This document discusses opioid analgesics, focusing on tramadol and butorphanol. It defines opioids and their receptor types. Tramadol is described as a centrally acting atypical analgesic that is a racemic mixture with both enantiomers contributing to its analgesic effects. Its mechanisms of action and pharmacokinetics are outlined. Butorphanol is introduced as a synthetic agonist-antagonist opioid with greater agonist and antagonist effects than pentazocin. Its proposed mechanisms of analgesia and adverse effects are summarized. Clinical uses of both drugs for various acute and postoperative pain conditions are mentioned.

1.  Presented by: DR VISHAL KUMAR
KANDHWAY

3.  “ opioid “ is a natural or synthetic drug that
binds to opioid receptors producing
agonist effects.
 “ opioid analgesic “ : analgesia (pain absence)
without resulting in loss of
consiousness/sleep.
“ opioid have been mainstay of
pain treatment for thousands of years
, and they remain…so today…..

4.  Natural Opioids :
Alkaloids like morphine , codine and
thebaine
 Semi-synthetic opioids :
Diacetylmorphine (heroin), pholcodeine,
Ethylmorphine
 Synthetic opioids :
Fentanyl ,meperidine ,pentazocin
methadone ,TRAMADOL, etc

5.  Mu ( mu1 & mu2 )
 Kappa ( k1 & k3 )
 Delta

6. oResponse o Mu -1 o Mu -
2
o Kappa o Delta
o Analgesia
o Respiratory
Depression
o Euphorai
o Dysphoria
o Decrease GI
motility
o Physical
Dependence
o Bradycardia
o Hypothermi

7.  PURE AGONIST: has affinity for binding plus
efficacy
 PURE ANTAGONIST: has affinity for binding
but no efficacy; blocks action of endogenous
and exogenous ligands.
 MIXED AGONIST-ANTAGONIST: produce an
agonist effect at one receptor and an
antagonist effect at another.
 PARTIAL AGONIST: has affinity for binding but
low efficacy

8. DRUGS MU kappa
PURE AGONIST:
Morphine,codine,fenta
nyl,meperdine,remifen
tanyl,
methadon,TRAMADOL,
etc
AGONIST AGONIST
AGONIST-
ANTAGONIST:
Pentazocin,BUTORPHE
NOL,
buprenorphine etc
ANTAGONIST AGONIST
PURE ANTAGONIST:
Naloxone,naltrexone,n
almefen
ANTAGONIST ANTAGONIST
PARTIAL AGONIST:
Pentazocin
PARTIAL AGONIST/
WEAK ANTAGONIST
AGONIST

10.  Tramadol is a centrally acting opoid .
 Atypical analgesic structurally releated to
morphine
 It is a racemic mixure of two enentiomers .
Both of which contribute to analgesic activity.
(+) tramadol -
responsible for
inhibition of
norepinephrine
uptake
(-) tramadol –
responsible for
inhibition of 5-
hydroxytryptamine
reuptake and
facilitation of its
release

11. Tramadol acts as a:-
 Mu-opiod receptor agonist:-
 Moderate affinity for Mu-opoid receptor
 Weak kappa and delta opoid receptor affinity.
 But is 5-10 times less potent than morphine as
an analgesic
 Serotonin reuptake inhibitor and
releasing agent
 Nor epinephrine reuptake inhibitor

12.  5-HTc receptor antagonist
 Nicotonic acetylcholyn receptor
antagonist
 M1 and M3 mucuranic
acetylcholyn receptor antagonist

13.  mild-moderate severe pain
 Mainly use for treatment of chronic
pain
 Less likely to generate addiction
 Not associated with major organ toxicity
 Less sedative effect
 Slow gastric emptying

14.  Around 40-60 % of the patient under regional
anaesthesia develop shivering
 Shivering increases metabolic rate and
oxygen consumption up to 100-600%
 May induce:-
 lactic acidosis
 increase IOP and ICT
 arterial hypoxemia
 interfers with ECGmonitoring ,pulse
rate,BP etc

15.  Tramadol is metabolise by hepatic P450
enzyme systems to form major metabolite
O-Desmythyltramadol.
 It also exerts modest stereoselective
analgesic effect.
 The elimination half life of racemic
tramadol is approximately 6 hrs ,
irrespective of the mode of administration ,
and about 8 hrs for O-
desmethyltramadol
 Half life may be prolong in people with
decreased liver or kidney function.

16.  Route of administration : tramadol can be
given by oral , intramascular (IM) or
intravenous (IV) route.
 Adult dose: 3mg/kg is effective for
treatment of moderate to severe pain
 Children : 1-2 mg/kg 4-6 hrly

17.  Nausea
 Dizziness
 Drymouth
 Indigestion
 Vertigo
 Vomitting
 Constipation
 Drowsiness and headache

18.  Hypotention
 Bradycardia
 Seizures
 Coma
 rhabdomyolysis

19.  Butorphanol is a synthetic opioid analgesic.
 It is structurally related to levorphenol.
 It is an agonist-antagonist opioid that
resembles pentazocin.
 But its agonist effects are 20 times greater
and antagonist actions are 10 to 30 times
greater than pentazocin

20.  It is speculated that butorphenol has:
 Low affinity for mu receptors to produce
antagonism
 Moderate affinity for kappa receptors to
produce analgesia and antishivering effect
 Minimal affinity on delta receptor ,so the
incidence of dysphoria is low

21.  :
Intracellular inhibition of
adenylate cyclase.
Closing of calcium channels
Opening of potassium
channels
Hyperpolarisation of cell
membrane potential
Supression of action potential
transmission of ascending pain
pathway

22.  Butorphanol is principally metabolise to
inactive hydroxybutorphenol , which is
eliminated largely in bile and to a lesser
extent in urine.
 The elimination half time of butorphanol is
2.5 to 3.5 hrs

23.  It has been used in a dose of 1-4 mg IM or IV
for postoperative and other short lasting
painful conditions
 It is rapidly and almost completely absorbed
after IM injection.

24. Parental injection is use for
 Moderate to severe pain associated with acute
pain such as orthopedic issues, burns ,renal colic
and surgical
 Labour analgesia: indicated for labor pain in full
term women without fetal distress in early labour
 Balanced anaesthesia.
 Postoperative use in patient controlled analgesia

25.  The nasal spray formulation is an effective
analgesic for the relief of moderate to severe
pain such as:
 Migrain attacks
 Dental
 Maxillofacial
 Other surgical pain

26.  Sedation
 Nausea ,vommiting
 Diaphoresis’
 Dysphoria
 Depression of ventilation
 Increase in systemic blood pressure
 Increase in pulmonary arterial blood pressure
 Increase in cardiac output

27.  Dizziness
 Nasal congestion
 Insomnia‘
 Effect of butorphenol on biliary and
gastrointestinal tract are mild .
 Withdrawl symptoms do occur after acute
discontinuation of chronic therapy

28.  References :-
Stoelting’s Pharmacology & Physiology.
Barash Clinical Anesthesiology.
KD Tripathi Essentials of Medical Pharmacology