Aznan Lelo

Dep. Farmakologi & Terapeutik,

Fakultas Kedokteran
15 Juli 2012, KONAS NYERI 2012, Medan

Why is this important?

Abdominal pain is one of the most common reasons for outpatient and ER visits Variation in degree of pathology is vast, some of which needs immediate attention Abdominal pain and diarrhea present in most patients A lot can happen in the abdomen and you need an organized approach

Types of Abdominal Pain

Visceral
Crampy, achy, diffuse,
Colicky abdominal pain is the major symptom

Poorly localized

Somatic, Parietal
Sharp, lancinating Well localized

Referred
Distant from site of generation Symptoms, but no signs

Abdominal Pain
Location Work-up
Acute pain syndromes Chronic pain syndromes

Scope of the problem Anatomic Essentials

Visceral Pain Parietal Pain Referred Pain

Acute abdominal pain

Generally present for less than a couple weeks
Usually days to hours old Dont forget about the chronic pain that has acutely worsened

More immediate attention is required

Acute abdominal pain

Surgical
Appendicitis Cholecystitis Bowel obstruction Acute mesenteric ischemia Perforation Trauma Peritonitis

Non-surgical
Cholangitis Pancreatitis Non-abdominal causes Choledocholithiasis Diverticulitis PUD/-itis Gastroenteritis

Functional Disorders
Functional disorders are conditions in which the patient has a variable combination of symptoms without any readily identifiable structural or biochemical abnormality. Several functional gastrointestinal disorders are recognizable .
Functional dyspepsia Irritable bowel syndrome (IBS) Functional abdominal pain Abdominal migraine Aerophagia
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Functional Abdominal Pain

The term is used in gastroenterology if no specific structural, infectious, inflammatory, or biochemical cause for the abdominal pain can be determined.
Because the exact etiology and pathogenesis of the pain are unknown and because no specific diagnostic markers exist, a diagnosis of functional bowel disorder often is viewed as a diagnosis of exclusion. The diagnosis is established by a constellation of criteria based on a careful history, physical examination, and minimum laboratory investigation.
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Pathogenesis Of Functional Bowel Disease

Pathogenesis Of Functional Bowel Disease

Psychosocial Factors Neurotransmitter ? Altered Motility
Spasm Distention

Visceral Hypersensitivity Pain

Bloating Urge to defecate
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Physiology of CNS Control

CNS
Cerebral cortex, Limbic system, Brain stem & Hypothalamus Vagal pathway Splanchnic pathway Enteric afferents & interneurons
Neurotransmitters, Neuropeptides, other chemical and mechanical stimuli

Enteric Nervous System (ENS)

Vagal efferents

Secretion

Motility
Blood flow

Vagal afferents

Neurogenic control of GIT motility

Enteric nervous system (ENS)

serosa Longitudinal Muscle

Myenteric Plexus Circular Muscle Submucosal Plexus submucosal mucosal

is a collection of nerves within the wall of the GI tract responsible for the autonomous gastrointestinal activity. myenteric (Auerbach's) plexus, responsible for motor control submucosal (Meissner's) plexus, regulates secretion, fluid transport, and vascular flow. Neurons in both plexuses release acetylcholine at their terminals. Parasympathetic : causes contraction of muscles in the wall of the intestine and relaxation of the sphincters and increases gland secretion
M2 and M3 receptors present in the GIT in a 4:1 ratio. M3 receptor is more important in muscle contraction

Autonomic nervous system (ANS)

Sympathetic: causes relaxation of muscles in the wall of the intestine and contraction of the sphincters

Rational approach
Pain Spasm No-Pain Relaxation

Acetylcholine

Hyoscine

SAR Atropine and Hyoscine

Atropine
Me N
N

NMe3 CH2 CH2

Hyoscine
Me

O
H CH2 OH O C O CH

C O

CH3
O H H O C O H CH2 OH CH
*

Relative positions of ester and nitrogen similar in both molecules Nitrogen in atropine is ionised Tertiary amine (ionised) or a quaternary nitrogen Amine and ester are important binding groups (ionic + H-bonds) Aromatic ring of atropine is an extra binding group (vdW) Atropine binds with a different induced fit - no activation Atropine binds more strongly than acetylcholine

Farmakodinamik hyoscine-N-butylbromide
Efek pada kelenjar saliva : 1/50 atropin Efek pada denyut jantung : 1/30 atropin Efek pada mata : 1/500 atropin Efek pada kelenjar keringat : 1/1000 atropin Efek yang paling besar di organ abdomen berongga

LD 50 ORAL : 3.000 MG / KG BB PADA MENCIT

Farmakokinetik Hyoscine-N-butylbromide
Absorpsi : cepat diserap oleh jaringan mukosa,deposit di traktus gastrointestinal, hati dan jaringan ginjal Distribusi : t plasma 2-3 menit afinitas jaringan tinggi bioavailabilitas sistemik rendah, kadar tinggi di lokasi kerja Metabolisme : ikatan plasma 8-13%, tidak melewati sawar darah otak Ekskresi : melalui ginjal t eliminasi terminal 4.8 jam setelah penggunaan oral

Buscopan
contains the active ingredient hyoscine-N-butylbromide, which is an antispasmodic alkaloid. It is used to relieve abdominal pain that is caused by painful spasms in the muscles of
Gastrointestinal (GI) Billiary or Genitourinary (GU) tract.

Hyoscine stops the spasms in the smooth muscle by preventing acetylcholine from acting on the muscarinic receptors. This allows the muscle to relax and reduces the painful spasms and cramps.

Pain scores at baseline in IBS patients and in response to hyoscine treatment

Buscopan preparation Oral
Constipation (n=36) Before After Diarrhea (n=21) Before After Pain and bloating (n=39) Before After

8.2 2.1 Suppository 7.8 2.6

5.3 2.2 5.0 2.6

10.3 2.3 10.2 2.2

3.2 1.1 4.3 1.6

13.5 3.4 13.6 3.8

6.1 2.6 8.4 2.2

Interactions between Symptoms and Motor and Visceral Sensory Responses of Irritable Bowel Syndrome Patients to Spasmolytics (Antispasmodics) Khalif IL, et al. J Gastrointestin Liver Dis 2009;18(1):17-22

Hyoscine butylbromide tunggal dan kombinasi (+ parasetamol)

Terapi rasional nyeri abdomen

Bergantung pada lokasi nyeri, nyeri akut atau kronis, perlu tindakan surgical atau non-surgical yang harus memahami mekanisme kejadiaan nyeri kolik. Saluran cerna memiliki system persyarafan tersendiri ENS, disamping ANS. Perangsangan syaraf parasimpatis akan menyebabkan kontraksi otot polos, bisa diikuti dengan nyeri kolik. Antimuskarinik hyoscine butylbromide dapat mengurangi spastic sal.cerna, sal.empedu dan sal.kemih. Pemberian tunggal sediaan hyoscine butylbromide dapat mengatasi nyeri abdomen. Kombinasi hyoscine butylbromide dengan parasetamol secara sinergis memberikan khasiat antinyeri abdomen yang sangat bermakna.

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