OPIOID & KORTIKOSTEROID

Aghnia Fuadatul Inayah, M.Farm.Klin., Apt.

Firasti Agus N.S., M.Biotech., Apt.

FARMAKOLOGI - FARMASI UMM

1
 OPIOID

2 FARMAKOLOGI - FARMASI UMM

 Opioid
Analgetika:
Obat yang mengurangi atau Non-Opioid
menghilangkan rasa sakit

Antipiretika :
Obat yang berkhasiat menurunkan
demam

Antiinflamasi:
Obat yang berkhasiat mengurangi
inflamasi

FARMAKOLOGI - FARMASI UMM

3
 FARMAKOLOGI - FARMASI UMM
4
 Analgesik Opioid

FARMAKOLOGI - FARMASI UMM

5
 OPIOID

Opioid endogen
(endorfin, enkefalin, dan
dinorfin)
Opioid

Opioid eksogen (alamiah

dan sintetik)

FARMAKOLOGI - FARMASI UMM

6
 OPIOID

Reseptor Opioid

Reseptor µ Reseptor δ Reseptor κ

analgesik, euforia,
analgesia, sedasi, dan
depresi nafas, miosis,
depresi nafas
penurunan motilitas
saluran cerna depresi nafas dan
penurunan
frekuensi nafas

FARMAKOLOGI - FARMASI UMM

7
Mekanisme Kerja Opioid pada Reseptor

FARMAKOLOGI - FARMASI UMM

8
 Golongan Opioid

1. Golongan Phenanthrenes : morfin, heroin, kodein,

dihidrokodein, oksikodon
2. Golongan Phenylheptylamines : metadon,
propoksifen
3. Golongan Phenylpiperidines : fentanil, afentanil,
meperidin, loperamid
4. Golongan Morphinans : levorfanol,
5. Golongan Benzilisokinolin : noskapin, papaverin
6. Tramadol

FARMAKOLOGI - FARMASI UMM

9
 Golongan Opioid
Batuk

1. Golongan Phenanthrenes : morfin, heroin, kodein,

dihidrokodein, oksikodon
2. Golongan Phenylheptylamines : metadon,
propoksifen Terapi rumatan
pecandu narkoba
3. Golongan Phenylpiperidines : fentanil, afentanil,
meperidin, loperamid Antidiare
4. Golongan Morphinans : levorfanol,
5. Golongan Benzilisokinolin : noskapin, papaverin
6. Tramadol
Batuk

1 FARMAKOLOGI - FARMASI UMM

0
 Golongan Opioid

1. Golongan Phenanthrenes : morfin, heroin, kodein,

dihidrokodein, oksikodon
2. Golongan Phenylheptylamines : metadon,
propoksifen
3. Golongan Phenylpiperidines : fentanil, afentanil,
meperidin, loperamid
4. Golongan Morphinans : levorfanol,
5. Golongan Benzilisokinolin : noskapin, papaverin
6. Tramadol • Campuran rasemat
• Toleransi terjadi lebih lambat dari pada
• Toleransi terhdap efek depresi Meperidin morfin
timbul lebih lambat dibanding morfin • Kejadian adiksi lebih kecil dari pada morfin
• Gejala putus obat timbul lebih cepat tetapi
berlangsung lebih singkat dari pada morfin
11 FARMAKOLOGI - FARMASI UMM
 Farmakokinetik

• Tidak dapat menembus kulit yang utuh

• Dapat diabsorbsi melalui kulit yang luka dan mukosa
(absorbsi kecil)
• Mula kerja setelah pemberian secara IV semua
golongan opioid cepat
• Dapat menembus plasenta barrier
• Sebagian kecil morfin bebas ditemukan di keringat
dan feses

12 FARMAKOLOGI - FARMASI UMM

 Farmakodinamik

13 FARMAKOLOGI - FARMASI UMM

 Efek Opioid pada Derajat Toleransi

14 FARMAKOLOGI - FARMASI UMM

 Efek Samping Opioid

15 FARMAKOLOGI - FARMASI UMM

 Interaksi Obat Opioid

16 FARMAKOLOGI - FARMASI UMM

 Intoksikasi Akut dan Adiksi

• Terjadi karena overdosis atau percobaan bunuh diri

• Dasar kejadian adiksi :
1. Habituasi psikis dan emosional
2. Ketergantungan fungsi fisiologi dan biokimia
3. Toleransi terhadap obat

17 FARMAKOLOGI - FARMASI UMM

 KORTIKOSTEROID

18 FARMAKOLOGI - FARMASI UMM

19 FARMAKOLOGI - FARMASI UMM
20 FARMAKOLOGI - FARMASI UMM
21 FARMAKOLOGI - FARMASI UMM
 Endogenous Glucocorticoids

Hydrocortisone

Corticosterone

22 FARMAKOLOGI - FARMASI UMM

23 FARMAKOLOGI - FARMASI UMM
 Corticosteroids are Gene-Active

24 FARMAKOLOGI - FARMASI UMM

25 FARMAKOLOGI - FARMASI UMM
 Glucocorticoids
Kinetics:
• Well absorbed orally

• Bound to corticosteroid-binding globulin and albumin

• Distributed all over the body & passes the BBB

• In the liver, cortisol is reversibly converted to cortisone &

conjugated with glucuronic & sulfuric acid

• Excreted in urine as 17-hydroxy corticosteroids

26 FARMAKOLOGI - FARMASI UMM

 Action of glucocorticoids
• Metabolic

• Anti-inflammatory

• Immunosuppressive

27 FARMAKOLOGI - FARMASI UMM

 Actions
1. Carbohydrate 8. Stomach
2. Protein 9. Blood
3. Lipid 10. Anti-inflammatory
4. Electrolyte and H2O 11. Immunosuppressant
5. CVS 12.Growth and Cell
6. Skeletal Muscle Division
7. CNS 13. Calcium metabolism

28 FARMAKOLOGI - FARMASI UMM

 Carbohydrate metabolism
• Gluconeogenesis
– Peripheral actions (mobilize glucose and glycogen)

– Hepatic actions

• Peripheral utilization of glucose

• Glycogen deposition in liver

(activation of hepatic glycogen synthase)

hyperglycemia
29 FARMAKOLOGI - FARMASI UMM
 Protein Metabolism
Negative nitrogen balance

• Decreased protein synthesis

• Increased protein breakdown

30 FARMAKOLOGI - FARMASI UMM

 Skeletal Muscles
Needed for maintaining the normal function of
Skeletal muscle

Addison's disease: weakness and fatigue is due to

inadequacy of circulatory system

Prolonged use: Steroid myopathy

31 FARMAKOLOGI - FARMASI UMM

 Lipid metabolism

• Redistribution of Fat

32 FARMAKOLOGI - FARMASI UMM

 Buffalo Hump

33 FARMAKOLOGI - FARMASI UMM

 Electrolyte and water balance

Act on DT and CD of kidney

– Na+ reabsorption

– Urinary excretion of K+ and H+

34 FARMAKOLOGI - FARMASI UMM

 CNS

• Direct
– Mood
– Behavior
– Brain excitability

• Indirect
– maintain glucose, circulation and electrolyte
balance

35 FARMAKOLOGI - FARMASI UMM

 Stomach

– Acid and pepsin secretion

– immune response to H.Pylori

36 FARMAKOLOGI - FARMASI UMM

 Blood

RBC: Hb and RBC content

(erythrophagocytosis)

WBC: Lymphocytes, eosinophils,

monocytes, basophils
Polymorphonucleocytes

37 FARMAKOLOGI - FARMASI UMM

 Actions on inflammatory cells
• Recruitment of N, monocytes, macrophage
into affected area
• Action of fibroblasts
• T helper action
• Osteoblast
• osteoclast

38 FARMAKOLOGI - FARMASI UMM

39 FARMAKOLOGI - FARMASI UMM
 Inflammatory mediators
• Reduced cytokines

• Reduced complement

• Reduced histamine

40 FARMAKOLOGI - FARMASI UMM

 Anti-inflammatory actions of corticosteroids

Corticosteroid inhibitory effect

41 FARMAKOLOGI - FARMASI UMM

42 FARMAKOLOGI - FARMASI UMM
 Growth and Cell division

• Inhibit cell division or

synthesis of DNA

• Delay the process of

healing

• Retard the growth of

children

43 FARMAKOLOGI - FARMASI UMM

 Calcium metabolism
• Intestinal absorption

• Renal excretion

• Excessive loss of calcium from bones (e.g.,

vertebrae, ribs, etc)

• Osteoporosis

44 FARMAKOLOGI - FARMASI UMM

 Pharmacological Actions
• synthetic glucocorticoids are used because
they have a higher affinity for the receptor

• have little or no salt-retaining properties.

45 FARMAKOLOGI - FARMASI UMM

 Clinical uses
• Replacement therapy

• Immunosuppressive / anti-inflammatory
therapy

• Neoplastic disease

46 FARMAKOLOGI - FARMASI UMM

 Types of Steroids
Replacement Therapy

• glucocorticoid (hydrocortisone)

• mineralocorticoid (fludrocortisone)

47 FARMAKOLOGI - FARMASI UMM

48 FARMAKOLOGI - FARMASI UMM
 Anti-inflammatory Therapy

• Short acting: hydrocortisone

• Intermediate acting: prednisolone,

methylprednisolone, triamcinolone

• Long acting: dexamethasone

49 FARMAKOLOGI - FARMASI UMM

50 FARMAKOLOGI - FARMASI UMM
51 FARMAKOLOGI - FARMASI UMM
52 FARMAKOLOGI - FARMASI UMM
53 FARMAKOLOGI - FARMASI UMM
54 FARMAKOLOGI - FARMASI UMM
55 FARMAKOLOGI - FARMASI UMM
 Side effects
• Not seen in replacement therapy

• Seen if used for anti-inflammatory property

• Excess of physiological actions

56 FARMAKOLOGI - FARMASI UMM

 Iatrogenic Cushing’s
syndrome

57 FARMAKOLOGI - FARMASI UMM

 Adverse effects (long term)
• Glucose intolerance
• Acne
• Hypertension, edema
• Susceptibility to infection (TB, fungal)
• Myopathy
• Behavior & mood changes

58 FARMAKOLOGI - FARMASI UMM

59 FARMAKOLOGI - FARMASI UMM
60 FARMAKOLOGI - FARMASI UMM
 Adverse effects (long term)
• Avascular necrosis of bone
• Cataract
• Peptic ulcer
• Skin atrophy, delayed wound healing
• Growth retardation (children)
• Suppression of HPA axis

61 FARMAKOLOGI - FARMASI UMM

62 FARMAKOLOGI - FARMASI UMM
 Drug Interactions
• Estrogens - decrease prednisone clearance

• Phenobarbital, phenytoin, and rifampicin - increase

metabolism of glucocorticoids

• May cause digitalis toxicity secondary to hypokalemia

• Monitor for hypokalemia with co-administration of

diuretics

63 FARMAKOLOGI - FARMASI UMM

 Read !

Monitoring while on steroids

Pregnancy and steroids
Infections and long term steroid
Surgery and steroids

64 FARMAKOLOGI - FARMASI UMM

65 FARMAKOLOGI - FARMASI UMM
 Long Term Steroids
• Monitor BP, electrolyte and blood sugar

• Advise moderate exercise

• Bone protection measures

• Gastric protection if needed

66 FARMAKOLOGI - FARMASI UMM

 • Give morning dose

• Every other day

• Minimum effective dose

• Steroid sparing agents

67 FARMAKOLOGI - FARMASI UMM

 Read

• Mineralocorticoids – action, side effects,

clinical uses

68 FARMAKOLOGI - FARMASI UMM

 Tambahan...
• Tau kisah talidomid?

69 FARMAKOLOGI - FARMASI UMM

70 FARMAKOLOGI - FARMASI UMM