Antiemetic Drugs

Question 1

Serotonin Receptor Antagonists

Answer 1

Ondansetron, Palonsetron, Dolasetron

Question 2

Ondansetron (Zofran) class

Answer 2

5HT3 receptor antagonists

Question 3

Ondansetron (Zofran) metabolism and excretion

Answer 3

extensive metabolism in liver by hydroxylation and conjugation CYP450, less than 5% metabolized by kidneys. excretion in urine 30-70% and feces 25%

Question 4

Ondansetron Bioavailability and Protein Binding

Answer 4

60% bio available, ~70% bound to proteins

Question 5

Side Effects of Ondansetron

Answer 5

headache, dizziness, diarrhea, constipation, QTC prolongation

Question 6

Palonsetron

Answer 6

• newest and most selective agent
• greater affinity for serotonin receptor by 100 fold
• long T1/2 of 40h, therapeutic effects 72h
• 80% excreted in urine over 6d and 1/2 excreted unchanged
• no data for kids <18 yet.

Question 7

Dolasetron (Anzemet)

Answer 7

• reduces activity of vagus nerve to limit activation of the vomiting center in the medulla oblongata
• lasts 4-9h, around 70% protein bound.
• t1/2 8 hours
• peak plasma time 36min
• active metabolite: hydrolasetron
• excretion: urine/feces

Question 8

Droperidol class and MOA

Answer 8

butyrpheone derivative structurally similar to haloperidol, dopamine receptor antagonist, blocks dopamine receptors that contribute to development of PONV

Question 9

Poperties of Droperidol

Answer 9

anxiolytic, sedative, hypnotic, antiemetic properties

Question 10

Droperidol Onset, Peak, Duration of Action, Metabolism, Excretion, SE

Answer 10

onset 3-10m
peak 30 min
duration 2-4h
metabolism: liver 
excretion: urine and feces
SE: QTC interval prolongation. monitor patient with EKG 2-3h after administration in PACU

Question 11

Prochlorperazine (Compazine) class, MOA

Answer 11

antipsychotic, antiemetic, affects multiple receptors: histaminergic, dopaminergic (D2), muscarinic

Question 12

Prochlorperazine DOA, Vd, Peak, Metabolism, half life, excretion, SE

Answer 12

3-4h DOA
91-99% protein bound
peak 2-4h
metabolized in liver
elimination t1/2 6-10h IV
excretion: biliary, inactive metabolites in urine
SE: may cause extrapyramidal and anticholinergic (muscarinic) SE, sedation, blurred vision, hypotension, dizziness, neuroleptic malignant syndrome, restlessness, dystonia

Question 13

Metoclopramide (Reglan) Class, MOA

Answer 13

dopamine receptor antagonist, antiemetic, upper GI motility stimulant, centrally acting as dopamine receptor antagonist in CTZ/vomit center (peripherally acting as cholinomimetic) in GI tract (facilities Ach transmission at muscarinic receptors)

Question 14

Metoclopramide uses, SE

Answer 14

increases lower esophageal sphincter tone, speeds gastric emptying time, lowers gastric fluid volume. efficacious for gastroparesis, GERD, aspiration PNA prophylaxis. SE include EPS in higher doses, contraindicated in parkinson’s disease, seizures, GI obstruction. rapid injection can cause abdominal cramping

Question 15

advtantage of metoclopramide:

Answer 15

lack of sedative properties

Question 16

metoclopramide onset, peak, metabolism, elimination, t1/2

Answer 16

onset: 3-5min IV
peak 1-2hours 
metabolism: liverr
elimination: renal excretion 
t1/2: 5-6h
excretion: urine 70-85%, feces 2%

Question 17

avoid metoclopramide in:

Answer 17

pheochromocytoma, can cause hypertensive crisis by releasing catecholamines from tumor

Question 18

aprepitant (emend) class, MOA

Answer 18

neurokinin-1 receptor antagonist. substance P is neuropeptide that interacts at NK1 receptors. MOA: NK1 antagonists inhibit substance P at central and peripheral chemoreceptors

Question 19

what is aprepitant recommended for?

Answer 19

high risk non pregnant patients

Question 20

aprepitant half life, metabolism, bioavailability, protein binding, excretion

Answer 20

9-13 hour half life
metabolized in liver by CYP3A4
bioavailability 60-65%
protein binding >95%
excretion: feces 86%, urine 5%

Question 21

aprepitant with dexamethasone

Answer 21

if administered with dexamethasone, reduce dexamethasone dose by half to maintain ok plasma concentrations since aprepitant increases activity of serotonin receptor antagonists

Question 22

aprepitant SE:

Answer 22

fatigue, dizziness, hypothesthesia, disorientation, N/D, anorexia, constipation, diarrhea, dyspepsia, heartburn, abdominal pain, gastritis, perforating duodenal ulcer, hiccups. contraception not as effective for 28d

Question 23

Dexamethasone class and MOA

Answer 23

long acting corticosteroid, synthetic glucocorticoid with anti inflammatory and immunosuppressant properties. MOA as antiemetic is unknown but does not act on area postrema

Question 24

Dexamethasone onset, peak, protein binding, bioavailability, metabolism, excretion, half life

Answer 24

onset 2h, peak 5-10 minutes, protein binding 77%, bioavailability 80-90%, metabolized in liver, excreted in urine. plasma half life 4-5h, elimination half life 36-54h.

Question 25

Dexamethasone adverse effects and absolute contraindications

Answer 25

adverse effects rare with one time dose, caution: perineal pruritus will occur if patient is awake. absolute contraindications: uncontrolled infections, known hypersensitivity, cerebral malaria, systemic fungal infection, concurrent treatment with liver virus vaccine

Question 26

Dimenhydrinate (Dramamine) MOA, class

Answer 26

H1 antagonist, competes with histamine at H1 receptor sites in the GI tract, blood vessels, and respiratory tract; blocks CTZ, depresses labrynthine function and vestibular stimulation to prevent N/V

Question 27

Dimenhydrinate (Dramamine) onset, duration, metabolism, excretion

Answer 27

immediate onset, 4-6h duration, metabolism: liver, excretion: metabolites excreted in urine

Question 28

dimenhydramine SE:

Answer 28

sedation, drowsiness, urinary retention, dry mouth, blurred vision, extrapyramidal effect

Question 29

Promethazine (Phenergan) MOA

Answer 29

antihistamine (H1 antagonist) and anticholinergic/muscarinig-blocking effects responsible for antiemetic activity

Question 30

Promethazine duration of action, metabolism, excretion, elimination, half life, bioavailability, protein binding

Answer 30

DOA 4-6h metabolism: hepatic (glucoronidation and sulfoxidation) excretion: kidney/biliary t1/2 10-19 hours bioavailability: 88% (decreases to 25% after 1st pass metabolism) protein binding: 93%

Question 31

promethazine SE

Answer 31

confusion, drowsiness, dry mouth, constipation (avoid in patients >65y). risk of significant sedation (esp with opioids)

Question 32

scopalamine MOA

Answer 32

muscarinic antagonist, inhibits action of Ach parasympathetic sites in smooth muscle, blocks communication between nerves of vestibule and vomit center in brain (may also directly block vomiting center)

Question 33

what is the chemical structure of scopalamine

Answer 33

tertiary amine.

Question 34

scopolamine anticholinergic need to know

Answer 34

esters of an aromatic acid combined with organic base-ester linkage is essential for effective binding of anticholinergics to Ach receptors

Question 35

scopolamine muscarinic receptor blockade

Answer 35

blockade leads to tachycardia (blocks SA node), inhibits secretion in respiratory tract, relaxes bronchial smooth muscle, decreased GI motility, prolonged gastric emptying time, mydriasis and cycloplegia, decreased ureter and bladder. urinary retention in elderly men esp for BPH, blurred vision happens

Question 36

scopolamine side effects

Answer 36

can cause cerebral depression, sedation, and amnesia,. avoid in patients with closed angle glaucoma, dry mouth, increased thirst, dry skin, constipation, drowsiness, dizziness, blurred vision, dilated pupils, light sensitivity. toxic psychosis, reported in pediatric/elderly patients

Question 37

scopolamine onset, DOA, metabolism, elimination half life, excretion

Answer 37

``` onset 2-4h DOA: 72h metabolism: liver t1/2: 4.5h excretion: kidneys ```