Curriculum Vitae

N a m a : Prof. DR. Dr. Rozaimah Zain-Hamid, MS, SpFK

Riwayat Pekerjaan: * Guru Besar Tetap Departemen Farmakologi
dan Terapeutik, FK USU
* Staf Pengajar Prodi S2 Biomedik, S3 Kedokteran FK USU; Prodi S2 &
PPDGS Prostodontie, Konservasi Gigi, Periodontie, Orthodontie
FKG USU
* Ex. Anggota Kom. Nas. Etik Penelitian Kesehatan (KNEPK) (2007-2011;
2011-2015)
* Ex. Anggota Komisi Etik Pengembangan dan Penelitian Kesehatan
Nasional (KEPPKN) (2015-2019)
* Ketua Pengembangan Organisasi Yayasan Asma Sumut (2011-sekarang)
Riwayat Pendidikan:
* Dokter (Dr), Fakultas Kedokteran, USU. Medan
* Magister Sains (MS), ‘Basic Medical Sciences’, Fakultas Pascasarjana,
Universitas Indonesia, Jakarta
* DR (Ph.D), ‘Clinical Pharmacology’, Institute of Post-graduated Studies,
Universiti Sains Malaysia, Malaysia
* Spesialis Farmakologi Klinik (Sp.FK), Dewan Penilai Kepakaran
Persatuan Dokter Ahli Farmakologi Klinik Indonesia (PERDAFKI) Pusat,
Jakarta.
PHARMACOLOGY OF ANALGESICS

Presented by:
Rozaimah Zain-Hamid

Department of Pharmacology & Therapeutics

Faculty of Medicine
Universitas Sumatera Utara
 Pain

 An upleasant sensory & emotional experience

associated with actual or potential tissue damage,
or described in terms of such damage

 Pain stimuli detected by nociceptors

via free nerve endings

 Chemical, mechanical or thermal stimuli

are involved

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
 Pain: The fifth vital signs

• Pulse
• Blood pressure Pain:
• Temperature Vital Signs
• Respiratory rate
American Pain Society Web site.
1

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
 Analgesia and the Pain Pathway
Pain Opioids
2 agonists
Centrally acting analgesics
Selective COX-2 NSAIDs
Ascending
input Descending
modulatio
n
Dorsal Local anesthetics
horn Opioids
2 agonists
Dorsal root
ganglion
Spinothalamic
tract Local anesthetics
Peripheral
Peripheral nociceptors
nerve Local anesthetics
Selective Cox-2 NSAIDs
Trauma Traditional NSAIDs

Adapted from Gottschalk A, Smith DS. Am Fam Physician 2001;63:1979-84

 Conditions associated with pain

Nociceptive Psychogenic Neuropatic

pain pain pain

Acute pain = Chronic pain

Warning  Malignancy
symptom of  Chronic infection
underlying  Osteoarthritis
problems Preemptive  Rheumatoid
analgesia arthritis, etc

Treatments that prevents establishment

of central sensitization caused by incisional
and inflammatory injuries
What should be considered
before treating the pain?

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
 Pain management

 Goals of pain management

 Relieve suffering
 Increase functional capacity
 Improve quality of life

 Ways to advocate for pain management

 Don’t use placebos
 Promote pain education
with all disciplines
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 Pain Rating Scales

VAS
0 1 2 3 4 5 6 7 8 9 10
Mild Moderate Severe
Pain threshold
Pain tolerance
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 Pain Management
• Elimination of the cause of the pain
• Lowering sensitivity nociceptors: antipyretic
analgesics, local anesthetics
• Interrupting nociceptive conduction in
sensory nerves: local anesthetics
• Supression of transmission of nociceptive
impulses in the spinal medulla:opioids
• Inhibition of pain perception: opioids, general
anesthetics
• Altering emotional responses to pain:
antideppresants
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
Origin and effects of prostaglandin
 Antipyretic analgesics
• Acetaminophen (paracetamol):
toothaches and headaches
• Acetysalicylic acid (ASA):
antiinflammatory effect (+)
• Ibuprofen
• Pyrazolone derivates
(aminopyrine and dypirone):
metamizole displays the highest efficacy

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
Antipyretic analgesics
 PAIN

inflammation severe
neurophatic
CNS origin

PAIN KILLER
adjuvant opioid
analgesic NSAID analgesic

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
 phospholipids
Corticosteroid
arachidonic acid

COX LOX
COX-2 COX-1
cyclic
endoperoxides 5-HPETE
NSAIDs
PGI2
inhibits platelet TXA2 LTA4
aggregation, stimulates platelet
vasodilator, aggregation,
vasoconstriction LTB4
hyperalgesia chemotaxis

LTC4
PGD2 PGE2 PGF2alfa
inhibits platelet bronchoconstriction LTD4 brochoconstriction
vasodilator, myometrial contr. increase
aggregation,
vasodilator hyperalgesia hyperalgesia vascular
LTE4
permeability
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
The evolution of NSAID chemistry
for the control of pain

Coxib
Class
Acetic
Oxicam Acid Celecoxib
Class Class Rofecoxib
Propionic
Acid Valdecoxib
Salicylic Piroxicam Diclofenac Etoricoxib
Acid Class Etodolac
Meloxicam Parecoxib
Class Lumiracoxib
Ibuprofen
Aspirin ketoprofen

1853 1970- 1980- 1990- 2000-

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
 NSAID classification

Acetosal Diclofenac Celecoxib

Indomethacin Ibuprofen
Ketorolac
Resveratrol
Piroxicam Ketoprofen
Meloxicam
Nimesulide
COXIB
Rofecoxib
Valdecoxib

preferentially non- preferentially

COX-1 COX-1 COX-2 COX-2
selective
selective selective selective selective
COX
inhibitor inhibitor inhibitor inhibitor
inhibitor
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 Current view in selecting analgesic
and antiinflammatory drugs
 Efficacy (indication)
(+)inflammation, bone fractur, renal colic,
dysmenorrhea, cancer
 Safety (side effect)
 Not only GI toxicity
 Cardiovascular toxicity
 Renal toxicity
 Bone healing impairment etc
 Pharmacokinetics
- Short half-life, long half-life
 Daily cost
 Evidence Based Medicine Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 Diclofenac Celecoxib
Acetosal IndomethacinIbuprofen
Ketorolac Piroxicam Ketoprofen
Meloxicam COXIB
Rofecoxib
Valdecoxib
Nimesulide

preferentially non- preferentially

COX-1 COX-1 COX-2 COX-2
selective
selective selective selective selective
COX
inhibitor inhibitor inhibitor inhibitor
inhibitor

anti-inflammatory
analgesic

Vane JR et al. Annu Rev Pharmacol Toxicol. 38:97-120,1998.

Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 More CV events and
Less GI side effects
other side effects . .
More GI side effects

Diclofenac Celecoxib
Acetosal Indomethacin Ibuprofen
Ketorolac Piroxicam Ketoprofen
Meloxicam
Nimesulide
COXIB
Rofecoxib
Valdecoxib

preferentially non- preferentially

COX-1 COX-1 COX-2 COX-2
selective
selective selective selective selective
COX
inhibitor inhibitor inhibitor inhibitor
inhibitor
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
NEPHROTOXICITY

AA
NSAIDs

LTs PGs
vaso- constriction vaso-dilatation
fluid & electrolyte

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
OCULAR TOXICITY

AA
NSAID

LTs PGs
vaso- vaso-
constriction dilatation

temporary
reversible
color-blindness
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 TOXICITY IN PREGNANCY
AA
NSAID

LTs PGs
utero-
contraction

NSAIDs
deplete folic acid levels and then prolong
increase the risks of birth defects gestation & labor
increase risk of miscarriage Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 RESPIRATORY TOXICITY
AA
NSAID

LTs PGs

bronchoconstriction bronchodilatation

NSAID-induced asthma
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 OPIOID ANALGESICS

• Opium alkaloid: morphine

• Semisynthetic derivatives: hydromorphone
• Synthetic derivatives: pentazocine, pethidine,
methadone, fentanyl
• Opioid receptors are found in various brain region &
spinal medulla, intramural nerve plexuses of
alimentary and urogenital track
• Induce hyperpolarization:
decrease synaptic activity
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
Papaver somniferum

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
 Endogenous Opioid Systems

• An agent found within the brain

that acts through an opioid
receptor is called as an
endogenous opioid

• Principally three classes

– enkephalins, endorphins,
dynorphins
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 Opioid Receptors

• Opioid receptors
– Binding sites not only for endogenous opiates
but also for opioid analgesics to relieve pain
• Several types of receptors:
– Mu, Kappa, Delta, Epsilon & Sigma.

Department of Pharmacology & Therapeutics

Faculty of Medicine, Universitas Sumatera
Action of endogenous and exogenous opioids
at opioid receptors
 Mechanism-Analgesia
• Block Calcium channel in presynaps
• Open Kalium channel in post synaps
Effects of opioids
 OPIOIDS

WEAK OPIOID STRONG OPIOID

• Tramadol • Morphine
• Codein: 1/10 morphine • Fentanyl
• Dihydrocodeine • Oxycodone
• Buprenorphine
• Hydromorphone
• Methadone
• Tapentadol
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
Choosing pain killer
and its combinations
10 Pain Intensity Scale

0 1 2 3 4 5 6 7 8 9 10
Mild Moderate Severe
paracetamol NSAID Strong opioid
or/+ ± ±
NSAID weak opioid NSAID
± ± ±
adjuvant adjuvant adjuvant
analgesic analgesic analgesic
Department of Pharmacology & Therapeutics
Faculty of Medicine, Universitas Sumatera
 Thank You

Money will buy a bed but not sleep;

books but not brains; food but not appetite;
finery but not beauty; a house but not a home;
medicine but not health; luxuries but not culture;
amusement but not happiness;
religion but not salvation;
a passport to everywhere
but not to heaven (Anonymous).