Gastrointestinal Drugs

Acid-Peptic Diseases

diseases that can lead to ulceration of the stomach

• occur when digestive forces (acid, enzymes) overwhelm protective agents

Stomach Anatomy

Parts:

• Fundus (dome shaped upper part)

• Antrum (lower part)

• Lower Esophageal Sphincter

• Pyloric Sphincter

Exocrine Cells:

• Chief Cells: Pepsinogen and Gastric Lipase Secretion

• Parietal Cells: H+ and Intrinsic Factor Secretion

• Mucous Neck Cells: secrete mucus

Enteroendocrine Cells:

• G Cells: Gastrin Secretion

• D Cells: Somatostatin Secretion

Acid Secretion Mechanisms

G Cell:

• activated by dietary peptides

• activated by Gastrin Releasing Peptide (via GRP-Receptor)

  • from enteric neurons

• releases gastrin

• gastrin has to go through blood vessel to reach targets

ECL Cell:

• Enterochromaffin Like Cell

• activated by gastrin (via G/CCK-B Receptor)

• activated by acetylcholine (via M₃ Receptor)

  • released by vagus nerve

  • parasympathetic

• releases histamine

Parietal Cell:

• activated by acetylcholine (via M₃ Receptor)

• activated by gastrin (via G/CCK-B Receptor)

• activated by histamine (via H₂ Receptor)

• releases H⁺ (via H⁺/K⁺ ATPase)

D Cell:

• activated by H⁺ (in luminal acid)

• inhibited by acetylcholine

• releases somatostatin

  • somatostatin inhibits G Cells

  • via Somatostatin Receptor

Parietal Cell Acid Production

• ATP Dependent

Acid Production:

• H₂O + CO₂ ⇄ H₂CO₃ (facilitated via Carbonic Anhydrase)

• H₂CO₃ ⇄ H⁺ + HCO₃^- (bicarbonate)

H⁺/K⁺ ATPase Action:

• ATP → ADP for energy

• pumps formed proton out the cell

• pumps potassium ion into cell

• allows H⁺ to exit into lumen

Chloride Ion:

• Bicarbonate exits into blood in exchange for chloride ion

  • facilitated by Bicarbonate-Chloride Antiporter

• Chloride ion leaves cell and enters lumen via chloride channel

  • reacts with proton to form HCl

  • also equalizes charge (H⁺ and Cl^- leave = net charge 0)

• Bicarbonate enters blood

  • causes slight increase in pH of blood (alkaline tide)

Acid-Peptic Diseases Examples

• Gastroesophageal Reflux Disease (GERD)

• Peptic Ulcer

• Stress-Related Mucosal Injury

All result in Ulceration

• over 90 of peptic ulcers caused by H. pylori or NSAIDs

Drugs for Acid-Peptic Diseases

Agents that Reduce Intragastric Acidity:

• Antacids

• H2 Receptor Antagonists

• Proton Pump Inhibitors

• GI Anticholinergics

Agents that Promote Mucosal Defense

• Sucralfate

• Bismuth Compounds

• Prostaglandin Analogue

Some combination therapies exist that combine both

Antacids

MOA: weak bases, direct neutralization of acid in stomach

• results in lower intragastric acidity

Acid Neutralization Capacity:

• varies among different formulations

• Factors: dissolution, water solubility, rate of reaction, rate of gastric emptying

Note: stomach produces about 45 mEq of acid per hour

Agents:

• Sodium Bicarbonate

• Calcium Carbonate

• Magnesium Hydroxide

• Aluminum Hydroxide

Related Drugs:

• Simethicone

• Alginates

Sodium Bicarbonate

Formula: NaHCO3

• reacts rapidly

• NaHCO₃ + HCl → NaCl + H2O + CO2↑

Adverse Effects:

• belching

  • due to CO₂ release

• metabolic alkalosis

  • in large doses; HCO₃ enters blood instead of reacting

  • or if with renal deficiency

  • decreases breathing rate (compensatory mechanism)

• Exacerbation of fluid retention

  • due to NaCl increase

  • consideration for hypertension or heart failure

Calcium Carbonate

Formula: CaCO₃

• less soluble, reacts more slowly

• CaCO₃ + 2 HCl → CaCl₂ + H2O + CO₂↑

Adverse Effects:

• belching

  • due to CO₂ release

• Milk-Alkali Syndrome:

  • Hypercalcemia

  • Metabolic Alkalosis

  • Kidney Dysfunction

Magnesium Hydroxide

Formula: Mg(OH)₂

• Mg(OH)₂ + 2 HCl → MgCl₂ + 2 H₂O

• no belching due to no gas production

• causes diarrhea

  • diarrhea caused by osmotic laxative action

• mnemonic: Mag-tatae

Aluminum Hydroxide

Formula: Al(OH)₃

• Al(OH)₃ + 3 HCl → AlCl₃ + 3 H₂O

• no belching due to no gas production

• causes constipation

• mnemonic: Ala-tae

Simethicone

Antacid Related Drug

• often used in combination with antacids

• Dimethicone + Silicon Dioxide (finely divided)

• Relieves gas

• MOA: lowers surface tension of mucus, therefore disperses and prevents gas pockets

Alginates

Antacid Related Drug

• often used in combination with antacids

• natural polysaccharide polymer from brown seaweeds

• MOA: forms gel-like barrier on top of gastric content

• alginate, instead of gastric acid, is refluxed

• literally blocks acid from refluxing back up

H₂ Receptor Antagonists

MOA: competitive inhibition with histamine at parietal H₂ receptor

• selective, does not affect H₁

• more effective at inhibiting nocturnal acid secretion (which depends largely on histamine)

• impact on meal-stimulated acid release is less

• longer effect than antacids

Ex: Cimetidine, Ranitidine, Famotidine, Nizatidine

Adverse Effects:

Common:

• diarrhea

• constipation

• headache

• fatigue

• myalgias (muscle ache)

Cimetidine: 

• men:

  • gynecomastia (breast enlargement)

  • impotence

• women:

  • galactorrhea

• via inhibition of estradiol metabolism

Proton Pump Inhibitors

MOA: inhibits H⁺-K⁺ ATPase irreversibly

• body must generate new pumps to counteract

• more efficacious than H2 blockers

Ex: Omeprazole, Esomeprazole, Lansoprazole, Dexlansoprazole, Rabeprazole, Pantoprazole

• but not Aripiprazole which is an anti-psychotic

Considerations: 

• are all prodrugs; activated inside parietal cell

• activated by reaction with acid

  • as such, must be formulated for enteric release

  • if activated in stomach, becomes charged, can no longer be absorbed

Structure: similar to ???

Proton Pump Inhibitor Activation

• activated by acid

  • H⁺ is attacked by Nitrogen

  • further electron rearrangements and a second H⁺ is attacked by Sulfur atom

• Important Steps:

  • formation of sulfenic acid intermediate

  • formation of pyridinium sulfenamide structure (activated form)

Action:

• forms disulfide bridge with SH residue in proton pump (cysteine residue)

• permanently inhibits proton pump

Proton Pump Inhibitor Pharmacokinetics

• absorption is inhibited by food

  • should administer 1 hour before meals

• short half-life (1.5 hours) but long effects (24 hours)

  • synthesis of a new pump is about 18 hours

Pharmacokinetically Ideal: 

• because it has a

  • short serum half life

  • is concentrated

  • only activates near site of action

  • and has a long duration of action

Proton Pump Inhibitor Indications and Adverse Effects

Clinical Uses:

• GERD

• Peptic Ulcer Disease

  • for H. Pylori Associated (take with Azithromycin)

  • for NSAID Associated

  • for Prevention of rebleeding of Ulcers

• Non-Ulcer Dyspepsia (Indigestion)

• Prevention of Stress-Related Mucosal Bleeding

• Gastrinoma/Other Hypersecretion

Adverse Effects:

• Diarrhea

• Headache

• Abdominal Pain

• Nutritional Effects

  • Subnormal Vitamin B₁₂ (esp. with prolonged therapy)

    • due to Vitamin B₁₂ needing acid to release from food

  • low absorption of minerals (iron, calcium salts, magnesium)

    • many need acidic condition to absorb (especially iron)

• Respiratory and Enteric Infection

  • acid acts as a defense against pathogens

• Effect on Gastrin Levels:

  • may cause transient gastric acid hypersecretion upon stopping administration

GI Anticholinergics

• inhibits ACh action in stomach, lowering acid secretion

  • decreases parasympathetic response (rest and digest)

Ex: Dicyclomine

• limited use due to many anticholinergic side effects

• ex: dryness of mouth, mydriasis, etc.

Sucralfate

Beginning of Mucosal Defense Drugs

• salt of sucrose complexed to sulfated aluminum hydroxide

MOA:

• in aqueous/acidic medium, forms viscous paste

  • binds selectively to ulcers/erosions

• believed that negatively charged sucrose sulfate binds to positively charged proteins at base of ulcers/erosions

  • forms barrier that prevents further caustic damage

Administration:

• 1 hour before meals, on empty stomach

Adverse Effects:

• not absorbed, virtually void of systemic effect

• may cause constipation (due to Aluminum)

• Interactions:

  • may bind other medications, lowering their absorption

Bismuth Compounds

Agents:

• Bismuth Subsalicylate

• Bismuth Subcitrate Potassium

MOA: precise mechanism not known

• coats ulcers/erosions, creates protective layer

• may stimulate Prostaglandin, Mucus, and HCO₃ secretion

• Bismuth has antimicrobial effect and binds enterotoxins

• Subsalicylate Specifically:

  • reduces stool frequency and liquidity (in acute infectious diarrhea)

  • Salicylate: inhibits prostaglandin and chloride secretion

Adverse Effects:

• excellent safety profile

• harmless blackening of stools/tongue due to bismuth sulfide

• prolonged use can cause salicylate toxicity

Clinical Use:

• prevention of traveler’s diarrhea (bacterial infection)

Prostaglandin Analogue

• a PGE1 Analogue

• Ex: Misoprostol

MOA:

• has acid inhibitory and mucosal protective properties

• also believed to stimulate mucus and bicarbonate secretion

Indications:

• prevention for NSAID-induced ulcers in high-risk patients

Contraindications:

• not to be used during pregnancy or women of child-bearing potential

  • induces uterine contraction

  • associated with abortion

• has abuse potential

Prostaglandin Analogue Specific Mechanism

• inhibits adenylyl cyclase → lowers cAMP

  • in parietal cell → lowers proton pump activity

• counteracts effects of histamine

Prokinetic Agents

• drugs that stimulate gut motor functions

Effects:

• increase lower esophageal sphincter pressures

  • useful for GERD

• improves gastric emptying time

  • useful for gastroparesis (stomach paralysis)

• stimulates intestinal peristalsis

  • for post-operative ileus (temporary GI paralysis)

  • for chronic intestinal pseudo-obstruction (digestive tract nerve dysfunction)

• enhance colonic transit

• may aid in relieving constipation

Neurotransmitter Action:

• Dopamine is inhibitory for GI Kinetics

  • dopamine receptor activation inhibits smooth muscle

• ACh and Calcitonin Gene-Related Peptide (CGRP) are stimulatory for GI Kinetics

Prokinetic Categories:

• Cholinomimetics

• Dopamine D2-Receptor Antagonists

Serotonin Action on Intestines

• released by enterochromaffin cells when gut stretch occurs

• binds to 5-HT₃ receptors

  • associated with vomiting

  • heads to CNS

• binds to 5-HT_IP receptor

  • nerve goes to enteric nervous system

  • releases ACh and CGRP

    • inhibited by 5-HT₄ receptor

Dopamine is inhibitory for this process

Cholinomimetics

Cholinomimetic Agonists:

• stimulates M₃ receptors

• Ex: Bethanechol (previous treatment for GERD and gastroparesis)

Acetylcholinesterase Inhibitors

• prevents the breakdown of ACh

• Ex: Neostigmine

  • can enhance gastric, small intestine, and colonic emptying

Not preferred due to cholinomimetic side effects (DUMBBELLS)

• Diarrhea

• Urination

• Miosis

• Bronchorrhea

• Bradycardia

• Emesis

• Lacrimation

• Lethargy

• Salivation & Sweating

Dopamine D2-Receptor Antagonists

Ex: Metoclopramide and Domperidone

MOA: blocks D₂ receptor, increases smooth muscle stimulation

• also blocks D₂ receptors in CTZ of medulla (chemoreceptor trigger zone)

Effects:

• increase esophageal peristaltic amplitude (strength of contractions)

• increases lower esophageal sphincter pressure

• enhance gastric emptying time

• antinausea and antiemetic action

• has no effect on intestine

Dopamine D2-Receptor Antagonists Indications and Adverse Effects

Clinical Uses:

• GERD

• impaired Gastric Emptying (ex: post-Basurgical disorders)

• non-ulcer dyspepsia

• prevention of vomiting

• postpartum lactation stimulation (due to prolactin antagonism)

Adverse Effects (Metoclopramide):

• restlessness, drowsiness, insomnia, anxiety, agitation

• extrapyramidal effects (Parkinson like)

Adverse Effects (Both):

• elevated prolactin levels

  • causes galactorrhea, gynecomastia, impotence, menstrual disorders

Laxatives

Useful for:

• constipation

• high blood pressure (to prevent straining)

  • straining can induce aneurysm

Sub-Classifications:

• Bulk-Forming

• Stool Softeners

• Lubricant

• Osmotic

• Stimulant

• Opioid Receptor Antagonists

• Serotonin 5HT4 Receptor Agonists

Can be abused by people trying to get slimmer

• note: generally dietary fiber is enough for regular use, should only use these with constipation

Bulk-Forming Laxatives

• indigestible, hydrophilic colloids

• absorb water, forms bulky emollient gel

• distends (stretches) colon → promotes peristalsis

Natural:

• Psyllium

• Methylcellulose

Synthetic:

• Polycarbophil

Notes:

• slow onset of action

• better for prevention rather than treatment

• side effect: bloating and flatus (farting) due to bacterial digestion

• Contraindication: GI obstruction (aka impaction)

• requires water due to water-absorbing mechanism

  • administration: mix powder with water then drink

  • DO NOT take dry powder; it expanding in stomach is BAD

  • expansion is more controlled when it expands externally

Stool Softener Agents

• also called emollient laxatives or surfactants

• softens stools, allows water and lipids to penetrate

• allows for interaction of multiple faces

Ex:

Docusate Salts:

• often prescribed to hospitalized patients to prevent constipation and minimize straining

• may take days to become effective

• must not be taken with mineral oil (surfactant property may enable systemic absorption of mineral oil)

Lubricant Laxatives

MOA:

• lubricate stools, making them easier to move out

• better for children than other laxatives

Ex: 

Mineral Oil:

• clear, viscous oil

• lubricates fecal matter

• retards water absorption from stool

• Adverse Effect: aspiration (can cause severe lipid pneumonitis if enters the lungs)

  • should take mineral oil orally in upright position to avoid this

• long term used can impair Vitamin ADEK absorption

  • will dissolve in mineral oil and get carried out instead

Glycerin Suppository:

• especially better for children

Osmotic Laxatives

• soluble, but not absorbable

• increases osmolarity of fecal fluid

  • which draws water into the colon

• causes increase in fecal fluid

• results in increased stool liquidity

Indications:

• acute constipation (treatment)

• chronic constipation (prevention)

Ex:

• Saline Laxatives:

  • Magnesium Hydroxide

  • Magnesium Citrate

  • Magnesium Sulfate

  • Sodium Phosphate

  • Adverse Effects:

    • cardiac arrhythmias or renal failure (due to electrolyte imbalance)

• Sugars:

  • Sorbitol

  • Lactulose

    • semisynthetic disaccharide sugar

    • metabolized by colonic bacteria into lactic, formic, acetic acids (responsible for osmolarity)

    • can also be used for encephalitis (brain inflammation) due to liver damage (via absorption of ammonia)

    • Side Effects: Cramps and Flatus

• Balanced Polyethylene Glycol Lavage Solution

  • contains PEG, sodium sulfate, sodium chloride, sodium bicarbonate, potassium chloride

  • designed so no significant IV fluid/electrolyte shift occurs

  • used for complete colon cleansing prior to GI endoscopic procedures

  • should be ingested rapidly

    • 2-4 Liters in over 2-4 hours

  • does not produce cramps of flatus

Stimulant Laxatives

• also called irritant laxatives

• MOA: poorly understood;

  • possibly direct stimulation of enteric nervous system + colonic electrolyte and fluid secretion

  • or can cause minor irritation which induces peristalsis

Ex:

• Anthraquinone Derivatives

  • from Aloe, Senna, Cascara sp.

  • poorly absorbed

  • produce bowel movement for:

    • 6-12 hours (PO)

    • 2 hours (rectal)

  • prolonged use leads to melanosis coli (pigmentation of intestine) - mostly benign

• Diphenylmethane Derivatives

  • ex: Bisacodyl

    • treatment for acute/chronic constipation

    • produced bowel movement for:

      • 6-10 hours (PO)

      • 30-60 mins (rectal)

    • minimal absorption: safe for short/long term use

    • Adverse Effect:

      • abdominal cramps

      • atonic colon (long term use)

  • Phenolphthalein

    • withdrawn from market due to cardiac toxicity

• Castor Oil

  • from Ricinus communis (castor bean)

  • broken down in small intestine to ricinoleic acid

    • acts as strong gut irritant

  • Contraindications:

    • pregnant women (may stimulate contraction)

Serotonin 5-HT₄ Receptor Agonist

• 5-HT₄ promotes release to enteric nervous system

• when stimulated, enhances release of ACh and CGRP (Calcitonin Gene-Related Peptide)

  • promotes peristaltic movement

Ex:

• Tegaserod

  • high affinity for 5HT₄,

    • no appreciable binding to 5-HT₃ or Dopamine receptor

  • used to be treatment for chronic constipation and IBS with predominant constipation

  • removed from market due to cardiovascular side effect

• Cisapride:

  • partial 5-HT₄ agonist

Antidiarrheal Agents

• generally safe

• do not use for:

  • bloody diarrhea

  • high fever

  • systemic toxicity

  • as it may exacerbate underlying condition

• Do not use in conditions where inhibition of peristalsis must be avoided (ex: ileus)

Classifications:

• Opioid Agonists

• Colloidal Bismuth Compounds

• Bile Salt-Binding Resins

• Octreotide

Related Drugs:

• Oral Rehydration Salts

Oral Rehydration Salts

• designed for diarrheal dehydration

• the first thing to advise patient to take

• Note: for diarrhea because of electrolyte and fluid loss

  • for normal thirstiness, just use water

  • don’t resort to drugs when you don’t need to

Sports Drinks:

• sports drinks are meant to add excess solute (especially glucose)

• generally cause hypertonicity

  • note: can cause osmotic laxative action, further exacerbating

• ORS are specialized to give normal amount

  • can use sports drink if no other choice, but generally ORS is better

Can not take with:

• Concentrates

• Powdered juice

• Carbonated drinks

Opioid Agonist

• opioids have constipating effect

  • because opioids are depressants; depress the activity

• MOA: 

  • inhibition of presynaptic cholinergic nerves in submucosal and myenteric plexus →

  • increases colonic transit time →

  • also increases water absorption

• Must not have CNS and addicting effects

ex:

• Loperamide

  • nonprescription

  • does not cross BBB

  • no analgesic effect

  • no addiction potential

  • for chronic and acute diarrhea

• Diphenoxylate:

  • prescription drug

  • has CNS effect at higher doses

  • can lead to dependence with prolonged use

Bile Salt-Binding Resins

• bile salts are normally absorbed in terminal ileum

• diseases of terminal ileum/surgical resection leads to malabsorption of bile salts

  • ex: Crohn’s Disease

  • surgical resection = removal of damaged tissue

• leads to colonic secretory diarrhea

  • when bile salts enter the colon, they can induce movement of chlorides to intestine

  • after which, water will follow

Bile-Salt Binding Resins:

• MOA: bind to the bile salts preventing action

  • negative bile acids bind to positive resins

Indications:

• for diarrhea due to excess bile acids

Agents:

• Cholestyramine

• Colestipol

• Colesevelam

Considerations:

• should be taken immediately before meal

  • as bile salts won’t really be present otherwise

• adverse effects:

  • bloating

  • flatulence

  • constipation

  • fecal impaction

• bind a number of drugs; do not use within 2 hours of other drug use

Octreotide

• similar to somatostatin

Somatostatin:

• 14 amino acid peptide

• Half-Life: 3 minutes

• Functions:

  • reduce gastrin secretion

  • reduce intestinal fluid secretion

  • other unrelated function

Octreotide:

• Half-Life: 1.5 hours (IV)

  • much longer than somatostatin

• mimics somatostatin

• inhibits bowel movement at higher doses

Indications:

• treatment of diarrhea due to vagotomy

  • vagotomy = damaged/cut vagus nerve

• Adverse Effects:

  • nausea

  • vomiting

  • abdominal pain

  • flatulence

  • gallstone formation

Emesis Pathophysiology

Physiology:

• Vomiting Center:

  • located in medulla oblongata

  • will cause vomiting when stimulated

Inputs for Vomiting Center:

will send signals to center to initiate emesis

• Chemoreceptor Trigger Zone:

  • located outside BBB

  • accessible to agents from blood and spinal fluid

  • when it detects emetic agent/toxin in blood/fluid, will send signal to VC

• Vestibular System:

  • located in ear

  • detects balance and spatial orientation

  • when dizziness is caused → induces vomiting

• Vagal and Spinal Afferent (Sensory) Nerves:

  • connected to digestive system

  • irritation due to chemotherapy, distention, etc. may cause vomiting signal

• Central Nervous System:

  • psychiatric disorders, stress, emotions and others may cause vomiting signal

Emesis Trigger Areas and Receptors

Vomiting Center:

• H₁ Receptor

• M₁ Receptor

• NK₁ Receptor

• 5-HT₃ Receptor

Chemoreceptor Trigger Zone:

• D₂ Receptor

• 5-HT₃ Receptor

• NK Receptor? (possible)

Vestibular System:

• M₁ Receptor

• H₁ Receptor? (possible)

GI Tract and Heart:

• Mechanoreceptors

• Chemoreceptors

• 5-HT₃ Receptor

Emetic and Antiemetic Agents

Emetic Agent:

• Ipecac Syrup

Antiemetic Agents:

• Serotonin 5-HT₃ Antagonists

• Corticosteroids

• Neurokinin 1 Receptor Antagonists

• Phenothiazines

• Butyrophenones

• Substituted Benzamides

• H₁ Antihistamines

• Anticholinergic Agents

• Benzodiazepines

• Cannabinoids

Note: antiemetics are generally prophylactic

• cause you can’t really take and absorb a drug while you’re vomiting

Ipecac Syrup

• from Carapichea ipecacuanha (Rubiaceae)

• active agent: emetine and cephaeline

  • used to induce vomiting

  • useful for cases of ingested poisons

  • not encouraged in modern use

  • note: risk of aspiration; may vomit toxic agent into lungs causing even more harm

Serotonin 5-HT₃ Antagonist

MOA:

• block 5-HT₃ receptors on intestinal, vagal, and spinal afferent nerves

• prevents transmission of vomiting signal to CNS

• action is restricted to emesis attributable to vagal stimulation and chemotherapy

Agents:

the -setrons

• Ondansetron

• Granisetron

• Dolasetron

• Palonosetron

Indications:

• chemotherapy induced nausea and vomiting

• post operative nausea and vomiting

• radiation nausea/vomiting

Adverse Effects:

• generally well-tolerated

• headache

• diziness

• constipation

Corticosteroids

MOA:

• enhance efficacy of 5-HT₃ receptor antagonists

• used in conjunction with the setrons

Indications:

• for prevention of acute/delayed Nausea & Vomiting in moderately to highly emetogenic chemotherapy regiments

Agents:

• Dexamethasone

• Methylprednisolone

Note: Efficacy vs Effectivity

Efficacy is how well it works in a controlled setting (ex: clinical trial)

Effectivity is how well it works in a real life setting

Neurokinin 1 Receptor Antagonists

Note: NK1-Rs are possibly on the chemoreceptor trigger zone

• and are present in the vomiting center

Clinical Use:

• prevention of nausea and vomiting in highly emetogenic chemotherapeutic regimens

• used in combination with 5-HT₃ receptor antagonists + corticosteroids for highly emetogenic

• process:

  • if setrons don’t work, add corticosteroids

  • if even that doesn’t work, add the NK1-R antagonist

Agents:

• Aprepitant

Adverse Effects:

• fatigue

• dizziness

• diarrhea

Phenothiazines

MOA: inhibition of dopamine and muscarinic receptors

• mainly antipsychotic

Agents:

• Prochlorperazine

• Promethazine

• Triethylperazine

Butyrophenones

MOA: central dopaminergic blockage

• also generally anti-Psychotic 

• ex: Droperidol

Substituted Benzamides

Indication:

• for prevention and treatment of nausea and vomiting

MOA:

• dopamine receptor blockade

Agents:

• Metoclopramide

• Trimethobenzamide

H₁ Antihistamines & Anticholinergics

• weak antiemetic property

• useful for motion sickness

H₁ Antihistamine Agent:

• Meclizine

Anticholinergic Agent:

• Scopolamine/Hyoscine

  • muscarinic receptor antagonist

  • patch placed behind the ear

Benzodiazepines

Indications:

• used before initiation of chemotherapy

  • reduces anticipatory vomiting caused by anxiety

Agents:

• Lorazepam

• Diazepam

(also can not vomit while asleep)

Cannabinoids

Agent: Dronabinol

• also called Δ9-tetrahydrocannabinol

• major psychoactive agent in marijuana

• appetite stimulant, anti-emetic properties

• uncommonly used for prevention of chemotherapy induced nausea and vomiting (better agents exist)

• adverse effect:

  • euphoria

  • dysphoria

  • sedation

  • hallucinations

  • dry mouth

  • increased appetite

Use of Medical Marijuana

At the very least for antiemetic purposes, why use it when better agents exist?