Classification-

Phenanthrene	Benzyl iso quinolone
Morphine	Papaverine
Codeine	Noscaepine
Tuebaine

 

pH  – 7.7- Water soluble molecule

Synthetic opioids: Morphine derivative- levorphanol, Benzomorphan derivative meperidine , fentanyl (mol wt-236-325)

 

OPIOIDS

1. Morphine
2. Fentanyl
3. Meperidine
4. Sufentanyl
5. Remifentanyl
6. Codeine
7. Dextromethorphan
8. Oxymorphane
9. Methadone
10. Herion

 

OPIOID– AGONIST

1. Pentazocine
2. Butarphenol
3. Nalbuphine
4. Buprenorphine
5. Bromazocine
6. Degocine

OPIOID ANTAGONSTS

1. Morphine: Nalaxone , naltrexone, nalmefene
2. Fentanyl- naltrexone
3. Methadone: nalbuphine

 

OPIOID RECEPTORS:ACTIONS

	MU1	MU2	KAPPA	DELTA
EFFECTS	ANALGESIA (SPINAL/SUPRA SPINAL)	ANALGESIA (SPINAL)	ANALGESIA (S/SS)	ANALGESIA (S/SS)
	EUPHORIA	DEPRESSION OF VENTILLATION	DYSPHORIA SEDATION	DEPRESSION OF VVENTILATION
	LOW ABUSE POTENTIAL	PHYSICAL DEPENDENCE	LOW ABUSE POTENTIAL	PHYSICAL DEPENDENCE
	MIOSIS	CONSTIPATION	MIOSIS	CONSTIPATION
	BRADYCARDIA			MINIMAL
	HYPOPTHERMIA
	URINARY  RETENTION
AGONIST	ENDORPHINS MORPHINE	ENDORPHINS MORPHINE	DYNORPHINS	ENKEPHALON
ANTAGONIST	NALAXONE	NALAXONE	NALAXONE	NALAXONE

 

Mechanism of action

Act via mu,kappa,and delta receptors.

Three steps during mechanism

• Recognition by receptors of extracellular opioid agonist.
• signal transduction mediated by G protiene.
• Altered production of intracellular second messenger.
• Act at pre and post synaptic sites in CNS AND PERIPHERAL TISSUES.
• Activate pain modulating system by their principle effects of decrease neurotransmition and inhibition of Dopamine,ACH,Norepinephrine and Substance-P.
• Increase K conductors leading to hyperpolarisation, calcium channel inactivation andInhibit adenyl cyclase.
• Depression of cholinergic transmisiion and decrease Ach release have important role in analgesia and other side effects.

Neuraxial opiods

• MU Receptors – Substantia gelatiniosa of spinal cord
• Decrease MAC of volatile anaesthetics
• Lipid solubleopiods fentanyl sufentanyl are more effective than morphine in epidural analgesia

 

SIDE EFFECTS:

 Four classic side effects-

1. Pruiritis
2. Nausea and vomiting
3. Urinary retention
4. Depression of ventilation

Others:

1. Viral reactivataion
2. Neonatal morbidity
3. Sexual dysfunction
4. Ocular dysfunction
5. GIT dysfunction
6. Thermo regulatory disturbances
7. Water retention

 

 

OPIOID	Pk	%IONISED  Ph	PROTEIN BINDING%	CLEARANCE ml/min	VOL OF DIST,N	PARTIAL COEFFICIENT	T1/2 HRS	T1/2 MIN	EFFECT MIN
MORPHINE	7.9	23	35	1050	224	1	1.7-3.3	15-200
MEPIRIDINE	8.5	7	70	1020	305	32	3-5
FENTANYL	8.4	8.5	84	1530	335	955	3.1-6.6	260	6.8
SUFENTANYL	8.0	20	93	900	123	1727	2.2-4.6	30	6.2
ALFENTANYL   REMI	6.5	89	92	238	27	129	1.4-1.5	60	1.4
FENTANYL	7.3	58	66-93	4000	30		0.17-0.38	4	1.1

 

MORPHINE:

• Prototype opiod
• Continuos dull pain is relieved more effectively than sharp intermittent pain.

 

pharmacokinetics :  onset of effect IM-15-30 min.

• peak effect 45 -90 min.
• duration 4hrs.
• GIT absorption not reliable.

FENTANYL:

• Phenyl peperidine
• Synthetic opiod agonist
• 75 to 125 times more potent than morphine

pharmakokinetics-

• IV: more rapid and duration of action than morphine
• Blood brain effect site equilibrium time is 6.4 min
• Lung : first pass pulmonary uptake is 75%
• Metabolism: N-de methylation- nor fentanyl
• T1/2: larger than morphine because its greater lipid solubility
• CPB: decrease in plasma concentration

 

Doses: 1-2 mcg/kg analgesia

2-20mcg/kg with adjunct to inhaled anaesthetics

 

Fentanyl is cardio stable

1. Lack of direct myocardial depresent effect
2. Absenxce of histamine release
3. Suppression of stress response

Disadvantages:

1. Failure to prevent sympathetic nervous system
2. Possible patient
3. Post op ventilation depression

Trans mucosal preparation: 5 – 20 mcg/kg

45 min before surgery

Trans dermal patch delivers 75-100mcg/hr

CVS: bradycardia with 10mcg/kg

Seizure activity : Rapid iv fentanyl , sufentanyl and alfentanyl cause seizure activity , ske;etal muscle rigidity.

dr.ajita