opioid analgesics for nursing students, Opioids, Morphine, History of opioids, side effects, uses of opioids

1. Dr. Resu Neha Reddy
MD Pharmacology
Osmania Medical College

2.  Opioid
 Compound with morphine-like activity
 Opiate
 Substance extracted from opium
 Exudate of unripe seed capsule of Papaver
somniferum

4.  Friedrich Wilhelm Serturner
 A German Pharmacist
 Isolated Morphine in 1803 and named it after the
Greek god of Dreams
 “MORPHEUS”

5.  A number of endogenous opioid peptides having
morphine like activity are found in brain, pituitary,
spinal cord, GIT
 β-Endorphins - 
 Enkephalins -  & 
 Dynorphins- 
 Endomorphins- 
 Nociceptin- NOP receptor (nociceptin opioid
peptide receptor)

6.  μ receptor
 κ receptor ANALGESIA
 δ receptor
 S Sedation  COMA
 A Analgesia  PAIN
 C Constipation Treat Diarrhea
 R Resp. Depression  C/I Asthma, COPD
 U eUphoria  Addictive drugs
 Tolerance (Except for constipation & constriction of pupil-
miosis)
 Dependence – physical (Cravings) & psychological (Withdrawl
symptoms)
 M Miosis  PIN POINT PUPIL

7. Central Nervous System Effects
Analgesia
 Pain consists of both sensory and affective (emotional) components.
 Opioid analgesics reduce both aspects of the pain experience, especially
the affective aspect.
 In contrast, nonsteroidal anti-inflammatory analgesic drugs have no
significant effect on the emotional aspects of pain.
Euphoria
 intravenous drug users experience a pleasant floating sensation with
lessened anxiety and distress (DA release in nucleus accumbance).
 However, dysphoria, an unpleasant state characterized by restlessness
and malaise, may sometimes occur.

8. Sedation
 Drowsiness
 clouding of mentation
 little or no amnesia
 No motor incoordination
 Sleep is induced in the elderly (can be easily aroused
from this sleep)

9. Respiratory Depression
 by inhibiting brainstem respiratory mechanisms.
 Alveolar PCO2 may increase, but the most
reliable indicator of this depression is a
depressed response to a carbon dioxide
challenge.
 In individuals with increased intracranial
pressure, asthma, chronic obstructive
pulmonary disease, or cor pulmonale, this
decrease in respiratory function may not be
tolerated.

10. Cough Suppression
 Codeine in particular
 However, cough suppression by opioids may allow
accumulation of secretions and thus lead to airway
obstruction and atelectasis.
Temperature regulating centre depression
 chances of hypothermia
Vasomotor centre depression
 Fall in BP

11. Morphine stimulates:
 CTZ (nausea, vomiting)
 Edinger Westphal nucleus of III nerve is
stimulated (miosis)
 Vagal centre (bradycardia)

12. Miosis
 Constriction of the pupils
 By stimulating Edinger Westphal nucleus of III
nerve
 Miosis is a pharmacologic action to which
little or no tolerance develops
 valuable in the diagnosis of opioid overdose.

13. Truncal Rigidity-
 Truncal rigidity reduces thoracic compliance
and thus interferes with ventilation.
 Truncal rigidity may be overcome by
administration of an opioid antagonist, which
of course will also antagonize the analgesic
action of the opioid.
 Preventing truncal rigidity while preserving
analgesia requires the concomitant use of
neuromuscular blocking agents.

14. Cardiovascular System
 Bradycardia
Meperidine is an exception (can result in
tachycardia)
 Hypotension - due to
-peripheral arterial and venous dilation
-depression of vasomotor centre
-release of histamine.
 Increased PCO2 leads to cerebral vasodilation
associated with a decrease in cerebral vascular
resistance, an increase in cerebral blood flow,
and an increase in intracranial pressure.

15. Gastrointestinal Tract
Constipation
 no tolerance
 Opioid receptors exist in high density in the
gastrointestinal tract
 constipating effects of the opioids are mediated
through an action on the enteric nervous system as
well as the CNS
 gastric secretion of hydrochloric acid is decreased
 propulsive peristaltic waves are diminished
 tone is increased
 this delays passage of the fecal mass and allows
increased absorption of water, which leads to
constipation
 so used in the management of diarrhea

16. BiliaryTract
 sphincter of Oddi may constrict
 contract biliary smooth muscle
 result in biliary colic
Renal
 Renal function is depressed by opioids
 decreased renal plasma flow
 enhanced renal tubular sodium reabsorption
 Ureteral and bladder tone are increased
 Increased sphincter tone may precipitate urinary
retention
 ureteral colic caused by a renal calculus is made worse
by opioid-induced increase in ureteral tone

17. Uterus-
 may prolong labor
 both peripheral and central actions of the opioids can
reduce uterine tone
Neuroendocrine-
 stimulate the release of ADH, prolactin, and
somatotropin
 inhibit the release of luteinizing hormone
Pruritus-
 CNS effects and peripheral histamine release may be
responsible for these reactions
 pruritus and occasionally urticaria (when administered
parenterally)

18. Miscellaneous
The opioids modulate the immune system by
 lymphocyte proliferation
 antibody production
 chemotaxis

19.  Mordern definition of opioid
 Molecule that interact with opioid receptor
 Opioid compound
 Opioid receptor agonists
 Antagonists
 Agonists-antagonists
 Partial agonists.
 Natural products
 synthetic
 semisynthetic compounds

20. Natural opium alkaloids: (  δ +++)
 Morphine
 Codeine
Semisynthetic opiates:
 Diacetylmorphine (Heroin)
 Pholcodeine
Synthetic opioids:
 Pethidine
 Fentanyl, Alfentanil, Sufentanil, Remifentanil
 Methadone
 Dextropropoxyphene
 Tramadol

21. Partial agonist ()
 Buprenorphine
Agonist () -antagonists ()
 Nalorphine
 Pentazocine
 Butorphanol
Pure antagonists (  δ #)
 Naloxone
 Naltrexone

22.  Morphine
 SACRUM
 Heroin
 100 times more addictive than morphine
 not used in practice
 Methadone
 Long acting
 De-addiction of opioids

23. Pethidine
Inactive Nor-pethidine
MAO-A inhibitors
Very small amount  no
problem
S/E as it is long acting
Thus everyday pethidine 
accumulation of Nor-pethidine
SEIZURES
MAO-A 99% 1%

24.  1/10th in analgesic potency
 Spasmodic action on smooth muscles is less
 Tachycardia (antimuscarinic action)- it is related to
atropine, even acts on opioid receptors
 Safer in asthmatics (less histamine release)
 Uses- analgesia, preanaesthetic medication
 Preferred opioid analgesic during labour (less
neonatal resp depression)

25.  Codiene
 Pholcodiene Anti-tussives
 Dextromethorphan Cough suppressants
 Noscapine DRY COUGH

26.  Loperamide/ Diphenoxylate
 Treatment of diarrhea
 Non infective diahhrea
 Opioids C/I in Infective diarrhea
 E. Coli, Shigella
 # GIT motility
 Thus bacteria inside GIT penetrate mucosa
 Reach blood
 Septecemia

27.  Tramdol &Tapentadol
   δ + = Analgesic action
 Additionally increase 5HT in spinal cord 
analgesic
 So opioid antaganist  cannot antagonise drug
effects

28.  Fentanyl
 Alfentanyl
 Sufentanyl
 Remifentanyl
Anesthesia
Post operatibe muscle rigidity
Post operative muscle PAIN – Sch
Most potent opioid
Shortest acting opioid 
metabolised by
pseudocholinesterase

29. Fentanyl
 80-100 times more potent than morphine
 few cardiovascular effects
 little propensity to release histamine.
 Because of high lipid solubility, it enters brain rapidly
and produces peak analgesia in 5 min after i. v.
injection.
 The duration of action is short: starts wearing off
after 30-40 min due to redistribution
 Transdermal fentanyl has become available for use in
cancer

30.  25-50 times more potent than morphine
 Sublingual route
 Slower onset & longer duration of action
 Postural hypotension is marked
 Cannot be used during labour (respi dep not
reversed by naloxone)
Uses-
 Long lasting pain- cancer
 Tt of morphine dependence

31.  Buprenorphine
 
 Partial agonist of   less resp. Depression
 CEILING EFFECT
 Advantages  less Resp. Depression
 Disadvantages  less analgesic effect

32.  Agonist () -antagonists ()
 Pentazocine
 Nalbuphine
 Butorphanol
 S/E - Hallucinations

33.    δ inhibit all
Naloxone Naltrexone
Short acting Long acting
IV ORAL
Treat acute opioid
poisoning
Maintainance of
opioid poisoning

34. Naloxone (, ,  antagonist)
 Antagonizes all morphine actions
 Sedation is less completely reversed
 Blocks placebo, acupuncture, stress induced
analgesia
Use
 Morphine poisoning
 Diagnostic test for opioid addiction
 Revert neonatal respi depression due to opioid
use during labour

35.  Naloxone- 0.1-0.4 mg IV repeated every 2hrs (short acting)
 Immediately rectify opium toxicity
 All symp totally reversed
 If treatment stopped
 Pt again go into COMA
 When pt is conscious
 Start treatment with Naltrexone 50-100 mg/day orally
 ORALLY, LONGACTING
 MAINTAINENCE dose

36. Short term
Few months
long term
Many years
Stop giving opioids
Cannot try stopping opioid
Withdrawal symptoms ++
Ventricular fibrillations
seizures
Withdrawal symptoms
Instead of stopping
Less addictive opioid
METHADONE
Long acting
Less euphoria
Delayed euphoria
Rx
Beta blocker
Clonidine
Tapering doseRx
BZD
Loperamide
Symp. System +
Tachycardia
HTN
palpitations
Opposite to SACRUM
No sleep
Diarrhea
Tachypnoea
Mydriasis
PREVENT RELAPSE - Naltrexone

37.  Before beginning therapy, perform a
thorough history regarding allergies, use of
other medications,health history, and
medical history.
 Obtain baseline vital signs
 Assess for potential contraindications and
drug interactions.

38.  Perform a thorough pain assessment, including
nature and type of pain, precipitating and
relieving factors, remedies, and other pain
treatments.
 Be sure to medicate patients before the pain
becomes severe as to provide adequate
analgesia and pain control.
 Pain management includes pharmacologic and
nonpharmacologic approaches. Be sure to
include other interventions as indicated.

39.  Oral forms should be taken with food to
minimize gastric upset.
 Ensure safety measures, such as keeping side
rails up, to prevent injury.
 Withhold dose and contact physician if there
is a decline in the patient’s condition or ifVS
are abnormal—especially if respiratory rate is
below 12 breaths/minute.

40.  Follow proper administration guidelines for
IM injections, including site rotation.
 Follow proper guidelines for IV
administration, including dilution, rate of
administration, and so forth.
 CHECK DOSAGES CAREFULLY

41.  Constipation is a common side effect and
may be prevented with adequate fluid and
fiber intake.
 Instruct patients to follow directions for
administration carefully, and to keep a record
of their pain experience and response to
treatments.
 Patients should be instructed to change
positions slowly to prevent possible
orthostatic hypotension.

42.  Patients should not take other medications or
OTC preparations without checking with their
physician.
 Instruct patients to notify physician for signs
of allergic reaction or adverse effects.

43.  Monitor for side effects:
 ShouldVS change, patient’s condition
decline, or pain continue, contact physician
immediately.
 Respiratory depression may be manifested by
respiratory rate of less than 12/min, dyspnea,
diminished breath sounds, or shallow
breathing.

44.  Monitor for therapeutic effects:
 Decreased complaints of pain
 Increased periods of comfort
 With improved activities of daily living,
appetite, and sense of well-being