These are used for acute severe pain
Acute Severe Pain
1. Visceral
pain (Acute visceral syndrome) à -
Acute pancreatitis
- Acute
cholecystitis
- Ureteric colics
- Thoracic viscera
- Pelvic viscera, etc.
2. Traumatic
pain à - Fractures
- Sever body
injury, etc.
3. Vascular
pain à - MI
- Dissection of the aorta, etc.
4. Post
operative pain
5. Labour
pain à At child birth, specially during
stage II from full dilatation to delivery with forceful contractions
6. Cancer
pain à Oral morphine is given
7. Tooth
aches, ear aches also may be severe
Quantifying
pain è
-
Pain is subjective
-
Usually there are; Perception &
Reactive components of pain
-
Can use a scale to quantify, as there
is a subjective variation
Strong Analgesics – Preparations
Opioides
è
- A
generic term used to indicate booth natural & synthetic preparations, which
antagonizes the opioid receptors, and have properties similar to morphine
- They
are blocked by opioid antagonists
Ô Morphine
è - Natural
preparation
-
Reference agent / Mother drug
-
Derived from poppy plant
-
Very variable versions throughout the ages
-
Oral & parenteral preparations
Ô Pethidine
i. Diamorphine
/ Di-acetyl morphine / Heroin - Synthetic
Not
available in Sri Lanka legally
ii. Buprenorphine - Synthetic
iii. Codeine - Natural
iv. Dihidro
codeine - Synthetic
v. Noscapaine
vi. Oxycodein - Synthetic
vii. Dextrapropoxyphene - Synthetic
viii. Fentanyl - Synthetic
ix. Tramadol - Synthetic
x. Paparvarathum - Natural
xi. Methadone - Synthetic
Only
some of these drug are available in Sri Lanka
This
is the most investigated drug class globally
Efficacy
Morphine
Pethidine
Diamorphine High efficacy
Methadone
Fentanyl
Paparvarathum
Pentazocin Medium efficacy
Buprinorphine
Codeine - Low efficacy
Mechanism of Action
Different
types of receptors & their various sub classes are involved – μ, κ, σ, δ
Act
both in CNS & out side the CNS eg: GIT
Different
actions are brought about by binding to different receptors
There
are also endogenous opioides à
eg:
encephalin, met encephalin, leu encephalin, etc.
-
They are small peptides, with 5 – 7
amino acids
-
They are programmed by a precursor
molecule, as a pre active stage
eg:
pro encephalin. pro met encephalin, pro leu encephalin, etc.
Morphine
© Derived
from poppy plants, grown in certain parts of the world
eg:
Arabia, Pakistan, etc.
© Resins
are collected from cut flowers, from the plant at a certain stage of the life
cycle
© A
crude preparation is collected and purified – get 10% pure morphine
© Also
produced codeine, paparvarathum, etc. from cruder opium
© Actions
è
Receptor
binding & G protein coupled stimulation (mostly)
Central
Nervous System à
Specially
bind to μ receptors
-
Respiratory depression
-
Pupillary constriction (myosis)
-
Analgesia
-
Sedation
-
Dysphoria
-
Euphoria – sense of well being
-
Cough suppression
-
Emesis
-
Increased excitability of reflexes
-
Increased excitability of CNS
-
Increased CSF pressure
GIT
à
-
Delayed gastric emptying
-
Gastric dilatation
-
Reduces / Inhibits peristalsis of
small & large intestine
-
Increases sphincter tone
-
Constriction of sphincters (smooth
muscles ) – billiary, pancreatic, etc.
GUT
à
-
Increases sphincter tone of bladder
-
Increases ureteric tone
CVS
à
-
Vasodilatation
© Pharmocokinetics
è
Usually
given parenterally, for severe pain, as quick action is needed
-
IV, IM, SC (In cancer patients given
orally)
Morphine
/ Pethidine à
-
Has variable protein binding
-
Carried all over the body & to the
tissue; specially lipid containing tissues
eg: liver lungs
kidney skeletal muscle
-
In infants enter the CNS because the
blood brain barrier is not developed well
-
Enters placenta & can cause
respiratory depression in the fetus
-
Metabolized in the liver
(glucuronidation) & produce inactive metabolites
-
Inactive metabolites are excreted
through the kidneys
© Uses
è
1. As
a strong analgesic
2. Acute
pulmonary odema / LVF / Acute HF – Morphine (not pethidine)
3. As
a hypnotic sedative – In highly
emotional situations, with mixture of emotions
A
lot of anxiety
Restlessness
eg:
abortions, bleeding, severe burns, etc.
4. Supplement
& complement of anesthetic drugs
eg:
specially fentanyl, but depends on the anesthetist
© Contra
indications è
Should
be used very carefully, because can kill patients if used in certain situations
Acute asthma
Chronic
asthma - Conditions where
respiratory function is compromised
Emphysema - Can cause respiratory
depression / failure & apnea
COPD
Heart
failure – Cardiac asthma
Head
injury à Patients
get drowsy, altered consciousness, increased CSF pressure & myosis due to
morphine it self
This may confuse & make difficult the diagnosis with
GCS
Undiagnosed
pain à Specially abdominal, thoracic (leaking
aortic aneurysm), may delay the diagnosis, irreversible damage & cause death
Increased
ICP
Myosis
© Precautions
è
Patient
must be in supine position when administering the drug à
To prevent falls & head injury
Facilities
for the reversal of the adverse actions of the drug must be available
eg: Opioide antagonists – Naloxone
© Cautions
è
When
given to reduce labour pain, just before the delivery it may cause birth
asphyxia and may lead to mental retardation & later cerebral palsy in the
neonates. Therefore if labour occurs a little time after administration, must
give the antagonist; to the mother before delivery & to the baby via the
umbilical vein
Hypo
tension à
May lead to further decrease of BP & can cause cardiogenic shock
Prostatic
hypertrophy à
Anticholinergic property of the drug can cause BOO
Pregnancy
& breast feeding à
Baby can become drowsy & poor suckling
Hepatic
impairment à
May lead to hepatic coma (Therefore be careful when giving to restless patients
after hematemesis)
Elderly
& debilitated (Cancer patients, wasted) à can’t tolerate, can get hypotension
& apnea, etc.
Dependence
à
Do not give to patients with past history of drug addiction
Paralytic
ileus
Convulsion
disorders
Alcoholism
Increased
ICP
© Side
effects è
Sedation
& drowsiness
Myosis
Nausea
& vomiting – therefore combine with an antiematic
Constipation
Larger
doses – Respiratory depression / failure
Cyanosis
Apnea
Hypo
tension / Postural hypo tension
Difficulty
in micturition
Dry
mouth – anticholinergic properties
Sweating
– specially with pethidine
Tachycardia
/ Palpitations
Hallucinations
Mood
changes
Pethidine
(Meperidine)
© Less
efficacious / Less potent analgesic
© Causes
less CNS side effects
Dose & Route of Administration
1. Morphine
à
15
mg (photo grain) – standard dose was given earlier
Now
given small doses – 2.5, 5, 7.5 mg
2.5
mg is the starting dose in kids
In
adults repeat on a needed basis - given 2 / 4 / 6 hourly
IV
bolus doses
IM
also can be given, but now not given very often
In
cancer patients - self control SC administration or oral 30 mg (slow release)
2. Pethidine
à
IM
injections
75,
100 mg
Start
with small doses
3. Buprinorphine
à
Sub
lingual preparations - Parenteral
Less
addictive effects
4. Pentazocin
à
Oral
& Parenteral preparations
Not
used now
5. Codeine
phosphate à
Tablets,
Syrups, etc.
Mild
efficacy
A
place in management of cancers
6. Fentanyl
à
-
Widely used by anesthetists
