Week 2 antiemetics & GI motility (3 of 4) Flashcards
What two anticholinergics can enter the CNS?
Scopolamine and Atropine.
Because these two anticholinergics can cross into the CNS, they can cause what problem?
Scopolamine and Atropine can cause central anticholinergic syndrome.
What do the symptoms of central anticholinergic syndrome look like? (4 answers)
Symptoms range: Restlessness, Hallucinations, Somnolence, Unconsciousness
Which anticholinergic does not cross the BBB?
glycopyrrolate
What drug is the reversal of central anticholinergic syndrome and what drug class is it?
Physostigmine which is a parasympathomimetic, or also called cholinergic receptor simulator agent.
The reversal drug for too much atropine would be?
physostigmine
What is the dose of physostigmine (lipid-soluble tertiary amine) to reverse central anticholinergic syndrome?
physostigmine 15-60 mcg/kg IV. Treatment may need to be repeated every 1-2 hours.
What three Acetylcholinesterase inhibitors are NOT effective antidotes against central anticholinergic syndrome and why?
Edrophonium, neostigmine, and pyridostigmine are not effective antidotes because their quaternary ammonium structure prevents these drugs from easily entering the CNS.
Anticholinergic over dose Produces rapid onset of symptoms characteristic of muscarinic cholinergic receptor blockade: what does that look like?
Mouth dry: swallowing and talking become difficult,
Vision blurred,
Photophobia,
Tachycardia is prominent,
Skin dry and flush,
Rash may appear especially on face/neck/upper chest
(most important is the dry mouth and tachycardia)
Why does the body temp increase with use of too much anticholinergic?
↑ in body temp. reflects inhibition of sweating by anticholinergic drugs, d/t innervation of sweat glands is by SNS nerves that release acetylcholine as the neurotransmitter.
(can’t sweat can’t cool off)
when is increase in body temp. with anticholinergics more likely to happen?
when environmental temp. is increased.
What lab is typically unchanged with anticholinergic over dose (even though you would expect it to be messed up)
ABGs are usually unchanged.
due to CNS stimulation and the impact of an increased physiologic dead space d/t bronchodilation what will also increase?
increased min. ventilation is possible.
What are three fatal events associated with anticholinergic over dose?
Seizures,
Coma,
Medullary ventilator center paralysis
even with therapeutic dose of an anticholinergic drug what can happen in children?
Atropine Fever
What age group is particularly vulnerable to developing life-threatening symptoms after an overdose with an anticholinergic?
small children and infants
Reversal of overdose of anticholinergic in children and infants?
Physostigmine 15-60mcg/kg IV
according to Hammon start on the low end
Why may you need repeated doses of physostigmine?
it is metabolized quickly
What is barrier pressure?
The difference between gastric pressure and lower esophageal sphincter pressure is “barrier pressure.”
What two meds and in what dose decreases lower esophageal sphincter pressure and decreases barrier pressure?
atropine 0.6mg IV or Glycopyrrolate 0.2-0.3 IV
Because atropine and glucopyrrolate decrease lower esophageal sphincter pressure, what is more likely to occur?
GERD
how long does atropine and glcopyrrolate last (in doses that cause increased GERD)
atropine lasts 40min. and glycopyrrolate lasts 60min.
Reglan (metoclopramide) is also known as what type of drug?
Benzamide
Benzamides (such as reglan and domperidone) stimulates GI tract via cholinergic mechanism resulting in: (three answers)
Contraction of lower esophageal sphincter and gastric fundus,
Increased gastric and small intestinal motility,
Decreased muscle activity in the pylorus and duodenum when stomach contracts
Why is domperidone not used in the U.S.?
Domperidone not used in U.S. d/t concern of use in lactating women increases milk production.
What medication would you NOT use on someone who has Parkinson’s and why?
Do not use Reglan bc it is an antidopanergic.
Reglan may have direct effect on what areas of the brain that is good for Nausea?
Reglan may have a direct effect on CRTZ and/or vomiting center b/c of its antidopaminergic effect.
Because of antidopaminergic activity, Reglan should be used with caution if at all in: (name three types of patient)
Parkinson’s disease
RLS
Pts with movement disorders related to dopamine inhibition or depletion.
what kind of body movements CAN Reglan cause?
dystonic extrapyramidal reactions
In pts with no known movement disorders dystonic extrapyramidal reactions occur in less than 1% who are treated chronically or acutely with Reglan?
Chronically
Reports of neurologic dysfunction related to the preoperative administration of what drug?
Reglan
What can happen after a single IV dose of Reglan that could cause a surgery to be cancelled?
Akathisia, a feeling of unease and restlessness in the lower extremities after IV dosing which are sometimes severe enough to cancel surgery.
What can you give prior to Reglan to ease the negative pre-op symptoms?
Versed
What does Reglan require (on a molecular/physiologic level) to be effective?
background cholinergic activity.
What three things does Reglan do the GI tract (mostly upper GI tract)?
Increased smooth muscle tension in the LES and gastric fundus
Increased gastric and small intestinal motility
Relaxation of the pylorus and duodenum during contraction of stomach
What does Reglan sensitize the GI smooth muscles to?
the effects of acetylcholine!
With conventional cholinergic drugs you do not have to have background cholinergic activity to be effective, but what med requires background cholinergic activity to be effective?
Reglan
what drug opposes reglan-induced increases in LES tone and GI hypermotility?
Atropine
Reglan acts as a WHAT-receptor antagonist?
dopamine-receptor antagonist
Can reglan cross the BBB?
YES!
Because Reglan can cross the BBB and because it is an antidopanergic, what does this all come together to mean?
can produce significant extrapyramidal side effects, and why it is not given to parkinson patients.
Reglan induced antagonism of the dopamine-agonist effects on the chemoreceptor trigger zone (outside the blood brain barrier) contributes to what effect?
antiemetic effect!
What drug can cause the release of acetylcholine from cholinergic nerve endings?
Reglan
There are cholinergic nerves in the walls of the GI tract, would you say Reglan does or does not act on these post-ganglionic cholinergic nerves?
Reglan does, (below explanation from ppt)
Atropine opposes reglan-induced increases in LES tone and GI hypermotility which indicates that reglan acts on post-ganglionic cholinergic nerves intrinsic to the wall of the GI tract.
What ways can reglan be given?
ORAL and IV
Reglan is rapidly absorbed after oral administration. Peak plasma concentrations occur at what time?
40-120 min
Does Reglan go through first -pass metabolism?
Extensive first-pass hepatic metabolism limits bioavailability to 75%
half-life of reglan?
2-4 hours
We already know that Reglan DOES cross the BBB but does it cross the placenta?
Yes
will you decrease the dose of reglan if someone has renal impairment?
Renal impairment prolongs elimination half life and necessitates a decrease in Reglan dose.
What are Reglans clinical uses?
pre-op decrease gastric fluid volume.
antiemetic effect
Treatment of gastroparesis
Symptomatic treatment of GERD
Intolerance to enteral feedings in patients who are critically ill
Speed gastric emptying for radiographic exam of small intestines
Has been used to improve effectiveness of oral medication if other drugs or the patient’s underlying condition slows gastric emptying
Reglan decreases gastric fluid volume, what dose do you give over what time period before induction for desired effects?
10-20 mg IV over 3-5 minutes administered 15-30 minutes before induction of anesthesia results in increased LES tone and decreased gastric fluid volume.
why do you not want to give Reglan rapidly IV?
May cause stomach cramping.
What are the benefits of gastric emptying potentially/ who benefits patient wise?
Patients who have recently ingested solid food
Patients with DM and symptoms of gastroparesis
Trauma patients (considered full stomachs)
Obese
Parturients (especially with esophagitis/heartburn suggesting LES dysfunction and gastric hypomotility
Do the effects of reglan on gastric fluid volume alter gastric fluid pH?
does NOT reliably alter gastric fluid pH
Will reglan reverse opioid induced inhibition of gastric motility?
ppt states that “may not be reversed with reglan”
what drug could you give around the same time as reglan that would make all it’s GI benifits be offset?
atropine
Obviously giving reglan or other prophylactic drugs such as antacids or H2 antagonists does not replace the need for WHAT?
Proper airway management!
Reglan has been shown to decrease chemotherapy-induced n/v and n/v after c-section BUT is not as effective as what other drug class?
5-HT3
the antiemetic property of reglan is probably a result of what?
antagonism of dopamine’s effects in the chemoreceptor trigger zone.
What two issues accompany the vomiting reflex?
gastric immobility and cephalad peristalsis.
this is what the antiemetic effects of Reglan reverse
The antiemetic effects of Reglan are due to what occurring in the GI tract? (like physically what is going on)
increases in LES tone and facilitation of gastric emptying in the small intestines.
Gastric stasis induced by what opioid is reversed by reglan?
Morphine
Reglan can blunt opioid induced WHAT?
N/V
Reglan should not be administered to what three types of patients?
Known Parkinson’s Disease
Restless Leg Syndrome
Movement disorders r/t dopamine inhibition or depletion.
Neurologic dysfunction has been reported r/t pre-op administration of what drug?
Reglan
If you antagonize the CNS actions of dopamine with a drug (such as antipsychotic drugs) what may happen?
Extrapyramidal rxn identical to parkinsonian syndrome
Akathisia after IV reglan could manifest after surgery in the PACU, what is Akathisia?
feeling of unease an restlessness in lower extremities
If Reglan is given in under 3 min what can occur?
abdominal cramping
What are some side effects of Reglan related to the heart or blood pressure?
Hypotension, tachycardia, bradycardia, cardiac arrhythmias,
What side effects are RARE after a single dose of Reglan?
RARELY after a single dose: Sedation, dysphoria, agitation ,dry mouth, glossal or periorbital edema, hirsutism and urticarial or maculopapular rash.
Why shouldn’t a patient who has had breast cancer not be treated chronically with Reglan?
breast enlargement, galactorrhea and menstrual irregularities
Reglan readily crosses the placenta, have adverse fetal effects been observed?
non have been observed with single doses of Reglan
Dopamine will cause inhibition of what mineralocorticoid?
aldosterone secretion.
So if Reglan is antidopaminergic and dopamine inhibits aldosterone secretion, then it can be concluded that reglan allows aldosterone to be secreted. So if more than normal aldosterone is being secreted (bc you blocked dopamine which blocks aldosterone secretion) you need to watch for what in said patient?
The possibility of sodium retention and hypokalemia should be assessed in patients who develop peripheral edema during chronic therapy with Reglan!
Reglan may increase sedative actions of CNS depressants and the incidence of extrapyramidal reactions cause by certain drugs: Should avoid administering in combination with: (4 answers)
Phenothiazine
Butyrophenone drugs
Patients with preexisting extrapyramidal symptoms
Seizure disorders
What issue with the bowels would keep you from giving someone Reglan?
Do not give to suspected or known mechanical obstruction to gastric emptying.
What type of psych/depression meds should be avoided with Reglan use?
Avoid in patients taking MOAI or Tricyclic antidepressants.
Reglan can decrease the bioavailability of what orally administered med by 25-50%? (think H2 blocker)
cimetidine
What types of GI surgeries would you not want to give Reglan to and why?
Do not administer after GI surgery such as pyloroplasty or intestinal anastomosis because it stimulates gastric motility and may delay healing.
Remember that with pregnancy you already have decreased plasma cholinesterase activity. Reglan inhibits the effect on plasma cholinesterase activity, thus anyone on Reglan but especially Pregnant women may have prolonged responses to what meds used in anesthesia?
succinylcholine and mivacurium.
Metabolism of ester LA COULD be slowed by reglan, why?
reglan induced decreases in plasma cholinesterase activity.
