2. ANALGESICS
Derived from the opium seed.
They are the drugs which relieves the deep seated
pain without causing loss of consciousness.
Pain is an unpleasant sensation which only the individual
himself can appreciate; it can’t be objectively defined
satisfactorily.
Pain receptors are distributed throughout the body.
3. Analgesics are divided into 2 groups:
1. Narcotic/ opioid/ morphine like analgesics.
2. Non_ narcotic/ non steroidal anti- inflammatory
analgesic _ antipyretic agents.
Opioid analgesics act primarily at the level of
spinal cord & brain which NSAIDS act primarily at
peripheral sites to inhibit the synthesis of pain
sensitizing substances like PGs.
4. Endogenous Opioid Peptides & its respective recepters
•Endorphins, Endomorphins : greater affinity to miu receptor
•Enkephalins: affinity to delta receptors
•Dynorphins: . more potent on kappa receptors .
•Found in hypothalamus, thalamus, arculate nucleus ,brain stem,
dorsal horn of spinal cord (Brain ,spinal cord & some in
periphery Like GIT)
•These opioid peptides function as neuromodulator or
neurotransmitter. They appear to regulate pain responsiveness
at spinal & supra spinal levels.
7. D. (µ)Mu receptors agonists with other mode of
action: - Tramadol
E. Those lacking analgesic activity & having other
activity:
Loperamide, Diphenoxylate: used in diarrhoea
Noscapine, Dextromethorphan: used in cough
8. OPIOID RECEPTOR TRANSDUCER MECHANISMS OR
ACTION OF OPIOID RECEPTORS
Action commonly produced at these opioid
receptors includes:
1. Inhibition of adenylyl cyclase leading to decrease in
intracellular cAMP with consequent decrease in
cell-excitability (mainly through miu & delta
receptors)
2. Activation of K+ channels and subsequent increase
in k+ conductance to produce hyperpolarisation of
neurons & a decrease in their excitability (mainly
through miu & delta receptors)
9. 3. Inhibition of ca+ conductance by suppressing
voltage gated N- type ca+ channels (mainly through
kappa receptors) → decrease the release of
neurotransmitters like substance-P and glutamate
from nociceptive terminals.
Morphine & other opioids apparently mimic the
action of these ‘endogenous opioid peptides’ by
binding to various types of opioid receptors.
10.
11. MORPHINE (Prototype opioid agonist):
A.CENTRAL PHARMACOLOGICAL EFFECTS:
C.N.S: Morphine has site specific depressant & stimulant
action in CNS.
1.Analgesia:
•Opioid induced analgesia involves both sensory as well
as affective (emotional) components. By acting on (µ)
periphery and both spinal & supra spinal brain areas,
particularly limbic system.
12. 2.Euphoria, Dysphoria & convulsions:
•produces a sense of emotional well being (µ)termed
euphoria. It eliminates the normal fear, panic,
withdrawal & flight response to pain & aids analgesic
action of morphine.
•Ability to produce euphoria even in the absence of
pain makes morphine one of the worst drugs of abuse.
•dysphoria (kappa) characterized by restlessness &
malaise.
•In high doses morphine increase : supra spinal
stimulation which can lead to convulsions.
13. 3. Sedation: Drowsiness & clouding of judgment
4. Respiratory depression: morphine produced
depression of respiration (µ) by direct depressant action
on brain stem respiratory centre
5.Cough suppression: Morphine & codeine : Cough
Centre is depressed
6.Temperature regulating centre: :hypothermia occurs
in cold
14. 7.Vasomotor centre: is depressed at high doses &
contribute to fall in B.P
8.Nausea & vomiting: initially opioids directly stimulate
the CTZ & produce emesis. Later they depress the
vomiting centre.
9.Miosis: Edingerr Westphal Nucleus of 3rd nerve
stimulation producing miosis- (pin point pupil at
overdose).
10. Miscellaneous: morphine produced a release of
ADH with resultant decrease in urinary output.
Administration of morphine reduces the effiency of
diuretics in pts. with CHF.
15. CVS: Morphine by a central action impairs
sympathetic tone & stimulates the vagal
centre causing dilatation of vessels
bradycardia
It also releases histamine (vasodilation).
16. B.Peripheral Pharmacological effects:
GIT & other smooth muscles::
Reduces propulsive peristaltic movements & leads to
constipation.
Relaxation of ureter: retention of urine
Increase the tone of bronchi & bronchioles causing
bronchospasm.
17. ADVERSE REACTIONS OF MORPHINE:
Constipation
Vomiting
Headache
Postural hypotension
Urinary retention
Respiratory depression
Bronchospasm
Urticaria , itching (due to histamine release)
Tolerance & dependence (on prolonged use)
A withdrawal syndrome may occur in a morphine
addict.
18. Therapeutic uses 0f Morphine:
1. For relief of pain in condition such as:
Acute MI (minimizes shock due to severe pain)
Fracture of long bones
Biliary colic (in combination with atropine
Burns
Terminal stages of malignancy
19. 2. Pre-anesthetic medication: for sedation to reduce
anxiety & apprehension.
3.Acute left ventricular failure (LVF): decrease the
preload and afterload
4. Pulmonary oedema.
IT REDUCES BOTH:
• Pre-load (by causing venodilatation)
and
After load (by causing arteriolar dilatation) to the
heart so it decreases myocardial O2 demand & cardiac
work.
21. CODEINE:
•acts as a prodrug to morphine
•less potent analgesic used as antitussive & included in
many cough syrups
HEROIN : ( Diamorphine, Diacetylmorphine, brown
sugar)
•About 3 times more potent than morphine
•Produces greater euphoria & has greater dependence
liability
22. PETHIDINE :(MEPERIDINE)
•about 110th as potent as morphine as an algesic.
•Onset of action is more rapid but duration of action
is shorter (2- 3 hrs). So used as analgesic in
gastroscopy, cytoscopy , pyelography etc.
•causes less histamine release , urinary retention,
constipation, & is safer in asthmatics
Overdose of pethidine produces many excitatory
effects :
_ Tremor
_ Mydriasis
_ Hyperreflexia
_ Delirium
_ Myoclonus
_ Convulsions
23. FENTANYL:
• A pethidine congener, 80-100 times more potent
than morphine.
• High lipid soluble enters brain rapidly & produces
peak analgesia in 5 mins after i.v injection
• Used in General Anesthesia ,
• t/t of acute pain, in neuroleptic – analgesic with
droperidol
• TRANSDERMAL PATCH is available.
24. Tramadol:
Unique dual action analgesic
•An agonist at miu receptors & inhibits neuronal
reuptake of 5HT & nor _ adrenaline & potentiate the
inhibitory effects of 5HT & nor _ adrenaline on pain
transmission in the spinal cord
•Physical Dependence liability is low
•Used for t/t of postoperative or chronic pain, labour
pain
25. ‘Used in diarrhoea as antimotility & antisecretory
agents”
1 Loperamide
2 Diphenoxylate
•These are opioid agonists
Intestine: Activation of miu receptor decreases peristaltic
movements & activation of delta receptors contributes
their antisecretory effects.
26. Opioid Receptor antagonists:
i.Naloxone
ii.Naltrexone
•Can rapidly reverese the effects of morphine & other
opioid agonists by blocking all receptors
•Naloxone :
•Fast onset of action (min)
•Used for t/t of ACUTE MORPHINE POISONING
(morphine overdose)
•Naltrexone :
•3 – 5 times as potent as naloxone
•Used for t/t of OPIOID DEPENDENCe
27. Treatment of morphine dependence:
•Opioids produce severe psychic & physical dependence.
1. Substitution Therapy: Gradual morphine withdrawal with
substitution of long acting agonists Methadone to decrease
severity of withdrawal syndrome. (because opioid receptors
remain occupied for a longer duration).
Then it can be withdrawn in tapering doses over a weeks.
OPIOID FREE PERIOD
2. Use of opioid Antagonist: Naltrexone to prevent relapse
benzodiazepines or Clonidine to prevent relapse
28. Agonist- Antagonist used as an analgesic
Pentazocine: (fortwin, fortral), Weak miu antagonist
& more marked kappa agonist
•Used for postoperative moderately severe pain such as
burns, labour pain & trauma etc.
• Abuse liability is lower than morphine.
Butorphanol: similar to pentazocine
•less dysphoric and less psychotomimetic than
pentazocin due to mild kappa-R agonist.
29. Buprenorphine:
•Strong partial agonist at miu receptor & Moderate
antaonist at kappa receptors
•Makes it an attractive to methadone for management of
opioid withdrawl.
•Sublingual prepration also available.
•Abuse potential is less than morphine.
