Phys pharm anatomy Flashcards
Pretreatment with which medications may attenuate LA-induced cardiotoxicity?
clonidine & dexmedetomidine
How long may the inflammation-induced expression of opioid receptors at peripheral injury sites & delivery of endogenous opioids to balance the nociceptive state of inflammation take to have effect?
Up to 96hours
What’s the receptor affinity of buprenorphine to mu receptors cf fentanyl or morphine?
24-fold & 50-fold (but it’s a partial agonist)
What’s a controversy with perineurial opioids?
Unclear if any benefits are due to local peripheral nerve effects or due to systemic effects
In which formulations of LA is the effect of adding sodium bicarbonate most apparent?
those with added epinephrine, given they are generally formulated with lower pH
What concentration of hyaluronidase is used for retrobulbar/peribulbar block?
150units/mLFE
How does hyalase come & how is it prepared for retrobulbar/peribulbar block?
Purified, sterile freeze-dried powder of the enzyme hyaluronidase
Mix the contents (1500IU/vial) into 1mL of sterile distilled water
this makes a 150IU/0.1mL solution
Add 0.1mL to 6mL of LA solution, making 25IU/mL concentration
Is there any evidence for benefit of regional NSAIDs?
Yes- level II evidence (150pts) showing parecoxib/ropivacaine improved quality & duration of brachial plexus block vs placebo/ropiv or IV parecoxib/ropiv
To which of the opioid adverse effects does tolerance typically not occur?
miosis, constipation
For which of the opioids has a local anaesthetic action been described?
pethidine
How is the analgesia of intrathecal opioids mediated?
opioid receptors in the substantia gelatinous of the dorsal horn; 70% of mu & delta receptors are presynaptic, kappa more commonly post-synaptic
spinal opioid receptors are 70% mu, 24% delta & 6% kappa
anti-nociception may be further augmented by descending inhibition from mu-opioid receptor activation in the periaqueductal grey matter of the brain
What are possible ceiling effect doses for the analgesia provided by neuraxial opioids?
morphine 50-150mg IT & 2.5-3.75mg epidural
Mechanism & evidence for usefulness of intrathecal morphine
relatively hydrophilic so slower onset but longer half-life (hence prolonged duration of action) in the CSF. Greater cephalad migration cf lipophilic opioids
Low-dose ITM prolongs LA block, reduces LA dose, reduces adverse effects & improves recovery for spinal anaesthesia
100microg ITM produces analgesia comparable to 400microg when combined with low-dose bupivacaine for LSCS
single 100microg dose of ITM prolongs time to first analgesic admin by 16-20hours (level 1 evidence 535 pts)
Pruritis more common with higher doses
ITM reduces IV PCA consumption following abdominal hysterectomy
Evidence regarding epidural opioids
When used mainly in combination with LA, level 1 evidence has not shown difference in VAS pain scores postop between epidural opioids but morphine vs fentanyl produced higher rates of nausea & vomiting
Does epidural fentanyl act via a spinal or systemic effect?
evidence conflicting (fentanyl lipid soluble, sequestered in the epidural fat & slowly released back into epidural space, smaller fraction reaches the CSF)
Level II evidence suggests less intraop fentanyl is required if it’s given via Tx epidural vs IV & also longer time to first postop analgesia request
Is there benefit to epidural vs systemic sufentanil or alfentanil?
No
How does the analgesic benefit of epidural hydromorphone compare to epidural morphine?
similar
Comparing IV to epidural hydromorphone, pts required twice as much IV to achieve same degree of analgesia cf epidural.
When may the IJV be pulsatile?
Severe TR
What dose of sugammadex for TOFC & PTC 0? and if TOFC 0 but PTC >=1? and if TOFC 1-4 but TOFR <0.9?
16mg/kg
4-8mg/kg
2mg/kg
what dose of neo if TOFC 1-3 but TOFR 0? How about TOFR 0.1-0.4? and 0.4-0.9?
50-70mg/kg (total body weight)
50mg/kg
20mg/kg
How long after sugammadex should roc (0.6mg/kg) be re-administered?
6hrs- 2x elimination half-life of sugammadex, but there will be interpatient variability
What are some benefits of TEA?
-superior analgesia cf systemic opioids for many indications including: rib fractures, open colonic resection
-reduced pulmonary morbidity & rates of pneumonia & duration of mechanical ventilation (probably due to early mobilisation, reduced opioid consumption, improved cough)
-decreases the duration of postoperative ileus; some studies suggest it promotes early return of gut function & reduces risk of anastomotic leak, provided systemic haemodynamic effects of TEA are adequately controlled (sympathetic supply of abdo viscera is T6-L1, PSNS supply (vagus) not blocked with TEA, so neuraxial provides sympatholysis with maintained parasympathetic innervation, so gut contracted, sphincters relaxed, peristalsis normal). Cochrane R/V 2016 1100pts abdo surg reduced time to first flatus/bowel movement w TEA vs opioid.
-reduced mortality with TEA after rib fracture, colectomy or lung resection (retrospective data) & after a range of intermediate-to-high risk non-cardiac surgery (retrospective cohort study)
-multiple retrospective studies show reduced rumour recurrence rate after TEA or PVB- through opioid sparing (morphine impairs NK cell activity & promotes tumor growth) & attenuation of the stress response which impairs host immune function
-attenuates postoperative neurohormonal stress response (catecholamine levels increase LV afterload & HR, decreasing time for coronary perfusion (stenotic coronaries don’t dilate w SNS stimulation); Raised CRH levels reduce cardiac NO release & increase endothelin production; stress induces a pro-coagulatory state in the absence of trauma; pro-inflammatory response after stressful event may activate MMPs leading to plaque instability)
-Some studies suggest it decreases postoperative cardiac morbidity & mortality eg. after cardiac surgery (better pain relief & reduction in post-op stress response & SNS activity reduce myocardial O2 demand)
What proportion of perioperative mortality is accounted for by cardiovascular causes in high-risk patients? low-risk?
63%
30%
What sensory dermatomal level is required for neuraxial for caesarean or postpartum tubal ligation?
T4
What sensory dermatomal level is required for neuraxial for THR, ORIF femur or hip, cervical cerclage, urological procedures?
T10
What sensory dermatomal level is required for neuraxial for peri-anal procedures?
S1
What sensory dermatomal level is required for neuraxial for TKR, knee arthroscopy?
L1
What sensory dermatomal level is required for neuraxial for foot surgery?
L2
Is chronic HIV infection a contraindication to spinal anaesthesia?
No, since CNS is infected early in the course of the disease
Is HSV or VZV a contraindication to neuraxial?
Yes during primary infection (viremia) but secondary infection (manifest with oral or genital lesions) is not provided needle not inserted through lesion.
Management of neuraxial in patients with preload-dependent cardiac lesions or hypovolemia?
Only initiate NA once volume status normalised.
Invasive BP monitoring.
Vasopressors.
Fluid administration.
Incremental initiation of neural blockade.
Is neuraxial anaesthesia contraindicated in pts with intracranial mass lesion or raised ICP?
yes, as risk cerebral herniation
From where are the cardioaccelerator fibres?
T1-4
From where does SNS innervation to abdominal viscera originate?
T6-L1
What levels are kidney innervation?
T10-L1
What’s the incidence of permanent injury from neuraxial anaesthesia?
optimistically 2, pessimistically 4.2 per 100,000 (NAP3, 2009)
2/3 of initially disabling injuries resolved fully
What’s the incidence of high or total spinal?
1:4000
What may be the consequences of unintended subdural neuraxial?
Patchy block
Slower onset than spinal but faster & higher cranial spread than expected with epidural
Potential space btwn dura & arachnoid mater
Motor block may be more extensive than expected
Other symptoms such as Horner’s syndrome, apnoea or unconsciousness are reported
How soon after dural puncture does PDPH typically occur?
6-72 hours
What’s the origin of afferent & efferent nerve signals to the bladder?
S2-4
What are the risk factors for postop urinary retention with neuraxial?
longer duration of spinal anaesthesia
longer-acting LA
intrathecal opioid
male sex
older age
prolonged surgery
What are the typical signs & risk factors for transient neurologic symptoms after neuraxial?
pain/dysesthesia 2-24hours after otherwise uncomplicated spinal anaesthesia
MRI & physical exam normal
usually improved with ambulation & NSAIDs
higher risk with lidocaine (1 in 5 with spinal lidocaine)
also with lithotomy & knee surgery
What’s the risk of spinal-epidural haematoma after epidural & spinal?
1:18,000
1:150,000
What are early & late signs of post procedure infection & what is the management if any signs of infection occur?
early: fever, back pain, headache, localised pain/erythema at insertion site
late: stiff neck, radiating pain, photophobia, loss of motor function, confusion
Remove immediately, imaging, neurology or infectious diseases consultation
What is the risk of epidural bleeding?
1:10,000 for surgical patients
For how many days should clopidogrel be withheld prior to thoracic epidural?
7
Which pathogen is usually responsible for epidural abscess? and meningitis?
staphylococcus aureus
streptococcus
how early may infectious complications arise after epidural?
Day 2-4
For how long after TEA catheter removal should neurological monitoring be continued?
24hr
For how long after TEA catheter removal should neurological monitoring be continued?
24hr
Why is it difficult to demonstrate the benefits of TEA in RCTs?
low event rate for complications, changes in surgical technique, necessity for large number of patients required + standardisation of insertion level, drug & infusion regimens, measurement parameters and methodology
How significant is the periop increase in BGL with dexamethasone?
The increase in BGL may be greater in patients without vs with diabetes and may be more profound for poorly controlled diabetics vs well-controlled diabetes.
median 65mg/dL among patients receiving dexamethasone 8mg vs 43mg/dL among patients receiving placebo.
Ketamine causes dose-dependent -ve inotropy, which isomer in particular? in practice do we see reduced CO with ketamine?
R isomer
no because ketamine stimulates SNS so we usually see incr HR & CO; & -ve inotropy & reduced CO only unmasked if impaired SNS tone or responsiveness (eg. B block, exhausted catecholamine stores, neuraxial)
How does ketamine impact on pulmonary vascular resistance?
increases- avoid in pulm HTN
What happens to the NMDA receptor when activated by glutamate?
Ca++ & Na+ in, K+ out
What’s the offset of ketamine mainly due to? duration of action?
redistribution (highly lipid soluble, Vd 3L/kg) vs clearance
10-20mins to wake up after bolus, amnesia lasts 60 mins
What’s the POBA, VD, onset time, PB, pKa, ionisation @ physiological pH, metabolism & clearance for ketamine?
20%
3L/kg
30-60secs after a bolus
20% PB
7.5, base, 44% unionised @ physiological pH
demethylation in liver to norketamine (30% potency, prolonged analgesia) then glucoronindation
high HER so Cl flow-dependent 15mL/kg/min
renal excretion 96% inactive, t1/2B 3 hrs
What’s the MAC & BGPC of nitrous, des & sevo?
105, 0.47
6, 0.42
1.8, 0.69
What properties does fluoridation vs chlorination impart for desflurane?
lower blood solubility & potency
higher VP close to atmospheric (less intermolecular attraction)
molecular stability
Which agent has the lowest potency among the volatiles?
Des, OGPC 19 & MAC of 6, minimal metabolism & distribution to fat
What’s the inter-threshold range?
range of core temperatures over which autonomic responses are not required for thermoregulation- normal ITR is 37+/-0.2deg C, established by the post hypothalamus
By how much does GA reduce BMR?
25-40%
What causes neuroleptic malignant syndrome?
dysautonomia
central dopamine blockade (eg. dopamine receptor blocking agents or withdrawal of dopamine agonists)
What’s the antidote for serotonin syndrome (if supportive care & Bad fail to improve agitation & correct vital signs)?
cyproheptadine (histamine receptor antagonist with weak anticholinergic activity).
anticholinergic toxicity?
red as a beet (peripheral- vasodilation)
dry as a bone (peripheral- anhidrosis)
hot as a hare
blind as a bat
mad as a hatter
anticholinergic toxicity?
red as a beet (peripheral- vasodilation)
dry as a bone (peripheral- anhidrosis)
hot as a hare
blind as a bat
mad as a hatter
What’s bulbar palsy?
A set of signs & symptoms linked to impaired function of the lower cranial nerves (IX, X, XI, XII), usually due to damage to their lower motor neurone or to the lower cranial nerve itself
What are some factors potentiating neuromuscular blocking drugs
hypothermia
hypermagnesemia
hypernatremia
ketamine
volatiles
gentamicin
amiodarone
*What are some chronotropes that act directly on the myocardium vs AV node?
isoprenaline, dobutamine, adrenaline
*how does digoxin impact HR? and isotropy?
slows AVN conduction
increases intracellular Ca++ by inhibiting NaKATPase so more ICF Na & NaCa exchanger not able to extrude Ca++
*effects & mechanism of adenosine?
-ve inotropy & chronotropy
-open K+ sensitive channels (Gi channels in AV & SA node); slows AVN conduction & shortens AP, -ve chronotropy SAN
-also bronchoconstriction, renal VC
What % change in plasma osmolality triggers the central osmoreceptors, promoting ADH from posterior pituitary?
1-2% increase plasma osmolality
How may mannitol be useful for renal protection?
osmotic diuresis may protect against acute renal failure (eg. in rhabdomyolysis).
Mannitol is freely filtered, not reabsorbed. effectively dilutes the Na+ in tubules, reducing Na+ reabsorption, promotes movement of Na+ IF–> tubular fluid. Expanded plasma volume & reduced viscosity improves flow to some organs including renal medulla; this washes out medullary interstitial concentrating gradient, impaired ability to concentrate urine & diuresis ensues.
How may mannitol be useful for renal protection?
osmotic diuresis may protect against acute renal failure (eg. in rhabdomyolysis).
Mannitol is freely filtered, not reabsorbed. effectively dilutes the Na+ in tubules, reducing Na+ reabsorption, promotes movement of Na+ IF–> tubular fluid. Expanded plasma volume & reduced viscosity improves flow to some organs including renal medulla; this washes out medullary interstitial concentrating gradient, impaired ability to concentrate urine & diuresis ensues.
What’s the alveolar gas equation?
PAO2= FiO2(Patm-PH2O) - PaCO2/RR Patm= 760mmHg, pH2O=47mmHg
What’s normal L) atrial pressure?
6-12mmHg
What’s DDAVP? how does it work for vWF?
synthetic analogue of ADH, has prolonged half-life & DoA cf ADH
acts mainly on kidneys (V2 selectivity) & less pressor action
DDAVP causes release of von Willebrand’s antigen from platelets & cells that line the blood vessels where it is stored. Von Willebrand’s antigen is the protein that carries factor VIII.
What is chassaignac tubercle?
paired anterior tubercles of the TPs of C6
What is Horner’s syndrome? how does it relate to stellate ganglion block?
caused by sympathetic blockade.
produces, on ipsilateral side of the face:
-ptosis
-meiosis
-anhydrosis
-conjunctival injection
-enophthalmos
What is the osmolality of glycine, sorbitol & mannitol (the most common nonconductive (nonelectrolyte) fluids used for surgical irrigation)?
glycine 1.5% (most commonly used) osmolality 200mosmol/kg
sorbitol 3% is 165mosmol/kg
mannitol 5% is 275mosmol/kg
so 5% mannitol almost isosmotic to plasma (280mosmol/kg)
What is the osmolality of glycine, sorbitol & mannitol (the most common nonconductive (nonelectrolyte) fluids used for surgical irrigation)?
glycine 1.5% (most commonly used) osmolality 200mosmol/kg
sorbitol 3% is 200mosmol/kg
mannitol 5% is 275mosmol/kg
so 5% mannitol almost isosmotic to plasma (280mosmol/kg)
