HOMEWORK 2

PHARMACOLOGY OF
ANALGESIC
ERLIN IRAWATI

OPIOID ANALGESICS

OPIOID ANALGESICS INCLUDE:

OPIOID ANALGESIC

FARMAKOKINETIK
(ABSORBSI)
Rute
pemberian
bisa
secara
subkutan,
intramuskular,
oral,
intravena, nasal insufflation, mukosa
oral via lozenges, transdermal via
transdermal patches.
Rute pemberian oral membutuhkan
dosis yang lebih tinggi agar dapat
menimbulkan efek terapeutik karena
metabolisme lintas pertama (firstpass metabolism).

FARMAKOKINETIK
(DISTRIBUSI)
Obat-obatan opioid berikatan dengan
protein plasma dengan afinitas yang
bervariasi.
Konsentrasi tertinggi obat ini adalah
di otak, paru, hati, ginjal, dan limpa.
Konsentrasi di otot rangka juga
cukup tinggi karena sebaran otot
rangka yang luas di tubuh.

FARMAKOKINETIK
(METABOLISME)
Opioid
dimetabolisme
menjadi
konjugat
glukuronida (metabolit yang lebih polar).
Morphine, which contains free hydroxyl
groups, is primarily conjugated to morphine-3glucuronide
(M3G),
a
compound
with
neuroexcitatory properties.
Approximately
10%
of
morphine
is
metabolized to morphine-6-glucuronide (M6G),
an active metabolite with analgesic potency
four to six times that of its parent compound.

FARMAKOKINETIK
(EKSKRESI)
Konjugat
glukuronida
analgesik
opioid yang merupakan metabolit
polar sebagian besar di ekskresikan
di urin. Sebagian kecil dari analgesik
opioid
diekskresikan
tanpa
perubahan bentuk (unchanged drug).
Sebagian kecil konjugat glukuronida
diekskresikan di empedu.

FARMAKODINAMIK

MECHANISM OF ACTION
Opioid agonists produce analgesia by binding to
specific G protein-coupled receptors that are
located in brain and spinal cord regions involved
in the transmission and modulation of pain.
The opioids have two well-established direct G
protein-coupled actions on neurons: (1) they
close
voltage-gated
Ca2+
channels
on
presynaptic nerve terminals and thereby reduce
transmitter release, and (2) they hyperpolarize
and thus inhibit postsynaptic neurons by
opening K+ channels.

Sites of action on the afferent pain transmission pathway from the

periphery to the higher centers are shown. A: Direct action of
opioids on inflamed or damaged peripheral tissues B: Inhibition
also occurs in the spinal cord. C: Possible sites of action in the
thalamus.

Brainstem local circuitry underlying the modulating effect of -opioid receptor (MOR)
mediated analgesia on descending pathways. The pain-inhibitory neuron is indirectly
activated by opioids (exogenous or endogenous), which inhibit an inhibitory (GABAergic)
interneuron. This results in enhanced inhibition of nociceptive processing in the dorsal
horn of the spinal cord

Opioid analgesic action on the descending inhibitory pathway. Sites of action

of opioids on pain-modulating neurons in the midbrain and medulla including
the midbrain periaqueductal gray area (A), rostral ventral medulla (B), and
the locus caeruleus indirectly control pain transmission pathways by
enhancing descending inhibition to the dorsal horn (C).

CLINICAL USED OF OPIOID

ANALGESICS

Analgesia
Severe, constant pain is usually relieved with opioid
analgesics with high intrinsic activity; whereas sharp,
intermittent pain does not appear to be as effectively
controlled.
The pain associated with cancer and other terminal
illnesses must be treated aggressively and often requires
a multidisciplinary approach for effective management.
Such conditions may require continuous use of potent
opioid analgesics and are associated with some degree of
tolerance and dependence.
Opioid analgesics are often used during obstetric labor.
The acute, severe pain of renal and biliary colic often
requires a strong agonist opioid for adequate relief.

Acute pulmonary edema

morphine can be particularly useful
when treating painful myocardial
ischemia with pulmonary edema.
Proposed mechanisms include
reduced anxiety (perception of
shortness of breath), and reduced
cardiac preload (reduced venous
tone) and afterload (decreased
peripheral resistance).

 BATUK
Suppression of cough can be obtained at doses lower than
those needed for analgesia.
DIARE
Diarrhea from almost any cause can be controlled with the
opioid analgesics. Now synthetic surrogates with more
selective gastrointestinal effects and few or no CNS
effects, eg, diphenoxylate or loperamide, are used
SHIVERING
Meperidine is reported to have the most pronounced antishivering properties. Meperidine apparently blocks
shivering mainly through an action on subtypes of the 2
adrenoceptor.

Applications in Anesthesia
The opioids are frequently used as premedicant drugs
before anesthesia and surgery because of their sedative,
anxiolytic, and analgesic properties. They are also used
intraoperatively both as adjuncts to other anesthetic agents
and, in high doses (eg, 0.020.075 mg/kg of fentanyl), as a
primary component of the anesthetic regimen
Opioids are most commonly used in cardiovascular surgery
and other types of high-risk surgery in which a primary goal
is to minimize cardiovascular depression.
Because of their direct action on the superficial neurons of
the spinal cord dorsal horn, opioids can also be used as
regional analgesics by administration into the epidural or
subarachnoid spaces of the spinal column.

NSAID

NSAID USED:
To suppress the signs and symptoms
of inflammation.
Exert antipyretic and analgesic
effects,
But it is their anti-inflammatory
properties that make them most
useful in the management of
disorders in which pain is related to
the intensity of the inflammatory
process.

PHARMACOKINETIC
All but one of the NSAIDs are weak organic acids as
given.
Most of these drugs are well absorbed, and food does
not substantially change their bioavailability.
NSAID metabolism proceeds, in large part, by way of the
CYP3A or CYP2C families of P450 enzymes in the liver.
While renal excretion is the most important route for
final elimination, nearly all undergo varying degrees of
biliary excretion and reabsorption (enterohepatic
circulation).
Most of the NSAIDs are highly protein-bound (~98%),
usually to albumin.

PHARMACODYNAMIC
The anti-inflammatory activity of the NSAIDs is
mediated chiefly through inhibition of
biosynthesis of prostaglandins.
Various NSAIDs have additional possible
mechanisms of action, including
Inhibition of chemotaxis,
Down-regulation of interleukin-1 production
Decreased production of free radicals and
superoxide
Interference with calcium-mediated
intracellular events.