Emetics

• Apomorphine
• Ipecac

Anorexogenics

• Amphetamine
• Diethylpropion
• Phentermine
• Mazindol
• Sibutramin

Orexogenic

• Dronabinol

Antiemetics

Anticholinergics

• Scopolamine

H₁ antagonists

• Dimenhydrinate

Dopaminergic antagonists

• Chlorpromazine
• Metaclopramide (Reglan)

Anxiolytics

• Diazepam

Corticosteroids

• Dexamethasone

Others

• Dronabinol

5HT Antagonists

• Ondansetron

General

• Emesis

Ø  both autonomic and somatic nervous reflex elements are involved

Ø  Vagal afferent fiber in the GI tract® nucleus and tractus solitarius in the brain stem® vomiting center, Chemoreceptor trigger zone, and dorsal motor nucleus of the vagus

Ø  Causes: motion sickness, pregnancy, surgery, cancer chemo, irradiation, vertigo, drugs

Ø  Drugs known to cause emesis: digitalis, morphine

• Nausea and Vomiting in Pregnancy

Ø  60% of women during the 1^st trimester

Ø  possible teratogenicity of H₁ antagonists (Bendectin removed from US shelves in 1983)

Emetic Drugs (cause you to vomit.)

Ipecac Syrup

• Mechanism

Ø  stimulates the peripheral sensory afferents in the stomach

Ø  once absorbed, stimulates the CTZ

• Given Orally
• Toxicity

Ø  Toxic to the Heart in Large Doses

Ø  Safe for home use.  1 dose bottles

Apomorphine

• Mechanism

Ø  Dopamine D₂ agonist

Ø  Directly stimulates the CTZ

• Given Parenterally
• Toxicity

Ø  CNS and respiratory depression

Ø  More toxic than ipecac

Antiemetic Drugs

Categories

1)     Motion Sickness – use drugs prophylactically

2)     CTZ stimulation

Ø  caused by drug metabolites, cancer chemo, products of cell damage, anesthesia, surgery, irradiation, more.

REMEMBER – anti-emetics are least effective when given AFTER nausea begins

Scopolamine – muscarinic antagonist

• mechanism

Ø  reduces the excitability of the labyrinthine receptors and therefore decreases or depresses transmission via the vestibular cerebellar pathway.

• Used for

Ø  motion sickness (most effective single agent)

Ø  pre-surgery

Ø  synergistic with dextroamphetamine or ephedrine

Ø  side effects limit its treatment for vertigo

• not effective for CTZ-mediated nausea
• Side effects

Ø  drowsiness, dry mouth, blurred vision

Ø  DON’T GIVE TO PATIENTS w/ BProstaticH or glaucoma

• given in a transdermally applied fashion

Dimenhydrinate – H₁ antagonist

• has antimuscarinic activity
• mechanism

Ø  blocks neural pathways in the labyrinth

Ø  antagonizes muscarinic cholinergic receptors

• Uses

Ø  motion sickness

Ø  vertigo

Ø  pregnancy, post-op

• not effective for CTZ mediated nausea
• Side Effects

Ø  sedation, dry mouth

• Other H_{1 ­}antagonists – Promethazine, Meclizine

Chlorpromazine – Dopamine Antagonist

• Mechanism

Ø  blocks D₂ receptors in the CTZ and vomiting center

Ø  inhibits peripheral transmission to the vomiting center via the vagus nerve

• Uses

Ø  Chemo

Ø  Irradiation

Ø  Post-op, other drugs, diseases

• not effective for motion sickness
• Side effects

1)     anticholinergic (SLUDS)

2)     extrapyramidal

3)     orthostatic hypoTN

4)     lower the seizure threshold

• Contraindicated in Parkinson’s disease

Metaclopramide – Dopamine antagonist

• D₂ antagonist that blocks D₂ receptors in the CTZ and vomiting center
• ALSO – prokinetic drug – dopamine in the GI tract inhibits release of acetylcholine from motor neurons. When you block it, you get Ach release and contraction of the GI smooth muscle.

Ø  increases lower esophageal sphincter pressure

Ø  stimulates upper GI motility

Ø  enhances peristalsis of the duodenum and jejunum

• High Dose drug acts as antagonist at 5-HT receptors in the vomiting center to depress
• In the GI tract, it is also a 5-HT antagonist and blocks visceral afferents to the NTS (like Ondansetron)
• Uses

1)     Chemo – given pre and post administration w/ dexamethosone

2)     Post-op

• not effective against motion sickness
• Side effects

1)     sedation

2)     diarrhea

3)     EPS – combined with diphenhydramine to counteract

4)     Enhanced prolactin production

Dronabinol – cannabinoid – D-9-tetrahydrocannibol

• uncertain mechanism of action
• principal psychoactive component of marijuana
• Uses

1)     Chemo

2)     Appetite stimulant

• not effective against motion sickness
• Side effects

1)     sedation

2)     dry mouth

3)     abuse potential

4)     orthostatic hypoTN

5)     psychoactive

6)     increased desire to eat

Dexamethasone – corticosteroid

• uncertain mechanism of action
• Use

1)     high dose with Chemo; effective against highly emetic antineoplastic agents

• Not effective against motion sickness
• Combined with metoclopramide and dimenhydrinate

Diazepam & Lorazepam – BZD – anxiolytic

• CNS depressant, anxiolytic
• Anterograde amnesia for 4-6 hours
• Lorazepam – used for prophylaxis to prevent anticipatory emesis
• Diazepam – treatment for vertigo; Meniere’s disease
• Not effective against motion sickness

Ondansetron – 5HT₃ antagonist

• 5HT₃ receptors are present in: CNS, PNS, enterochromaffin cells of the intestinal mucosa
• mild adverse reactions
• No EPS symptoms
• Use

1)     post operative

2)     Cancer chemo – drug of choice now

• Other 5HT₃ antagonist – Granisetron

Cancer Drugs with…               Give …

1) low emetic potential                        phenothiazine or dexamethasone

2) moderate emetic potential              metaclopramide & dexamethasone or  a phenothiazine & dexamethasone

3) high emetic potential                       ondansetron and dexamethasone or diphenhydramine or lorazepam

Anorexogenic Drugs

• Two different ways to give sensations

1)     produce aversion to food (decrease the appetite)

2)     promote satiety

Amphetamine, Methamphetamine – sstimulate release and inhibit reuptake of the catecholamine neurotransmitters, norepinephrine and dopamine

• marginally effective for control of appetite
• HIGH RISK OF DEPENDENCE
• Adverse Reactions

1)     CNS stimulation

2)     Sympathetic Stimulation – dry mouth, blurred vision, arrhythmias, HTN

Diethylpropion -

• mechanism

Ø  similar to amphetamine

• CNS side effects less that amphetamine
• Low incidence of psychic and physical dependence
• Contraindications

1)     severe cardiovascular disease

2)     HTN

3)     Pregnancy

Phenteramine

• related to amphetamine (mechanism similar)
• CNS side effects considerably lower than amphetamine
• Incidence of insomnia > as compared to diethylpropion
• Low abuse potential
• Contraindications

1)     CV disease

2)     HTN

3)     Pregnancy

Mazindol

• structurally similar to the TCAs
• Mechanism

Ø  blocks reuptake of NE, DA, and 5-HT

• no euphoria
• no dependence
• lower and less incidence of side effects than with the amphetamine derivatives
• Contraindications

1)     CV disease

2)     Pregnancy

Phenylpropanolamine – direct a-adrenergic agent – Dexatrim, Acutrim

• poor CNS penetration (Less likely to become addicted)
• Adverse effects of CNS stimulation or HTN rare
• Given with close attention to those with HTN, depression, CV disease, diabetes, thyroid disease

Fenfluramine

• no longer available – valvular heart damage and pulmonary HTN
• stimulate the release of 5-HT and block its reuptake
• PROMOTES SATIETY

Tags: Anorexogenics, Anticholinergics, Anxiolytics, Apomorphine, cancer chemo, Corticosteroids, Dexamethasone, Dopaminergic antagonists, Dronabinol, drugs, Ipecac, irradiation, Metaclopramide, motion sickness, Ondansetron, Orexogenic, pregnancy, Scopolamine, surgery, vertigo

This entry was posted on Sunday, July 26th, 2009 at 5:00 am and is filed under Pharmacology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.