine Poisoning: occurs if >50 mg (Lethal dose –
250 mg), Gastric lavage with KMNO4, Specific antidote:
Naloxone: 0.4 to 0.8 mg IV repeatedly in 2-3 minutes till
respiration picks up
10. Tolerance and dependence
Morphine – Therapeutic uses
• Analgesic:
1. Long Bone Fracture
2. Myocardial Infarction
3. Terminal stages of cancer
4. Burn patients
5. Postoperative patients
6. Visceral pains – pulmonary embolism, pleurisy, acute
pericarditis
7. Biliary colic and renal colic
8. Obstetric analgesia
9. Segmental analgesia
Morphine – Other
Therapeutic uses
• Preanaesthetic Medication
• Balanced anaesthesia and surgical analgesia
• Acute Left ventricular failure – Cardiac
asthma
• Cough – not used but Codeine is used
• Diarrhoea – colostomy -
Loperamide, Diphenoxylate
Morphine -
Contraindications
1. Two Extremes of Age
2. Bronchial asthma
3. Respiratory insufficiency - empysema
4. Head Injury
5. Shock – Hypotension
6. Undiagnosed acute abdomen
7. BHP
8. Renal Failure, Liver diseases and hypothyrodism
9. Unstable personalities
Opioids - Classification
1. Natural Opium Alkaloids: Morphine and Codeine
2. Semi-synthetic: Diacetylmorphine (Heroin) and
Pholcodeine
3. Synthetic Opioids:
• Phenylpiperidines:
• Pethidine (Mepiridine) and its congeners – Diphenoxylate
and Loperamide
• Fentanyl and its congeners – sufentanil, remifentanil and
alfentanil
• Phenyl-heptylmines: Methadone and congeners like
Propoxyphene and Dextropropoxyphene
• Benzomorphans: Pentazocine
• Morphinan compounds and congeners: Levorphanol
and
Butorphanol
Pethidine
• Morphine Vs Pethidine:
– 1/10th as potent as Morphine, but Efficacy is similar
– Produces as much sedation, euphoria and respiratory
depression in equianalgesic dose and similar abuse
potential
– Less spasmodic action in smooth muscles – less miosis,
constipation and urinary retention
– Rapid but short duration of action (2-3 Hrs)
– Vagolytic effect - Tachycardia
– Devoid of antitussive action
– Less histamine release – safer in asthmatics
– Better oral absorption
Pethidine – contd.
• Pharmacokinetics
– Well absorbed orally, bioavailability 50%
– Effects appear in 10-15 min. after oral
absorption
– On parenteral administration action lasts for
2-3 Hrs
– Metabolized in liver – mepiridinic acid and
norpethidine
– Norpethidine accumulates on chronic use
– Excreted in urine
Pethidine – contd.
• Adverse Effects:
• Similar to Morphine
• Atropine like effects – dry mouth, blurred vision,
tachycardia
• Overdose – tremors, mydriasis, delirium and convulsion due
to norpethidine accumulation
• Uses:
• Analgesic as substitute of Morphine
• Ptreanaesthetic medication
• As analgesic during labour – less fetal respiratory
depression
• Dose 50-100 mg IM/SC, oral – 50-100 mg tabs.
Methadone
• Chemically dissimilar but similar in most of pharmacological
actions – analgesic, respiratory depression etc.
• High action orally as well as parenterally
• Single dose effect is – same with Morphine including
duration of action
• Cumulation – on repeated administration (t1/2 24-36
Hrs)
• Highly bound to plasma protein 80 to 90%
• Metabolized in liver by – demethylation and
cyclization
• Excreted
low in urine
• Slow action and less subjective effect – abuse
potential is
• Used as substitution therapy as opioid dependence: 1:4mg
and 1:20 mg of Morphine and Pethidine respectively
• Codeine is used as substitution in Methadone addiction
Tramadol
• Centrally acting analgesic
• Very low action on opioid receptors (
• Other mechanisms involved in analgesic action – 5-HT and
NA reuptake inhibition – spinal inhibition of pain
• Effective both orally and IV (100mg = 10 mg Morphine)
• Side effects are similar to Morphine but less prominent
• Well tolerated and low abuse potential
• Only Partially reversed by Naloxone
• Used in chronic neuropathic pain and short diagnostic
procedures
• Dose: 50-100 mg IM/IV/Oral
(Contramol)
Opioid Receptors
• Mainly 3 (three) types of receptors – μ (mu), κ (kappa) and δ
(delta)
• Subtypes: μ1, μ2, κ1, κ2, κ3, δ1 and δ2
• Location: Peripheral Nerve endings, SG in spinal chord,
Periaqueductal gray (PAG) in midbrain and Brain stem
(medulla, hypothalumus and also amygdala
• Opioids are – agonists, partial agonist or competitive
antagonists of these receptors
• Overall effect depends on nature of interaction and affinity
to these
• Morphine is agonist of all but affinity is higher for mu
Effects of Different Opioid Receptor Stimulation:
μ receptor κ receptor δ receptor
Location μ1 – supraspinal κ1 – spinal Spinal
μ2 - spinal κ3 -supraspinal supraspinal
Effects Analgesia Spinal analgesia Spinal

Respiratory Dysphoria analgesia
depression Affective
Sedation
Sedation behaviour
Psychomimetic
(Supraspinal)
Physical
Euphoria Respiratory
dependence
depression
Miosis (nalorphine
type Reduced GI
Physical
Agonists Pentazocine
) motility
depende
nce
Fentanyl and
pentazocine weakly
Effects of Opioid
Receptor Stimulation
Effects of Opioid Receptor
Stimulation – contd.
Opioid Receptors – Intracellular
mechanism
• All are G-protein coupled receptors
• Located on prejunctional neurones
• Inhibits release of transmitters – NA, DA, 5-HT,
GABA and Glutamate
• Activation reduces intracellular cAMP formation
-
Opening of K+ channel via μ and δ. and supression
of N type of Ca++ channels
• Ultimately Hyperpolarization and reduced
intracellular Ca++ Reduced
Neurotransmitter release
Endogenous Opioid Peptides
• Endorphins:
• Derived from POMC
• ß-endorphins: 2 Types - ß-endorphin1 and ß-
endorphin-2
• Primarilty μ agonist and also has δ action
• Enkephalins:
• Derive from Proenkephalin
• Met-ENK and leu-ENK
• Met-ENK - Primarily μ and δ agonist and
leu-ENK – δ agonist
• Dynorphins:
• Derive from Prodynorphin: DYN-A and DYN-B
• Potent κ agonist and also have μ and δ
action
Opioid Antagonists
1. Pure antagonists: Naloxone, Naltrexone and
Nalmefene
• Affinity for all receptors (μ, δ and κ)
• Can displace opioids bound to α-receptors
• No action on Normal person but reverses poisoning and
withdrawal symptoms in addicts
2. Mixed Agonist-antagonists: Nalorphine, Pentazocine,
Butorphanol and Nalbuphine
3. Partial/weak μ agonist and κ antagonist:
Buprenorphine
Nalorphine
• Not used anymore
• Previously used as Opioid antagonist
• But, antagonism is restricted to
μ- receptor only and agonist of κ-
receptor
• Drawbacks - dysphoria and
psychomimetic effects
Pentazocine
• Weak α-receptor antagonist, but agonist of κ-receptor
• One of the commonly used agents, given orally and IM
• Low abuse liability
• Pharmacokinetics:
– High 1st pass metabolism but effective orally
– Half life = 3-4 Hrs
– Metabolized in liver by glucoronide conjugation
– Dose: orally 50-100 mg and parenterally 30-60 mg IM
• Uses:Moderately severe pain in Injury, Burns, Fracture
Trauma, Cancer and Orthopaedic manuevers
(Fortwin, Fortagesic)
Pentazocine Vs Morphine
• Spinal analgesia via kappa receptor
• Dose is 30 mg Vs 10 mg and low ceiling effect
• Sedation and Respiratory depression at lower doses
• Tachycardia and rise in BP – dangerous in MI
• Lesser smooth muscle spasms
• Vomiting and other side effects are less
• Subjective effects – lower ceiling (psycomimetic effects)
• Tolerance develops on repeated use, but lesser than
Morphine
• Withdrawal symptoms – both Morphine and
Nalorphine like
• Good analgesic in subjects not exposed to Morphine
• Precipitate withdrawal – in Morphine addicts
Buprenorphine
Given Sublingually or parenterally but not oral – high 1st pass
• Synthetic thebaine congener and highly lipid soluble
•
metabolism
• Selective μ-agonist analgesic
• 20-30 times more potent than Morphine
• Slow but longer duration of action upto 24 Hrs
• Pharmacological effects are similar to Morphine
• Has ceiling effect in analgesic and respiratory
depression
• Good analgesic for naive patients but addicts –
precipitates
withdrawal syndrome
• Lower tolerance and physical dependence than
Morphine and abuse liability
• Withdrawal syndromes are similar to Morphine
Buprenorphine – contd.
• Adverse Effects:
– Hypotension (Postural)
– Respiratory depression (fatal in neonates) and cannot be
reversed by Naloxone
• Uses:
– Long lasting painful conditions – cancer
– Postoperative pain
– Myocardial infarction
• Preparations: Norphine, Tidigesic
• 0.3 mg/ml injections and 0.2 mg sublingual tablets
Naloxone
• Competitive antagonist of all types of opioid
receptors
• But, blocks μ-receptors at much lower
dose
• Always injected IV (0.4 t0 0.8 mg) - All
symptoms
of Morphine action are antagonized – respiratory
stimulation
• At higher doses 4-10 mg: antagonizes actions of
Nalorphine and Pentazocine – dysmorphic and
psychomimetic effects are not suppressed (δ)
• Withdrawal symptoms: 0.4 mg doses – Morphine
and 4-5 mg doses – Nalorphine and Pentazocine
Naloxone – contd.
• Buprenorphine actions are prevented but not
reversed fully – tight bond with receptors
• Also acts on endogenous opioids
• Antagonizes respiratory depression of Diazepam
and N2O
• Uses:
• Acute Morphine Poisoning (0.4 – 0.8 mg IV 2-3 min,
maximum 10 mg.
• New Born – opioid poisoning
• Reverse respiratory depression intr-aoperatively
• Diagnosis of Morphine addiction
• Alcohol intoxication

Opioid Analgesic Agents Leah Nabirye

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Opioid Analgesic Agents Leah Nabirye

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Opioid Analgesic Agents

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• Medications that relieve pain without causing

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Temporary (disappears more than six months

removed) due to neural stimulation or

 Associated anxiety less obvious especially with

• Most common and well-described

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Tissue injury causes the release of:

There are two types of nerves stimulated:

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“A” Fibers “C” Fibers

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• Types of pain related to proportion of

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• These pain fibers enter the spinal cord

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• This gate regulates the flow of sensory

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• Activation of large “A” fibers CLOSES gate

– Limits perception of pain

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• Activation of small “B” fibers OPENS gate

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• Gate innervated by nerve fibers from brain,

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• Body has endogenous neurotransmitters

• Produced by body to fight pain

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Rubbing a painful area with massage or

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• Pain relievers that contain opium,

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Ethyl morphine C2H5 H

Heroine COCH3 COCH3

Ib) Dihydromorphine derivatives

Dextromethorphan -CH3 H -CH3

Meperidine CH3 COOC2H5 H

Bemidone CH3 COOC2H5 H

Properidone CH3 COOCH(CH3)2 H

Ketobemidone CH3 COC2H5 H

Alphaprodine CH3 COOC2H5 CH3

Lofentanil COOCH3 CH3

Methadone C6H5 COC2H5 -CH2-CH(CH3)N(CH3)2

Isomethadone C6H5 COC2H5 -CH(CH3)CH2N(CH3)2

Normethadone C6H5 COC2H5 -CH2-CH2N(CH3)2

Dipanone C6H5 COC2H5

α-Acetyl Methdone C6H5 -CH2-CH(CH3)N(CH3)2

Phenadoxone C6H5 COC2H5

Propoxyphene or CH2 C6H5 OCOC2H5 -CH(CH3)-CH2N(CH3)2

Pentazocine CH2-CH=C(CH3)2 CH3

Phenazocine CH2-CH2-C6H5 CH3

Metazocine CH3 CH3

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Three classifications based on their actions:

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• Large “A” fibers

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Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.