DRUGS USED IN THE MANAGEMENT OF PAIN Flashcards
What is pain?
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.
Its a perception and a sensation!
Drugs that have analgesic actions act by modulating the pain neural pathways in various ways that include:
Inhibition of activity at nociceptors
Inhibition of synthesis of mediators of nociception and pain transmission
Inhibition of transmission of pain signals
Potentiation of mediators that inhibit transmission of pain signals
Classification
of Pain
Acute Pain: occurs over a brief
period and usually associated with
a temporary disorder
Chronic Pain: continuous and
recurrent and sustained by
different mechanisms.
Pain syndromes may also be classified into:
- Nociceptive pain: may be “referred” – e.g.
injury to the hip referred to the knee - Neuropathic pain
- Psychogenic pain
- Idiopathic pain
Pharmacological Methods of Pain Management
- NSAIDs
- Opioids
- Adjunctive agents
- Local anesthetics
- General anesthetics
Non-Pharmacological Methods of Pain Management
- Counseling
- Acupuncture
- TENS
- Massage
Analgesic Ladder: Stepwise management of pain
Step 1. Start with non-opioid
(e.g. NSAID or paracetamol)
Step 2. Use an opioid for mild or
moderate pain if pain persists
e.g. codeine
Step 3. Use opioid for moderate
to severe pain if pain persists
e.g. morphine, fentanyl
Gate Control Theory Melzack and Wall 1965.
Pain stimulus is transmitted from
pain receptors, through peripheral nerves to the spinal cord to the brain. Through two different types of nerves fibres:
*A-delta “fast pain” and C-fibers “slow pain” nerve fibers.
Physiological and psychological
interactions suggests spinal gates
in the dorsal horn at each
segment of the spinal cord
*Competition at each gate for
heat, touch or pain to be
transmitted at each point
How does nociceptive pain occur?
①Transduction: Mediators, PG, HT, Histamine Sub P released, Generator Potentials (NSAIDS)
②Transmission via nerve fibers
③Modulation by PG, amines, neurokinins, GABA, neurotensin, cannabinoids (OPIODS)
④Perception (OPIODS)
NSAIDS: Nonselective Cox Inhibitors:
Aspirin
Ibuprofen
Piroxicam
Meclofenamate
Diclofenac
Indomethacin
NSAIDS: Selective Cox Inhibitors:
➢ Celecoxib
➢ Rofecoxib
➢ Meloxicam
NSAID common pharmacological effects
Analgesic (CNS and peripheral
effect)
Antipyretic (CNS effect)
Anti-inflammatory (except
acetaminophen)
Some are Antiplatelete: inhibit
activation, adhesion and
aggregation of platelets &
release of lysosomal enzymes
Some are Uricosuric
Opioids: Nomenclature
Opium: is the dried powdered mixture of alkaloids obtained from poppy
Opiate: Any agent derived from opium
Opioid: All substances (exogenous or endogenous) with morphine -like properties
Opiods: Classification
①Alkaloid: derived from poppy plant
*Morphine
*Codeine
②Semisynthetic: modification of morphine
functional groups:
* Diacetylmorphine (heroin)
*Hydrocodone
*Hydromorphone
* Oxycodone
* Oxymorphone
③Synthetic: progressive reduction in the number of fused rings in phenanthrene moiety:
*Meperidine
*Fentanyl
*Sufentanil
*Alfentanil
Opioid Receptor Classification
①mu receptor 1 (MOR1): most endogenous, natural or synthetic for SUPRASPINAL ANALGESIA
②)mu receptor 2 (MOR2): morphine, RESPIRATORY DEPRESSIONS, CVS
③kappa receptor (KOR): Ketocyclazocine and dynorphin for SPINAL ANALGESIA, SEDATION AND MIOSIS
④delta receptor (DOR): Enkephalins for SPINAL ANALGESIA
⑤sigma receptor: N-allylnormetazocine for PSYCOTOMIMETIC EFFECTS
Opioid Intrinsic Activity
Agonists produce a maximum
biologic effect.
Antagonists have no intrinsic
activity and prevent the access of
agonists to the receptors .
Partial agonists have a submaximal
response
Opioid Partial agonism:
interaction at a single receptor type
e.g. buprenorphine on mu receptors
Opioid Mixed Agonist-antagonists:
have divergent activities at different receptors, acting simultaneously as an
agonist at one receptor and an antagonist at another;
e.g. ①pentazocine: antagonist on mu, agonist on sigma and kappa
➁butorphanol: antagonist on mu, agonist on sigma and kappa
③nalbuphine: antagonist on mu, partial agonist on sigma and agonist on kappa
MoA of Opioid agonists= analgesia
- Activate the descending pathways
from the midbrain and brain stem
and exert a strong inhibitory effect
on dorsal horn transmission - Inhibit excitation of sensory nerve
terminals in the periphery (increase
pain threshold)
Primary Effect of Opioid Receptor
Activation
Release of pain-signaling
neurotransmitters is regulated by
endogenous opioid peptides or by
exogenous opioid agonists.
Through presynaptic inhibition of substance P release, thereby producing analgesia
Involves changes in transmembrane ion conductance
Increase potassium conductance
(hyperpolarization)
Inactivation of calcium channels
Pharmacological Effects of Opioids
①Sedation and anxiolysis
* Drowsiness and lethargy
* Apathy
* Cognitive impairment
* Sense of tranquility
➁Depression of respiration
* Main cause of death from opioid overdose.
* Combination of opioids and alcohol is
especially dangerous.
③Cough suppression
* Opioids suppress the “cough center” in the
brain.
④Pupillary constriction
* pupillary constriction in the presence of
analgesics is characteristic of opioid use.
⑤Nausea and vomiting
Stimulation of receptors in an area of the medulla called the chemoreceptor trigger zone causes nausea and vomiting
Unpleasant side effect, but not life threatening
⑥Gastrointestinal symptoms
Opioids relieve diarrhea as a result of their direct actions on the intestines
Billiary tract spasm, especially of the sphincter of Oddi
Reversible by naloxone, nitroglycerin
⑦Other effects
Opioids can release histamines causing itching or more severe allergic reactions including bronchoconstriction
Opioids can affect white blood cell function and immune function
Morphine: Prototype of
the group
Routes: PO, IM, IV, SQ,
nebulized & rectal
Morphine: conjugated
in the liver
Has several active
metabolites
Diamorphine (Heroin)
Derived from morphine
Higher potency than morphine
More lipid soluble than morphine, so
enters the CNS more readily
Causes more euphoria than morphine
and has higher abuse potential
Pethidine (meperidine)
*Less potent than morphine
*Less respiratory depression compared to morphine and has no effect on the cough reflex
*Causes tremors, muscle twitches
and rarely convulsions (due to a
toxic metabolite – norpethidine)
*Unlike other opioids, large doses cause pupil dilatation, tachycardia (has anti-muscarinic effects) and hyper-active reflexes (due to norpethidine)
*Pethidine is preferred to morphine in the relief of labour pain because it has a shorter duration of action and causes less respiratory depression in the newborn (the newborn does not have glucuronidation enzyme for morphine and therefore cannot metabolise morphine)
*Pethidine is also the preferred opioid analgesic in biliary and ureteric colic since it causes less smooth muscle spasm.
