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