Pharmacology of opioids

Dr Ritu Pradhan

1
• Pharmakinetic
• pharmacodynamic

2
 Definitions
• Opium: A mixture of alkaloids from the
poppy plant- Papaver Somniferum.
• Opioid: Any naturally occurring, semi-
synthetic or synthetic compounds that bind
specifically to opioid receptors and share the
properties of one or more of the naturally
occurring endogenous opioids.

3
 Opiate: Any naturally occurring opioid
derived from opium (eg morphine).
• Narcotic: From the Greek meaning “to numb
or deaden”. It is often used to denote an
opioid but also widely used to describe drugs
of addiction and hence includes non-opioid
compounds.

4
 Types of opioid receptor
• · MOP (mu opioid peptide receptor)- two
types :µ1and µ2
• · KOP (kappa opioid peptide receptor)-three
types: κ1,κ2,κ3
• · DOP (delta opioid peptide receptor)-two
types : δ1, δ2
• · NOP (nociceptin orphanin FQ peptide
receptor)

5
 Endogenous opiods
• Enkephalin
• β orphanin FQ or nociceptin
• endorphin
• dynorphin

6
• These endogenous compounds are peptides
that have variable potency and are
preferentially bound by different opioid
receptors.
• They have numerous actions including
modulation of pain and control of the
cardiovascular system, particularly in shock.

7
 Classification of opioids
• Traditional: based upon analgesic potency
• Origin of drug: ie naturally occurring or
manufactured
• Function: their action at the opioid receptor

8
9
Pharmacologic action of opioids and
opioid receptors in animal model

10
 Mechanism of action
• Opioids produce their actions at a cellular level by
activating opioid receptors.
• These receptors are distributed throughout the central
nervous system (CNS) with high concentrations in the
nuclei of tractus solitarius, peri-aqueductal grey area (PAG),
cerebral cortex, thalamus and substantia gelatinosa (SG) of
the spinal cord.
• They have also been found on peripheral afferent nerve
terminals and many other organs.
• The efficacy of centrally applied opioids is well recognised,
but when applied peripherally, for example in post-
traumatic and inflammatory states, their actions are less
reliable.

11
• . Opioid receptors are coupled with inhibitory G-
proteins and their activation has a number of
actions including:
• 1.closing of voltage sensitive calcium channels;
• 2. stimulation of potassium efflux leading to
hyperpolarization and reduced cyclic adenosine
monophosphate production.
• Overall, the effect is a reduction in neuronal cell
excitability that in turn results in reduced
transmission of nociceptive impulses
12
13
Pharmacologic action of opioids in CNS
• Analgesia
• Sedation
• Euphoria
• Hallucination
• miosis
• Tolerance and depencence
• Pruritus
• Antishivering

14
 Analgesia
• Most effective in relieving dull, continuous
and poorly localised pain arising from deeper
structures, for example the gut.
• Less effective against superficial and sharp
pain.
• Neuropathic pain can be very resistant, but
patients may report that pain is still present,
but the intensity is decreased

15
 sedation
• Drowsiness, feeling of heaviness and difficulty
in concentrating are common.
• Sleep may occur with relief of pain, although
they are not true hypnotics.

16
 Euphoria and dysphoria
• Morphine and other opioids cause a sense of
contentment and well-being (euphoria).
• If there is no pain, morphine may cause
restlessness and agitation (dysphoria).

17
 Hallucination
• These are more common with KOP agonists,
but morphine and other MOP agonists may
also cause hallucinations.

18
 miosis
• Morphine and most µ- and κ-agonists cause
constriction of the pupil by an excitatory
action on the parasympathetic nerve
innervating the pupil.
• Opioids abolish cortical inhibition of the
Edinger-Westphal nucleus, thereby resulting
in papillary constriction

19
 Tolerance and depndence
• Tolerance is the decrease in effect seen despite
maintaining a given concentration of a drug.
• The mechanism is not fully understood but could involve
down regulation of opioid receptors or decreased
production of endogenous opioids.
• Dependence exists when the sudden withdrawn
of an opioid, after repeated use over a prolonged
period, results in various physical and
psychological signs. These include; restlessness,
irritability, increased salivation, lacrimation and
sweating, muscle cramps, vomiting and
diarrhoea.
20
 pruritus
• Neuroaxial opioid induced pruritus by acting
on mu receptor

21
 Shivering and thermoregulation
• Opioid-based anesthesia probably reduces
thermoregulatory thresholds to an extent
similar to that of the potent inhaled agents.
However, meperidine is unique among opioids
in its ability to effectively terminate or attenuate
shivering.
• The antishivering effect of meperidine is
primarily related to a reduction in the shivering
threshold and mediated by meperidine's
activity on the κ-receptor
• Dose 0.5mg/Kg

22
 Effect on cardiovascular system
• Mild bradycardia is common as a result of
decreased sympathetic drive and a direct
effect on the sino-atrial (SA) node.
• Peripheral vasodilatation caused by histamine
release and reduced sympathetic drive may
result in a slight fall in blood pressure that
may be significant in hypovolaemic patients.

23
 Effect on respiratory system
• Respiratory depression is mediated via MOP
receptors at the respiratory centres in the
brainstem.
• Respiratory rate falls more than the tidal volume
and the sensitivity of the brain stem to carbon
dioxide is reduced.
• Respiratory depression may be augmented.
Concurrent use of other CNS depressants, for
example benzodiazepines or inhalation agents
• Opioids can suppress cough, airway reflexes, the
mechanism not clear
24
 Factors augmenting the respiratory
depressant effect of morphine
• High dose
• Sleep
• Old age
• Central nervous system depressant Inhaled anesthetics,
alcohol, barbiturates, benzodiazepines
• Renal insufficiency
• Hyperventilation, hypocapnia
• Respiratory acidosis
• Decreased clearance
• Reduction of hepatic blood flow
• Secondary peaks in plasma opioid levels: Reuptake of
opioids from muscle, lung, fat, and intestine

25
 Gastrointestinal system
• Stimulation of the chemoreceptor trigger zone
causes nausea and vomiting.
• Smooth muscle tone is increased but motility
is decreased resulting in delayedabsorption,
increased pressure in the biliary system
(spasm of sphincter of Oddi) and constipation.

26
 Endocrine system
• The release of ACTH, prolactin and
gonadotrophic hormone is inhibited
• Secretion of ADH is increased

27
 Musuloakeletal system
• Large doses of opioids may occasionally
produce generalised muscle rigidity especially
of thoracic wall and interfere with ventilation.

28
 Immune system
• Direct effects of opioid agonists include
modulation of immune cellular activity, as
well as modulation of specific enzymatic
degradation and regulation processes.
• Several immune cell populations, including T
cells, macrophages, and natural killer (NK)
cells, serve as targets for the effects of
opioids.

29
• All opioids cross the placenta and if given
during labour, can cause neonatal respiratory
depression.
• Chronic use by the mother may cause physical
dependence in utero and lead to a withdrawal
reaction in the neonate at birth that can be
life threatening.

30
Pharmacokinetic of opioids

31
 Action depends on
• Lipid solubility
• Plasma protein binding
• PH

32
 metabolism
• Glucuronidation
• Oxidation and reduction
• Ester hydrolysis

33
Factors affecting the pharmacokinetic
and pharmacodynamic of opioids
1. Age
2. Body weight
3. Renal failure
4. Hepatic failure
5. Cardiopulmonary bypass
6. Acid base status
7. Hemorrhagic shock

34
 Anesthetic Techniques Using Opioids
• Analgesia
• Sedation
• Balance anesthesia
• TIVA
• Neuroleptanalgesia-Neuroleptanesthesia
• Other additional effects of opioids : transdermal
delivery system, transcutaneous delivery system,
sustain release oral tablet, ionotophoresis

35
•Thank you

36