Week 6 GI Flashcards
Emesis is controlled by the vomiting centre, also known as the:
Central Pattern Generator (CPG)
Where is the Chemo Receptor Trigger Zone located? (CTZ)
Dorsal surface of the medulla oblongata
Where does the CTZ (chemo receptor trigger zone) receive input from?
Blood bound drugs and hormones
What causes blood bound drugs and hormones to stimulate the CTZ (chemoreceptor trigger zone)? (4)
Drugs
Toxins
Chemo
Hypoxia
What is the medulla oblongata?
Continuation of the spinal cord into the skull
Lowest part of the brain stem
Contains control centres for heart, lungs and CTZ
What are of the brain is responsible for motion sickness?
Vestibular apparatus
What area of the brain is responsible for vomiting r/t psychiatric disorders, stress, anxiety, anticipation?
Cerebral Cortex
What stimulates the visceral afferent nerves in the GI tract to send signals to the vomiting centre? (3)
Distention
Chemo
Radiation
- in the medulla oblongata of the brainstem
- has permeable capillaries and sensory neurons
- detects circulating chemical messengers in blood and transduces them into neural signals and networks
- sensory transducer = integrates blood-to-brain autonomic functions
- detection of circulating hormones involved in vomiting, thirst, hunger, and blood pressure control
Neurotransmitters responsible for N and V are located in? 3()
- The vomiting centre
- CTZ
- GI tract
The CTZ is composed of?
AP (area postrema)
NTS (nulceus tractus soliatarius)
What to do 1st to tx Nausea and Vomiting? (4)
1-identify CAUSE
2-identify PATHWAY
3- what neurotransmitter involved? what will act on this?
4- what worked in the past?
Muscarinic receptors
acetylcholine activates muscarinic receptors, allowing for a parasympathetic reaction in any organs and tissues where the receptor is expressed (parasympathetic, except for sweat glands= sympathetic)
extrapyramidal sx
Dystonia (continuous spasms, muscle contractions)
Akinesia (motor restlessness)
Parkinsonian sx (rigidity, bradykinesia)
Tremor, tardive dyskinesia
Drug that can induce heart arrhythmias and cardiac arrest (esp in pt over 60 or dose > 30mg od)
Domperidone
Which antiemetic drugs have significant anticholinergic effects?
Prochlorperazine
Promethazine
Drug for motion sickness that causes significant dry mouth?
Scopolamine
What drug should be given pre- nausea?
Ondansetron
(serotonin 5- HT3 antagonists)
** take too long to work
Individual factors affecting emetogenic potential of chemo drugs:
- Hx of motion sickness
- > 50 years old
- Female
- Anxiety
- Absence of heavy alcohol use
- Poor performance status
Things that can effect emetogenic potential:
- Infusion time (longer time= less nausea)
- Dose (higher dose= worse)
- Number of drugs
Chemo drug with very high emetogenic potential?
Cisplatin > 50mg
Best antiemetics for CINV:
Type 5 – HT3 (serotonin) receptor antagonists
Neurokinin – 1 receptor antagonists
Glucocorticoids
When does delayed emesis occur after chemo?
> 24 hours
usually with Cisplatin
Aprepitant is a?
Dose?
NK1-R receptor antagonist
80 mg po daily on day 2 and 3
Side effect: fatigue
First choice for DELAYED CINV?
Dexamethasone
4-8 mg PO BID
Side effects of dexamethasone?
Agitation
Insomnia
Hyperglycemia
How long should PPIs take to be effective?
4-8 weeks
Red flag sx for GERD needing endoscopy followup urgently
Vomiting bleeding abdominal mass unexplained weight loss bleeding choking dysphagia
Goals of GERD therapy? (5)
reduce/eliminate sx heal esophageal mucosa prevent recurrence prevent complications identify triggers
What are some medications that may help with GERD but have side effects that limit their use?
Metoclopromide
Domperidone
Baclofen (increases LES tone)
Why should tablet formation of bismuth subsalicylates be avoided with concurrent h. pylori therapy?
Contains calcium bicarbonate and decreases effectiveness of tetracycline abx
5 causes of GERD?
LES pressure changes impaired esophageal clearance delayed gastric emptying hiatus hernia lifestyle/ diet
Tx goals for GERD
- Reduce/eliminate sx
- Heal esphageal mucosa
- Prevent recurrence
- Prevent complications
- Identify triggers
Causes of peptic ulcer disease?
- ZES
- H Pylori
- NSAIDS
- Smoking
- Alcohol
- Ischemia
- Bile acids
- -stress (non-ulcer dyspepsia)
- genetics
Duodenal ulcers are sometimes relieved by?
Eating (food in stomach)
Gastric ulcers are sometimes releived by?
Not eating (acid is then secreted in duodenum instead)
Which NSAIDS are the highest and lowest risks?
Highest= Piroxicam, indomethacin, ketoralac
Lowest risk= low dose ibuprofen
When are H2RAs NOT recommended?
H2RA are not recommended for use in erosive esophagitis, H.
pylori related ulcers or NSAID induced ulcers
Which PPI is the most expensive with possilble increase side effects?
Dexlansoprazole
Dexlansoprazole causes…
Increased risk of adverse events
• Increased risk of nonfatal serious events
• Increased risk of cardiovascular events in Dex 30
• Increased risk of injury-related adverse events
In which conditions is BID dosing of PPIs recommended in primary care?
gastric acid hypersecretory
conditions
H. pylori eradication therapy
Examples of hyergastrinemia states?
Gastric outlet obstruction
Gastric dysmotility states
ZES (Zollinger-Ellison Syndrome)
Why is BID dosing of PPI not recommended?
Hasn’t demonstrated consistent clinical benefit.
Drugs approved for 8 week tx to heal errosive esophagitis?
dexlansoprazole 60mg
esomeprazole 40mg
PPI not working try?
Changing to different PPI
or
change to BID (try to taper down after effective)
BID PPI may be considered in the following pts? (2)
- Patients with severe sx despite standard OD PPI dosing
- Severe esophagitis (confirmed by endoscopy)
Which PPI has the most CYP450 drug interactions?
Omeprazole
Pantoprazole = the least
Meds used to tx TB
Rifampin (plus)
isoniazid
ethambutol
pyrazinamide
Risk associated with statin therapy? (2)
Rhabdomyolysis
myopathy
Ways to prevent rhabdomyolysis and myopathy from statin tx?
Avoid adding cytochrome P450 3A4 inhibitors to statins metabolized by CYP3A4 (atorvastatin, lovastatin, simvastatin)
Interupt statin tx for short period when interacting drug required (i.e. macrolide)
Reduce statin dosage if interacting drug needed (i.e. Simvastatin 20mg with amiodarone).
Switch to statin with lower pharmakokinetic interactions (Pravastatin)
Watch for muscle related sx (muscle pain, weakness, dark urine)
Avoid combos (i.e. fibrate with statin)
True or False: Fibrates WITH statins reduce risk of CHD events?
False
Classic triad for rhabdomyolysis?
myalgia, weakness, and tea-colored urine
