Prof. DR. dr. Hadyanto Lim, M.

Kes,SpFK,FESC,FIBA, FAHA
Department of Pharmacology and Molecular Science,
Faculty of Medicine, Methodist University of Indonesia - Medan
Molecular Biology Research,
Postgraduate School, University of Sumatra Utara - Medan



Blok VII Emergency &Trauma, FK UMI
Analgesic
February 28, 2012
Pain Mediators
BK, bradykinin, PG, prostaglandin
Page C, et al. Integrated Pharmacology, p. 251, 2006
Pain
Acute pain
Persisting only for the duration of the tissue
damage, representing a natural, physiologic
defense reaction of the body.

Chronic pain
When the normal healing mechanisms are
complete; rheumatic arthritis, may persist for
weeks, months, or years.
Pain Perception
Pain detection in peripheral tissue by
specialized pain sensors (nociceptor).

Transmission of pain information from the
periphery to the dorsal horn of the spinal cord.

Passage of pain information to higher brain
centers, from which an appropriate action can
be initiated.
Pain Perception
Page C, et al. Integrated Pharmacology, p. 251, 2006
A fiber, responsible for sharp
pain , intense.

C fiber, for dull pain, burning.
Pain Pathways
NMR, nucleus magnus
raphae
LC, locus ceruleus
SP, subtance P
Glu, glutamate
5-HT, 5-hydroxytriptamine
NE, norepinephrine
Enk, enkephalin
Ascending pain pathways :
1. Sensory discriminative
componenet, to the
cerebral cortex
2. Motivational affective
component, to the limbic
cortex


Analgesic
Opioid Analgesics : act primarily in the spinal
cord and brain to inhibit the neurotransmission
of pain.

Non-opioid Analgesics : act primarily in
peripheral tissues to inhibit formation of
algogenic or pain- producing substances such as
prostaglandins also called nonsteroidal anti-
inflammatory drugs (NSAID).
Structures of
Morphin and Its
Derivatives
Mechanisms of Opioid Action
Morphin and other opioid activate
presynaptic (mu), (delta) or (kappa)
opioid receptors on primary afferent
neuron

The receptors are coupled negatively to
adenylyl cyclase (AC) via G proteins (Gi).

Inhibition of cyclic adenosine
monophosphate (cAMP) formations leads
to opening of potassium channels and
closing of calcium channels.

Potassium efflux causes membrane
hyperpolarization, whereas closing of
calcium channels inhibits the release of
neurotransmitter such as substance P

Adverse Effects
Respiratory depression, causing death in severe
overdoses (the stimulation of respiratory centers
by increased carbon dioxide levels).
The respiratory depressant effects of opioids
are rapidly reversed by the intravenous
administration of an opioid antagonist such as
naloxone.


Itching due to stimulate mast cell to release of
histamin.

Nausea and vomiting due to stimulating the
chemoreceptor trigger zone.

Allergic reaction. But allergic to opioid will
probably not be allergic to propoxyphene or
fentanyl

Adverse Effects
Tolerance and Physical Dependence
Tolerance is a decrease in initial pharmacologic
effect observed following chronic or long term
administration.
Opioid tolerance is usually accompanied by a
similar degree of physical dependence a
physiology state in which a persons continued use
of a drug is required for his or her well-being.
The neuron become less responsive to the opioid
while requiring continued opioid inhibition to
maintain cellular homeostasis.

Rheumatoid Arthritis
The Arachidonic Cascade and COX-1 and COX-2
Inhibition










Arachidonic acid
COX-1 COX-2
Nonselective
NSAID
COX-2
selective
Inhibitor
Body Homeostasis
. Gastric integrity
. Renal Function
. Platelet Function

Inflammation
Pain
Needleman P, et al. J Rheumatol. 1997;24:6-8.
Simon LS, et al. J Clin Rheumatol. 1996;2:135-40.
Choice of Analgesic
Acute pain caused by trauma, surgery, or short-
term medical conditions can be effectively
managed with an analgesic and appropriate
treatment of the underlying condition.

The risk of producing drug dependence is
extremely low.

Pain associated with arthritis, neuropathy, and
other chronic but nonterminal conditions is often
managed with a combination of analgesic,
coanalgesic (antiepileptic drugs, and the
antidepressant drugs), psychotherapy, physical
therapy and other treatment modalities.

Both opioid analgesics and nonopioid analgesics
are useful in the management of chronic pain
syndromes.

Choice of Analgesic
KaplanMeier Curves for 28-Day Survival in the Intention-to-Treat Population
De Backer D et al. N Engl J Med 2010;362:779-789.
Mortality Rates

De Backer D et al. N Engl J Med 2010;362:779-789.
De Backer D et al. N Engl J Med
2010;362:779-789.