TRAMADOL

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