Preoperative medications Exam 1 Flashcards
What cells release endogenous histamine?
Basophils & Mast cells
What physiological mechanisms occur from general histamine release? (3)
- Bronchostriction
- Stomach acid secretion
- CNS neurotransmitter release (ACh, NE, 5HT)
What drugs can induce histamine release? (4)
“MMAP”
Morphine
Mivacurium
Atracurium
Protamine
Are anti-histamines competitive antagonists?
No, they are inverse agonists
they dont prevent the release of histamine, they block Histamine receptor sites
What would be used to treat drug-induced histamine release?
H1 & H2 antagonists
Histamine-1 receptor activation can mimic these other receptor types. (4)
- Muscarinic
- Cholinergic
- 5HT3
- α-adrenergic
Histamine-2 receptor activation can mimic these other receptor types? (2)
- 5-HT3
- β-1
Histamine binding to H1 receptors generally elicits what effects? (3)
- Hyperalgesia
- Inflammatory pain (insect stings)
- Allergic rhino-conjunctivitis s/s
Histamine binding to H2 receptors generally elicits what effect?
Stomach acid secretion
↑ cAMP (β-1 like stimulation)
How prone are H1 antagonists to tachyphylaxis?
Very little tachyphylaxis development
What signs/symptoms occur with excessive H1 & H2 activation?
- Hypotension (from NO) release
- ↑capillary permeability
- Flushing
- Prostacyclin release
What are the side effects of H1 antagonists?
Drowsiness/sedation (1st Gen)
Blurred vision
Urinary retention
Dry mouth
What are four examples of H1 receptor antagonists?
- Diphenhydramine (Benadryl)
- Promethazine (Phenergan)
- Cetirizine (Zyrtec)
- Loratidine (Claritin)
What is diphenhydramine’s primary use and secondary uses?
Antipruritic
Pre-treatment of known allergies (IV dye)
Anaphylaxis
What is the E ½ time of diphenhydramine?
7-12 hours
What salt of diphenhydramine is useful for motion sickness and why?
Dimenhydrinate (dramamine) is thought to inhibit the afferent arc of the oculo-emetic reflex.
What H1 antagonist stimulates ventilation? Can this overcome narcotics?
Diphenhydramine (Benadryl)
No
What is normal dosing of Benadryl?
25 - 50mg IV
What is promethazine’s primary use? What is its E ½ time?
Rescue anti-emetic
9-16 hours
What are the black box warnings associated with promethazine?
2005: children under 2 shouldn’t take (resp depression)
2009 - Tissue extravasation injuries
What is the dosing of promethazine and when would one expect onset to occur?
12.5 - 25mg IV
Onset: 5 minutes
When are H2 antagonists most often utilized and what is their mechanism of action?
- Duodenal ulcer, GERD
- ↓ Gastric volume, ↑ gastric pH
What side effect(s) is/are especially pertinent with long term H2 antagonist administration? Why does this occur?
Bacterial overgrowth → pulmonary infections, weakened mucosa, and candida albicans.
This bacterial overgrowth occurs from chronically alkalotic stomach fluid.
What considerations should be given for renal patients when giving H2 receptor antagonists?
Chronic H2 antagonist = creatinine ↑ by 15%
tubular secretion competition
What is the overall side effect list for H2 antagonists?
Diarrhea
Headache
Skeletal muscle pain
↑ stomach bacteria
HA, & confusion
Bradycardia
↑ serum creatinine
What CNS effects might be seen from H2 antagonist administration? When would this occur more often?
Headache/confusion from CNS H2 receptors (occurs more in the elderly)
What examples of H2 antagonists were given in lecture?
Cimetidine*
Ranitidine
Famotidine
Which H2 antagonist strongly inhibits CYP450’s?
Cimetidine
What can occur with rapid infusion of cimetidine? How can this be avoided? What other adverse effects does cimetidine have?
Bradycardia & hypotension (from cardiac H2 receptors)
Give over 30 min
↑ prolactin & impotence
What is the dose for cimetidine? What is the renal dose?
150 - 300 mg IV
150 mg IV
Describe cimetidine, ranitidine, and famotidine’s interactions with CYP450 enzymes.
Cimetidine: strong CYP450 inhibition
Ranitidine: weak/no CYP450 inhibition
Famotidine: no CYP450 inhibition
What is normal ranitidine dosing? What is the renal dosing?
50 mgdiluted in 20cc’s over 2 minutes
25 mg diluted in 20cc’s over 2 minutes
Which H2 antagonist is most potent and has the longest E ½ time? What is this E ½ time?
Famotidine: E½ = 2.5 - 4 hours
What adverse effect can occur with famotidine?
Hypophosphatemia (look for fractures)
What is the dose of famotidine? What is the renal dose?
20mg IV
10mg IV
How do proton pump inhibitors work? What is the onset of action for proton pump inhibitors?
Irreversible binding to H⁺ pumps preventing acid creation.
3-5 days for full result.
What is the most effective drug for controlling gastric acidity and volume?
PPI’s»_space; H2 antagonists
For what four conditions are PPI’s indicated?
Esophagitis
Ulceration
GERD
Zollinger-Ellison (excess acid)
What five serious conditions have been associated with PPI’s?
Bone fractures
Lupus
Acute interstitial nephritis
C-diff
Deficient Vit B12 & Mg⁺⁺
What coagulation considerations have to be made with PPI’s?
PPI’s inhibit warfarin metabolism = warfarin overdose
PPI’s block clopidogrel = plavix won’t work.
What is the maximum acid inhibition that can be achieved by omeprazole? What is omeprazole’s dosing?
66%
40mg/100cc over 30min or PO >3hours prior to sx.
What are the most common side effects of omeprazole?
HA, agitation, & confusion (crosses BBB)
Bacterial overgrowth
N/V
Flatulence & abdominal pain
What are the benefits of pantoprazole over omeprazole?
Better bioavailability & longer E½
Fast: can be given 1 hour prior to sx.
What is pantoprazole dosing?
40mg in 100mL over 2-15 minutes
In what situations is an H2 blocker preferred over a PPI?
Aspiration Pneumonitis possibility (H2 blocker works faster)
Intermittent symptoms
Cost
In what situations are PPI’s superior to H2 blockers?
Any ulcerations
GERD
Acute upper GI hemorrhage
Drug of choice for NSAID ulcerations
Omeprazole (+ D/C NSAID)
What types (and subtypes) of antacids exist?
Particulate:
* Aluminum & Magnesium
Non-particulate:
* Na⁺, carbonate, citrate, & HCO₃⁻ based
Why are non-particulate antacids superior to particulate antacids?
Non-particulates neutralize acid & decrease gastric volume.
Particulate aspiration just as bad as normal aspiration.
What is a general concern with long-term antacid use? (2)
Food breakdown inhibited
Acid rebound
What is a concern with long-term magnesium based antacids? (2)
Osmotic diarrhea
Neuromuscular impairment
What is a concern with long-term calcium based antacids?
Hypercalcemia
What is a concern with long-term sodium based antacids?
Hypertension
What is the mechanism of sodium citrate (Bicitra)?
Base + stomach acid = salt, CO₂, and H₂O
neutralizes acid, increase intra-gastric volume
What is the time of onset for sodium citrate? How long does it last? What is the dose?
Immediate onset
Loses effectiveness in 30-60min
15 - 30 mL PO
What is sodium citrate used for and what are its downsides?
Protects against aspiration pneumonia (↑pH) (not aspiration)
Increases gastric volume & increases aspiration risk.
What are dopamine blockers used for in the preoperative setting? What is the mechanism of action?
Stimulation of gastric motility:
- increases lower esophageal sphincter tone
- stimulates peristalsis
- relaxes pylorus & duodenum
What are the downsides of dopamine receptor blockers?
Extrapyramidal reactions (crosses BBB)
Orthostatic hypotension
No change in gastric pH
Name the three dopamine blockers discussed in lecture?
Metoclopramide
Domperidone
Droperidol
What drug is used for diabetic gastroparesis?
Metoclopramide (Reglan) 10-20 mg IV
15-30 mins before induction
What drugs can potentially cause neuroleptic malignant syndrome? What are the symptoms of this syndrome?
Metoclopramide & Droperidol
↑temp, muscle rigidity, ↑HR, & confusion
Which dopamine blocker can decrease plasma cholinesterase levels? What is the consequence of this?
Metoclopramide
↓ metabolism of succinylcholine, mivacurium, & ester local anesthetics (increased drug effect)
What is the dosing for metoclopramide? When should it be given?
10-20 mg IV over 3-5min
15-30 min prior to induction
Which dopamine blockers can potentially increase prolactin secretion? Where is prolactin secreted from?
Metoclopramide < Domperidone
Pituitary gland
In which three ways is Domperidone unlike other dopamine blockers?
No anticholinergic activity
No BBB crossing
Unavailable in USA
What was droperidol originally developed for?
Schizophrenia/Psychosis
What blackbox warning is associated with droperidol?
↑↑↑ doses cause prolonged QT & torsades
+ drug interactions
What is the dose of Droperidol?
0.625 - 1.25 mg IV
What dopamine blocker is more effective than Reglan and equally as effective as Zofran?
Droperidol
Where is serotonin released from and how does it cause emesis?
Released via chromaffin cells of small intestine → vagal stimulation via 5HT3 receptors
Where are the highest concentration of serotonin receptors found? Where else are they commonly found?
Brain & GI tract
Kidney, liver, lung, stomach
What is the greatest general benefit of 5HT3 antagonists? What are they not useful for?
Very few side effect, great for PONV
Not useful for motion sickness
ondansetron 1st drug
What is the E ½ time of Ondansetron? Why is this relevant?
4 hours: dose must be given so that effect peaks towards end of the case.
What is the normal dose of Ondansetron?
4 - 8 mg IV
what kind of antagonist is ondansetron?
competitive antagonist to serotonin on 5HT3 receptors
If side effects are seen with ondansetron, what might be seen?
Slight QT prolongation, headache, diarrhea
What are the three prevailing theories for corticosteroid’s mechanism in treatment of PONV?
- CNS prostaglandin inhibition suppressing endorphin release
- ↑ effectiveness of 5HT3 antagonists & droperidol
- Anti-inflammatory = less opioid usage.
A patient is on 100mg hydrocortisone Q8 for 24 hours post-operatively, what dose of dexamethasone would you give?
No Dexamethasone
What is the time till onset of Dexamethasone? How long does efficacy persist?
Onset: 2 hours (time accordingly)
24 hours of efficacy
What is the primary adverse effect of dexamethasone?
Perineal burning/itching
What is the normal dosing for dexamethasone? When would one consider giving more?
4 - 8 mg
Consider >12mg if difficult airway or swelling exists.
How does scopolamine work?
Muscarinic Antagonist with central & peripheral effects.
When do scopolamine patches need to be applied? When does concentration peak?
Onset: 4 hours (pre-op, posterior-auricular)
Peak concentration: 8-24 hours
What is scopolamine dosing and where do the patches need to be applied?
140mcg priming & 1.5mg/72 hours.
Apply to post-auricularly or on the back
What is scopolamine’s best indication? What three adverse effects are most prevalent?
Motion-sickness
Mydriasis, sedation, & photophobia
How much of a benefit does a preoperative bronchodilator give?
15% increase in FEV 6 minutes after 2 puffs.
(Not a lot)
Beta agonists MOA
- Gs protein stimulation
- activate cAMP
- decrease calcium entry
- decrease contratility
How many seconds should one take a deep breath when being administered a β2 agonist?
5-6 seconds + hold breath
How much of a bronchodilator reaches the lungs with an inhaler method of delivery? How much does this decrease/increase with an ETT?
Inhaler: 12% of drug reaches lungs
ETT: 30-50% of drug reaches lungs
What are the side effects of β2 agonists?
Tremor
Tachycardia
Hyperglycemia
Temporary decrease in PaO₂
