Antiemetic Drugs for diarrhea constipation

Antiemetic , Drugs for diarrhea &constipation

Drugs Used to Control Nausea and vomiting
Two brainstem sites have key roles in the vomiting reflex pathway.
1. Chemoreceptor trigger zone (in area postrema at the caudal end of fourth ventricle) is outside the blood‐brain barrier.
2. Vomiting center (in the lateral reticular formation of the medulla, coordinates the motor mechanisms of vomiting).
• The vomiting center also responds to afferent input from the vestibular system, the periphery (pharynx and gastrointestinal tract), and higher brainstem and cortical structures.
• The vestibular system functions mainly in motion sickness.
Causes of nausea and vomiting
 Motion sickness
 Pregnancy
 Hepatitis
 Chemotherapeutic agents

Classes of Anti Emetic

 Phenothiazines
Serotonin‐receptor blockers
 Benzamides
 Butyrophenones
 Benzodiazepines
 Corticosteroids
 Cannabinoids
 Substance P/neurokinin‐1‐receptor blocker


Phenothiazines , prochlorperazine , Thiethylperazine
 Blocking dopamine receptors
 They are effective against low or moderately emetogenic chemotherapeutic agents
Side Effects
1. Hypotension
2. Extrapyramidal symptoms and sedation.
Serotonin‐R Receptor Blockers (5‐HT3 Receptor Blockers)
Ondansetron
Granisetron
Palonosetron
Dolasetron
Mechanism of Action of 5‐HT3 Receptor Blockers
 Selectively block 5‐HT3 receptors
 In the periphery (visceral vagal afferent fibers)
 In the brain (chemoreceptor trigger zone).
Pharmacokinetic of 5‐HT3
Receptor Blockers
 These drugs can be administered as a single dose prior to chemotherapy (intravenously or orally)
 Long duration of action.
 Metabolized by the Liver to an active metabolite ,eliminated through the urine.
Side Effect of 5‐HT3 Receptor Blockers
1. Headache (common side effect).
2. Prolongation of QT Interval(with dolasetron)


Benzamides
Metoclopramide is highly effective at high doses against cisplatin, preventing emesis in 30-40%
Side Effects
Antidopaminergic side effects (sedation, diarrhea)

Butyrophenones , Droperidol , Domperidone , Haloperidol

 Act by blocking dopamine receptors.
 Moderately effective antiemetics.
 Droperidol had been used for sedation in endoscopy and surgery ( in combination with opiates or benzodiazepines).
 Haloperidol or metoclopramide uesd for preventing cisplatin‐induced emesis.
 The most important side effects is prolong the QT interval

Benzodiazepines , Lorazepam , Alprazolam

 Used in treating anticipatory vomiting.
 Beneficial effects due to their sedative, a nxiolytic properties.

Corticosteroids , Dexamethasone , Methylprednisolone

 Their antiemetic mechanism may involve blockade of prostaglandins.
 Effective against mildly to moderately emetogenic chemotherapy.
 Used alone or in combination with other agents.


Cannabinoids , Marijuana Derivatives (Dronabinol & Nabilone)
 Effective against moderately emetogenic chemotherapy.

Side Effects

 hallucinations, sedation, vertigo & disorientation.

Substance P/Neurokinin‐1‐Receptor Blocker Aprepitant

 Antagonist to neurokinin receptor in the brain.
 Administered orally with dexamethasone and palonosetron
 little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors
 Used for chemotherapy-induced nausea & vomiting and postoperative nausea and vomiting
 Metabolisd by CYP3A4.
 Can also induce this enzyme
Side Effects
 Constipation and fatigue (the major side effects).

Combination Regimens

Combination of Antiemetic Drugs
 Increase antiemetic activity
 Decrease toxicity.
 Dexamethasone + metoclopramide, a 5‐HT 3 antagonist, phenothiazine, butyrophenone, a cannabinoid, or a benzodiazepine
 Antihistamines (diphenhydramine + metoclopramide or corticosteroids)
Antidiarrheals
1. Antimotility agents
2. Adsorbents
3. Agents that modify fluid and electrolyte transport


Antimotility agents
Diphenoxylate
Loperamide
 Have opioid‐like actions on the gut, activating presynaptic opioid receptors in the enteric nervous system (inhibit Ach release and decrease peristalsis).
Side Effects
 Drowsiness, abdominal cramps, and dizziness.
 Toxic megacolon (they should not be used in young children or in patients with severe colitis).
Mechanism of Action
 Loperamide acts directly on circular and longitudinal intestinal muscles, through the opioid receptor
 Inhibits peristalsis
 Reduces fecal volume
 Increases viscosity
 Diminishes fluid and electrolyte loss
 Has antisecretory activity
 Increases tone on anal sphincter

Adsorbent Agents

Kaolin
Pectin
Methylcellulose.
less effective than antimotility agents, causing constipation & interfere with absorption of other drugs.


Agents that Modify Fluid and Electrolyte
Transport
NSAIDs (aspirin and indomethacin)
 Effective in controlling diarrhea (due to inhibition of prostaglandin synthesis).

Bismuth Subsalicylate

 Salicylate component, inhibits intestinal PG & Cl secretion (decreases fluid secretion in the bowel ) ,used for traveler's diarrhea
 Has antimicrobial effects and binds enterotoxins
 Has activity against H pylori

Side Effect of Bismuth Subsalicylate

1. Stool blackening
2. Darkening of tongue
3. Encephalopathy (headaches, confusion, seizures)

Laxatives

 Accelerate the movement of food through GIT.

Classification According to Mechanism of Action

1. Irritants & stimulants of the gut
2. Bulking agents
3. Stool softeners


Irritants and Stimulants
Castor Oil
 Castor oil is broken down in the small intestine to very irritating acid to the gut
 Increases peristalsis
 Stimulate uterine contractions (avoided in pregnant woman)

Cascara, Senna& Aloe

 Stimulate colonic activity
 Taken orally
 Causes evacuation of the bowels within 8 to 10 hours
 It also causes water and electrolyte secretion into the bowel.
Bisacodyl
 Potent stimulant of the colon. It acts directly on nerve fibers in the mucosa of the colon
 Available as suppositories and enteric-coated tablets
 Cause abdominal cramps and potential for atonic colon with
prolonged use.

Bulk Laxatives

Hydrophilic Colloids
 From indigestible parts of fruits and vegetables
 Form gels in the large intestine
 Causing water retention and intestinal distension& increasing peristaltic activity.


Methylcellulose
Psyllium Seeds
Bran
 Have similar actions
 May cause intestinal obstruction.
Saline and osmotic laxatives
Saline cathartics (magnesium citrate, magnesium sulfate, sodium phosphate, and magnesium hydroxide)
 Nonabsorbable salts ,hold water in the intestine by osmosis and distend the bowel, increasing intestinal activity and producing defecation in a few hours.
Lactulose
 Semisynthetic disaccharide sugar ,acts as an osmotic laxative (not hydrolyzed by intestinal enzymes). Oral doses are degraded in the
colon by colonic bacteria into lactic, formic, and acetic acids.
This increases osmotic pressure, thereby accumulating fluid, distending the colon, creating a soft stool, and causing defecation.
Stool softeners (emollient laxatives or surfactants)
Docusate sodium
Docusate calcium
Docusate potassium
 Surface-active agents (become emulsified with the stool produce softer feces
 Take days to become effective.
Lubricant laxatives
 Mineral oil and glycerin suppositories are considered to be lubricants(facilitate the passage of hard stools)
 Mineral oil should be taken orally in an up right position (to avoid its aspiration & lipid or lipoid pneumonia).
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