31 the rational therapy of abdominal pain
TRANSCRIPT
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Aznan LeloDep. Farmakologi & Terapeutik,
Fakultas Kedokteran
15 Juli 2012, KONAS NYERI 2012, Medan
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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
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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
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Abdominal Pain
• Location• Work-up
– Acute pain syndromes– Chronic pain syndromes
• Scope of the problem • Anatomic Essentials
– Visceral Pain– Parietal Pain– Referred Pain
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Acute abdominal pain
• Generally present for less than a couple weeks– Usually days to hours old– Don’t forget about the chronic pain that has
acutely worsened• More immediate attention is required
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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
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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
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Pathogenesis Of Functional Bowel Disease
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Psychosocial Factors
Altered Motility
Visceral Hypersensitivity
SpasmDistention
PainBloating
Urge to defecate
Neuro-transmitter
?
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Physiology of CNS ControlCNS
Cerebral cortex, Limbic system,Brain stem &
Hypothalamus
Enteric Nervous System (ENS)
Secretion
MotilityBlood flow
Vagal pathway
Splanchnic pathway
Vag
al e
ffere
nts
Vag
al a
ffere
nts
Enteric afferents & interneurons
Neurotransmitters, Neuropeptides, other chemical and mechanical
stimuli
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Neurogenic control of GIT motilityEnteric nervous system (ENS)• 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 acetylcholineat their terminals.
Autonomic nervous system (ANS)• 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
• Sympathetic: causes relaxation of muscles in the wall of the intestine and contraction of the sphincters
serosa
Longitudinal Muscle
Myenteric Plexus
Circular Muscle
Submucosal Plexus
submucosal
mucosal
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Rational approach
AcetylcholineAcetylcholine HyoscineHyoscine
SpasmPain
RelaxationNo-Pain
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SAR Atropine and Hyoscine
Atropine Hyoscine
*
N
H
OC
O
Me
CH
CH2OHO
HH
N
OC
O
Me
H
CH
CH2OHC
O
O CH3
NMe3
CH2CH2
• 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
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Farmakodinamikhyoscine-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
•
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Farmakokinetik Hyoscine-N-butylbromide
• Absorpsi :– cepat diserap oleh jaringan mukosa,deposit di traktus
gastrointestinal, hati dan jaringan ginjal• Distribusi :
– t½ 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– t½ eliminasi terminal 4.8 jam setelah penggunaan oral
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Buscopan• contains the active ingredient hyoscine-N-butyl-
bromide, 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.
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Pain scores at baseline in IBS patients and in response to
hyoscine treatmentBuscopan
pre-paration
Constipation (n=36)
Diarrhea (n=21)
Pain and bloating (n=39)
Before After Before After Before After
Oral 8.2 ±2.1
5.3 ±2.2
10.3 ±2.3
3.2 ±1.1
13.5 ±3.4
6.1 ±2.6
Suppository 7.8 ±2.6
5.0 ±2.6
10.2 ±2.2
4.3 ±1.6
13.6 ±3.8
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
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Hyoscine butylbromide tunggal dan kombinasi (+ parasetamol)
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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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