A32. Antiemetic drugs. Prokinetic agents. Drugs for irritable bowel disease (IBS). Flashcards
Why is Eryhtromycin used as a prokinetic agent?
Erythromycin which is a macrolide, promotes motility by stimulating motilin receptors.
Which cholinomimetic is used as prokinetic agent?
Bethanechol is a cholinomimetic used for non-obstructive GI dysmotility (like in post up ileus, neurogenic ileus). Remember the major effects of cholinomimetics (BP ↓, bronchoconstriction, all GI secretions (e.g. saliva,acid))… similar to the ACE-I effect w/ DUMBBELSS [diarrhea, urination, miosis, bronchospasm, bradycardia, lacrimation, emesis, salivation, sweating]. It is also contraindicated with peptic ulcer, hyperthyroidism, obstructive ileus, asthma.
List the D2 antagonists that can be used as a prokinetic agent.
- Metoclopramide
- Domperidone: D2 receptor blocking in area postrema → GI motility ↑.
What are prokinetic agents and their indications?
Prokinetic agents/drugs stimulate upper GI motility and are helpful for gastroparesis, post-surgical gastric emptying. Also GERD patients can benefit (helps LES pressure ↑). Previously cholinomimetic agents were used, but less-so now.
List the prokinetic agents.
- D2 antagonists: Metoclopramide, Domperidone.
- Cholinomimetics: Bethanechol
- Erythromycin (Macrolide)
List the serotonin agonists.
- Lorcaserin
List the Anorexiants/ Appetite suppressants.
- Diethylpropion
- Phentermine
(Riba said all of these are no longer indicated for obesity.)
What lipase inhibitor is used for Weight loss and what is it’s MOA?
Orlistat (only licensed one for now)
MOA: inhibits gastric and pancreatic lipases → decreased breakdown of dietary fat into smaller molecules → less absorption. fat absorption ↓ by ~30% → less calories → weight loss.
What can be given in obesity?
- Lipase inhibitors (most important) 2. Anorexiants/ “appetite suppressants” 3. serotonin agonists
Name the receptors modified pharmacologically. ***
- Muscarinic receptor antagonists: scopolamine is best against motion sickness. 2. H1-antagonists (+ additional muscarinic ATG). 3. D2 antagonists. 4. 5-HT3 Antagonists / Serotonin receptor blockers 5. Substance P/ NK-1 Antagonists: drugs = Aprepitant, Fosaprepitant 6. Cannabinoids: CB-1 agonists 7. Vitamin B6: glucocorticoids
How are glucocorticoids used in this category/topic?
Glucocorticoids can enhance antiemetic action (less important). Dexamethasone and Methylprednisone are moderate-mild in effect. More likely used in combo with others.
When can Vitamin B6 be used in this category of drugs?
Vitamin B6/ pyridoxine can be used to reduce pregnancy-related nausea.
How can cannabinoids be used in this regard?
Cannabinoids: CB-1 agonists have excellent anti-emetic action. Original idea of using cannabinoids as medicine was not nausea, but pain or loss of appetite. first licensed indication was AIDS in terminal phase. now in some countries, cancer is an indication. It increases appetite, decreases nausea, decreases pain. THC/dronabinol as medicinal name. more expensive than a joint. The “problem” is the psychoactive effects. Nabilone: synthetic cannabinoid agonist.
Name some Substance P/Nk-1 antagonists.
Substance P / NK-1 Antagonists: 1. Aprepitant 2. Fosaprepitant.
What is the MOA and purpose of 5-HT3 antagonists/Serotonin receptor blockers as an antiemetic agent.
5-HT3 antagonists / serotonin receptor blockers act in the GI, cause constipation. It is the most potent antiemetics. Primarily anti-cancer drug nausea, also for post-op nausea.
D2 Antagonists
D2 antagonists block dopamine in area postrema CTZ. It’s a very efficient anti-emetics. Practically any anti-psychotic can be used as antiemetic, but obviously don’t use haloperidol etc for this. Droperidol is indicated for post-op nausea, even in children. Dose is way less than antipsychotic dose (parenterally given). May however prolong QT. o selective D2: mainly peripherally-acting, don’t really act on other receptors • metoclopramide: more or less enters brain • domperidone: doesn’t penetrate brain, but there’s no BBB in area postrema so it still has antinausea effect. Doesn’t have extrapyramidal side effects like metoclopramide. • pro-kinetic effect, actually opens the pylorus and stomach emptying is easier → increase propulsion. block nauseating reflexes. Occurs via 5-HT4 (not D2! Asked on midterm) • used for post-op nausea, IBS, ↓ nausea in cancer patients (esp metoclopramide).
How and why are H1 antagonists used as antiemetics?**
H1-antagonists (+ additional muscarinic ATG): Typical selective H1 antagonist anti-allergic drugs are not good for nausea, but H1 + muscarinic antagonism can help. Not as strong as scopolamine, but still have some anticholinergic action. Dimenhydrinate also used for motion sickness. Most important side effect is sedation
How can Muscarinic receptor antagonists be used as an anti-emetic?
Muscarinic receptor antagonists such as scopolamine is best against motion sickness.
Physiology: Nausea reflex**
nausea reflex o efferent: parasympathetic (smooth muscle) + motoneurons (skeletal muscle) o afferent: • reticular formation: collects impulse from gut, chemoreceptor zone, labyrinthic fibers/nuclei. decides whether there will be nausea or not. at least 3 receptors + neurotransmitters ▪ Muscarinicreceptors (M1probably),H1histamine,D2dopamine • area postrema: chemoreceptor trigger zone (CTZ) ▪ found in 4th ventricle. no BBB here, any chemical agent can enter here and sense the chemical structures to induce nausea. nauseating chemicals can be toxins or drugs or some foods ▪ dopamine 2 and serotonin 3 receptors can be activated then go to reticular formation • GI: anything we digest appears there. may send information upward. ▪ involves serotonin 3, dopamine 2, others – very complicated. neurokinin-1 receptor probably ▪ enteralstimulusgoestosolitarytractnucleusandacts. • labyrinthic reflex: important in motion sickness. ▪ mostlymuscarinicreceptorstimulation,H1too ▪ any drug which enhances labyrinthic reflex, e.g. opioids, can cause nausea. morphine often provokes vomiting • note that any sensory input may lead to nausea. smell, taste, see, feel something disgusting, even just thinking.
