OPIOIDS

ABEL ABRAHAM
I MDS
TABLE OF CONTENTS

• PHARMACOKINETICS
• ADVERSE EFFECTS
• CONTRAINDICATIONS
• USES
• OTHER DRUGS
PHARMACOKINETICS

• Oral absorption – unreliable

• 30% bound to plasma proteins
• Higher concentration in liver, spleen, kidney compared to plasma
• Small fraction enters the brain
• Crosses placenta freely
• Primarily metabolized in liver by glucuronide conjugation
• Plasma t ½ ~ 2-3 hours
• Elimination is almost complete in 24 hours
ADVERSE EFFECTS
• Idiosyncrasy
• Allergy
• Apnoea
• Acute Morphine Poisoning
• Tolerance and dependence:
- partly pharmacokinetic (enhanced rate of metabolism), but mainly
pharmacodynamic (cellular tolerance).
- Tolerance is exhibited to most actions, but not to constipating and miotic
actions.
- Addicts tolerate morphine in grams: lethal dose is markedly increased.
- pronounced psychological and physical dependence, its abuse liability is rated
high
 - Withdrawal of morphine is associated with marked drug-seeking behaviour
- lacrimation, sweating, yawning, anxiety, fear, restlessness, gooseflesh, mydriasis,
tremor, insomnia, abdominal colic, diarrhoea, dehydration, rise in BP, palpitation and
rapid weight loss.
• Treatment: consists of withdrawal of morphine and substitution with oral methadone
(long-acting, orally effective) followed by gradual withdrawal of methadone.
CONTRAINDICATIONS
USES

• As analgesic Opioid analgesics are indicated in severe pain of any type

• Only provide symptomatic relief without affecting the cause
• For more severe and longer lasting pain, a NSAID should be combined
with the opioid; helps to enhance analgesia while keeping the opioid dose
low.
• Preanesthetic medication – Morphine, pethidine
• Balanced anaesthesia and surgical analgesia
• Relief of anxiety and apprehension
• Acute left ventricular failure (cardiac asthma)
• Morphine (i.v.) affords dramatic relief by reducing preload on heart due to vasodilatation
and peripheral pooling of blood.
• Also tends to shift blood from pulmonary to systemic circuit; relieves pulmonary
congestion and edema.
• Allays air hunger by depressing respiratory centre.
• Cuts down sympathetic stimulation by calming the patient, reduces cardiac work.
• It is also indicated to relieve pulmonary edema due to infarction of lung and other causes,
but not due to irritant gases.
• Cough – Codeine or its substitutes
• Diarrhoea - Codeine, diphenoxylate and loperamide
OTHER DRUGS
CODEINE

• It is methyl-morphine, occurs naturally in opium, and is partly converted

in the body to morphine.
• It is less potent than morphine (l/10th as analgesic)
• It is more selective cough suppressant (only 1/3rd as potent as morphine);
subanalgesic doses (10-30 mg) suppress cough
HEROIN (DIAMORPHINE, DIACETYLMORPHINE)

• It is about 3 times more potent than morphine

• More lipid soluble: enters brain more rapidly
• It is considered to be more euphorient (especially on i.v. injection) and
highly addictive
PETHIDINE

• Dose to dose l/lOth in analgesic potency with respect to morphine

• Analgesic efficacy is greater than codeine
• After i.m. injection, the onset of action is more rapid but duration is shorter (2-
3 hours).
• It does not effectively suppress cough.
• Spasmodic action on smooth muscles is less marked - miosis, constipation and
urinary retention are less prominent.
• It is equally sedative and euphoriant, has similar abuse potential.
• The degree of respiratory depression seen at equianalgesic doses is
equivalent to morphine.
• Tachycardia (due to antimuscarinic action) occurs instead of bradycardia.
• It causes less histamine release and is safer in asthmatics.
• It is well absorbed orally
FENTANYL

• A pethidine congener
• 80-100 times more potent than morphine, both in analgesia and respiratory
depression
METHADONE

• A synthetic opioid
• Chemically dissimilar but pharmacologically very similar to morphine
• In single doses it is only slightly more potent than morphine
• Has comparable duration of action (4-6 hours on i.m. injection)
• The abuse potential is rated lower than morphine.
• Tolerance develops more slowly.
DEXTROPROPOXYPHENE

• It is nearly ½ as potent as codeine and has a lower oral: parenteral activity

ratio
• Dextropropoxyphene (60-120 mg) is used as a mild oral analgesic
THANK YOU