GI Pharmacology Flashcards
What are some ways for managing peptic ulcer with drugs
Reducing gastric acid secretion
Neutralizing secreted gastric acid
Increase mucosal resistance to acid-pepsin attacks
Eradicating H. pylori
What classes of drugs could help in reducing gastric acid secretion
H2-receptor antagonists
Proton pump inhibitors and
Muscarinic receptor antagonists
What class of drug could be used to neutralize secreted gastric acid
Antacids
Which class of drugs could be used to Increase mucosal resistance to acid-pepsin attacks
Misoprostol or chelates
What is the MOA of histamine H2 receptor antagonists
Competitive blockade of histamine on the H2 receptor
What are some examples of histamine H2 receptor antagonist drugs
Cimetidine and ranitidine
What are some indications for histamine H2 receptor antagonists
Peptic ulcer and GORD
What are some contraindications for cimetidine
Cimetidine not given to patients stabilized on warfarin, phenytoin, and theophylline
What are some adverse effects of histamine H2 receptor antagonists
Dizziness
Fatigue
Rashes
Low sperm count due to antiandrogenic effects
What are some examples of PPIs
Omeprazole, Esomeprazole
What is the MOA of PPIs
Irreversible inhibition of H+/K+ ATPase responsible for proton secretion from parietal cells. They are pro-drugs, converted at acid pH to sulphonamide, which combines covalently with sulphydryl groups on the H+/K+ ATPase
What are some indications of PPI
Short-term treatment of peptic ulcers, eradication of H. pylori, oesophagitis, Zollinger-Ellison syndrome
What are some adverse effects of PPIs
GI upsets, nausea, headaches, gastric atrophy with long term treatment
What are some examples of muscarinic receptor antagonists
Atropine
Pirenzepine
Dicyclomine (dicycloverine)
What is the MOA of muscarinic receptor antagonists
Inhibition of parasympathetic activity, causing relaxation of GI smooth muscle as well. They may be of value in peptic ulcer since the condition may be accompanied by increased muscle spasm
What are the indications of muscarinic receptor antagonists
As adjuncts in the management of peptic ulcer
What is an example of a mucosal strengthener drug
Misoprostol
What is the MOA of mucosal strengtheners
Synthetic analogue of PG E, imitating the action of endogenous PGE2 and PGI2, thereby maintaining the
integrity of the gastroduodenal barrier. It therefore promotes healing
What are some indications for given mucosal strengtheners
Ulcer healing and prophylaxis with NSAID use
What are some contraindications of mucosal strengtheners
Hypotension, pregnant and
breast-feeding women
What are some adverse effects of mucosal strengtheners
Diarrhoea, nausea and abdominal pain
What are some examples of chelates
Bismuth chelate and sucralfate
How do chelates protect the mucosa
Inhibiting the action of pepsin
Promoting the synthesis of protective prostaglandins
Stimulating the secretion of bicarbonate
They are given orally and well tolerated
Give some examples of neutralizing secreted acid with antacids
Aluminium hydroxide, magnesium hydroxide and sodium bicarbonate
What is the MOA of antacids
Antacids consist of alkaline Al3+, Mg2+ and Na+ salts that are used to raise the luminal pH of the stomach
They neutralize acid and as a result, may reduce the damaging effects of pepsin which is pH dependent.
Additionally, Al3+ and Mg2+ salts bind and inactivate pepsin
What are some indications for antacids
Symptomatic relief of ulcers and GORD
What are some contraindications of antacids
Aluminium and magnesium hydroxides should not be given to patients with hypophosphataemia
Sodium bicarbonate should be avoided in patients on a salt-restricted diet (e.g. heart failure and in hepatic and renal impairment)
What are some side effects of neutralizing secreted acid with antacids
Constipation and diarrhea
Sodium Bicarbonate may lead to alkalosis
Complexation with tetracyclines
Talk about alginates
Alginate containing antacids (eg. Gaviscon) are administered orally
It forms an impenetrable raft that floats on the surface of the gastric contents. The layer prevents gastric acid from refluxing into the oesophagus, useful in GORD
It is well tolerated but no effect upon acid secretion or healing
Give some facts about H. pylori in relation to peptic ulcer
H. pylori plays a significant role in the pathogenesis of ulcer
It does not cause ulcer in all infected patients (50-80%)
90% of ulcer patients have H. pylori infection
Rate of recurrence of duodenal ulcers relatively low with H. pylori eradication regimes compared with non-involvement of H. pylori eradication regimes
What are some current eradication regimes for H. pylori
Classic therapy: omeprazole, clarithromycin, amoxycillin or metronidazole , tetracycline for 1 or 2 weeks. 90% elimination, but compliance, resistance and adverse effects!
Dual therapy: Omeprazole + single antibiotic, amoxycillin or Clarithromycin-less effective
What is nausea
It is an unpleasant feeling in the upper abdomen and throat which usually precedes vomiting.
It may be experienced without vomiting
What is vomiting
Vomiting is the forceful expulsion of GIT contents through the mouth
Which part of the brain stem is responsible for nausea and vomiting
The vomiting centre and the chemoreceptor trigger zone (CTZ) in the brainstem are responsible for the central regulation of nausea and vomiting
Describe what the CTZ contains
The CTZ contains dopamine and serotonin receptors. It receives input from H1 receptors in the vestibular nuclei. The vomiting centre contains muscarinic receptors
What are some causes of nausea and vomiting
GI irritation
Motion sickness
Vestibular disease
Hormonal disturbances
Drugs and radiation
Exogenous toxins
Pain
Psychogenic factors
Intracranial pathology
A liquid causes gastric irritation resulting in emesis to relieve nausea
What is the name of this liquid
Ipechacuanha
What is one positive use of vomiting
Emesis (vomiting) may be induced to rid the GIT of ingested exogenous toxins
What are some classes of antiemetic drugs
H1 receptor antagonists
Phenothiazines
Dopamine antagonists
5-HT3 receptor antagonists
What are some examples of H1 receptor antagonists
Cyclizine and cinnarizine (stugeron)
These are antiemetic antihistamines. They have little effect on nausea and vomiting induced by substances acting directly on the CTZ. They are however effective in motion sickness and vestibular disorders
What class of drug is this
H1 receptor antagonist
What are the routes of administration of cyclizine and cinnarizine
Cyclizine (Oral, IM. IV)
Cinnarizine (Oral)
What are the indications of H1 receptor antagonists
Motion sickness
Vestibular disorders
What are some adverse effects of H1 receptor antagonists
Drowsiness, dry mouth, blurred vision
What are some cautions in using a H1 receptor antagonists
Use with caution in urinary retention, glaucoma
What is the most widely used antiemetic in the class of phenothiazines
Prochlorperazine (Stemetil) is the most widely used antiemetic in this class
What is the MOA of phenothiazines
Numerous effects; It blocks dopaminergic, histaminic and muscarinic receptors
What are the routes of administration for phenothiazines
Oral, rectal and intramuscular
What are some indications for phenothiazines
Nausea, vomiting, vertigo, psychosis
What are some contraindications for phenothiazines
It may exacerbate Parkinsonian symptoms
What are some adverse effects of phenothiazines
Sedation
Postural hypotension
Extrapyramidal symptoms
What are some examples of dopamine antagonist drugs
Domperidone (Motilium) and metoclopramide (Maxolon)
What is the MOA for dopamine antagonist drugs
They block dopamine receptors and act on the CTZ. Their antiemetic effect is enhanced by promoting gastric emptying and small intestine peristalsis.
What is the route of administration for metoclopramide or domeperidone
Metoclopramide (Oral, IM, IV) Domperidone (Oral, Rectal)
What are some indications for dopamine antagonists
Nausea and vomiting
What are some contraindications to metoclopramide, a dopamine antagonist
Metoclopramide not given to patients under 20 due to increased risk of extrapyramidal side effects
Give an example of a 5-HT3 receptor antagonists
Ondansetron
What is the MOA for 5-HT3 receptor antagonists
Antagonism of 5-HT3 (serotonin) receptor in the CTZ is believed to be responsible for the antiemetic effects
What are the routes of administration for 5-HT3 receptor antagonists
Oral, rectal, intramuscular, iv
What are some indications for 5-HT3 receptor antagonists
Nausea & vomiting especially associated with cytotoxic therapy
What are some adverse effects of 5-HT3 receptor antagonists
Constipation & headache
What are some classes of drugs which affect intestinal motility
Motility stimulants
Antispasmodics
Laxatives
Antidiarrhoeals
What are motility stimulants
Agents that increase GI motility without a laxative effect are used clinically for motility disorders. Eg. GORD, Gastric stasis (slow stomach emptying), Diagnostics e.g. Duodenal intubation
Which two drugs increase intestinal
motility by unknown mechanisms
Domperidone and metoclopramide
What are the two classes of antispasmodics
Antimuscarinics
Drugs acting directly on smooth muscle
Antispasmodics have smooth muscle relaxant properties, therefore useful as adjuncts for which diseases
Non-ulcer dyspepsia
Irritable bowel syndrome
Diverticular disease
Give two examples of antimuscarinics
Propantheline, dicycloverine (dicyclomine)
What is the MOA for antimuscarinics
Inhibition of parasympathetic activity
Causing relaxation of GI smooth muscle
What is the route of administration for antimuscarinics
Oral
What are some indications for antimuscarinics
Non-ulcer dyspepsia
Irritable bowel syndrome
Diverticular disease
What are some contraindications for antimuscarinics
Antimuscarinic drugs relax the LOS therefore should be avoided in GORD, also myasthenia gravis
What are some adverse effects of antimuscarinics
Dry mouth
Blurred vision
Dry skin
Tachycardia
Urinary retention
What are some examples of drugs acting directly on smooth muscle
Mebeverine, alverine, peppermint oil
What is the MOA for drugs acting directly on smooth muscle
Direct relaxants of smooth muscle
What is the route of administration for drugs acting directly on smooth muscle
Oral
What are some indications for drugs directly acting on the smooth muscle
Irritable bowel syndrome
Diverticular disease
What are laxatives
They are drugs used to hasten transit time in the gut and encourage defecation. They are useful to prevent undue straining at stool as this may produce hernia
Laxatives/purgatives may be given to
To remove poisons from the alimentary canal
Prepare patients for radiological examination of the colon
Remove parasites from the body after anthelminitic therapy
Empty the bowel before surgery
Counteract the constipating effect of drugs
What are some other terms used in place of laxative
Aperient
Lenitive
Laxative
Evacuative
Purgative
Cathartic
Arranged in order of increasing severity.
Effect however depends on:
Dose
The individual
The agent
Mention the types of laxatives
Bulk-forming laxatives
Osmotic laxatives
Stimulant laxatives
Faecal softners
What are some examples of bulk-forming laxatives
Bran
Methyl-cellulose
Ispaghula husk
What are some examples of osmotic laxatives
Lactulose and saline purgatives
What are some examples of stimulant laxatives
Senna, danthron, bisacodyl, sodium picosulphate, castor oil
What are some examples of faecal softeners
Liqiud paraffin, docusate sodium
What is the MOA for bulk forming laxatives
They increase the volume of non-absorbable solid residue in the gut, causing distending of the colon and stimulating peristalsis
What is the ROA for bulk forming laxatives
Oral
What are some indications of bulk forming laxatives
Constipation
What are some adverse effects of bulk forming laxatives
Flatulence, abdominal distension, GI obstruction
Note: Adequate fluid intake is encouraged, onset may be several days
What is the MOA for osmotic laxatives
Poorly absorbed substances that increase the water content of the bowel by osmosis
Lactulose, a semi-synthetic disaccharide not absorbed from the GIT. Magnesium and sodium salts are poorly absorbed and can be osmotically active
What is the ROA of osmotic laxatives
Oral
What is the indication for osmotic laxatives
Constipation
What are some contraindications to bulk forming laxatives
Intestinal obstruction, colonic atony, dysphagia
What are some contraindications to osmotic laxatives
Intestinal obstruction
What is the MOA for stimulant laxatives
Increase GI peristalsis and water and electrolyte secretion by the mucosa possibly by stimulating enteric nerves
What is the ROA for stimulant laxatives
Oral and rectal
What are the indications of stimulant laxatives
Constipation and bowel evacuation prior to medical/surgical procedures
What is the contraindication for stimulant laxatives
Intestinal obstruction
What are some adverse effects of stimulant laxatives
Intestinal cramps, possible damage to nerve plexi leading to deterioration of intestinal function and atonic colon. Danthron, potentially carcinogenic.
Note: Give stimulant laxatives for short periods only
What is the MOA for lubricants
Promote defaecation by softening (Docusate sodium) and/or by lubricating (liqiud paraffin) faeces to aid their passage through the GI tract
What are the ROAs for lubricants
Oral, docusate sodium can be given rectally.
What are some indications for lubricants
Constipation, haemorrhoids
What are some contraindications to lubricants
Not in children less than 3 years
What are some adverse effects of lubricants (fecal softeners)
Prolonged use of liquid paraffin impairs the absorption of fat-soluble vitamin A and D
Note: Prolonged use not recommended
What are the four approaches to the treatment of severe acute diarrhea
Maintenance of fluid and electrolyte balance through Oral Rehydration Therapy (ORT)
Use of anti-microbial drugs
Use of opiate-like anti-motility drugs
Use of stool modifiers and adsorbents
Should be the first priority in the treatment of acute diarrhoea
What therapy is this
Oral rehydration therapy
What does a standard ORT contain
NaCl
KCl
Sodium citrate
Glucose in appropriate concentrations
IV rehydration therapy recommended if dehydration is severe
What are some functions of zinc supplements
Protein synthesis,
Cell growth and differentiation,
Immune function,
Intestinal transport of water and electrolytes
Zinc deficiency is associated with an increased risk of gastrointestinal infections and impaired immune function
Which antibiotic is used to treat severe cholera or salmonella typhimurium infection
Tetracycline
Which antibiotic treatment is used in Shigella-caused diarrhea
Ampicillin
Which antibiotic treatment is used in Campylobacter jejuni - caused diarrhea
Erythromycin or Cipro
Which antibiotic is given in an amoebic diarrhoea, giardiasis
Metronidazole
What are some examples of opiate-like antimotility drugs
Loperamide & codeine
What is the MOA for opiate-like antimotility drugs
These act on opioid receptors in the GIT which increases the tone and rhythmic contraction of the intestine, but lessens propulsive activity
Decrease in propulsive activity leads to an increase in transit time and hence absorption of electrolyte
Overall effect is constipation.
Loperamide and codeine also have an antisecretory action
Which opiate-like antimotility drugs also have an anti-secretory action
Loperamide and codeine
What is the ROA for opiate-like antimotility drugs
Oral
What are some indications for opiate-like anti-motility drugs
They have a limited role as an adjunct to fluid and electrolyte replacement in acute diarrhoea. Also as adjunctive therapy in some chronic diarrhoeal conditions
What are some contraindications to opiate-like anti-motility drugs
Acute ulcerative colitis or antibiotic associated colitis. Not recommended for children
What are some adverse effects of opiate-like anti-motility drugs
Nausea, vomiting, abdominal cramps, constipation, drowsiness
What is the MOA for stool modifiers/adsorbents
Adsorption of toxins or coating and protecting the intestinal mucosa.
They also add solid matter to the colonic contents and improve the consistency of the faeces
What are some examples of stool modifiers/adsorbents
Kaolin, chalk, charcoal, ethylcellulose, pectin
What is the ROA for stool modifiers
Oral
What are some contraindications for stool modifiers
Not recommended for acute diarrhea
What are some adverse effects of stool modifiers
Inhibit the absorption of other drugs
