OPIOIDS

Dr. GANGA BHAVANI

MD ANESTHESIA
• OPIATE :All naturally occuring substances having
morphine like properties.
• OPIOID :Synthetic substances that have affinity
for opioid receptors.

• ENDOGENOUS OPIOIDS : a) endomorphins

b)encephalins c)endorphins d)dynorphins
e)neoendorphins
 CLASSIFICATION
NATURAL SEMISYNTHETIC SYNTHETIC

Morphine Heroin(Diacetylmorphine) Morphinan

series(levorphanol,butorph
anol)

Codeine(methylmorphine) Dihydromorphone Diphenylpropylamine

series(methadone)

Papaverine Morphinone Benzomorphan

series(pentazocine)

Thebaine Thebaine Phenylpiperidine

derivatives(etorphine,bupr series(meperidine,fentanyl
enorphine) ,sufentanil,alfentanil,remif
entanil)
MECHANISM OF ACTION
 OPIOID RECEPTORS
U K Delta
M- Miosis C- Constipation Analgesia
U- Urine retention A- Analgesia
S- Sedation P- Psychomimetic effect
C- Constipation D- Dysphoria
A- Analgesia
R- Respiratory depression
I- Increased muscle rigidity
N- Negate bile flow
E- Euphoria

•Pentazocine causes tachycardia,hypertension and mydriasis .

•Bradycardia is seen with all opioids except meperidine(pethidine) as its structure is
similar to atropine and it produces tachycardia.
•Unlike other opioids meperidine causes mydriasis due to its anticholinergic effect.
• Opioid induced respiratory depression is
mediated by the action on U2 receptors in the
brainstem respiratory respiratory centres.
• DOC for opiod induced respiratory depression is
naloxone.
• Respiratory depression can be prolonged when
opioids are taken with other CNS substances
like alcohol,barbiturates,BZD,inhalational
anesthetics and other sedatives.
• CODEINE : Morphine and codeine are natural opium alkaloids.
Codeine is a more selective cough suppressant than morphine and widely used
as an antitussive agent.
• HEROIN : It is a derivative of morphine and it is more potent than morphine.
• FENTANYL : It is available as a transdermal patch for chronic pain.
It is DOC for rescue analgesia and post op analgesia.
Sufentanil and fentanyl are metabolized in liver and undergoes renal
excretion.
It causes wooden chest syndrome(chest wall rigidity).
• REMIFENTANYL : It is fastest acting .It has a rapid onset of action.
Analgesic action(peak) is achieved within 1 to 1.5min following IV
administration.

ANALGESIC ACTION DURATION FOR PEAK ACTION

Fentanyl 5min
Sufentanil 5min
Meperidine 15min
• REMIFENTANIL : It is shortest acting(t1/2 is 8 to 20min).
It is metabolized by plasma esterase and doesnot require intact
hepatic and renal excretion.It ius safely given in hepatic and renal
failure.
It is opioid of choice in day care surgery.
It is not used for intrathecal administration as glycine is used a
preservative.
• SUFENTANIL : Sufentanil is the opioid among the following
having the highest plasma protein binding. More than 90% of
sufentanil is bound to α acid glycoprotein in plasma.
Opioid Plasma protein binding
Morphine 36%
Meperidine 65-75%
Fentanyl 80-85%

• Fentanyl and Remifentanyl are 100 times more potent than

morphine. Alfentanyl is 20times more potent than morphine and
sufentanil is 1000 times more potent than morphine.
• Morphine : Morphine is least efficacious when administered through
sublingual route.
It is used as an analgesic (labour pain,cancer pain,MI),used in pulmonary
edema and used as an anti tussive.
It is metabolized in liver and excreted by kidney.
C/I :-head injury,bronchial asthma,renal failure,emphysema,biliary
colic,hypotension,shock.

• Meperidine (Pethidine) : It has local anesthetic properties.

It is DOC for treatment of post operative chills.
Pethidine causes excitatory syndrome due to metabolite norpethidine
consisting of hallucinations,tremors,muscle twitches and convulsions.
It is contraindicated in renal failure as there is accumulation of
norpethidine and subsequent increase in risk of excitatory syndrome.
Histamine release is common with meperidine.Codeine,Morphine and
Hydromorphone are also associated with histamine release.On the other
hand, fentanyl, alfentanil and remifentanil do not lead to histamine
release.
Meperdine,tramadol,dextromethorphan and methadone inhibit neuronal
uptake of serotonin leading to serotonergic overactivity. This can cause
serotonin syndrome in patients receiving MOA inhibitors.
• TRAMADOL : It is a synthetic analog of codeine and a weak opioid
agonist.
It is less potent than morphine. It has 1/6000th potency of
morphine.
It causes less respiratory depression.
It is contraindicated in epileptics and in patients with MOA
inhibitors use.

• METHADONE :It is a long acting µ receptor agonist with a plasma

half life of 15-40 hours.
It is used as a replacement therapy for opioid(heroin) dependence
because of its good oral bioavailability and long half life.
It is substituted with opioid during detoxification to avoid
withdrawal symptoms.
Onset of analgesia is 10-20min after parenteral route and 30-60min
after oral route of administration.
It is associated with prolonged QT syndrome.Serious cardiac
arrhythmias including torsades de pointes have been noted with
methadone use.
 MIXED OPIOIDS(AGONIST-ANTAGONIST)
• Pentazocine, Butorphanol, Buprenorphine, Nalorphine, Nalbuphine
and decozoine are agonist and antagonist opioids.
• All opioid agonist-antagonist are µ antagonists and K agonists except
pentazocine and buprenorphine.
• Pentazocine is full agonist at K and partial agonist at µ. Analgesia is
mediated by K receptors.It may precipitate withdrawal symptoms in
opioid dependent patients.
• Buprenorphine is a partial agonist at µ and antagonist at K.
• Butarphanol is available as nasal spray for use in painful conditions.
• Nalorphine reverses morphine actions but has K agonist action.
• CEILING EFFECT : On increasing dose analgesic effect does not
increase proportionally. After a specific dose it remains stagnant.
Respiratory depression with morphine does not have a ceiling
effect.On the other hand, Pentazocine, Nalbuphine and butorphanol
are agonist-antagonist compounds. A ceiling effect occurs at higher
doses limiting the progression of respiratory depression.
 PURE ANTAGONISTS

CENTRAL PERIPHERAL
•Naloxone(parenteral for toxicity) •Methyla naltrexone
•Nalmefene(parenteral for toxicity) •Alvimopan
•Naltrexone(oral for relapse) •Naloxegol
•Naltrindone(δ antagonist)
•Naloxone(1-2hrs) is shorter acting than nalmefene(8-10hrs). Naltrexone is longer acting
than nalmefene.
It is the DOC for opioid overdose and for reversing neonatal asphyxia due to opioid using
during labour. . It can be used in emergencies (opioid toxicity)
•Naltrexone is more potent than naloxone.It is orally active.
It does not suppress the craving in opioid addicts.It suppress the cravings in alcoholics.
It is used as a maintenance therapy for opioid addiction.It blocks the effects of opioids and
prevents the user from experiencing subjective symptoms of opioid intoxication such as
euphoria on subsequent use.Because the user does not experience these symptoms he does
not develop craving for the suibstance.Thus naltrexone prevents relapses.
It is used for prevention of relapse only after initial opioid detoxification. The patient should
be opioid free for 7-10days and have a negative naloxone challenge(no withdrawal after
naloxone administration).
• METHYLNALTREXONE : It is a peripheral µ receptor antagonist.It
is an opioid with predominant peripheral action.
It is a quaternary ammonium compound and hence does not
cross BBB.
It does not interfere in the central analgesic action of opioids.It
can reverse the effects mediated by peripheral opioid effects
mediated by peripheral opioid receptors and spares CNS.
It is indicated in reversal of opioid induced constipation in
patients on chronic opioid therapy.
• NALTRINDOLE : It is a new non peptide drug which has a
selective antagonist activity on δ receptor.
• NALOXEGOL : It is naloxone conjulated to PEG polymer.
 OPIOID DEADDICTION
• Opioid withdrawal symptoms :
Lacrimation,sweating,yawning,anxiety,fear,restlessness,mydriasis,inso
mnia,abdominal colic,diarrhea,rise in blood pressure,palpitations,rapid
weight loss,piloerection.

• Steps of deaddiction :
1)To decrease severity of withdrawal symptoms :Opiod agonists such
as methadone and buprenorphine suppress craving and prevent
relapses. They suppress withdrawal symptoms and are used in the first
stage of detoxification and opioid deaddiction.
symptomatic treatment is given with β blockers or clonidine or
lofexidine.
2)Prevent relapse : opioid relapse antagonist is naltrexone. Naltrexone
doesnot suppress craving in opiod addiction but it suppresses craving
in chronic alcoholics.
Neuroleptic anesthesia : Fentanyl+Droperidol+N2O
Propofol is not included in neuroleptic anesthesia.
Neuroleptic analgesia : Fentanyl+Droperidol.
Neuroleptic analgesia is characterised by analgesia,the absence
of clinically apparent motor activity, suppression of motor
reflexes, maintenance of cardiovascular stability and amnesia.
• WHO ANALGESIC LADDER:

Step 3 : moderate to severe pain

persisting after step 2.
Strong
opioids(morphine,fentanyl,methadone)
+/- non opioids+/- adjuvants.

Step 2 : Pain persisting after step 1.

Mild opiods
(codeine,oxycodone,tramadol,bupre
norphine)+/- non opioids +/-
adjuvants

Step 1: mild to moderate pain

Non opioid (acetaminophen or
NSAID) +/-
adjuvants(Aantidepressant,anticonvu
lsants,anxiolytics,corticosteroids)