Preoperative Medications (Exam I) Flashcards
What cells release endogenous histamine?
- Basophils & Mast cells
What physiological mechanisms occur from
general histamine release?
- Bronchostriction
- Stomach acid secretion
- CNS neurotransmitter release (ACh, NE, 5HT)
Does histamine release cause aspiration?
No, but if aspiration happens, it will be much worse due to the increase in acid in the stomach from the histamine release
What drugs can induce histamine release?
- Morphine
- Protamine
- Mivacurium (only lasted 12 min)
- Atracurium
Are anti-histamine’s competitive antagonists?
No, they are inverse agonists.
What would be used to treat drug-induced histamine release?
- H1 & H2 antagonists
Histamine-1 receptor activation can mimic these other receptor types.
- Muscarinic
- Cholinergic
- 5HT3
- α-adrenergic
Histamine-2 receptor activation can mimic these other receptor types?
- 5-HT3
- β-1
Histamine binding to H1 receptors generally elicits what effects?
- Hyperalgesia
- Inflammatory pain (insect stings)
- Allergic rhino-conjunctivitis s/s
Histamine binding to H2 receptors generally elicits what effects?
- Stomach acid secretion
- ↑ cAMP (β-1 similar stimulation)
How prone are H1 antagonists to tachyphylaxis?
- Very little tachyphylaxis development
What signs/symptoms occur with excessive H-1 & H-2 activation?
- Hypotension (from NO) release
- ↑capillary permeability
- Flushing
- Prostacyclin release
- Tachycardia
Where do we want H1 receptor antagonists to work?
- Vestibular system
- Airway smooth muscle
- Cardiac Endothelial Cells
What are the side effects of H1 antagonists?
- Drowsiness/sedation (1st gen, all cross BBB)
- Blurred vision
- Urinary retention
- Dry mouth
What are four examples of H1 receptor antagonists?
- Diphenhydramine (Benadryl)
- Promethazine (Phenergan)
- Cetirizine (Zyrtec)
- Loratidine (Claritin)
Last 2 are Gen 2, Do not cross BBB so no drowsiness
Benefits of H1 Antagonists
- Cheap
- Work well
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 it’s E ½ time?
- Rescue anti-emetic
- 9-16 hours
Can reduce peripheral pain levels with its anti-inflammatory effects
What are the black box warnings associated with promethazine?
- 2005: children under 2 shouldn’t take (resp depression and arrest)
- 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 disease and GERD
- ↓ Gastric volume and ↑ 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%
What is the overall side effect list for H2 antagonists?
- Headache
- Confusion
- Skeletal muscle pain
- ↑ serum creatinine
- ↑ stomach bacteria
- Diarrhea
- Bradycardia
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 (Tagemet)
- Ranitidine (Zantac)
- Famotidine (Pepcid)
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 mg diluted 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
Examples of PPI Meds
Omeprazole (Prilosec)
Pantoprazole (Protonix)
Lansoprazole (prevacid)
Dexlansoprazole (dexilent) - Works really well, very expensive
For what four conditions are PPI’s indicated and more effective at than H2 Antagonists?
- Healing Esophagitis
- Healing Ulceration
- GERD
- Zollinger-Ellison (excess acid)
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.
Which PPI drug is enteric coated, a prodrug, and only inhibits the pumps that are present?
Omeprazole (Prilosec)
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: Works as fast as Zantac (ranitidine)
- can be given 1 hour prior to sx.
What is pantoprazole dosing?
- 40mg in 100mL over 2-15 minutes
In what situations are PPI’s superior to H2 blockers?
- Any ulcerations
- GERD
- Acute upper GI hemmorhage
What situations would H2 blockers be superior to PPIs?
- Aspiration pneumonitis concerns (they work faster)
- intermittent symptoms taken PRN
- more cost effective since not taking every day
If gastric volume already in stomach, which drug would you give? PPI’s, H2, or H1 antagonists?
None of the above will help
- need antacids
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?
- Food breakdown inhibited
- Acid rebound
What is a concern with long-term magnesium based antacids?
- Osmotic diarrhea
- Neuromuscular and neurologic 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 action for sodium citrate (Bicitra) ?
- Base + stomach acid = salt, CO₂, and H₂O
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 it’s downsides?
- Protects against aspiration pneumonia (↑pH)
- commonly given to C-section women
- Increases gastric volume & increases aspiration risk.
What pts should be considered to have a full stomach?
- Trauma pts
- pregnant women
- gallbladdar pts
- Diabetics
- Liver pts
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, not good for Parkinson’s or Huntington’s pts)
- Orthostatic hypotension
- No change in gastric pH
Name the three dopamine blockers discussed in lecture?
- Metoclopramide
- Domperidone
- Droperidol (Inapsine)
What drug is used for diabetic gastroparesis?
- Metoclopramide (Reglan)
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.
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.
- Lots of 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
If you give this drug, you want to avoid giving other CNS depressants, Barbs, Opioids, and general anesthetics:
Droperidol (Inapsine)
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 effects
- Not useful for motion sickness
What were 5HT3 antagonists originally used for?
CINV (chemotherapy-induced N/V)
Examples of 5HT3 antagonists
- Ondansetron (Zofran)
- Granisetron (Kytril)
- Dolasetron (Anzemet)
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
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
- 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
- Peak concentration: 8-24 hours
Apply 4 hrs pre-op
What is scopolamine dosing and where do the patches need to be applied?
- 140mcg priming & 1.5mg over the next 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
Why choose scopolamine patch over atropine or Glycopyrrolate?
- Better at causing sedation
- Better antisialagogue (drys up saliva)
- Does not increase HR
- Better at preventing motion sickness induced nausea
How much of a benefit does a preoperative bronchodilator give?
- 15% increase in FEV1, 6 minutes after administering.
How many seconds should one take a deep breath when being administered a β2 agonist?
- 5-6 seconds
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 (increased surface area in alveoli)
What five serious conditions have been associated with PPI’s when given long term?
- Bone fractures
- Lupus (SLE)
- Acute interstitial nephritis
- C-diff
- Deficient Vit B12 & Mg⁺⁺
Which beta agonist would you give a pt who had severe aortic stenosis?
Try Levo-albuterol (Xopenex) first to avoid the tachycardia side effect of Proventil (albuterol)
