L:10

Pharmacology of Opioids analgesics

and Local Anesthetics

Department of Pharmacology & Toxicology

College of Pharmacy, UQU, Makkah
 OPIOID ANALGESICS
(NARCOTIC ANALGESICS)
What is the difference between opiates and Opioids ?

Classically, the term opiate refers to natural substances that come from opium. ... Thus,
examples of opiates are morphine and codeine. Opioids. There are also products that work by
binding to the same receptors as opiates, but do not occur naturally, known as semi-synthetic or
synthetic opioids.
Opiates = of Natural origin (Morphine, Codeine).
Opioids = semi-or pure Synthetic opoioid receptor agaonists : e.g., Fentanyl, Sofental, etc.
Generally, they have rapid onset (2-3 min) and short duration ( 40-60 min) than natural opiates.
 Papaver somniferum

• Opium is obtained from the

Papaver somniferum.
• Opium contains:
Morphine, codeine , papaverine,
thebaine and noscapine.
 1. Classification of opiates
• Natural opiates: morphine, codeine, papaverine and
thebaine;
• Semi-synthetic opiates: hydromorphone, hydrocodone,
oxycodone, diacetylmorphine (Heroin), etc.
• Fully synthetic opioids: fentanyl, pethidine, methadone,
tramadol and propoxyphene;
• Endogenous opioid peptides: endorphins, enkephalins,
dynorphins, and endomorphins.
Analgesic Effect of Opioids & NDAIDs
Opioids NDAIDs
(Morphine) (Aspirin)
Site CNS Mainly Peripherally & but
may be also CNC
Mechanism Activation of opiate Inhibition of PGs synthesis
receptors inhibit pain (PGs cause pain by stimulation of
pathway in CNS pain receptors on body tissues)
Efficacy Strong analgesic effect. Less effect than opioids.
Can relief all types of pain, only effective on mild to
but used mainly for acute moderate dull pain (eg,
sharp pain musculoskeletal & rheumatic
pain, teeth pain, headache,
Dysmenorrheal pain, etc.
Narcosis Yes No
a state of euphoria, confusion stupor, or arrested activity
similar to that of alcohol intoxication
Addiction Yes No
Hyperacidity No Yes
Antagonist Yes (naloxone) No
Pharmacological Effect of each Opioid Receptor

μ opioid κ opioid d opioid

receptor receptor receptor
Analgesia Analgesia Analgesia
Respiratory depression dysphoria
Euphoria/sedation Pupil constriction
Physical dependence
Decreased GI motility
Pupil constriction Antagonist act at μ, κ, d receptors
•Naloxone
•Naltrexone
• They are used in treatment of
acute opioid toxicity
 Morphine

4.1 Pharmacological effects:

A Analgesia:
- Raises the pain threshold at the spinal cord level,
alters nociception in the brain.
- Relieves anxiety and fear
B Euphoria:
- Produces a powerful sense of contentment and well-
being.
 Morphine
C. Sedation (Narcosis):
- Causes stupor, drowsiness and clouding of mentation,
even disrupting sleep
D. Gastrointestinal effect:
- Decreases motility of smooth muscle and
increases tone, which causes constipation and ttt
diarrhea.
- Increases pressure in the biliary tract (worsens
abdominal colic, eg. Sphincter oddi contraction), thus
contraindicated in biliary colic when given alone. If we
use it in this pain, we should add atropine.
 Morphine
C. Respiration: contraindicated in asthmatic patients. Why??
- Causes respiration depression by reduction of the
sensitivity of respiratory center neurons to carbon
dioxide
. Increase histamine release, so produce bronchospasm.
D. Depression of cough reflex: (antitussives):
- May allow accumulation of secretions and thus lead to airway
obstruction and atelectasis.
- Now, we can use a synthetic opioid with safer antitussive
effect and no addiction (eg. Dextromethorphan)

Q: Mention 3 reasons for why morphine is contraindicated in Asthmatic patients

 Morphine
E. Miosis:
- The pinpoint pupil (sever miosis)is
the characteristic of morphine toxicity.
Also miosis is found in addicting persons

F. Emesis: (only in early doses)

- Causes vomiting by stimulating the
chemoreceptor trigger zone (CTZ) in the
brain medulla.
 Morphine

H Cardiovascular :
- Has no major effects on the cardiovascular system.
-Is usually contraindicated in individuals with severe
brain injury (because that increased PCO2 induced by
respiration depression leads to cerebral vasodilation and
consequential increase in cerebral blood flow and intracranial
pressure).
- Causes postural hypotension sometimes.
 Morphine

I: Histamine release:
- Causes pruritus, urticaria, sweating, vasodilation
and bronchoconstriction.

J: Immune depression
 Morphine
Therapeutic uses:
A: as Analgesic to relief pain sensation:
- Used for various pain, especially acute-constant pain
(e.g. burn, cancer pain);
- Not used continuously to avoid the development of
addiction (= dependence), but using fixed interval of
administration may reduce development of tolerance
and dependence.
Q: Mention the types of pain in which morphine is contraindicate??
Pain in which morphine is contraindicated Reason Why?

Acute Head injury

Undiagnosed acute abdominal pain
Alone in pain due to Obstructive Biliary coloic
Obstetrical pain at delivery
 Morphine
Q: Can we use morphine in ttt of
B: In Cardiac asthma: cardiac asthma? Why??

- In acute left ventricular heart failure with pulmonary

edema. Benefits of morphine in this disease:
i. - Reduces anxiety, cardiac preload and afterload.
ii. - Particularly useful for painful myocardial ischemia
with pulmonary edema.
C: Treatment of diarrhea:
but using synthetic analogue (Loperamide) which act
only on u receptor on GIT (and not cross blood
brain barrier) is better than morphine and this to
avoid development of tolerance and addiction.
Q: Why Loperamide is better than morphine in ttt of diarrhea?
 Morphine

D. Relief of cough: synthetic antitussives that

not cause addiction (eg, dextromethorphan)
are now used.
E. Premeditate drugs before anesthesia :
sedative, anxiolytic, and analgesic properties.
For high-risk surgery administered
systemically; for local (epidural) anesthesia.
Caution: respiratory suppression
 Morphine

Adverse effects:
- Respiratory depression, so contraindicated in asthma
- Vomiting, constipation, biliary colic.
- Acute urine retention in prostatic hypertrophy.
- Dysphoria
- Allergy-enhanced or postural hypotensive effects
-Elevation of intracranial pressure (so contraindicated in
acute head injury)
- Immune depression
 Morphine
Contraindications:
• Women during labor or lactation (neonatal asphyxia)
• New-born infants (cause respiratory depression)
• Bronchial Asthma & Chronic obstructive pulmonary
disease (COPD).
• Acute head injury.
• Undiagnosed acute appendicitis … Why?
• Obstructive Biliary coloic. Why? Because it increases
biliary pressure by constriction of Oddi's sphincter to induce
biliary colic. If there is severe biliary or renal colic you can
give morphine but in combination with atropine
 Morphine

Tolerance and Physical Dependence

• Repeated use produces tolerance to the
respiratory depression, analgesic, euphoric and
sedative effects, but there is no tolerance to
pupil-constricting and constipating effects.
• Physical and psychologic dependence readily
occur for strong μagonists, especially used on
necessities.
 Morphine
Tolerance and Physical Dependence
• Withdrawal symptoms: a series of autonomic,
motor and psychological response that
incapacitate the individual (rhinorrhea,
lacrimation, yawning, chills, gooseflesh,
hyperventilation, hyperthermia, mydriasis,
muscular aches, vomiting, diarrhea, anxiety, and
hostility).
 2- Codeine
1. pharmacologic effects are similar to morphine,
but its analgesic potency is 1/12 of morphine,

cough depressant potency is 1/4 of morphine.

2.less sedation, less respiratory depression and fewer gastrointestinal

effects.

3.use: mild to moderate pains and severe cough by oral administration.

4.physical dependence can occur n long administration,

so dextromethorphan is better as anti-cough.

 3- Methadone
• analgesia
• suppression of withdrawal syndrome
• treatment of morphine, heroin users.
• Why methadone is used in treatment of opioid
addiction?
Answer:
• Methadone orally administered to gradually
substitute the addicting opioid(eg, morphine,
heroin, etc), and patient is then slowly weaned
from methadone.
• physical dependence occurs slowly with
methadone and withdrawal syndrome is mild.
 Fentanyl
1.Effects
analgesic effect is 80-100 times as
effective as morphine with short
duration(15 to 30 min) and rapid onset.

2.uses”
anesthesia or anesthesic adjunct.
 Alfentanil
• effects
Alfentanil has a more rapid than
fentanyl.
• uses
adjunct to general anesthetics
anesthetic inducing agent.
 Opioid Antagonist:
Naloxone, Naltrexone
Only Used To Treat Acute
Opioid Toxicity
• Competitive blocker of opioid receptors.
• Actions: used only in treatment of acute opioid
poisoning conditions to:
---reverses the coma and respiratory depression of
opioid overdose
--- eliminates some adverse effects with opioids.

NB: when given to opioid addict persons, they will precipitate

withdrawal symptoms
 Others: Tramadol

• Tramadol: weak µ receptor agonist, but

also increase brain levels of NEP and
serotinine by preventing their uptake.
• As analgesic, tramadol is effective on
moderate to severe acute and chronic
pain.
• Highly addicting, and almost have the
same side effects of morphine.
LOCAL ANESTHETICS
 What do you mean
by local
anesthesia?
• Local anesthetics produce a transient and reversible loss
of sensation in a circumscribed region of the body
without loss of consciousness.

• Normally, the process is completely reversible.

 What do you mean
by local
anesthesia?
• Local anesthetics produce anesthesia by inhibiting
excitation of nerve endings or by blocking conduction in
peripheral nerves.

• Mechanism of action: The local anesthetic blocks the

sodium channel of a nerve. When the sodium channel of
a nerve is blocked, the nerve signals cannot be
transmitted.
 Sequence of Local
anesthesi
a of pain and temperature sensation
•Loss
•Loss of proprioception
( = reception of information about body position movements by the sensory
systems)

•Loss of touch and pressure sensation

•Loss of motor function
 Members of Local Anesthetics:

Ester Local Amide Local

Anesthetics: Anesthetics
• Cocaine • Lidocai
• Benzocaine ne
• Procaine • Mepiva
• Tetracaine caine
• Chloroprocaine
• Prilocai
ne
Local Anesthetics:
Onset of Action
AGENT ONSET (MIN)
Local Anesthetics: Duration
 Describe the different techniques of use of
local anesthetics
1. Surface (Topical) anesthesia: Topical application on skin
and mucous membranes.
2. Infiltration (Infiltrative anesthesia).

3. Regional Block local anesthesia: = injection in the target

localized area (e.g., arm, foot, etc.).
1. Nerve block (Inject a drug around the nerve).
2. Intravenous Regional Block Anesthesia.
4. Epidural anesthesia (in epidural space).
5. Intrathecal block/ spinal anesthesia.
 Precautions during
using Surface
•
anesthesia
The most common topical anesthetics used are those
containing benzocaine or lidocaine.
• To prolong their duration and Slow systemic absorption
Add vasoconstrictor ( e.g. adrenaline)

except
except when surface anesthesia used for peripheral
areas with low blood supply such as fingers, toes,
nose, etc … why?? Because adrenaline in this case
will severely vasoconstrictor blood vessels and
severely decrease blood supply leasing necrosis
and death an sloughing of this peripheral tissue.
 Infiltrative Local Anesthesia
Local cutaneous infiltration is the most
commonly used anesthetic technique and
involves direct injection into the area requiring
anesthesia.

Standard Procedure for Infiltrative Anesthesia

Cleanse the injection site (for intact skin, alcohol wipes are as effective or povidone/
iodine)

Rapidly insert the needle (27- to 30-gauge) through the skin into the subcutaneous layer,
using distraction techniques as necessary.

Slowly and steadily inject small volumes of anesthetic while withdrawing the needle

Test the area for adequate anesthesia

 Regional Nerve block
• Inject a local anesthetic
drug around the nerve

• Anaesthetise a region
Epidural & Spinal Local
Anesthesia
 Systemic Side Effects of
local anesthetics

• Excitation – anxiety, agitation,

restlessness
• Convulsions
• Reduced myocardial contractility
• Vasodilatation
 Manufacturers
’ Recommended
Dose
Maximum Dosage Maximum Total
Anesthetic
mg/kg mg/lb Dosage
Lidocaine 2%
4.4 2.0 300mg
1:000,000 epi
Mepivacaine 3% 4.4 2.0 300mg
plain
Articaine 4%
1:100,000 epi 7.0 3.2 500mg

Prilocaine 4%
8.0 3.6 600mg
plain
Bupivacaine
0.5% 1:200,000 1.3 0.6 90mg
epi
Thank you