CAM202 Pharmacology Logbook PDF

CAM202 Pharmacology Logbook **Treatments to Reduce Gastric Acid** Proton Pump Inhibitors *Omeprazole, esomeprazole.* Pharmacodynamics *Mechanism* Irreversibly inhibit the H+/K+ ATPase (the proton pump) on parietal cells therefore inhibit the final step of acid secretion (= inhibits both basal...

CAM202 Pharmacology Logbook **Treatments to Reduce Gastric Acid** Proton Pump Inhibitors *Omeprazole, esomeprazole.* Pharmacodynamics *Mechanism* Irreversibly inhibit the H+/K+ ATPase (the proton pump) on parietal cells therefore inhibit the final step of acid secretion (= inhibits both basal and food-stimulated acid secretion). *Effects* Reduce gastric acid secretion by up to 99%. Long duration of action due to accumulation in the canaliculi (as they are weak bases and canaliculi is acidic). Pharmacotherapeutics *Indications:* First line in GORD, NSAID and H. pylori-induced ulcers, recurrent dyspepsia and reflux. *Contraindications:* Some inhibition of cytochrome P450 enzymes occurs therefore caution with drugs such as warfarin. *Administration:* Injection, oral. *Adverse Effects:* Headache, GI upset. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------ ------------ ----------------- ------------ Omeprazole Liver Majority 0.5-1 hour H~2~ Receptor Antagonists *Famotidine, nizatidine.* Pharmacodynamics *Mechanism* Competitively inhibit H~2~ receptors on parietal cells -\> inhibit histamine and gastrin stimulated acid secretion. *Effects* Reduce gastric acid secretion by 90%. Decrease both basal and food-stimulated acid secretion. Can promote healing of gastric and duodenal ulcers. However, relapses are likely to follow after cessation of treatment. Pharmacotherapeutics *Indications:* Mild or intermittent symptoms of GORD, or if PPI not suitable, recurrent dyspepsia and reflux. *Contraindications:* Renal impairment. *Administration:* *Adverse Effects:* Well tolerated Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------ ------------ ----------------- ----------- Famotidine nil Majority 2-4 hours Antacids Pharmacodynamics *Mechanism* Basic salts that neutralise gastric acid. *Effects* Symptomatic relief. Pharmacotherapeutics *Indications:* Mild, intermittent, or breakthrough symptoms of GORD, dyspepsia, reflux. *Contraindications:* Renal impairment (aluminium + magnesium +sodium), hypertension, heart failure, ascites, peripheral oedema (sodium). *Administration:* Oral *Adverse Effects:* Constipation (aluminium + calcium), diarrhoea (magnesium) **Treatment of Constipation** Bulk-Forming Laxatives *Psyllium, ispaghula* Pharmacodynamics *Mechanism + Effects* They are polysaccharide polymers that are not broken down by digestion. They absorb water -\> increase the volume, bulk and moisture of non-absorbable intestinal contents -\> distend the bowel + intestinal wall -\> stimulates propulsive movements of gut muscles. Pharmacotherapeutics *Indications:* First line laxative for constipation. *Contraindications:* Intestinal obstruction, colonic atony, dysphagia, fluid restriction, immobility. *Administration:* Oral with water (onset 2-3 days). *Adverse Effects:* Flatulence, bloating, abdominal discomfort. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ---------- ------------ ----------------- ----------- Psyllium nil nil nil Osmotic Laxatives *Glycerol, lactulose, saline, sorbitol* Pharmacodynamics *Mechanism + Effects* Are poorly absorbed therefore increasing the volume of fluid in the lumen (as water remains in the bowel when molecules are not absorbed). This increased volume accelerates the transfer of the gut contents and leads to increased defecation. Pharmacotherapeutics *Indications:* Constipation. +-----------------------+-----------------------+-----------------------+ | *Glycerol | *Lactulose, sorbitol | *Saline laxatives | | suppositories | and macrogol | (oral, rectal)* | | (rectal)* | laxatives (oral)* | | +=======================+=======================+=======================+ | ◦ Osmotic effects, | ◦ Used for relief of | ◦ Contain poorly | | lubricating | constipation, faecal | absorbed ions such as | | properties, may also | impaction, bowel | magnesium, sulphate, | | act as a stimulant by | preparation. | phosphate and | | local irritant | | citrate. | | effects. | ◦ Onset of action: | | | | 1-3 days. Larger | ◦ Onset of action: | | ◦ Onset of action is | doses have a faster | oral: 0.5-3 hours, | | 5-30 minutes (rapid | onset (0.5-3 hours). | rectal: 2-30 minutes | | relief when stool is | | (bowel | | in the lower rectum). | ◦ *Adverse effects*: | preparation/procedure | | | nausea, vomiting, | s). | | ◦ Well tolerated | diarrhoea, | | | (local effect). | distension, cramps. | ◦ *Adverse effects*: | | | | nausea, bloating, | | | | fluid and electrolyte | | | | disturbance. | +-----------------------+-----------------------+-----------------------+ *Administration:* Oral - drink Pharmacokinetics Drug Metabolism Renal Excretion Half Life ---------- ------------ ----------------- ----------- Sorbitol nil Majority Stimulant Laxatives *Senna, bisacodyl* Pharmacodynamics *Mechanism + Effects* Unknown, may irritate nerve endings in colon to increase motility + water secretion by mucosa. Pharmacotherapeutics *Indications:* Opioid-induced constipation, short term use for severe constipation unresponsive to bulking agents or osmotic laxatives, constipation in spinal damage, neuromuscular disease, etc. *Contraindications:* Intestinal obstruction, acute abdominal conditions, inflammatory bowel condition. *Administration:* Oral (onset 6-12 hours), rectal (onset 5-60 minutes). *Adverse Effects:* Diarrhoea, cramping, nausea, discolouration of faeces + urine. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------- ------------ ----------------- ----------- Senna Gut 3-6% Stool-Softening Laxatives *Docusate, liquid paraffin* Pharmacodynamics *Mechanism + Effects* Surfactants -- lower surface tension, allowing water and lipids to penetrate the stool -\> hydrates and softens the stool. (Liquid paraffin is a lubricant not surfactant). Pharmacotherapeutics *Indications:* Constipation (usually with a stimulant or osmotic laxative), prevent straining after rectal surgery, etc. *Contraindications:* Paraffin -- dysphagia, bedridden patients. *Administration:* Oral (onset 1-3 days). *Adverse Effects:* Well tolerated. Other Laxatives ***Methylnaltrexone*** Pharmacodynamics *Mechanism + Effects* Peripherally acting competitive opioid receptor antagonist. Pharmacotherapeutics *Indications:* Opioid-induced constipation when other laxatives inadequate. *Contraindications:* *Administration:* SC injection. *Adverse Effects:* Abdominal cramping, diarrhoea. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------------ ------------ ----------------- ----------- Methylnaltrexone Majority \ stimulates cAMP production -\> increased Ach release -\> increased GI motility. Pharmacotherapeutics *Indications:* Chronic idiopathic constipation when other laxatives inadequate. *Contraindications:* Intestinal obstruction, severe inflammatory bowel condition. *Administration:* Oral. *Adverse Effects:* Abdominal cramping, diarrhoea. Pharmacokinetics Drug Metabolism Renal Excretion Half Life -------------- ------------ ----------------- ------------- Prucalopride nil 84% 18-20 hours **Treatment of Diarrhoea** Antidiarrhoeals *Loperamide, diphenoxylate \[with atropine\]* Pharmacodynamics *Mechanism + Effects* Opioid receptor agonists -\> decrease cAMP -\> decrease Ca^2+^ -\> decreased excitation therefore blocks peristaltic contractions. Pharmacotherapeutics *Indications:* Short term diarrhoea relief. *Contraindications:* Children. *Administration:* Oral. *Adverse Effects:* Abdominal pain and bloating, nausea, vomiting, constipation, dizziness, drowsiness. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------ ------------- ----------------- ------------ Loperamide Extensively 1% 10.8 hours **Treatment of Nausea and Vomiting** D~2~ Receptor Antagonists *Metoclopramide, domperidone, prochlorperazine* Pharmacodynamics *Mechanism + Effects* Block the action of dopamine on D~2~ receptors in the CTZ → decreased stimulation of the vomiting centre (VC) → decreased vomiting. Metoclopramide and domperidone (this one doesn't cross BBB so ok for Parkinsosn's) also activate 5-HT4 receptors in the stomach → increased ACh release → activation of M3 receptors in stomach → increased smooth muscle contractility → increased stomach emptying. Prochlorperazine and droperidol also block H~1~ and M~1~ receptors in the vomiting centre and vestibular nuclei. Pharmacotherapeutics *Indications:* Nausea and vomiting, nausea from toxin, gastric stasis. *Contraindications:* GI obstruction, Parkinson's. *Administration:* Oral, IM, IV. *Adverse Effects:* Drowsiness and fatigue, movement disorders (Nigrostriatal pathway), galactorrhoea (increased milk production). Antimuscarinic effects for prochlorperazine and droperiodol. Less adverse effects for domperidone as it doesn't cross BBB. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ---------------- ------------ ----------------- ----------- Metoclopramide Yes Predominantly 5-6 hours 5HT~3~ Receptor Antagonists *Ondansetron, dolastron* Pharmacodynamics *Mechanism + Effects* Block the action of serotonin on 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) and vagal afferent nerves → - CTZ: decreased excitability of interneurons between CTZ and vomiting centre → decreased stimulation of the vomiting centre. - Vagal afferents: decreased excitability of vagal afferents between GIT and VC and between the GIT and CTZ. Pharmacotherapeutics *Indications:* Nausea and vomiting -- often after chemo etc. *Contraindications:* *Administration:* Oral, IM, IV. *Adverse Effects:* Constipation, headache, dizziness. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------- ------------ ----------------- ----------- Ondansetron Yes Yes 3-4 hours NK-1 Receptor Antagonists *Aprepitant, fosaprepitant* Pharmacodynamics *Mechanism + Effects* Block the action of substance P on NK-1 receptors in the CTZ, VC and vagal afferents: - CTZ: decreased intracellular calcium → decreased excitability of interneurons between CTZ and VC. - VC: decreased vomiting. - Vagal afferents: decreased excitability of vagal afferent nerves between GIT and VC and between the GIT and CTZ. Pharmacotherapeutics *Indications:* Prevention of nausea + vomiting associated with chemotherapy. *Contraindications:* *Administration:* Oral, IV *Adverse Effects:* Diarrhoea, fatigue, headache, dizziness, weakness, hiccups. *Interactions*: Inhibits, induces and is metabolised by CYP3A4 and also induces CYP2C9 therefore drugs that are also metabolised by these enzymes may have increased or decreased therapeutic/adverse effects (e.g. OCP) Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------ ------------ ----------------- ------------ Aprepitant Yes nil 9-13 hours Corticosteroids *Dexamethasone, prednisolone* Pharmacodynamics *Mechanism + Effects* Unclear -- inhibit PG synthesis, decrease serotonin turnover, release endorphins that elevate mood? Pharmacotherapeutics *Indications:* Prevent post-operative or chemotherapy nausea and vomiting, IBD. *Precautions:* Diabetes, osteoporosis, heart failure, psychiatric disorders. *Administration:* Oral, IV *Adverse Effects:* Fluid retention, hypertension, hyperglycaemia, increased appetite, dyspepsia, Cushing's syndrome (hypertension, thinning of the skin, susceptibility to infection, easy bruising, fat redistribution, osteoporosis, hyperglycaemia). Pharmacokinetics Drug Metabolism Renal Excretion Half Life --------------- ------------ ----------------- ----------- Dexamethasone Yes Predominantly 4 hours Antihistamines *Promethazine, doxylamine* Pharmacodynamics *Mechanism* Sedating antihistamines -- block H~1~ receptors in the vomiting centre and vestibular nuclei → decreased excitability of neurons in these areas. Also antimuscarinics -- block Ach action on M~1~ receptors in vomiting centre + vestibular nuclei. *Effects* Prevention of motion sickness. Pharmacotherapeutics *Indications:* Prevention of motion sickness. *Contraindications:* Elderly, under 2 years *Administration:* Oral. *Adverse Effects:* Sedation, antimuscarinic adverse effects - dry mouth, dry eyes, blurred vision, constipation, urinary retention, etc. Pharmacokinetics Drug Metabolism Renal Excretion Half Life -------------- ------------ ----------------- ------------- Promethazine Yes Predominantly 12-15 hours Antimuscarinics *Hyoscine hydrobromide* Pharmacodynamics *Mechanism* Block Ach action on M~1~ receptors in vomiting centre + vestibular nuclei. *Effects* Prevention of motion sickness. Pharmacotherapeutics *Indications:* Prevention of motion sickness. *Contraindications:* Under 2 years *Administration:* Oral. *Adverse Effects:* Dry mouth, dry eyes, blurred vision, constipation, urinary retention, etc. **Treatment of Inflammatory Bowel Disease** Corticosteroids *Budeosonide, prednisolone* Pharmacodynamics *Mechanism* Bind to glucocorticoid receptors in the cytoplasm of many cells, causing a conformational change -\> The drug-receptor complex translocates into the nucleus, and then changes gene transcription -\> induce or repress gene transcription of inflammatory mediators and cells. *Effects* Anti-inflammatory and immunosuppressive effects -- increased synthesis of anti-inflammatory factors, decreased production of inflammatory mediators, decreased action of inflammatory cells. Pharmacotherapeutics *Indications:* Induction therapy in IBD, prevent post-operative or chemotherapy nausea and vomiting. *Precautions:* Diabetes, osteoporosis, heart failure, psychiatric disorders. *Administration:* Oral, local e.g. suppository, IV -- local preferred. *Adverse Effects:* Fluid retention, hypertension, hyperglycaemia, increased appetite, dyspepsia, Cushing's syndrome (hypertension, thinning of the skin, susceptibility to infection, easy bruising, fat redistribution, osteoporosis, hyperglycaemia). 5-Aminosalicylates *Mesalazine, olsalazine* Pharmacodynamics *Mechanism + Effects* Exact mechanism unknown -- exerts local inflammatory effects, possibly by: - Scavenging reactive oxygen species. - Inhibiting production cytokines, prostaglandins and leukotrienes. - Decreasing neutrophil chemotaxis. The action of 5-ASA is believed to be predominantly topical at the site of inflammation, especially within the colon. Pharmacotherapeutics *Indications:* Ulcerative colitis, Crohn's if colonic involvement. *Administration:* Oral, rectal *Adverse Effects:* Nausea, rash, headache, diarrhoea. Sulfasalazine has more adverse effects due to the sulphapyridine component. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------ ------------------- ----------------- ------------ Mesalazine Mostly intestinal Predominantly 40 minutes Immunosuppressants *Azathioprine, mercaptopurine* Pharmacodynamics *Mechanism + Effects* Inhibition of B and T cells + anti-inflammatory properties. Pharmacotherapeutics *Indications:* IBD *Interactions*: Allopurinol -- inhibits metabolism of mercaptopurine -- risk of bone marrow toxicity. *Administration:* Oral *Adverse Effects:* Dose-related myelosuppression (e.g. leucopoenia, thrombocytopenia, anaemia), infection, alopecia, diarrhoea, anorexia, nausea and vomiting, mouth ulceration and oesophagitis. Pharmacokinetics Drug Metabolism Renal Excretion Half Life -------------- ------------ ----------------- ----------- Azathioprine Yes nil 5 hours *Methotrexate* Pharmacodynamics *Mechanism + Effects* 'Antifolate' - Competitively inhibits dihydrofolate reductase, thereby inhibiting the synthesis of tetrahydrofolate. Tetrahydrofolate is required for purines synthesis, DNA synthesis and cell division -\> therefore methotrexate inhibits cell proliferation (cytotoxic, immunosuppressive and anti-inflammatory actions). Pharmacotherapeutics *Indications:* IBD - refractory to standard therapy. *Contraindications:* Serious or latent infection, pregnancy, breastfeeding. *Administration:* Oral, SC, IM. *Adverse Effects:* myelosuppression, nausea and vomiting, oral mucositis, pulmonary toxicity hepatotoxicity, skin reactions (e.g. photosensitivity). *Monitoring*: FBC, LFTs. Pharmacokinetics Drug Metabolism Renal Excretion Half Life -------------- ------------ ----------------- ------------ Methotrexate nil Predominantly 3-10 hours TNF-α Antagonists *Infliximab, adalimumab* Pharmacodynamics *Mechanism + Effects* Monoclonal antibodies -- made identical to immune cells -\> bind to TNF- α (there is an increased amount of this in IBD) -\> inhibit its action as it cannot bind to the TNF receptor if bound to the monoclonal antibody (usually cause apoptotic cells death + inflammation). Pharmacotherapeutics *Indications:* IBD *Contraindications:* Serious/latent infection, history of lymphoproliferative disease in last 5 years. *Administration:* SC injection. *Adverse Effects:* Infections, rash, headache, autoantibodies. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------ ------------ ----------------- -------------- Infliximab Predominantly 7.7-9.5 days α4 β7 Integrin Antibodies *Vedolizumab* Pharmacodynamics *Mechanism + Effects* Monoclonal antibody against the α4β7 integrin on T cells -\> inhibits adhesion of T cells to MAdCAM-1 in the GIT -\> inhibits the migration of T cells across the endothelium into GI tissue and inhibits GI inflammation. Pharmacotherapeutics *Indications:* IBD. *Precautions:* Active infections, latent infections. *Administration:* IV, SC *Adverse Effects:* Arthralgia, headache, cough, infections, hypersensitivity reactions. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------- ------------ ----------------- ----------- Vedolizumab Negligible 25 days IL-12/IL-23 Antibodies *Ustekinumab* Pharmacodynamics *Mechanism + Effects* Monoclonal antibody that inhibits the activity of cytokines IL-12 and IL-23. Pharmacotherapeutics *Indications:* IBD. *Precautions:* Infections, malignancy. *Administration:* IV, SC. *Adverse Effects:* Infections, headache, arthralgia, myalgia. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------- ------------ ----------------- ----------- Ustekinumab Predominantly 19 days  **Alcohol** Ethanol Pharmacodynamics *Mechanism* CNS depressant -- impairs transmission by unknown mechanism: \- Enhances the action of inhibitory neurotransmitters (GABA -- ligand gated Cl^-^ channels) and inhibits the action of excitatory neurotransmitters (Glutamate -- ligand gated Ca^2+^ channels). Alcohol increases Cl^-^ conductance through GABA~A~ receptors and decreases Ca^2+^ conductance through NMDA receptors. *Effects* Pharmacotherapeutics *Contraindications:* Pregnancy *Adverse Effects:* Dependence + withdrawal \- Cardiovascular - Acute: vasodilation (especially in the skin) -\> warm feeling, increased heat loss. - Chronic: hypertension, arrhythmias, cardiomyopathy. \- Gastrointestinal - Acute: stimulation of gastric acid secretion and salivation. - Chronic: nutritional deficiencies, gastritis, pancreatitis, hepatitis, cirrhosis. \- Endocrine - Acute: inhibition of ADH secretion -\> diuresis and dehydration. - Chronic: hormone imbalances -\> stress, reproductive deficits, body growth defect, thyroid problems etc. Pharmacokinetics Metabolised in liver via 2 steps: Alcohol -\> acetaldehyde (catalysed by alcohol dehydrogenase). Acetaldehyde -\> acetic acid (catalysed by aldehyde dehydrogenase). Saturable metabolism -- constant. Drugs For Alcoholism *Disulfiram* Pharmacodynamics *Mechanism + Effects* Irreversibly inhibits aldehyde dehydrogenase -\> blocks acetaldehyde breakdown, causing unpleasant effects if alcohol is taken. Pharmacotherapeutics *Indications:* Alcoholism *Contraindications:* CVD/stroke, psychosis. *Adverse Effects:* Drowsiness, nausea, headache, fatigue. *Naltrexone* Pharmacodynamics *Mechanism + Effects* Reversible opioid receptor antagonist -\> prevents positive conditioning (pleasurable) effects, reduces cravings. Pharmacotherapeutics *Indications:* Alcoholism *Contraindications:* Liver impairment. *Adverse Effects:* Nausea, headache, dizziness. *Acamprosate* Pharmacodynamics *Mechanism + Effects* Similar chemical structure to GABA, may involve restoration of normal activity in glutamate and GABA-ergic systems. Pharmacotherapeutics *Indications:* Alcoholism *Contraindications:* Severe hepatic impairment. *Adverse Effects:* Rash, diarrhoea, changes in libido. **Treatment of Complications of Liver Disease** **Oesophageal Varices** Non-selective Beta Blockers *Propranolol* Pharmacodynamics *Mechanism* β1 blockade -\> decreased cardiac output → decreased portal blood flow. β2 blockade -\> decreased β2-mediated vasodilation → unopposed α1-mediated vasoconstriction → arteriolar splanchnic vasoconstriction → decreased portal blood flow *Effects* Prevention of bleeding. Pharmacotherapeutics *Indications:* Oesophageal varices. *Precautions:* Asthma and COPD, bradycardia, peripheral vascular disease, diabetes mellitus. *Administration:* Oral. *Adverse Effects:* Bradycardia, fatigue, cold extremities, bronchoconstriction, nightmares, hypoglycaemia. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------- ------------ ----------------- ----------- Propranolol Yes Predominantly 8 hours Vasopressin Analogues *Terlipressin* Pharmacodynamics *Mechanism* Activates V1 receptors in smooth muscle of arterial vasculature -\> increased phospholipase C -\> increased IP3 and DAG -\> increased intracellular calcium -\> vasoconstriction -\> decreased portal blood flow -\> decreased variceal bleeding. *Effects* Management of bleeding. Pharmacotherapeutics *Indications:* Oesophageal varices, hepatorenal syndrome. *Contraindications:* Ischaemic CVD, pregnancy. *Administration:* IV *Adverse Effects:* Respiratory failure, dyspnoea, bronchospasm, abdominal pain, hypertension. Pharmacokinetics Drug Metabolism Renal Excretion Half Life -------------- ------------ ----------------- ----------- Terlipressin Yes Minority 0.9 hours Somatostatin Analogues *Octreotide* Pharmacodynamics *Mechanism* Activates somatostatin receptors -\> inhibits growth hormones + GI hormone release (e.g. vasoactive intestinal peptide, a vasodilator). Also has direct vasoconstrictor effect via inhibition of adenylate cyclase and activation of phospholipase C -\> decreased portal blood flow -\> decreased variceal bleeding. *Effects* Management of bleeding. Pharmacotherapeutics *Indications:* Oesophageal varices. *Precautions:* Diabetes, pregnancy. *Administration:* SC, IM *Adverse Effects:* Abdominal pain, flatulence, nausea, vomiting, diarrhoea, gallstones. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ------------ ------------- ----------------- ----------- Octreotide Extensively 32% 0.2 hours **Hepatorenal Syndrome** Terlipressin + Albumin Pharmacodynamics *Mechanism* Terlipressin activates V1 -\> splanchnic vasoconstriction -\> increases MAP -\> decreased portal venous blood flow -\> decreases activity of renin causing vasoconstriction. Albumin is a colloid intravenous fluid --\> increases central blood volume. **Ascites** Spironolactone Pharmacodynamics *Mechanism* Aldosterone antagonist -\> inhibits aldosterone-induced increase in Na+ channels in the luminal membrane and Na+/K+ ATPase pumps in the basolateral membrane of the collecting tubules -\> increased loss of Na and water, decreased loss K in the urine. Pharmacotherapeutics *Indications:* Ascites *Precautions:* Asthma and COPD, bradycardia, peripheral vascular disease, diabetes mellitus. *Administration:* Oral. *Adverse Effects:* Hyperkalaemia, gynaecomastia, menstrual disorders, testicular atrophy. Pharmacokinetics Drug Metabolism Renal Excretion Half Life ---------------- ------------- ----------------- ----------- Spironolactone Extensively Primarily 1.4 hours **Hepatic Encephalopathy** (accumulation of neurotoxic substances (e.g. ammonia), which are normally removed by the liver.) Lactulose Pharmacodynamics *Mechanism* Non-absorbable sugar -\> Degraded by colonic bacteria to lactic, acetic and formic acids -\> decreasing the pH of the colonic contents -\> ratio of ammonium ion to ammonia increases. *Effects* \- Less absorption of ammonia. \- Back-diffusion of ammonia from the blood into the intestinal lumen. \- Shorter colonic transit time (osmotic laxative effect) -\> time for ammonia generation reduced, decreased ammonia absorption. Pharmacotherapeutics *Indications:* Constipation, hepatic encephalopathy. *Administration:* Oral, drink.