Module 2: Metoclopramide Flashcards
What is the drug classification for metoclopramide?
Dopamine D2 receptor antagonist
What are common indications for metoclopramide?
Chemotherapy-induced N/V prophylaxis
Diabetic gastroparesis - relief of symptoms (complication of diabetes where stomach muscles don’t function properly, causing delayed emptying of food from the stomach d/t nerve damage from high blood sugar)
Post-op N/V prophylaxis (esp. where NG suction is undesirable)
Small bowel intubation (postpyloric feeding tube placement)
GERD - short term in pt’s that don’t respond to conventional therapy
What are the anticipated clinical outcomes for metoclopramide?
Prevention/relief of nausea and vomiting
Decreased symptoms of gastric stasis
Facilitation of small bowel intubation
Decreased symptoms of GERD. Should not be used for more than 12 wk d/t risk of tardive dyskinesia
What is the MOA for metoclopramide?
Blocks dopamine and (in higher doses) serotonin receptors in CTZ of the CNS
Enhances response to acetylcholine of tissue in upper GI tract = enhanced motility and accelerated gastric emptying
Increases lower esophageal sphincter tone
What are the pharmacokinetic considerations for metoclopramide?
A: oral well absorbed from GI tract
D:There is a first-pass metabolism after oral administration and bioavailability varies from 30-70%. 40% bound to plasma proteins. Volume of distribution is high. Crosses blood-brain barrier.
M: Primarily metabolized by liver via CYP2D6 isoenzyme, smaller portion by CYP1A2 enzyme; the CYP2D6 isoenzyme exhibits genetic polymorphism (approx. 7% of population may be poor metabolizers and may have significantly increased metoclopram ide concentrations and increase risk of adverse effects).
E: 85% urine, feces.
Can metoclopramide be used in pregnancy?
Used for N/V r/t to pregnancy as well as hyperemesis gravidarum. Used during all stages of pregnancy. Crosses the placenta with no apparent associated risk of congenital defects or fetal or newborn adverse effects. Pregnant women should be monitored for known adverse effects such as depression and extrapyramidal symptoms.
Can metoclopramide be used in lactation?
2 hours after drug administration, can be found in the breast milk of nursing mothers at concentrations double found in plasma. Safe under 45mg daily – use with caution d/t to serious CNS side effects
What are common expected side effects of metoclopramide?
Drowsiness, dysgeusia (intranasal), extrapyramidal reactions (group of movement disorders that can be a side effect of medication), restlessness
What are common adverse effects of metoclopramide?
Neuroleptic malignant syndrome (reaction to use of neuroleptic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction – is life-threatening)
What are significant drug interaction considerations for metoclopramide?
Metoclopramide increases upper intestinal motility and gastric emptying rate, absorption of other oral drugs may be effected
Other drugs that block D2 receptors (antipsychotics and antiemetics) combined can result in tardive dyskinesia
What are contraindications for metoclopramide?
Hypersensitivity
Children <1
CYP2D6 poor metabolizers
What are cautions with metoclopramide?
Hx of depression
Diabetes (may alter insulin response)
Cirrhosis or HF (increase risk of fluid retention)
Chronic use > 12weeks d/t increase risk for TD
What are the monitoring parameters for metoclopramide?
Assess for N/V, abd distention and bowel sounds before and after administration
Assess for extrapyramidal side effects (EPS)
Monitor for tardive dyskinesia (type of EPS) = involuntary facial movements after long term use
Monitor for neuroleptic malignant syndrome
Assess for signs of depression periodically through therapy
Monitor for signs r/t hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction)
May alter hepatic function test results = may increase serum prolactin and aldosterone concentrations.
What is the onset, duration, peak and half-life of metoclopramide?
Onset: Oral = 30-60 mins
Duration: 1-2 hours regardless of route
Half-life for adults: 5-6 hours (varies by age, dose and route)
Peak = 1-2 hours
What are considerations with renal or hepatic impairment?
Renal mod-severe impairment = 2 fold increase in serum concentration up to 3.5 fold increase in patients with ESRD on dialysis
Hepatic, severe = clearance reduced by approx 50%
CYP2D5 poor metabolizers (genetic) = elimination may be slowed
