Anti-motility/Anti-diarrhea drugs COR CHRISTI MEDICINE 2014

Drug Characteristics MOA Pharmacokinetic Absorption Pharmacokinetic Metabolism & Distribution Undergo 1 pass effect Exhibit significant individual variation in metabolism Primarily metabolized by CYP2D6 Undergoes sulfation and glucoronide conjugation by liver Bioavail: 30-100% Peak concentration occur within 1 hr after a single oral dose Duration of action: 1-2 hrs T : 4-6 hrs
st

Pharmacokinet ic Excretion

Indication

Adverse Effects

Anti-motility Metoclopramide

Para aminobenzoic acid and are structurally related to procainamide Dopamine Receptor Antagonist

Site of action: upper porition of GIT (Esophagus,stomach, small intestine) & chemoreceptor trigger zone.

Domperidone

Dopminergic Antagonist; AntiEmesis

MOA: 1. Promotes motility by: a. Inhibition of presynaptic and postsynaptic D2 receptor b. Stimulation of presynaptic 5-HT4 receptor c. Antagonism of presynaptic inhibition of muscarinic receptors release Ach 2. Anti emesis effect produced by inhibition of D2 and 5-HT3 receptor in the CTZ Antagonism at D2 receptor in the chemoreceptor trigger zone and upper GIT Effect: -accelerates gastric emptying by: 1. increase the amplitude of esophageal motor function 2. enhancing antraldeuodenal contraction 3. coordinated persitalsis across the pylorus

Oral and parenteral (IM/IV) Onset of action: Oral: 3060mins IM: 10-15 mins IV: 1-3 mins

EXCRETION: Renal 30-30% excreted unchange d in the urine

1. Nausea and vomiting Post-operatively Cancer chemotherapy induced emesis 2. GERD 3. Gastroparesis (delayed gastric emptying) 4. As adjunct in dx procedures i.e. contract radiography of GIT, intestinal intubation

1. Extra-pyramidal effects a. Dystonias b. Parkinsonian-like symptoms c. tardive dyskinesia 2. Galactorrhea 3. Drowsiness, fatigue, lethargy 4. Depression

Oral and IM Onset: Oral: 30mins IM: 10-30mins

Undergo first pass effect both hepatic and stomach wall Metabolism by CYP3A4 to inactive metabolites Poor penetration of the BBB 25% protein bound

Elimination T : 7.5 hrs Ff oral drug admin, 32% of the drug is excreted in the urine and 66% is found in the feces

1. Dyspepsia 2. Nausea and vomiting a. Function, organic, infectious b. Radiotherapy and cancer chemotherapy induced emesis c. Drug induced (E.g. Levodopa, Bromocriptine) 3. GERD 4. Gastroparesis

1. 2. 3.

Transient intestinal cramps Galactorrhea Allergic reaction

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Anti-motility/Anti-diarrhea drugs COR CHRISTI MEDICINE 2014

Anti-diarrhea Paregoric Camphorated Opium Tincture contains the equivalent of 2 mg of morphine per 5 ml (0.4 mg/mL) Narcotic Loperamide an opioid 40-50 times more potent than Morphine as an antidiarrheal low abuse potential more effective as an antidiarrheal than Diphenoxylate Agonist at: Pls refer to the tranx kasi walang symbol for that eh sorry. Ung mga symbol for the specific receptor. Wala ako dito sa msword peripheral m receptor agonist decrease intestinal motility and prolong transit time reduction in water and electrolyte losses restoration of the consistency of stools 40% of an oral dose is absorbed peak plasma concentration is attained in 3-5 hours poor CNS penetration half life 11 hours excretion of unchanged drug and its metabolites occurs mainly through the feces A. For the symptomatic relief of acute, noninfectious diarrhea including: travelers diarrhea diarrhea associated with inflammatory bowel disease Colostomy and ileostomy to reduce the volume of discharge CNS Effects: Lightheadedness, dizziness, sedation, nausea, vomiting 2. Euphoria, dysphoria, constipation, pruritus 1. CNS depression especially in children 2. Paralytic ileus 3. Constipation 1.

metabolized by CYP3A4 undergoes extensive first pass hepatic metabolism

B. C.

Racecadotril

Antisecretory also known as Acethorphan

o peripherally acting enkephalinase inhibitor protects endogenous enkephalins from degradation Enkephalin - opioid neurotransmitter that binds to delta receptors to reduce the levels of cAMP selective

oral and parenteral formulation rapidly absorbed after oral administration,

rapidly metabolized to its active metabolite Thiorphan

Headache vomiting, nausea Vertigo less constipating

onset of action in 30 minutes peak plasma concentration of Tthiorphan is reached 60 min after administration of a single oral dose of Racecadotril. T : 3 hours

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Anti-motility/Anti-diarrhea drugs COR CHRISTI MEDICINE 2014

Clonidine Antimotility/Antisecretory a2 agonist interact with specific receptors in enteric neurons and enterocytes stimulate absorption and inhibit secretion of fluid and electrolytes decrease intestinal transit time inhibits secretion of serotonin, gastrin, vasoactive intestinal peptides, insulin, secretin, etc. 1. 2. Chronic diarrhea among diabetics Diarrhea cause by opiate withdrawal 1. 2. 3. Hypotension Depression fatigue

Ocreotide

Somatostatin analogue effective for severe secretory diarrhea

given intravenously as a bolus or subcutaneously T1/2: 1-2 hrs absorption is rapid and complete after SC injection

peak plasma conc is attained within 30 min given intravenously, biphasic elimination with half lives of 10 and 90 mins given subcutaneously, half life is 100 min

primary elimination in the feces about 32% excreted unchanged in the urine

1.

2. 3. 4. 5.

6. 7. 8.

Secretory diarrhea due to hormone secreting tumors of the pancreas and GIT Chemotherapy-induced diarrhea Diarrhea associated with HIV Diabetes associated diarrhea Dumping syndrome secondary to gastric surgery and pyloroplasty Variceal bleeding control bleeding acutely decrease bleedingrelated mortality

1. Acute transient nausea, bloating, pain at sites of injection 2. Chronic gallstone formation hypo or hyperglycemia

Attapulgite

Mg aluminum disilicate binds with water also binds enterotoxins

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