Transcript OPIOID ANALGESICS

Opioid Analgesics
BY
PROF. AZZA EL-MEDANY
CLASSIFICATION
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Natural ( Morphine)
Semisynthetic ( Codine )
Synthetic ( Mepiridine, Methadone,
Fentanyl, Tramadol )
Another Classification
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Strong agonist
Moderate agonists
Mixed agonists /antagonists
Pure antagonist
Mechanism of actions
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Binding to opioid receptors (mu,delta,
kappa ,sigma ) at presynaptic nerve fibres
resulting in decreasing calcium influx
leading to decrease in releasing excitatory
neurotransmitters
Post synaptic activation of receptors
increase potassium efflux
(hyperpolarization )
Morphine ( Natural & Strong
agonist)
PHARMACOKINETICS :
 ROUTES OF ADMINISTRATION
 METABOLISM
 DISTRIBUTION
 EXCRETION
Routes of administration
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Oral absorption is erratic
IMI , SC injection are preferred
Chronic pain , slow release preparation
Non medical route , inhalation of powder
or smoke
Metabolism & excretion
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In liver to active metabolite ( morphine -6
glucuronide & morphine -3 glucuronide
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Half-life
4-6 hours.
Crosses BBB & placental barrier
Excreted in urine
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Pharmacological actions
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Analgesia
Without loss of consciousness
Severe type of pain
Sedation
Euphoria
Respiration
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Respiratory depressant which is dose
dependent
Large dose causes respiratory failure &
death
Reduce the sensitivity of respiratory
center to CO2
Eye
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Miosis ( pin point pupil)
Through mu & kappa receptors at
Edinger westphal neuclus of 3rd
nerve
Cough center
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Antitussive
Potent depressant for cough center
Histamine release
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From mast cells ( urticaria, sweating ,
vasodilataion , bronchospasm )
Endocrinal effect
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Decrease : LH, FSH, ACTH ,
testosterone
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Increase : Prolactin, growth hormone,
ADH leading to urine retention
Nausea & Vomiting
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Stimulation of CRTZ
GIT
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Constipation
Constrict biliary smooth muscle may
result in biliary colics
Sphincter of Oddi may constrict
resulting in reflux of biliary &
pancreatic secretions & elevated
plasma lipase & amylase
Urinary System
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Decrease in renal function
Urine retention
Spasm of smooth muscles of ureter
causing renal colics
Uterus
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Prolong labor
CVS
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Large dose causing hypotension &
bradycardia
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With respiratory depression & retention
of CO2 causing cerebral vasodilataion
& ↑ in CSF pressure
CLINICAL USES
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CANCER PAIN
SEVERE BURN
SEVERE VISCERAL PAIN ( except, renal &
biliary colics , acute pancreatitis )
DIARRHOEA
COUGH
ACUTE PULMONARY OEDEMA
Myocardial ischemia
PREANAESTHETIC MADICATION
ADVERSE EFFECTS
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RESPIRATORY DEPRESSION
NAUESEA & VOMITING
CONSTIPATION
URINE RETENTION
HYPOTENSION
ALLERGY
TOLERANCE ( not to mitotic, convulsant, or
constipating effects )
ADDICTION ( abstinence syndrome)
Withdrawal manifestations
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Severe body ache
Insomnia
Diarrhea
Goose flesh
Lacrimation
CONTRAINDICATIONS
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HEAD INJURY
PREGNANCY
BRONCHIAL ASTHMA or impaired
pulmonary function
Liver & Kidney diseases (including
renal& biliary colics )
Endocrine diseases ( myxedema &
adrenal insufficiency)
Continue
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Old people are more sensitive (
decrease in metabolism , lean body
mass & renal function )
Not given to infants
With MAOI
Meperidine ( Pethidine)
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Synthetic
Strong agonist
More effective on kappa receptors
PHARMACOKINETICS
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Well absorbed orally
(Has a high oral bioavailability )
Given also by IMI
Half-life ( short ) 2-4 hours
Give an active metabolite which has
CNS stimulant effect
Excreted in urine
Pharmacological Actions
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Less analgesic , less constipating (
weak effect ) , less depressant on
foetal respiration than morphine
Atropine –like action
Smooth muscle relaxant effect
No cough suppressant effect
CLINICAL USES
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Cancer pain
Severe burn
Severe visceral pain( renal & biliary
colics )
Obstetric analgesia
Preanaesthetic medication
ADVERSE EFFECTS
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Tremors & Convulsions
Hyperthermia
Hypotension
Tolerance & Addiction
Burred vision
Dry mouth
Urine retention
METHADONE
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SYNTHETIC OPIOID
POTENT ANALGESIC AS MORPHINE
GIVEN BY ORAL , I.V., S.C., AND
RECTAL
HAS A HIGHER ORAL
BIOAVAILABILITY THAN MORPHINE
CONTINUE
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LONG PLASMA HALF- LIFE ( 24 hrs )
LESS EUPHORIC THAN MORPHINE
PRODUCES MILD WITHDRAWAL
SYMPTOMS
TOLERANCE & PHYSICAL
DEPENDENCE DEVELOP MORE
SLOWLY THAN MORPHINE
CLINICAL USES
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Control withdrawal symptoms of
dependant abusers from heroin &
morphine
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Neuropathic & cancer pain
CODEINE
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Synthesized commercially from
morphine
Less analgesic & euphoric than
morphine
Given orally
Potent antitussive
Always given in combination with
aspirin or acetaminophen
Addicting drug
DEXTROMETHORPHAN
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FREE OF ANALGESIC & ADDICTIVE
EFFECTS
LESS CONSTIPATING THAN CODEINE
POTENT AS ANTITUSSIVE
Fentanyl
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Synthetic drug
More potent as analgesic than
morphine
Rapid onset & very short duration of
action (15-30 min )
Used as I.V. anaesthesia
IN cancer pain as transdermal patches
Has a respiratory depressant effect
Sufentanyl, Alfentanyl &
Remifentanil
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Sufentanyl more potent than fentanyl
Other two are less potent with shorter
duration of action
Heroin
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Strong agonist
Crosses BBB
Converted to morphine
No medical use
Strong addicting drug
TRAMADOL ( Synthetis )
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Centrally acting analgesic through
inhibition uptake of norepinephrine &
serotonin
Binds to mµ receptor.
Less potent as analgesic than morphine
Undergoes extensive metabolism
CONTINUE
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Given orally ( high oral bioavailability)
& by different other routes
Used in :
mild & moderate acute & chronic
visceral pain
during labor
ADVERSE EFFECTS &
CONTRAINDICATIONS
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Seizures , Nausea , Dry mouth,
Dizziness , Sedation
Less adverse effects on respiratory &
C.V.S.
Contraindicated in patients with
history of epilepsy
Loperamide
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Can not cross BBB
Lacking analgesic effect
Used for treatment of chronic diarrhea
OPIOIDS WITH MIXED
RECEPTORS ACTIONS
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BUPRENORPHINE
Partial Mu receptor agonist
Long duration of action
Poor oral bioavailability
Given parntrally ,Sublingually , Or as
nasal spray
Excreted in the bile & urine
CONTINUE
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Acts as morphine in normal patient &
precipitate withdrawal symptoms in
morphine users.
Causes less : sedation , respiratory
depression , hypotension than
morphine.
Used in detoxification & maintenance
of heroin abusers
Pentazocine
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Agonist at KAPPA & antagonist at MU
Receptors
Given orally or parentrally
Has a short duration of action
Less potent , less euphoric than
morphine
High doses causes respiratory
depression
Adverse effects
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Hallucination , nightmares , convulsions
Increase Blood Pressure & Heart rate
Precipitate withdrawal symptoms when given
to patients dependent on morphine
CONTRAINDICATIONS
With Morphine
Heart diseases & Hypertension
Epilepsy
OPIOID ANTAGONISTS
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NALOXONE
PURE ANTAGONIST AT MU RECEPTORS
HAS a rapid onset of action (SECONDS ) &
Short duration of action (30-60min )
Is available for I.V. route
Teatment of OPIOID overdoses ( ACUTE
TOXICITY )
NOTICE
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Naloxone completely reverse
respiratory depression produced by
opioid over doses ,
Incompletely reverse their analgesic
effects.
Naltrexone
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Has a Long duration of action (10 HRS )
Given Orally
Used clinically in :
1- Treatment of chronic Alcoholism
2-Control withdrawal symptoms of addicts
3- Reduce craving for alcohol in chronic
alcoholics
OPIOID ANTAGONISTS
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In normal individual do not produce any
effect.
IN dependent individual Precipitate
withdrawal symptoms
NO Tolerance TO Their Antagonistic action
NO withdrawal symptoms When Withdrawn
After Chronic Use