antiemetic and antimigraine Flashcards
what is vomiting and the sequence of events in the act of vomiting?
I. Vomiting:
A physiological protective antiperilstatic response resulting in forceful expulsion of the GI contents as a result of a series of integrated events.
II. Sequence of Events in the act of vomiting:
1. Nausea: Increased salivation, pupillary dilatation, sweating and pallor.
2. Retching: Contraction of abdominal muscles, antiperistaltic movement.
3. Vomiting: Contraction of diaphragm and forceful expulsion of GIT contents through mouth.
what are 5 causes of nausea and vomiting?
III. Causes of Nausea and Vomiting:
1. Drug induced (iatrogenic)
All Cytotoxic drugs (Cisplatin, Methotrexate, Nitrogen mustards)
Opioids (morphine and its congeners), Cholinomimetics
Cardiac glycosides - Digoxin
L-Dopa, Bromocriptine, High dose estrogen (ethinyl estradiol)
Experimental Use: Emetine, Apomorphine
2. Infectious G.I. disorders
Bacterial and viral toxins
3. Noninfectious G.I.T. disorders
Gastric outlet obstruction
Gastric irritants
4. During early pregnancy (first trimester, morning sickness due to high estradiol in circulation).
5. CNS related
Motion sickness, Menier’s disease, CNS toxic agents
Increased intracranial pressure, Stroke
Before reviewing antiemetic agents, let us look at Appendix -1 Taken from the Text Book of Pharmacology by Goodman & Gilman with permission.
for antiemetics, what is anti histamines and what are the uses and adverse effects?
Anti Histamines: eg. Diphenhydramine, Doxylamine, Dimenhydrinate (Gravol), Cyclizine, Meclizine.
H1 receptors - in the solitary tract nucleus and involved in transmission from the vestibular apparatus to the emetic center. They block H1 receptors and prevent peripheral stimulation of the emetic center.
Uses: Most effective in Motion Sickness and inner ear dysfunction (Menier’s disease and Labrynthitis)
Adverse effects: Drowsiness, Sedation, Blurred vision, Dry mouth (because they block muscarinic receptors).
for antiemetics what are anticholinergics?
- Anticholinergics: eg. Scopalamine (and not atropine)
Block peripheral stimulation of the emetic center.
Uses: In Motion Sickness.
Adverse effects: Dry mouth, Drowsiness, Blurred vision and Tachycardia
what are benzodiazepines?
- Benzodiazepines (BDZs): eg. Lorazepam, Alprazolam
Prevent central cortical induced vomiting, enhance effectiveness of anti-emetic regimens.
Uses: For anxiety and anticipatory Emesis - Chemotherapy.
Adverse effects: Drowsiness
for emetics what are dopamine antagonists?
. Dopamine antagonists:
4. a) Non-selective DA Ant.: eg. Phenothiazines.
4. b) D2 selective Ant.: Metoclopramide, Domperidone
Act at the chemoreceptor trigger zone (CTZ) by inhibiting dopaminergic transmission and also decrease vomiting caused by gastric irritants by inhibiting the stimulation of peripheral Vagal and sympathetic afferents
Adverse effects: Acute dystonic reaction, Orthostatic hypotension, Extrapyramidal side effects and blood dyscrasias.
4. b) D2 Selective Antagonists: eg. Metoclopramide, Domperidone.
Selective blockade of D2 receptors in the CTZ.
Adverse effects: Metoclopramide precipitates extrapyramidal side effects, domperidone does not,
Uses: Both Selective and non-selective antagonists are effective anti-emetic agents in controlling nausea and vomiting encountered during cancer chemotherapy.
for antiemetics what are 5-HT3 selective antaonists?
. 5-HT3 selective Antagonist:
1st Generation 5-HT3 antagonists: Ondansetron, Granisetron,
2nd Generation: Palonosetron (More potent, Long Acting)
They inhibit serotonin mediated responses by blocking 5HT3 receptors that are involved in the initiation of vomiting reflex. Most Effective antiemetic.
Uses: Vomiting encountered in Cancer chemotherapy.
for antiemetics what are cannabinoids and corticosteroids?
- Cannabinoids: eg. Tetrahydrocannabinol, Nabilone
Uses: Control of emesis when all other agents fail.
Adverse effects: Hallucination, Bulemia- Corticosteroids: eg. Dexamethasone. Mech. unknown.
Uses: Controls Emesis in Motion Sickness, Mountaineering Effective when combined with D2 and 5HT3 Antagonists.
Adverse effects: Osteoporosis, hyperglycemia, peptic ulcer, psychosis, pituitary, adrenal suppression, susceptibility to infection (Superinfection - Candidiasis).
- Corticosteroids: eg. Dexamethasone. Mech. unknown.
- Substance P Antagonist (NK1 Antagonist): Aprepitant
(New kid in the block.)
what is combination treatment for chemotherapy induced nasuea - vomiting (CINV)?
Remember when cisplatin /anticancer agents are used, there is Chronic Intractable Nausea/Vomiting [CINV] Combination with Palonosetron [2nd Generation 5-HT3 antagonist] + Aprepitant [NK-1 Antagonist] + Cosrticosteroid [Dexamethasone] provides long lasting relief in cancer patients who have severe Pain + NV.
what’s the definition of a migraine?
Definition: A chronic disorder characterized by recurrent attacks of headache. The disease is familial in 60-80% of patients, more common in women and usually has its onset in early adolescence through young adulthood, waning with advancing years.
Symptoms: Unilateral pulsating or throbbing headache associated with nausea and vomiting, photophobia, phonophobia and osmophobia.
Duration: Attack lasts for 1-2 hrs to a few hrs
Frequency of attack: One attack a year to two or more a week.
what are the triggers and two types of migraines?
Triggers: Stress, sleep disturbances, bright light, dietary changes, menses and Food (chocolate and certain cheese). Two Types: Common migraine (85%): (without Aura)
Classical Migraine (15%) : (with Aura). Patients with classical migraine have visual scotomas or even hemianopia & speech abnormalities followed by unilateral headache.
for serotonin (5-HT) agonists helping to overme migraine: what is the vascular hypothesis?
- Vascular Hypothesis: Collateral Cranial Vessels drain blood rather more quickly to the Venous side without adequate perfusion to all parts of brain/scalp regions.
To compensate, the blood vessels in the anoxic regions that do not receive adequate O2/blood supply dilate, stretch the perivascular nerve fibers and cause one sided pain.
Goal: Constrict selectively collateral blood vessels using 5HT1B/ID Selective Agonist (Sumatriptan, Naratriptan) & Dihydroergotamine [perhaps activates a1 and/or 5-HT-R?] as these collateral vessels are more sensitive to these agonists.
for serotonin (5-HT) agonists helping to overme migraine: what is the neurogenic hypothesis?
Neurogenic Hypothesis: Pain is transmitted by afferent serotoninergic nerve fibers. When 5HT1B/ID selective agonists are given, it cuts down the pain transmission by acting on an interneuron (similar to presynaptic α2 adrenergic receptor activation leading to NE release by acting on presynaptic receptors) and reduce 5-HT mediated pain transmission. This is the basis for using sumatriptan and analgesics in the management of migraine.
what is the gtreatment for a migraine
Treatment of Migraine:
Symptomatic: (for an acute attack)
Prophylactic (if one has >3 attacks/month) that are resistant to symptomatic treatment. Next Slide Presents Appendix – 1.
how do you treat a mild migraine? what about a moderate migriane?
Symptomatic Treatment
1) Mild Migraine: Non-narcotic analgesics or combination analgesics (eg. acetaminophen or aspirin or ibuprofen with mild vasoconstrictor or a sedative).
2) Moderate Migraine:
Combination analgesics, NSAIDs [acetaminophen+ Dichlorophenazone]
Ergotamine or Dihydroergotamine (DHE) Cafergot
Triptans like - Sumatriptan, Naratriptan, Zolmitriptan
Butorphanol (partial opioid agonist) in conditions of severe pain with diarrhoea
