Pharm 2 - Exam 2 Flashcards
How fast do nonparticulate antacids lose their effectiveness?
30-60 minutes after injection
Why are traumas always considered a full stomach?
GI motility slowed
Antacids slow the rate of absorption of what drugs?
Digoxin
Cimetidine
Ranitidine
Antacids increase the rate of elimination of what drugs?
Phenobarbital
Metoclopramide is CI with what patients?
Parkinsons
Rapid IV of metoclopramide
Abdominal cramping (CI w/ complete bowel obstruction)
What receptor does Narcan have affinity for?
Opioid Mu
Narcan class
Competative opioid antagonist
Diphenhydramine class
competitively blocks H1 receptors
What properties do H1 blockers have?
Antimuscarinic and antiserotonergic
The antimuscarinic property of H1B contributes to what side effect?
dry mouth
The antiserotonergic activity of H1B provides this action?
antiemetic
What 2 actions do H2B accomplish?
decrease GI fluid volume
Raise pH of GI content
H2B are used for what perioperative goal?
reduce the risk of aspiration pneumonia
which drug increases LES tone, speeds GI emptying, and lowers GI fluid volume?
Metoclopramide
What receptor does Metoclopramide work on?
It enhances the stimulatory effects of Ach on intestional smooth muscle
Which 3 drugs selectively block Serotonin 5-HT3 receptors (w/ little-no effect on Dopamine)?
Ondansetron, granisetron, dolasetron
5HT3 receptors are located only centrally. True or False
peirpherally and centrally
What role do 5HT3 receptors play?
initiation of vomiting reflex
Class of Ketorolac?
parenterally administered NSAID
How does Ketorolac provide analgesia?
Inhibits prostaglandin synthesis
What drug is most selective A2 agonist?
Precedex
Narcan reverses agonist activity assoicated w/ what opioid compounds?
endogenous and exogenous
What is 2 parameters are considered aspiration pneumonia risk?
GI volume > 25 mL (0.4mL/kg) AND GI pH <2.5
What 8 factors palce pt aat risk for aspiration?
- full stomach
- intestinal obstruction
- hiatal hernia
- obestiy
- pregnancy
- reflux disease
- emergency surgery
- inadequate depth of anesthesia
What approaches are used to reduce potential aspiration
Sellick’s (cricoid pressure)
RSI
Do cricoid pressure and RSI eliminate pulmonary aspiration risk?
No only offer limited protection
How do anesthetics increase the risk of passive aspiration?
decrease LES tone
decrease or olibterate the gag reflex
What areas is histamine found?
CNS, GI mucosa, other peripheral tissues
How is histamine synthesized?
by decarboxylation of the amino acid histidine
Where are histaminergic neurons lcoated?
Primarily at the posterior hypothalamus bute have wide projections int he brain
What role does histamine play in the sotmach?
Major role in the secretion of hydrochloric acid by parietal cells
Where are the highest concentration of histamine found?
Storage granules of circulating basophils and mast cells throughout the body
Where are mast cells concentrated?
connective tissue juste beneath epithelial(mucosal) surfaces
How is histamine release (degranulation) triggered from mast cells?
chemical, mechanical, or immunological sitmulation
How is secretion of hydrochloric acid mediated?
By gastrin-induced histamine release from enterochromaffin-like cells (ECL) in the somtach
What is a way that acid secretion by GI parietal cells can be increased INDIRECTLY?
By Ach via stimulation of M3
What is a way that acid secretion by GI parietal cells can be increased DIRECTLY?
By gastrin through an increase in intracellular Ca+ concentration
How do prostaglandin E2 (PGE2) inhibit acid secretion?
Decreases cAMP (cyclic adenosine monophosphate); activity
What receptors mediate the effects of histamine?
H1, H2, H3
H1 receptor moa
Activates phospholipase C
H2 receptor moa
increases cAMP
H3 receptor moa
Mediates NEGATIVE FEEDBACK, inhibiting the syntehsis and release of additional histamine
Where are H3 receptors primarily located?
Histamine-secreting cells
What does Histamine-N-methyltransferase do?
Metabolizes histamine to inactive metabolites that are excreted in URINE
Histamines CV affects of BP, HR, and contractility
Lowers ARTERIAL BP
Increases HR
Increases myocardial contractiliy
H1 receptor stimulation cardiovascular effects
increases capillary permeability and enhances VENTRICULAR IRRITABILITY
H2 receptor stimulation cardiovascular effects
Increases Hr and contractility
Both H1 and H2 stimulation CV effects
mediate peripheral arteriolar dilation and some coronary vasodilation
H1 stimulation respiratory effect
constricts bronchiolar smooth muscle;
some pulmonary vasodilation
H2 sitmulation respiratory effects
may produce mild bronchodilation (smooth muscle)
may be responsible for pulmonary vasoconstriction (blood vessel effect)
Histamines effects on pulmonary vasculature are _____.
variable
H2 stimulation (GI)
increases GI acid secretion
H1 stimulation (GI)
contraction of intestinal smooth muscle
The classic wheal-and-flare response of the skin to histamine results from increased ______ and _______.
capilarry permability and vasodilation
Dermal effect from histamine are primarily due to what receptor?
H1 activation
Histamine is a major mediatory of what kind of immunological reaction?
type 1 hypersensitivity reaction
H1 stimulation (immune)
attracts leukocytes and induces synthesis of prostaglandin
H2 sitmulation (immune)
activate suppressor t lymphocytes
Promethazine class
phenothiazine derivative w/ H1B activity as well as antidopaminergic and alpha blccking activity
What receptors does promethazine (phenergan) block?
H1, dopamine, alpha
What class is diphenhydramine?
ethanolamine
Uses of benadryl?
- suppression of allergic reactions & s/s of upper resp. tract infection (uritcaria, rhinitis, conjunctivitis)
- vertigo, n/v
- sedation
- cough suppression
- dyskinesia
What diseases is benadryl beneficial in?
Menieres disease (inner ear/vertigo) parkinsonism
H1B respiratory effect
PREVENT bronchoconstriction that occurs in reponse to histamine
Do H1B treat bronchial asthma?
no
What histamine blocker do you use to prevent the hypotensive effect of Histamien?
H1 + H2 (must be administered together)
Do H1 blockers affect ventilatory drive?
Unaffected in the absence of other sedatives;
Combined with sedatives potentiates sedation
What antihistaminic drugs in particular have antiemetic and mild hypontic properties?
Benadryl
Promethazine
Hydroxyzine
What 2 antihistaminic drugs were often cmobined with opioids to potentiate analgesia?
Promethazine
Hydroxyzine
Second-generateion antihistamines produce little-no sedation d/t _____.
Limited penetration of BBB
2nd gen antihistamines
Loratadine
Fexofenadine
Cetirizine
Preparations for allergic rhinitis often contain what 2 drugs?
antihistamines Pseudoephedrine (vasocontrictors)
What 2 antihistamines are used primarily as antiemetic?
Meclizine
Dimenhydrinate
What antihistamine is used for Cushings, carcinoid, and vascular (cluster) HA?
Cyproheptadine (also has serotonin blocking activity)
Usual dose of benadryl
25-50 mg (0.5-1.5 mg/kg) Q4-6H
H1B potentiate what other drugs?
CNS depressants such as barbiturates, Benzos, and opiods (d/t sedative effect)
What are 4 H2B?
Cimetidine
Famotidine
Nizatidine
Ranitidine
H2B MOA
Competitively inhibit histamine binding to H2 receptors
H2B 2 actions:
- reduce gastric acid output
2. raise gastric pH
What is the onset of Reglan?
1-3 minutes
What is the normal dose of IV Reglan?
10 mg
Which H2B are most effective in treating Peptic, duodenal, and gastric ulcers, hypersecretory states (Zollinger-Ellison syndrome), and GERD?
ALL are EQUALLY effective
Duodenal and gastric ulcers are treated w/ H2B and ____.
Combo of Bismuth, Tetracycline, and Flagyl
What infection are duodenal and gastric ulcers associtaed w/?
Helicobacter pylori
What happens to the pH of Gi content after admin of H2B?
These drugs affect the pH of only those gastric secretions that occur after administration
How do H2B reduce the perioperative risk of aspiration pneumonia?
By decreasing gsatric fluid volume nad Hydrogen ion content
(for drug-induced allergic reaction) Pretreatment with combo of H1 and H2 blockers _____ histamien release
does not reduce
(for drug-induced allergic reaction) Pretreatment with combo of H1 and H2 blockers ______ subsequent hypotension
may decrease
Combo of H1 and H2 blockers provides _______ against drug-induced allergic reaction (IV contrast, blue dyes)
some protection
What two H2B do you want to avoid rapid IV injection?
Cimetidine and Ranitidine
Rapid injection of Cimetidine (particularly in critically ill) and Ranitidine can rarely cause
Hypotension
Bradycardia
Arrhythmias
Cardiac arrest
_____ is a H2B that can be safely injected over 2 minutes
Famotidine
How do H2B change the gastric flora?
By virtue of their pH effects
Complications of long-term Cimetidine therapy
Hepatotoxicity
Interstitial nephritis
Grnulocytopenia
Thrombocytopenia
Besides binding to H2 receptors, Cimetidine also binds to ____ receptors, occasionally causing ______.
Androgen
gynecomastia and impotence
Which H2B causes changes in mental status ranging form lethargy and hallucinations to seizures?
Cimetidine
The mental status changes associated with Cimetidine adminsitration are most common in what population?
Eldelry
Which 3 H2B penetrate the BBB poorly?
Ranitidine
Nizatidine
Famotidine
When do you administer H2B as a premedication?
At bedtime and again at least 2 hours before surgery
How are H2B eliminated?
Kidneys
When do you reduce H2B dose?
With significant renal dysfunction
Cimetidine can cause drug interactions becuase it _____
may reduce hepatic blood flow and bind to the P450 mixed-function oxidases
Cimetidine can slow the metabolism of what drugs?
Lidocaine Propranolol Diazepam Theophylline Phenobarbital Warfarin Phenytoin
Which H2B is a weak inhibtior of P450?
Ranitidine
Which H2B does not affect P450?
Famotidine and Nizatidine
Antacids MOA
neutralize the acidity of gastric fluid by providing a base that reacts w/ H+ ions to form water
What is the base that antacids provide?
Usually Hydroxide, Carbonate, Bicarbonate, Citrate, or Trisilicate
Uses of antacids:
Treatment of gastric and duodenal ulcers, GERD, Zollinger-Ellison syndrome
What are antacids use in anesthesia?
Provide protection against the harmful affects of aspiration pneumonia by raising the pH of gastric contents
antacids onset
immediate (this is unlike H2B)
Con of antacids?
Increases intragastric volume
Particulate antacid examples
aluminum or magensium hydroxide
Aspiration of particulate antacids is comparable to waht?
the abnormalities in lung function of those that occur following acid aspiration
Examples of nonparticulate antacids?
sodium citrate or sodium bicarb
Pros of nonparticulate antacids
much less damaging to lung alveoli if aspirated
Mix with gastric contents better
Usual dose of Bicitra or Polycitra
15-30 mL PO 15-20 minutes prior to induction
What is Bicitra
sodium citrate and citric acid
what is polycitra
sodium citrate, potassium citrate, and citric acid
Antacids alter ____ and ____ pH
gastric and urinary
Reglan acts peripherally as ______
cholinomimetic (ie facitilates Ach transmission at selective muscarinic receptors)
Reglan acts centrally as _______
dopamine receptor blocker
Do Reglan stimualte secretions?
No
Reglan’s prokinetic action in the UGIT is not dependent upon _______ but is abolished by _________.
vagal innervation
antichlinergic agents
What 3 actions does Reglan achieve through stimulating Ach on intestinal smooth muscle?
Increases LES tone
Speeds GI emptying
Lowers gastric fluid volume
Reglan works on what 2 receptors
Ach/selective muscarinic
Dopamine
Reglan is used for treatment of waht two things?
Diabetic gastroparesis
GERD
Reglans affect on the secretion of gastric acid
None
Reglan’s affect on teh pH of gastric fluid?
None
Reglan is used prophylactically to?
Decrease risk for aspiration pneumonia
How does Reglan produce an antiemetic effect?
Blocks dopamine receptors in the CTZ of the CNS
Reglan’s ability to reduce PONV is _____ when given during perioperative period
negligible at these doses
Rapid IV admin of REglan?
Abdominal cramping
Reglan is CI with what patients?
Complete bowel obstruction
Parkinsons
Reglan can _____ in patients with pheochromocytoma.
Induce HTN crisis by releasing catecholamines from tumor
Uncommon s/e of Reglan
sedation, nervousness, extrapyramidal s/s (akathisia)
Rare CV effects of Reglan
Low BP and arrythmias
Reglan increases what two hormones during short term therpay
aldosterone
prolactin
Adult dose of Reglan
10-20 mg (0.25 mg/kg)
Route of Reglan
PO, IM, IV
How fast do you inject Reglan?
Over 5 minutes
Onset of IV Reglan
3-5 minutes
Onset of PO Reglant
30-60 minutes
How is Reglan excreted?
Urine
Decrease Reglan with what?
Renal dysfunction
What dose Reglan is used during chemo to prevent emesis?
1-2 mg/kg - Large dose
What medications can block the effects of Reglan?
Antimuscarinic such as Atropine and Robinul
What drug does Reglan decrease the absorption of?
PO Cimetidine
PPI examples
Omeprazole (Prilosec) Lansoprazole (Prevacid) Rabeprazole (Aciphex) Esomeprazole (Nexium) Pantoprazole (Protonix)
Protonix MOA
Bind to proton pump of parietal cells in the gastric mucosa and inhibit secretion of H+
PPI Uses:
treats: duodenal ulcer, GERD, and Zollinger-Ellison syndrome
heal: peptic ulcers and errosive GERD
Do PPIs or H2B heal ulcers and erosive GERD quicker?
PPIs
Concern when PPIs are taken with _____ drug due to inadequate ______ therapy when the drugs are combined
clopidogreal (Plavix0
antiPLT
Are PPIs tolerated well?
Generally, b/c they cause few s/e
Most common s/e of PPI
Gi system (nausea, abd. pain, constipation, diarrhea)
PPI rare s/e
myalgia
anaphylaxis
angioedema
severe dematologic reaction
Why does long-term use of PPIs increase risk of pneumonia?
bacterial colonization in the higher pH environment
Long-term PPI use has been associated w/ hyperplasia of the?
gastric enterochromaffin cell
PO doses of Omeprazole and Rabeprazole?
20 mg
PO dose of Protonix
40 mg
PO dose of Lansoprazole
15 mg
When do you decrease dose of PPI?
with severe liver impariement
How are PPIs eliminated?
liver
How often does PONV occur in general population (w/o prophylaxis)?
20-30%
How often does PONV occur in high risk (w/o prophylaxis)?
70-80%
As anesthetic duration increases, PONV risk _____
increases
WHich society provides a scoring system for PONV?
Society of Ambulatory Anesthesia (SAMBA)
Obesity, anxiety, and reversal of NMBD are or are not independent risk factors of PONV?
ARE NOT
What drugs are used in the treatment and prophylaxis of PONV?
5-HT3 blockers Butyrophenones Dexamethasone Neurokinin-1 receptor blockers (aprepitant, Emend) Antihistamines Transdermal scopolamine
Risk factors for pONV (7 total)
female nonsmoking history of PONV use of volatiles NO opioids duration of surgery
Each duration of ______ of surgery increases the baseline risk of PONV by 60%.
30 minutes
How many PONV interventions do you do for those at moderate risk?
1-2
How mnay PONV interventions do you do for those at high risk?
multiple
Where is serotonin 5-HT present in the body?
Large quantiites in PLT and the GI tract
NT in multiple areas of CNS
What part of the GIT ahs serotonin 5-HT?
enterochromaffin cells and the myenteric plexus
How is serotonin formed?
By hydroxylation and decarboxylation of tryptophan
What inactivates serotonin into 5-hydroxyindoleacetic acid (5-HIAA)?
Monoamine oxidase
How many receptors of serotonin are there?
At least 7, most w/ subtypes
What serotonin receptor mediates vomiting?
5-HT3
Where is the 5-HT3 receptor found?
GI tract and the brain (area postrema)
5-HT2a
responsilbe for smooth muscle contraction and PLT aggregation
5-HT4
in the GI tract and mediate secretion and peristalsis
5-HT6 and 5-HT7
located primarily in limbic system where they appear to pay a role in depression
All except ____ receptor are coupled to G proteins and affect either adenylyl cyclase or phospholipase c. (serotonin)
5-HT3
How are the effects of 5-HT3 mediated?
via an ion channel
Serotonin is a powerful ____ of arterioles and veins.
vasoconstrictor
What areas of the body lack serotonin’s vasoconstrictive properties?
heart and skeletal muscle
What effect does serotonin have on the heart’s vessels?
vasodilator effect, (endothelium dependent*)
When the myocardial endothelium is injured, serotonin produces _____.
vasoCONSTRICTION
What 2 vasculatures are sensitive to serotonin’s arterial vasoconstrictive effect?
pulmonary and renal
Modest and transient _____ in cardiac contractility and HR may occur after serotonin release;reflex ____ often follows.
increases
bradycardia
What affect does released serotonin have on respiratory system?
contraction of smooth muscle –> increased airway resistance
bronchoconstrictioN
Prominent feature associated w/ released serotonin of carcinoid syndrome?
bronchoconstriction
Does serotonin affect secretions?
No
Serotonin directly contracts GI smooth muscles via what receptor?
via 5-HT2
Serotonin-induced release of Ach in the myenteric plexus occurs via what receptor?
via 5-HT3
Serotonin 5-HT2 and 5-HT3 do what for the GI system?
greatly augement peristalsis
Activation of ____ serotonin receptors causes PLT aggregation.
5-HT2
What 3 meds selectively block 5-HT3 receptors, with no effect on dopamine receptors?
Ondansetron (Zofran)
Granisetron (Kytril)
Dolasetron (Anzemet)
5HT3 receptors are located peripherally in _____ and centrally at ________.
abdominal vagal afferents
CTZ of the area postrema and nucleus tractus solitarius
What serotonin receptor plays a roel in initiation of vomiting reflex?
5HT3
The 5HT3 receptors of the CTZ are ______ the BBB.
outside
How does the CTZ trigger zone initiate vomiting?
trigger zone is activated by substances such as ansethetics adn opioids, sends signal to neclues tractus soiatrious resulting in vomiting
What activates teh CTZ?
anesthestics
opioids
How does the GIT stimulate PONV?
emetogenic stimuli (in a similar manner to CTZ vomiting activation)
