GIT - Anti-emetics - Drugs used in nausea & vomiting Flashcards Preview

systemic pharmaco > GIT - Anti-emetics - Drugs used in nausea & vomiting > Flashcards

Flashcards in GIT - Anti-emetics - Drugs used in nausea & vomiting Deck (25):
1

Sites that trigger the vomiting centre

1. Chemoreceptor Trigger Zone
- in the area postrema of the floor of the 4th ventricle
- stimulated by blood borne toxins
- D2, NK-1 & 5-HT3 receptors
2. GIT & heart, visceral afferents
- stimuli from pharynx & stomach (mechanoreceptors, chemoreceptors, CN IX/X afferents, release of serotonin from gut enterochromaffin cells)
- 5-HT3 receptors on vagal afferents
3. Vestibular System
- motion sickness/disease eg labyrinthitis
- H1 & ACh M1 receptors on vestibular afferents
4. Higher Centres in the CNS

2

Classes of anti-emetics & examples

1. Serotonin 5-HT3 Antagonist (Ondansetron)
2. Corticosteroids (Dexamethasone, methylprednisolone)
3. Neurokinin Receptor Antagonist (substance P antagonist) (Aprepitant - oral, Fosaprepitant - IV)
4. Dopamine Receptor Antagonist (Metoclopramide)
5. Muscarinic Receptor Antagonist (Hyoscine - scopolamine)
6. H1 Histamine Receptor Antagonist (H1 + M1 - Diphenhydramine, D2 + H1/M1 - promethazine, droperidol)
7. Benzodiazepines (Lorazepam, Diazepam)

3

Mechanism of action of ondansetron

Acts on 5-HT3 receptors primarily in the GIT

4

Uses of ondansetron

1. Acute chemotherapy-induced vomiting (IV/orally 30min/1h before)
- generally not effective for delayed nausea & vomiting (>24h after chemo)
- enhanced by corticosteroids & NK1 receptor antagonists

5

Toxicity of ondansetron (2)

Generally well tolerated
1. Headache, dizziness, constipation
2. Cardiac arrhythmia (prolongation of QT interval) - small risk

6

Mechanism of action of corticosteroids

Mimics effects of cortisol, basis for anti-emetic effect unknown

7

Uses of corticosteroids

1. Acute & delayed nausea & vomiting
- with moderately to highly emetogenic chemo regimens
- often used with 5-HT3 antag

8

Toxicity of corticosteroids

Unlikely with short term use
1. Iatrogenic Cushing's Syndrome
- redistribution of fat (rounded face), muscular wasting, dysphonia, thinning of skin, easy bruising, hyperglycemia, later diabetes, osteoporosis, immunosuppression

9

Mechanism of aprepitant

Acts on Neurokinin-1 receptors in area postrema (CTZ)

10

Uses of aprepitant

1. Acute & delayed nausea & vomiting (due to highly emetogenic chemotherapy)

11

Toxicity of aprepitant (4)

1. Fatigue
2. Dizziness
3. Diarrhea
4. Interacts with chemotherapeutic agents (docetaxel, etoposide, irinotecan, imatinib, vinblastine) & may be influenced by CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, verapamil)

12

Mechanism of action of metoclopramide

Dopamine (especially D2) receptor antagonist, acts on CTZ

13

Uses of metoclopramide (2)

1. Anti-emetic
2. Prokinetic to stimulate GI motility

14

Toxicity of metoclopramide (3)

1. Extrapyramidal side effects - restlessness, dystonias, parkinsonian symptoms - esp elderly
2. Irreversible tardive dyskinesia (involuntary repetitive motor movements) - long term
3. Elevated prolactin levels - galactorrhea, gynecomastia, impotence, menstrual disorders

15

Mechanism of action of hyoscine

Muscarinic receptor antagonist (anti-cholinergic) - action in estibular system and vomiting centre

16

Uses of hyoscine

1. Motion sickness

17

Toxicity of hyoscine

Increases when given orally - transdermal patch
1. Anticholinergic (parasympatholytic) adverse effects - dry mouth, blurring of vision, constipation, reduced secretions

18

Mechanism of diphenhydramine

M1 cholinergic receptor antagonism + H1 histamine receptor antagonism - acts on vomiting centre & vestibular system

19

Uses of diphenhydramine (2)

1. Motion sickness
2. Emesis due to chemotherapy (sedative effects)

20

Toxicity of diphenhydramine (2)

1. Sedation (H1 receptors antagonism)
2. Anticholinergic (dry mouth, constipation, vision blurring)

21

Mechanism of action of mixed D2, M1/H1 receptor antagonists (anti-psychotics)

Dopamine receptor antagonism - CTZ
M1/H1 receptor antagonism - vomiting centre, vestibular system

22

Toxicity of mixed D2, M1/H1 receptor antagonists (4)

1. Sedative
2. Extrapyrimidal side effects
3. Hypotension
4. Droperidol - prolognation of QT interval - risk of cardiac arrhythmias

23

Mechanism of action of benzodiazepines

Binds to allosteric site on GABA receptors - increase chloride conductance

24

Uses of benzodiazepines

1. Anxiolytic - reduces anticipatory vomiting/vomiting caused by anxiety

25

Toxicity of benzodiazepines + Contraindications (2+1)

1. Sedative/hypnotic
2. Additive effects with other sedative drugs/depressants - respiratory depression on overdose

1. Pregnancy (esp 1st trimester) - teratogenic, risk of cleft palate