2 December 1951

Bukit Tinggi

SpFK, Clinical Pharmaco

PB-IDI & FK UI, 1995

Professor
MD, FK USU, 1978
Head of Department
Pharmacology & Therap
PhD in Clinical PharmacologySchool of Medicine, USU
FUSA-Flinders Medical Centre
Jln. Tridharma 22
Australia, 1988
Kampus USU, Medan

Aznan Lelo
Dep. Farmakologi & Terapeutik,

Fakultas Kedokteran
Universitas Sumatera
Utara
8 Oktober 2011,
KONKER IPS, Jakarta

Rational prescription
(WHO,1995)
Patient receive
appropriate medicines
according to their
clinical needs
at an appropriate
dosage,
administration
& duration
and in a way
that encourages
the patient compliance
and
at the lowest cost
to the community

Appropriate patient
( Tepat Pasien )
Appropriate indication
( Tepat Indikasi )
Appropriate drug
( Tepat Obat )
Appropriate dosage,
administration & duration

(Tepat dosis, cara & lama pemberian)

Appropriate information
( Tepat Information )
Appropriate cost
( Tepat biaya )

Critical approaches
in selecting medicines
Therapeutic Adverse reaction
effect
Minimal Maximal

Maximal
Minimal

Yes
?

?
No

Factors to consider when

choosing a pain killer

Drug issues
Efficacy
Tolerability
Safety
Dosage
Cost

BENEFITS
efficacy

RISKS
safety

Patient issues
Type, severity
Risk factors: GI,
platelet, renal and
cerebro-cardiovascular
system.
Co-prescription.
Co-morbidity.
Compliance.

Inappropriate treatment of pain

This includes :
Non-treatment,
Under-treatment,
Over-treatment, and
Ineffective treatment.
Administration of the wrong medication,
Failure to monitor side effects,
Inappropriate medication prescription, and
Incorrect prescription

opioids are inappropriately used and prescribed

Atluri SL, Sudarshan G. Development

of a screening tool to detect the risk of
inappropriate prescription opioid use
in patients with chronic pain. Pain
Physician 2004; 7:333-338.
90 percent of people in the United States
receiving treatment for pain management
are prescribed opiate medication.
Of that number, 18 percent to 41 percent
had opiate abuse/addiction problems.

Principles of Medical
Ethics
in Pain Management
Principles

Pharmaco-therapeutic
approaches

BENEFICENCE :

Pain killer (analgesic),

potent, rapid onset

NON MALEFICENCE :

Minimal ADR,
not deteriorate other clinical
problems

JUSTICE :

Rational

AUTONOMY :

Religion, Preference, PRN,

pharmaco-economics

mengutamakan
kepentingan pasien
tidak memperburuk
keadaan pasien

tidak mendiskriminasikan
pasien, apapun dasarnya
menghormati hak pasien
dalam memutuskan

Critical approaches
in selecting medicines
Adverse
reaction
NNH

Therapeutic
NNT
effect
GREATEST
Minimal Maximal
SMALLEST
(> 100)

SMALLEST
(2-4)

Maximal
GREATEST
Minimal

Yes
?

?
No

There are two reasons to withdraw from the treatment e

no efficacy (NNT very high) or
serious adverse reactions (NNH very low).

number needed to treat (NNT) for at least 50%

pain relief over 4-6 hours in patients with
moderate to severe pain, all oral analgesics
except morphine, pethidine and ketorolac

platelet
aggregation

fewer
heart attack

COX-1
inhibitor
GI
bleeding

platelet
aggregation

more
heart attack
platelet
aggregation

GI
bleeding

GI
bleeding

COX-2
inhibitor

Celecoxib vs Etoricoxib
CV & Renal Safety Profile

Blood pressure change

Zhang J et al. JAMA 2006;296:1619-32; Schwartz JI et al. J Clin Pharmacol 2007;47:1521-31

Lowest GI risk

NSAID GI
Toxicity
generally
varies
with halflife of
the
agent

Shortest half-life

NSAID

Diclofenac

Naproxen

Piroxicam

Dose (mg/d)

100

750

20

Half-life (hr)

1.5

14

50

24 hr fecal blood
loss (mL)

0.53 +/- 0.21

2.76 +/- 2.22

1.16 +/- 0.62

Henry, et al. BMJ.312:1563,2000; Scharf, et al. Aust N Z J Med

Acute vs Chronic Pain

Drug
Duration of
pain

Component

Acute

Chronic

Rapid onset

Long duration

Short, self limiting, Persists after healing,

well-characterized
3 months

Nociceptive

Nociceptive
Neuropathic

Mild vs Severe Pain

Drug

Mild

Severe

Low dose

High dose
Potent agent

Concentration

Correlation between absorption,

T-max and onset of action
NSAID short half life

NSAID long half life

rapid onset

long duration

but short duration

but slow onset

NSAID
medium half life
Effective concentration

Time
Acute

Slowly Chronic

US FDA APPROVAL
for Celecoxib on Acute Pain

http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020998s018,019lbl.pdf

do not care .
to the correct and clear drug
prescription

CELEXA for CELEBREX?

A Case of Medication Sample Error
Moyer B, Shrading W, Burkhart KK
Int J Med Toxicol 3(2):7,2000

citalopram (Celexa). a selective serotonin (5-HT) reuptake inhibitor

Classification of Pain by
Pathophysiology
Nociceptive
Pain

Mixed Type
(eg, Postoperative pain,
chronic back pain)

Neuropathic
Pain
CRPS

Visceral
Abdominal
Obstetrical

Head

Headache
NSAID
Orofacial

Musculoskeletal
Osteoarthritis
Rheumatoid Arthritis
Low Back Pain
CRPS =
complex regional pain syndrome.

Postherpetic
Neuralgia

Adjuvant Trigeminal
Neuralgia
ANALGESIC
Low Back Pain
Central
Poststroke Pain

Other
Postoperative
Cancer Pain

Distal
Polyneuropathy
(eg, diabetic, HIV)

International Association for the Study of Pain. IASP Pain Terminology.

Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57

Pharmacologic Agents
Affect Pain Differently
Inhibition of
Ascending
Pain Pathways
Opioids

PNS

Peripheral
Sensitization

BRAIN

Descending Modulation
CNS

Spinal
Cord

Dorsal
Horn
NSAIDs
Antiarrhythmic
Local Anesthetics
Topical Analgesics
Anticonvulsants
Tricyclic Antidepressants
Opioids

Anticonvulsants
Opioids
Tricyclic/SNRI Antidepressants

Central Sensitization
Alpha-2 Delta agonists
Anticonvulsants
Opioids
NMDA-Receptor Antagonists
Tricyclic/SNRI Antidepressants

FDA-Approved Treatments for

Neuropathic Pain
Adjuvant
Analgesia

Trigeminal
Neuralgia

Carbamazepine
Duloxetine
Gabapentin
Pregabalin
Lidocaine
TCA

PHN

PDN
+
+

+
+
+
+

+
+

NNT and NNH

adjuvant analgesia
Drug
Phenytoin
TCAs
Carbamazepine
Pregabalin
Gabapentin
Mexiletine
Codeine

NNT
2.1
2.4
3.3
3.3
4.7
10
18

NNH
9.5
2.7
1.9
3.7
2.7
510
2

Do surgical patients benefit from

perioperative gabapentin/pregabalin?
A systematic review of efficacy and safety.
Tiipana EM, Hamunen K, Kontinen VK, Kalso E.
Anesth Analg. 2007 Jun;104(6):1545-56.

Systematic analysis of 22 RCTs on

perioperative administration of
gabapentinoids for postoperative pain relief
demonstrated the both agents effectively
reduce postoperative pain,
opioid consumption (20-67%), and
opioid-related adverse effects after surgery.

Pregabalin

S-(+)-3-isobutyl GABA
Readily crosses blood-brain barrier
Not metabolically converted to GABA
Not a GABA agonist or antagonist
binds to the 2- subunit of voltagegated calcium channels in the CNS
not a vascular calcium channel inhibitor,
and does not effect heart function
6 X more potent than gabapentin
can be effective in gabapentin failures
Silverman et al.1991, Taylor CP 1995; Vartanian et al. 2003

Pregabalin binds to the 2- subunit of

voltage-gated Ca2+ channels in the CNS
Taylor. CNS Drug Rev. 10:183-8,2004

Modulates calcium influx in hyper-excited neurons

Reduces excitatory neurotransmitter release e.g.
glutamate, Substance P, noradrenaline

NNT and NNH Pregabalin

in patients with chronic
pain
Condition

Post-Herpetic
Neuralgia
Painful Diabetic
Neuropathy
Fibromyalgia
Central Neuropathic
Pain

Dose (mg) NNT (95%CI)

300

4 ( 3 7)

300

7 ( 5 17)

300
600

10 (7 17)
4 (3 7)

NNH (95%Cl)
All conditions

300

7 (6 9)

The Rational of Pain Management

COX-1 specific inhibitor (Ketorolac) will cause GI
events, while COX-2 specific inhibitor (Etoricoxib)
will cause CV events
Preferential COX-2 inhibitor (Celecoxib) will give
less both GI and CV events
Mixed pain needs a combination of NSAID with
adjuvant analgesic
2- subunit of voltage-gated calcium channels
blockers (ex. Pregabalin) offer additional treatment
options
Opioids are not recommended to be regularly
prescribed

KEBANGGAAN
INDONESIA UNTUK
DUNIA

Be a smart
doctor
and the right
one too

KEBANGGAAN INDONESIA UNTUK

DUNIA

Pharmacologic Profile of
Antidepressants
Type of Action

Receptor Type

TCAs
Amitriptyline
Clomipramine
Imipramine

Desipramine
Maprotiline*
Nortriptyline

SNRIs

SSRIs

Duloxetine
Venlafaxine

Citalopram
Fluoxetine
Paroxetine
?
?
?

Sodium channel
Calcium channel

+
+

+
+

( )

Monoamine
transporter
blockade

5-HT
Norepinephrine
Dopamine

+
+

( )

+
+

-Adrenergic
H1-Histaminergic

+
+

+
+

Receptor
Muscarinicblockade
+
+
cholinergic
*Tetracyclic antidepressant.
+
+
+=present; (+)=weak; =notNMDA
present; ?=unknown; 5-HT=serotonin.
Sindrup S, Jensen T. Hansson P, Fields H, Hill R, Marchettini P, eds. Neuropathic Pain: Pathophysiology
and Treatment Progress in Pain Research and Management. Seattle, Wash: IASP Press;2001:169-183.

( )

Ion channel
blockade