Download presentation
1
Opioid Analgesics BY PROF. AZZA EL-MEDANY
2
CLASSIFICATION Natural ( Morphine) Semisynthetic ( Codine )
Synthetic ( Mepiridine, Methadone, Fentanyl, Tramadol )
3
Another Classification
Strong agonist Moderate agonists Mixed agonists /antagonists Pure antagonist
4
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 )
5
Morphine ( Natural & Strong agonist)
PHARMACOKINETICS : ROUTES OF ADMINISTRATION METABOLISM DISTRIBUTION EXCRETION
6
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
7
Metabolism & excretion
In liver to active metabolite ( morphine -6 glucuronide & morphine -3 glucuronide Half-life hours. Crosses BBB & placental barrier Excreted in urine
8
Pharmacological actions
Analgesia Without loss of consciousness Severe type of pain
9
Sedation Euphoria
10
Respiration Respiratory depressant which is dose dependent
Large dose causes respiratory failure & death Reduce the sensitivity of respiratory center to CO2
11
Eye Miosis ( pin point pupil) Through mu & kappa receptors at
Edinger westphal neuclus of 3rd nerve
12
Cough center Antitussive Potent depressant for cough center
13
Histamine release From mast cells ( urticaria, sweating , vasodilataion , bronchospasm )
14
Endocrinal effect Decrease : LH, FSH, ACTH , testosterone
Increase : Prolactin, growth hormone, ADH leading to urine retention
15
Nausea & Vomiting Stimulation of CRTZ
16
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
17
Urinary System Decrease in renal function Urine retention
Spasm of smooth muscles of ureter causing renal colics
18
Uterus Prolong labor
19
CVS Large dose causing hypotension & bradycardia
With respiratory depression & retention of CO2 causing cerebral vasodilataion & ↑ in CSF pressure
20
CLINICAL USES CANCER PAIN SEVERE BURN
SEVERE VISCERAL PAIN ( except, renal & biliary colics , acute pancreatitis ) DIARRHOEA COUGH ACUTE PULMONARY OEDEMA Myocardial ischemia PREANAESTHETIC MADICATION
21
ADVERSE EFFECTS RESPIRATORY DEPRESSION NAUESEA & VOMITING CONSTIPATION
URINE RETENTION HYPOTENSION ALLERGY TOLERANCE ( not to mitotic, convulsant, or constipating effects ) ADDICTION ( abstinence syndrome)
22
Withdrawal manifestations
Severe body ache Insomnia Diarrhea Goose flesh Lacrimation
23
CONTRAINDICATIONS HEAD INJURY PREGNANCY
BRONCHIAL ASTHMA or impaired pulmonary function Liver & Kidney diseases (including renal& biliary colics ) Endocrine diseases ( myxedema & adrenal insufficiency)
24
Continue Old people are more sensitive ( decrease in metabolism , lean body mass & renal function ) Not given to infants With MAOI
25
Meperidine ( Pethidine)
Synthetic Strong agonist More effective on kappa receptors
26
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
27
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
28
CLINICAL USES Cancer pain Severe burn
Severe visceral pain( renal & biliary colics ) Obstetric analgesia Preanaesthetic medication
29
ADVERSE EFFECTS Tremors & Convulsions Hyperthermia Hypotension
Tolerance & Addiction Burred vision Dry mouth Urine retention
30
METHADONE SYNTHETIC OPIOID POTENT ANALGESIC AS MORPHINE
GIVEN BY ORAL , I.V., S.C., AND RECTAL HAS A HIGHER ORAL BIOAVAILABILITY THAN MORPHINE
31
CONTINUE LONG PLASMA HALF- LIFE ( 24 hrs ) LESS EUPHORIC THAN MORPHINE
PRODUCES MILD WITHDRAWAL SYMPTOMS TOLERANCE & PHYSICAL DEPENDENCE DEVELOP MORE SLOWLY THAN MORPHINE
32
CLINICAL USES Control withdrawal symptoms of dependant abusers from heroin & morphine Neuropathic & cancer pain
33
CODEINE Synthesized commercially from morphine
Less analgesic & euphoric than morphine Given orally Potent antitussive Always given in combination with aspirin or acetaminophen Addicting drug
34
DEXTROMETHORPHAN FREE OF ANALGESIC & ADDICTIVE EFFECTS
LESS CONSTIPATING THAN CODEINE POTENT AS ANTITUSSIVE
35
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
36
Sufentanyl, Alfentanyl & Remifentanil
Sufentanyl more potent than fentanyl Other two are less potent with shorter duration of action
37
Heroin Strong agonist Crosses BBB Converted to morphine No medical use
Strong addicting drug
38
TRAMADOL ( Synthetis ) Centrally acting analgesic through inhibition uptake of norepinephrine & serotonin Binds to mµ receptor. Less potent as analgesic than morphine Undergoes extensive metabolism
39
CONTINUE Given orally ( high oral bioavailability) & by different other routes Used in : mild & moderate acute & chronic visceral pain during labor
40
ADVERSE EFFECTS & CONTRAINDICATIONS
Seizures , Nausea , Dry mouth, Dizziness , Sedation Less adverse effects on respiratory & C.V.S. Contraindicated in patients with history of epilepsy
41
Loperamide Can not cross BBB Lacking analgesic effect
Used for treatment of chronic diarrhea
42
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
43
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
44
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
45
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
46
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 )
47
NOTICE Naloxone completely reverse respiratory depression produced by opioid over doses , Incompletely reverse their analgesic effects.
48
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
49
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
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.