Week 2 Antiemetics & GI motility 1 of 4 Flashcards
Aspiration Occurrence in adults and children:
Adults: 1 in 8,500
<16 yrs: 1:4,400
Incidence of Aspiration undergoing elective surgery:
1: 4,500
Incidence of aspiration undergoing emergent surgery:
1: 400
What are associated with higher risk of aspiration, associated pulmonary complications, and death?
- Emergencies
2. ASA 3 or higher
Studies showed that aspiration occurs at what rates and during what?
- 1/3 during intubation
- 1/3 during extubation
- 1/3 during procedure
Role of oral antacids is to
- neutralize (remove H ions) from gastric contents
- decrease secretions of HCl into the stomach
Best example of oral antacid:
NaHCO3 (sodium bicarbonate)
-combines with HCL to produce NaCl, H2O and CO2
High pH decreases symptoms of
gastritis
Consequence of high pH
delay digestion of food
Pts with HTN and heart disease may not tolerate the sodium load associated with the chronic use of this drug:
NaHCO3 (sodium bicarb)
What can lead to acid rebound?
rapid antacid action, such that pH is raised to a neutral value
Name the drug:
- prompt neutralization of gastric acid.
- Not assoc. w/acid rebound.
- Has laxative effect.
- Systemic absorption may be sufficient to cause neurologic, neuromuscular, and CV impairment in pts with renal dysfunction.
- Renal dysfunction can also lead to metabolic alkalosis in some pts.
Magnesium Hydroxide (MOM)
Name the drug:
- can produce metabolic alkalosis w/crhonic therapy.
- symptomatic hypercalcemia may occur w/renal dx.
- may result in hypophosphatemia.
- Appendicitis has been reported d/t impact calcium carbonate fecaliths.
Calcium Carbonate
What is a fecalith?
a stone made of feces. It is a hardening of feces into lumps of varying size and may occur anywhere in the intestinal tract but is typically found in the colon.
It is also called appendicolith when it occurs in the appendix and is sometimes concomitant with appendicitis.
Name the drug:
- mix. of aluminum hydroxide, aluminum oxide, and some fixed CO2 as carbonate.
- System absorption may be high in renal dx.
- Encephalopathy in pts undergoing HD has been attributed to intoxication w/aluminum, especially in pts who ingest solutions containing citrate.
- Slows gastric emptying and causes constipation.
Aluminum Hydroxide
Name the Drug:
-Less likely to cause foreign body reaction if aspirated and mixing with gastric fluid is more complete than with particulate antacids (i.e. Tums, Rolaids)
Sodium Citrate (non particulate antacids)
Tums or Rolaids can lead to what if aspirated?
- pneumonitis
- histological changes in lungs
Dosage and admin for Sodium Citrate:
dose: 15-30 ml of 0.3 mol/liter
admin: PO, 30 mins before induction of anesthesia
Sodium Citrate is effective in increasing gastric pH in what kind of patients?
- Pregnant
- Non -pregnant
Name 5 Complications associated with Antacid Therapy:
- Chronic use symptoms
- Acid Rebound
- Milk-Alkali Syndrome
- Phosphorus Depletion
- Hypophosphatemia
Symptoms and consequences of Antacid Therapy / Chronic Use -
- alkalized gastric and urine pH resulting in bacterial overgrowth in duodenum and small intestine, and UTI.
- Increased urine pH > 24hrs after admin - leads to changes in renal elimination of drugs
Symptoms and consequences of Antacid Therapy Milik Alkali Syndrome:
- Hypercalcemia
- Increased BUN and CRT
Acid Rebound is unique to
calcium containing acids
System Alkalosis from milk alkali syndrome (marked decrease in renal fxn) is most commonly associated with
ingestion of large amounts of calcium cabronate and > 1L milk every day
Ingesting large doses of aluminum salts does what?
Binds phosphate ions in the GIT and prevents their absorption.
- can cause phosphorus depletion
Ingesting aluminum salts to induce phosphorus depletion may be helpful for what pts?
-Renal patients
b/c it can decrease their plasma phosphate concentration but renal pts may develop toxicity from the aluminum.
Symptoms and consequences of Antacid Therapy Phosphorus depletion:
- Osteomalacia
- Osteoporosis
- Fractures
If aluminum containing antacids are given chronically, what should we consider supplementing?
phosphate
Gastric alkalization increases gastric emptying resulting in
faster delivery of drugs into the small intestines
Aluminum hydroxide accelerated absorption and increases bioavailabilty of:
Diazepam
*MOA is unknown!
Antacids decrease bioavailability of oral cimetidine by
~ 15%
The capacity of some drugs to form complexes with antacids may decrease
their bioavailabilty
Antacids containing aluminum and a lesser extent calcium or magnesium interfere with absorption of:
- tetracyclines and possible
- digoxin
from the gi tract
What interferes with absorption of tetracyclines and possible digoxin from gi tract
Antacids containing aluminum and a lesser extent calcium or magnesium
Examples of 1st Gen H1-Receptor Antagonists
First generation:
- Chlorpheniramie
- Cyproheptadine
- Diphenhydramine
- Hydroxyzine
Examples of 2nd Gen. H1-Receptor antagonists
Second Generation:
- Loratadine
- Acrivastine
- Azelastine
“LAA” say LAA because you’re not sedated! :D
Histamine Receptor Antagonists 1st generation
- tend to produce sedation
- activate muscarinic, cholinergic, 5-hydroxytryptamine (serotonin), or Alpha-adrenergic receptors
Second Gen. H1 - Histamine Receptor Antagonists Pharmacokinetics
- low water solubility
- not available for parenteral use
H1-Receptor antagonists Clinical Uses:
- most widely used of all medications
- Prevent allergic rhinoconjunctivitis (sneezing, nasal/ocular itching, rhinorrhea, tearing, etc.)
- Less effective for nasal congestion characteristic of a delayed allergic reaction
- may provide some protection against bronchospasm (induced by histamine, exercise, cold dry air)
- admin w/Epi in the tx of acute anaphylaxis
- pruritus
- uricaria
- angioedema
- prophyactically for anaphylactoid reactions to radiocontrast dyes
- Little benefit in the tx of upper RTI
- no beneift in mgmt of otitis media
First Generation H1-Receptor antagonists SE’s
-Tachycardia
-QTc interval prolongation
CNS effects
-somnolence
-slowed reaction time
-cognitive impairment
Muscarinic /anticholinergic effects:
- dry mouth
- blurred vision
- urinary retention
- impotence
Examples of H2 Receptor Antagonists:
- Cimetidine
- Famotidine
- Nizatidine
- Ranitidine
H2 Receptor Antagonists MOA:
competitively and selectively inhibit the binding of Histamine to H2 Receptors
-thereby decreasing the intracellular concentration of cAMP and the subsequent secretion of hydrogen ions by parietal cells.
H2 Receptor Antagonist potency of inhibition of secretion of gastric ions
(least to most)
Varies from 20-50 fold:
Cimetidine least potent and famotidine the most potent
H2 Receptor Antagonists Clinical Uses:
- tx duodenal ulcer disease
- chemoprophylaxis (to increase GI pH prior to induction)
- decrease risk of acid pneumonitis if inhalation of gastric fluid were to occur in pre-op period
- decrease gastric fluid volume
H2 Receptor Antagonists Drug Interactions:
-most common with Cimetidine
principal type of interaction with Cimetidine is impairment of the hepatic metabolism of another drug bc of the binding of cimetidine to the heme portion of the cytochrome p450 oxidase system.
- Retards metabolism of propranolol, diazepam
- may slow metabolism of Lidocaine
H2 Receptor Antagonists SE’s:
Interaction with cerebral H2 receptors
- H/a
- Somnolence
- confusion
Interaction with Cardiac H2 receptors
- bradycardia
- HB
- Hypotension
Hyperprolactinemia Acute pancreatitis Increased Hepatic transaminase levels Alcohol dehydrogenase dehydration Thrombocytopenia Agranulocytosis Interstitial nephritis Interference w/drug metabolism by Cytochrome P450
In some patients with refractory urticaria, concurrent treatment with an H2-receptor antagonist (cimetidine, ranitidine) may enhance
relief of pruritus.
H2 receptors account for what % of all histamine receptors in the vasculature?
10-15%
Which H1 inhibitor is prescribed as a sedative, antipruritic, and as an antiemetic?
diphenhydramine
Diphenhydramine, when administered alone, it modestly stimulates ventilation by
augmenting the interaction of hypoxic and hypercarbic ventilatory drives
Diphenhydramine, when administered in combination with systemic or neuraxial opioids to control nausea and pruritus, there is the risk of
depression of ventilation (resp suppression)
*however Diphenhydramine counteracts to some extent the opioid-induced decreases in ventilatory response to CO2 and does not exacerbate the opioid-induced depression of the hypoxic ventilatory response during moderate hypercarbia
Does HD remove Second generation H1 antagonists?
no
what types of patients may be especially prone to adverse cardiovascular effects of H1 antagonists?
- Hepatic dysfunction
- Cardiac d/o assoc w/QTc prolongation
- Hypokalemia
- Hypomagnesemia
Dimenhydrinate is a
theoclate salt of Diphenhydramine; is an H1 antagonist.
Dimenhydrinate has been use to tx motion sickness as well as
PONV
What drug may attenuate or block the oculocardiac reflex and decrease the incidence of PONV in strabismus surgery?
Dimenhydrinate
Increased concentrations of cAMP activates the
proton pump of gastric parietal cells (as enzyme designated as hydrogen-potassium-ATPase) to secrete hydrogen ions against a large concentration gradient in exchange for Potassium ions.
Which H2 blocker does NOT undergo significant hepatic first pass metabolism?
What does this do to its bio-availability after PO admin?
Nizatidine
- bio-availability approaches 100% (all others around 50%)
Which H2 blocker does NOT undergo significant hepatic first pass metabolism?
What does this do to its bio-availability after PO admin?
Nizatidine
- bio-availability approaches 100% (all others around 50%)
Cimetidine is widely distributed in most organs but no
fat
*about 70% of the total body content of cimetidine is found in skeletal muscles.
H2 - Volume of distribution in renal disease
is not altered
H2 - volume of distribution in severe hepatic disease
is Increased
H2 drugs are present in what?
This means the drugs can:
Breastmilk
-Cross the placenta and BBB
Cimetidine may need to be decreased in pts with what disease process?
Some reasons why?
Hepatic disease
- Presence of cimetidine in CSF is increased
- to avoid mental confusion in these pts.
H2 volume of distribution in elderly is:
decreased about 40% (d/t decreased muscle mass)
H2 elimination occurs by
- combination of hepatic metabolism
- Glomerular filtration
- renal tubular secretion
Principal excretion pathway for H2 blockers:
renal
All four H2 blockers have an increased elimination half time in pts with
renal dysfunction
The elimination half-life of ranitidine and famotidine (H2 antagonist) may be increased
up to twofold in elderly patients
When determining the dose of H2 antagonist what must be considered?
increasing age
- clearance decreases 75% in pts b/w the ages of 20 and 70 yrs. (pg 705)
When determining the dose of H2 antagonist what must be considered?
increasing age
- clearance decreases 75% in pts b/w the ages of 20 and 70 yrs. (pg 705)
Cimetidine may slow metabolism of Lidocaine and thus
increase the possibility of systemic toxicity.
What drugs specifically mentioned in Flood are not altered by cimetidine -induced effects on P450 enzyme activity?
Benzodiazepines such as oxazepam and lorazepam
plasma concentrations of bupivacaine after epidural anesthesia are impacted by cimetidine how?
they’re not impacted!
Cimetidine may slow metabolism of Lidocaine and thus
increase the possibility of systemic toxicity.
H2 antagonists competition w/Creatinine, serum CRT levels are increased about what %?
15%
Famotidine has been reported to interfere with phosphate absorption leading to
hypophosphatemia
All four H2 antagonists have the potential to alter absorption of some drugs by
increasing the gastric fluid pH
enhanced absorption of alchohol from teh stomach has been reported with
Cimetidine
If administered concurrently, the hepatic metabolism of what drug may be enhanced with phenobarbital?
Cimetidine
If administered concurrently, the hepatic metabolism of what drug may be enhanced with phenobarbital?
Cimetidine
PPI are more effective that H2 antagonist for
relieving Heart burn
What is the cardinal feature of GERD?
heart burn
H2 antagonists are probably more cost effective than PPI’s for these pts:
those w/o esophagitis and infrequent symptoms
Omeprazole acts as a
prodrug that becomes a PPI
is omeprazole a weak acid or base?
weak base
Omeprazole concentrates in the secretory canaliculi of
gastric parietal cells
Where is omeprazole pronated to its active form which INHIBITS the enzyme pump?
gastric parietal cells
Omeprazole only works on the
proton pumps that are present
As the body generates more proton pumps what is required? (for omeprazole)
more omeprazole dosing
how long does it take omeprazole to exert maximal inhibitory effect on gastric acid secretion?
several days
b/c of new pump generation
What PPI provides prolonged inhibition of gastric acid secretion regardless of stimulus; timing or meal acid secretions?
omeprazole
What heals duodenal and possible gastric ulcers more rapidly than H2 blockers?
PPI - Omeprazole
Treatment for pts w/ bleeding PUD and signs of recent bleeding?
-omeprazole
Why is omeprazole first line therapy for bleeding PUD?
decreases the rate of bleeding
-decreases the need for surgery
Omeprazole as a pre-op med, is effective as it increases _____ and decreases ____.
increases pH gastric fluid (less acidic)
decreases gastric fluid volume
Onset of gastric anti-secretory effect after a single 20 mg dose of Omeprazole occurs in
2-6 hours.
Omeprazole Duration of action
is prolonged > 24 hours
Omeprazole administered the night before surgery, increases gastric fluid pH, whereas
administration on day of surgery (up to 3 hours before) fails to improve the environment of gastric fluid
prior to anesthesia it is suggested that omeprazole be given
> 3 hours prior to anesthesia
Can omeprazole cross the BBB?
yes
Side effects of omeprazole include:
H/A agitation confusion abd. pain N/V flatulence
does the dose need to be adjusted for PPIs in renal or hepatic dysfunction/
no need to adjust
pre-op oral dose of omeprazole:
20mg
the loss of the inhibitory effect of gatric acid results in increased plasma concentration of
gastrin
esomeprazole is the levoratatory isomer of
omeprazole
A potent, fast acting PPI is
pantoprazole (Protonix)
how do pantoprzole and ranitidine given IV, 1 hour before induction compare in effectiveness in decreasing gastric fluid vol and pH?
studies have found them equally as effective.
p.710
Motility modulating drugs exert their therapeutic effects by:
- increasing LES tone
- Enhancing peristaltic contractions
- accelerating gastric emptying
Metoclopramide and Domperidone are both what kind of GI motility modulators:
Dopamine Blockers
Metoclopramide is the only drug FDA approved for the tx of
diabetic gastroparesis
metoclopramide does not alter:
gastric hydrogen ion secretion
Domperidone, like metoclopramide, acts as a specific dopamine antagonist that stimulates peristalsis in the GIT, speeds gastric emptying, increases LES tone but is/does not:
- marketed in US
- cross the BBB easily
- appear to have any anticholinergic activity
Main concern about domperidone that the FDA refused to give approval of sale for:
- prolactin secretion by the pituitary
- concerns about lactating women using domperidone to increase breast milk production (b/c of increased cardiac risks associated w/use).
metoclopramide induced antagonism of dopamine-agonist effects on the chemoreceptor trigger zone (located outside the BBB) contributes to an
antiemetic effect
Metoclopramide should not be given to pts with known:
- Parkinson disease
- Restless leg
- movement disorders r/t dopamine inhibition or depletion
Akathisia:
a feeling of unease and restlessness in the lower extremities
-may follow IV administration of metoclopramide
presentation of what symptom after administration of metoclopramide would result in cancellation of scheduled surgery
Akathisia
metoclopramide has an inhibitory effect on _____.
Which may explain occasional prolonged responses to succinylcholine and mivacurium in pts receiving these drugs.
plasma cholinesterase activity
metoclopramide-induced decreases in plasma cholinesterase activity could also slow the metabolism of
ester LA’s
