Pharmacology pt 2 Flashcards
Metabolic ALKALOSIS is common following the administration of which diuretics?
Loop and thiazide
- loss of extracellular volume with constant extracellular HCO3
What receptors do loop diuretics act on in the ascending LOH?
Na-K-Cl transporter
What receptors do thiazide diuretics act on in the distal convoluted tubules?
Na-Cl reabsorption
Metabolic ACIDOSIS is common following the administration of which diuretics?
acetazolamide (carbonic anhydrase inhibitor)
- inhibits the rxn btwn H2O, CO2, Carbonic acid, and bicarb -> bicarb builds up in urine
- d/t bicarbonate excretion
Potassium sparing diuretics (spironolactone, amiloride)
You should not use acetazolamide in Pts with what lung condition ?
COPD
- can also impair CO2 elimination (not just increase HCO3 excretion)
What two metabolic disturbances are associated with diuretics?
Metabolic ALKALOSIS
- loops
- thiazide
Metabolic ACIDOSIS
- acetazolamide
- spironalactone
What diuretics act at:
- distal convoluted tubule?
- collecting ducts
distal convoluted tubule
- thiazide
collecting ducts
- spironalactone
Which pain medication is associated with QT prolongation?
Methadone
- concurrent use with other meds that also inhibit CYP3A4 -> cardiac arrhythmia
Half-life of methadone
20-60 hours
Metabolism of most drugs occurs via 2 processes - Phase I and Phase II reactions
- What is Phase I?
oxidative and reductive reactions
- hydrolytic reactions
- catalyzed by cytochrome P450
Metabolism of most drugs occurs via 2 processes - Phase I and Phase II reactions
- What is Phase II?
Conjugation of drug or its metabolites w. substrates (ie. glucuronic acid)
- once metabolized -> eliminated from body
What reaction occurs after large and prolonged thiopental dosing?
desulfurization reaction
–> produces pentobarbital -> CNS depressant activity
Remifentanil is metabolized by:
ester hydrolysis in the blood by plasma esterases
- safe in pts with ESRD
Buprenorphine MOA
u-opioid partial agonist
k-antagonist
Buprenorphine potency vs morphine
- effects at high dose
24-40x potency of morphine, half life of 3 hours
High dose - partial agonist ceiling effect
- (less respiratory depression)
Spironolactone MOA
competitive aldosterone antagonist
- K sparing diuretic
- retention K
- excretion Na
_____ is the major counterregulatory hormone to insulin
Glucagon
Glucagon effects on the heart
Inotropic and chronotropic response
- activates G protein coupled receptors -> adenylyl cyclase -> increase cAMP
Glucagon is contraindicated in which 2 disease states?
Pheochromocytoma
- risk for hyperglycemia and severe HTN
Insulinoma
- risk of severe hypoglycemia
Glucagon resembles which vasopressors?
Epi
Norepi
*Inotropic and chronotropic response
Isoproterenol MOA
Nonselective Beta agonist
-> - activates G protein coupled receptors -> adenylyl cyclase -> increase cAMP
*Very similar to glucagon
How does ASA irreversibly inhibit platelet function?
Blocking formation of thromboxane A2
How many days does it take for your entire platelet pool to be replenished?
7 days
- 10% per day
What is the MOA of:
Clopidogrel (Plavix)
Ticagrelor (Brilinta)
Prasugrel (Effient)
Inhibit ADP receptor activation
What is the MOA of:
Eptifibatide (Integrilin)
Abciximab (Reopro)
Tirofiban (Aggrastat)
Blocks GP IIb/IIIa receptors
Example of antiplatelet agents
- Irreversibly inhibit plt function, so even if med no longer present, effect on plt still persists
- ASA
- Clopidogrel
- Ticagrelor
- Dipyridamole
- Abciximab
- Eptifibatide (integrillin)
*limited list
Examples of anticoagulation agents
- works via diff mechanisms, but can continue/hold perioperatively
- Warfarin
- heparin
- Fondaparinux
- Dabigatran (pradaxa)
- Rivaroxaban (xarelto)
- Apixaban (Eliquis)
MOA of:
Dabigatran (pradaxa)
Rivaroxaban (xarelto)
Apixaban (Eliquis)
Dabigatran (pradaxa)
- direct thrombin inhibitor
Rivaroxaban (xarelto)
Apixaban (Eliquis)
- direct factor Xa inhibition
NMBs are (hydrophilic/hydrophobic) w/t quaternary amine structure - importance?
Hydrophilic
- (cirrhosis, CHF, RF): an increase in body water -> increase volume of distribution -> DECREASES plasma [ ] of NMBs, so you need to INCREASE the intubating dose
Which NMBs will have INCREASED duration of action with impaired hepatic metabolism?
- Roc
- Vecuronium
- Pancuronium
Sodium nitroprusside toxicity is a direct side effect of ____ and ____ toxicity.
- Triad of:
1. Elevated mixed venous oxygen (PVO2)
2. Tachyphylaxis
3. metabolic acidosis
cyanide
thiocyanate
Sodium nitroprusside toxicity is a direct side effect of cyanide and
thiocyanate toxicity.
- What Triad is seen?
- Elevated mixed venous oxygen (PVO2)
- Tachyphylaxis
- metabolic acidosis
Antidote for cyanide poisoning
Amyl nitrate
- converts Hgb to Methgb (which binds cyanide)
In pts with biliary disease, how does morphine affect the common bile duct?
Induce Biliary colic
- Opioids inhibit efferent innervation (smooth m) to bile duct -> frequent muscle contraction
Max dose of neostigmine (acetylcholinesterase inhibitor)
- 07 mg/kg
- too much can INCREASE risk of developing weakness
Which anesthetic gas produces that largest [ ] of fluoride ions upon metabolism?
Methoxyflurane and Sevoflurane
- fluoride induced nephrotoxicity to the collecting ducts, inhibiting ADH
*Halothane causes HEPATOtoxicity
How does halothane decrease BP?
Mainly by reducing cardiac output
*the other inhaled anesthetics lower BP by decreasing SVR
How does nitrous oxide decrease BP?
It generally doesnt
Can nitrous oxide be used in laparoscopic or bariatric surgery?
Yes
- duration is more important than the type of surgery (>4 hours)
- but avoid if bowel is already distended or ischemic
How fast can nitrous oxide expand a pneumothorax?
double in 10 min
triple in 15 min
Which anesthetic drug below will cause the least dmg with local tissue extravasation (vesicant)?
propofol, diazepam, phenytoin, promethazine, thiopental
propofol
Can pts with PCN allergy with no h.o severe reaction (whether IgE or non IgE mediated) receive cephalosporin abx?
Yes
*rash does NOT count as a severe rxn
Difference btwn LMWH and UFH?
UFH: inactivate factor Xa and IIa
LMWH: inactivate factor Xa only
PTT is used to assess _____ pathway.
Used to monitor ____.
Intrinsic (VIII, IX, XI, XII)
and common pathway (II, V, X, fibrinogen)
Unfractionated heparin
PT is used to assess _____ pathway.
Used to monitor ____.
Extrinsic pathway ( Tissue factor and VII) and common pathway (II, V, X, fibrinogen)
Warfarin
Anti-Xa assay is Used to monitor ____.
LMWH
*PTT is used to monitor UF
Norepinephrine is a naturally occurring catecholamine secreted at the _________ synapses and is release from the _______
postganglionic sympathetic
adrenal gland
The ____ reflex mediates a decrease in HR secondary to increase blood pressure from an increase in SVR
baroreceptor
Beta 1 activity
increase HR, contractility, and cardiac output
Norepi has alpha 1 and beta 1 activity, which one predominates?
alpha > beta
- leads to more arterio/venoconstriction than increasing HR
- worsen renal and splanchnic blood flow
Dosing for NDMB prior to succinylcholine (1 mg/kg) to prevent fasciculations?
10% of ED95 dose
ie: roc 0.03 mg/kg
vecis 0.05 mg/kg
cis is 0.05 mg/kg
*ED is effective dose, NOT intubating dose
What does ED50 mean?
Median effective dose that will produce an effect in 50% of the population that it is administered to
What does ED95 mean?
Median effective dose that will produce an effect in 95% of the population that it is administered to
- different meaning with NMBDs
- 95% twitch suppression in 50% of the population
What happens when you mix propofol with lidocaine?
It decreases the stability of propofol w/in 30 min, inc risk of PE
- give immediately after mixing
Most effective way to reduce pain associated w/ injection of propofol
- injection in antecub vein
2. modified bier block
Anesthetic drugs associated with myoclonus
Etomidate Ketamine Methohexital Suxx Propofol
*pretreatment with midazolam helps
Transdermal fentanyl patch max plasma [ ] ? How long does it take to decrease [ ] by 50%?
30 hours
24hours
Following neostigmine administration, how does this affect succinylcholine?
Phase I augmentation
- prolonged DOA (~30 min)
- common after laryngospasm
Milrinone MOA.
WHere is it excreted?
PDE III inhibitor
- acts on cAMP -> inodilator
Kidneys /urine
- Lower dose if RF