Download - 31 the Rational Therapy of Abdominal Pain
Aznan LeloDep. 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– Don’t 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
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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
?
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
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
Rational approach
AcetylcholineAcetylcholine HyoscineHyoscine
SpasmPain
RelaxationNo-Pain
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
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
•
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
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.
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
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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