Flashcards in GERD, Prokinetic, Anti-emetic and Antidiarrheal drugs Deck (34):
What is GERD (gastroesophageal reflux disease)?
Abnormal relaxation of the LES (lower esophageal sphincter) -- a circular band of muscle at the bottom of the esophagus allows the stomach acid into esophagus
--stomach acid in the esophagus affects the GERD symptoms
What are some non pharmological treatment of GERD?
Avoid bed time acid rich drinks
Elevated head of the bed to 6-8 inches
lifestyle modifications (smoking and drinking)
What drugs are used for GERD?
PPI +/- H2 blockers
Prokinectic drugs are used in GI disorders, what does this mean?
Relieve GI symptoms of abdominal discomfort, bloating, heart burn, nausea, vomiting, that could be associated with GERD or gastroparesis or GI movement disorders
What are the Prokinetic disorders used in GI disorders?
First up is metoclopramide, what is the MOA and therapeutic uses?
--5HT3 and D2 receptor blocker (acts as anti-emetic)
accelerates gastric emptying and intestinal motility
--diabetic, post op gastroparesis and relief of symptoms in GERD
What are the adverse effects of Metoclopramide?
--sedation, diarrhea, and parkinsonian effects limit its high doses and long term use
The next prokinetic drug is Cisapride. What is this drug and the side effects?
Uses: gastroparesis, GERD, and constipation via stimulating Ach
Side effects: Arrhythmias (not used anymore)
The next prokinetic effect drug are the Cholinomimetics: Neostigmine and Bethanechol. what are their uses?
--used in the colonic pseudo-obstruction in hospitalized patients
--resistant to cholinesterase; long duration of action, used in post operative bowel and bladder atony
Finally the last prokinetic agent to discuss are the Macrolides. What is their use?
Erythromycin acts on motilin receptors of GIT used IV
--used for gastric emptying before upper GI endoscopic procedures
--tolerance may develop in gastroparesis
Moving on to Emesis: what is this?
Vomiting or throwing up is an involuntary, forceful expulsion of contents of stomach through the mouth or sometimes from nose
Review the Emesis diagram number 49 of the GI slides (pharm)
1.Sensory input (pain, smell, sight) as well as memory, fear and anticipation all are factors that act on the HIGHER CORTICAL CENTERS and lead to n/v
2.D2, 5HT3 (GI distention, or acute GI infection activates the 5HT3) ,Opioid/Ach and substance P receptors as well as chemotherapy is the CHEMORECEPTOR TRIGGER ZONE (AREA PROSTREMA 4TH VENTRICLE) (outside of BBB)
3. Chemotherapy and Radiotherapy act on the STOMACH AND SI and lead to n/v
4. Muscarinic and H1 receptors act on LABYRINTHS (this is responsible for motion sickness)
ALL 4 of these bolded centers act on the medulla which is the vomiting center
What are the major categories of antiemetics?
1. 5HT3 inhibitors
2. H1 antihistamines and antimuscarinics
3. NK1 receptor blockers
5. D2 receptor antagonist
First anti-emetic drug is Ondansetron, what is the MOA and clinical indications?
--block 5HT3 in the gut and CNS
--chemotherapy induced--moderate to severe emesis or post operative nausea and vomiting
--route of administration usually IV and for prophylaxis they are given orally
2nd anti-emetic drug are the H1 antihistamines and Antimuscarinics. What are these drugs?
H1 antihistamines: Diphenhydramine, Cyclizine and Meclizine: used in motion sickness and chemotherapy induced sickness
Antimuscarinics: Scopolamine: effective in emesis due to motion sickness
3rd anti-emetic drug are the NK1 receptor blockers, Aprepitant and Fosaprepitant. What are some features?
--NK1 receptor blocker in CNS
--effective in both decreasing early and delayed emesis in cancer chemotherapy
--Adverse effects of both: dizziness, fatigue, diarrhea, CYP interaction may occur
4th anti-emetic drug are the corticosteriods, Dexamethasone or Methylprednisolone. What are some features?
Corticosteriods can be combined with Ondansetron to provide greater anti-emetic effect.
What is the choice of CINV (chemotherapy induced nausea and vomiting)?
Dexamethasone or Methylprednisolone + Ondansetron or aprepitant combination is quite effective
5th Anti-emetic drug are the D2 receptor antagonists. Phenothiazines. What are these drugs?
--antagonist at D2 receptors and muscarinic receptors
--side effects: extrapyramidal symptoms, hypotension and sedation
--anti-dopaminergic and anticholinergic. Used as an antiemetic, antipsychotic effects and sedative
--anti-dopaminergic, antiemetic, antipsychotic and neuroleptic analgesic agent
6th anti-emetic drugs are Benzodiazepines (lorazepam, alprazolam and diazepam). What are the features?
Antiemetic potency of lorazepam, alprazolam and diazepam is low
--their beneficial effects may be due to their sedative, anxiolytic and amnesic properties
--useful in anticipatory vomiting
The last anti-emetic is Cannabinoids: Dronabinol. What is the use?
Acts on CB1 receptors as an agonist
Moving on now to Anti-Diarrheals, what are they?
First up are Loperamide (Imodium) and Diphenoxylate (Lomotil) which are opiate derivates. What are some features?
--slow gut motility with negligible CNS effects
--via GI mu-opioid receptors (inhibit acetylcholine release and decrease peristalsis)
Diphenoxylate is formulated with atropine to reduce abuse potential (high doses will have CNS effects)
Risk of toxic megacolon in children or patients with severe colitis
Next Anti-diarrheal is the Somatostatin Analog: Octreotide as SQ injection. What is the MOA?
Potent inhibitor of GH, glucagon, and Insulin
--used in diarrhea and flushing associated with carcinoid syndrome and diarrhea in ppl with VIP secreting tumors (VIPomas)
Third Anti-diarrheal is Bismuth Subsalicylate: what is the MOA?
Used as muco-protective (Antacid) and antidiarrheal
--decreases inflammation binds with toxins (E. coli)
Moving on to Laxatives, how are they classified?
Bulk forming agents
Chloride Channel Activator
Opioid Receptor Antagonist
First up are the stimulants, what are they?
Castor Oil, Senna and Bisacodyl
--may cause cramping
--chronic use may lead to habit of perceived need for laxatives
2nd are the bulk forming agents, what are they?
Insoluble indigestible derivatives from fruits and vegetables; hydrophilic colloids.
--Methycellulose, Psyllium, Bran
Non-absorbable; increase water retention and stools become bulky. The distention of bowel leads to peristaltic stimulation of gut.
3rd are the osmotic agents for laxatives, what are these?
Magnesium Citrate, Magnesium Hydroxide
--are saline cathartics
Osmotically draw water into the lumen of GIT, which stimulates motility
Used in simple constipation, bowel prep for endoscope
What are some features about lactulose
Lactulose: osmotic laxative
--large doses are degraded by colonic bacteria to form lactic formic and acetic acid (Which increases osmotic effect)
--used in hepatic encephalopathy (draws out ammonia NH3 from the body and is useful for preventing hyperammonia)
What are additional osmotic agents
PEG (polyethylene glycol)
--used for colonic lavage for endoscopic and radiological procedures
It induces a hyperosmotic effect
can be used as enema
Next laxatives are stool softeners, what are these?
Mineral Oil and Docusate Sodium (Colace):
--emulsify stool and soften it, lubricate it making it easy for passage
Senna in combo with Docusate
--treat opioid induced constipation
Next laxative are the chloride channel activator, what is this?
--chloride channel activator that increases secretion into GI this increases fluid content