Download - Opioid analgesics 2-prof azza
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Opioid Analgesics
BY
PROF. AZZA EL-MEDANY
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CLASSIFICATION
Natural ( Morphine) Semisynthetic ( Codine ) Synthetic ( Mepiridine, Methadone,
Fentanyl, Tramadol )
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Another Classification
Strong agonist Moderate agonists Mixed agonists /antagonists Pure antagonist
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Mechanism of actions
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 )
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Morphine ( Natural & Strong agonist)
PHARMACOKINETICS : ROUTES OF ADMINISTRATION METABOLISM DISTRIBUTION EXCRETION
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Routes of administration
Oral absorption is erratic IMI , SC injection are preferred Chronic pain , slow release preparation Non medical route , inhalation of powder
or smoke
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Metabolism & excretion
In liver to active metabolite ( morphine -6 glucuronide & morphine -3 glucuronide
Half-life 4-6 hours. Crosses BBB & placental barrier Excreted in urine
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Pharmacological actions
Analgesia
Without loss of consciousness
Severe type of pain
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Sedation
Euphoria
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Respiration
Respiratory depressant which is dose dependent
Large dose causes respiratory failure & death
Reduce the sensitivity of respiratory center to CO2
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Eye
Miosis ( pin point pupil)
Through mu & kappa receptors at
Edinger westphal neuclus of 3rd nerve
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Cough center
Antitussive
Potent depressant for cough center
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Histamine release
From mast cells ( urticaria, sweating , vasodilataion , bronchospasm )
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Endocrinal effect
Decrease : LH, FSH, ACTH , testosterone
Increase : Prolactin, growth hormone, ADH leading to urine retention
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Nausea & Vomiting
Stimulation of CRTZ
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GIT
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
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Urinary System
Decrease in renal function Urine retention Spasm of smooth muscles of ureter
causing renal colics
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Uterus
Prolong labor
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CVS
Large dose causing hypotension & bradycardia
With respiratory depression & retention of CO2 causing cerebral vasodilataion & ↑ in CSF pressure
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CLINICAL USES
CANCER PAIN SEVERE BURN SEVERE VISCERAL PAIN ( except, renal &
biliary colics , acute pancreatitis ) DIARRHOEA COUGH ACUTE PULMONARY OEDEMA Myocardial ischemia PREANAESTHETIC MADICATION
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ADVERSE EFFECTS
RESPIRATORY DEPRESSION NAUESEA & VOMITING CONSTIPATION URINE RETENTION HYPOTENSION ALLERGY TOLERANCE ( not to mitotic, convulsant, or
constipating effects ) ADDICTION ( abstinence syndrome)
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Withdrawal manifestations
Severe body ache Insomnia Diarrhea Goose flesh Lacrimation
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CONTRAINDICATIONS
HEAD INJURY PREGNANCY BRONCHIAL ASTHMA or impaired
pulmonary function Liver & Kidney diseases (including
renal& biliary colics ) Endocrine diseases ( myxedema &
adrenal insufficiency)
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Continue
Old people are more sensitive ( decrease in metabolism , lean body mass & renal function )
Not given to infants With MAOI
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Meperidine ( Pethidine)
Synthetic Strong agonist More effective on kappa receptors
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PHARMACOKINETICS
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
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Pharmacological Actions
Less analgesic , less constipating ( weak effect ) , less depressant on foetal respiration than morphine
Atropine –like action Smooth muscle relaxant effect No cough suppressant effect
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CLINICAL USES
Cancer pain Severe burn Severe visceral pain( renal & biliary
colics ) Obstetric analgesia Preanaesthetic medication
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ADVERSE EFFECTS
Tremors & Convulsions Hyperthermia Hypotension Tolerance & Addiction Burred vision Dry mouth Urine retention
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METHADONE
SYNTHETIC OPIOID POTENT ANALGESIC AS MORPHINE GIVEN BY ORAL , I.V., S.C., AND
RECTAL HAS A HIGHER ORAL
BIOAVAILABILITY THAN MORPHINE
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CONTINUE
LONG PLASMA HALF- LIFE ( 24 hrs ) LESS EUPHORIC THAN MORPHINE PRODUCES MILD WITHDRAWAL
SYMPTOMS TOLERANCE & PHYSICAL
DEPENDENCE DEVELOP MORE SLOWLY THAN MORPHINE
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CLINICAL USES
Control withdrawal symptoms of dependant abusers from heroin & morphine
Neuropathic & cancer pain
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CODEINE
Synthesized commercially from morphine Less analgesic & euphoric than
morphine Given orally Potent antitussive Always given in combination with aspirin
or acetaminophen Addicting drug
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DEXTROMETHORPHAN
FREE OF ANALGESIC & ADDICTIVE EFFECTS
LESS CONSTIPATING THAN CODEINE POTENT AS ANTITUSSIVE
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Fentanyl
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
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Sufentanyl, Alfentanyl & Remifentanil
Sufentanyl more potent than fentanyl Other two are less potent with shorter
duration of action
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Heroin
Strong agonist Crosses BBB Converted to morphine No medical use Strong addicting drug
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TRAMADOL ( Synthetis )
Centrally acting analgesic through inhibition uptake of norepinephrine & serotonin
Binds to mµ receptor. Less potent as analgesic than morphine Undergoes extensive metabolism
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CONTINUE
Given orally ( high oral bioavailability) & by different other routes
Used in :
mild & moderate acute & chronic visceral pain
during labor
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ADVERSE EFFECTS & CONTRAINDICATIONS
Seizures , Nausea , Dry mouth, Dizziness , Sedation
Less adverse effects on respiratory & C.V.S.
Contraindicated in patients with history of epilepsy
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Loperamide
Can not cross BBB Lacking analgesic effect Used for treatment of chronic diarrhea
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OPIOIDS WITH MIXED RECEPTORS ACTIONS
BUPRENORPHINE Partial Mu receptor agonist Long duration of action Poor oral bioavailability Given parntrally ,Sublingually , Or as
nasal spray Excreted in the bile & urine
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CONTINUE
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
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Pentazocine
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
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Adverse effects
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
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OPIOID ANTAGONISTS
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 )
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NOTICE
Naloxone completely reverse respiratory depression produced by opioid over doses ,
Incompletely reverse their analgesic effects.
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Naltrexone
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
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OPIOID ANTAGONISTS
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