m and m 10 - analges agents Flashcards
4 types of opioid receptors are
mu
kappa
delta
sigma
second messengers associated with opioid receptor activation are (2)
- inhibition of adenylyl cyclase (decrease intracellular AMP)
- activation of phospholipase C
two ion channels affected by opioids are?
inhibit voltage gated ion channels
activated inwardly rectifying potassium channels
Four examples of opioid agonists / antagonists are?
nalbuphine
nalorphine
butorphanol
pentazocine
True or false - opioids cause the release of presynaptic neurotransmitters?
False, they Inhibit release of these NTs
True or false - opioids are also located on the peripheral NS?
True, think receptors in the GI tract that cause constipation
What are the two isomers possible for opioids and which are more potent?
Levorotary and Dextrorotary - levorotary are more potent
Maximal effects of IM hydromorphone, morphine and meperidine after how long?
20-60 minutes
What property(s) of fentanyl favor transdermal absorption?
Low molecular weight, hight Lipid solubility
Why Is transdermal fentanyl not Instantaneously effective?
It takes time for local skin to establish a reservoir that allows for effective serum concentrations
Amount of time for steady state after a fentanyl patch? Steady state can persist for how long?
SS in 14-24 hrs, persists for up to 72 hours
Morphine, meperidine, fentanyl, sufentanyl, alfentanil and remifentanil. Which is least lipid soluble?
Morphine
Morphine, meperidine, fentanyl, sufentanyl, alfentanil and remifentanil. Which is most lipid soluble? (2)
Fentanyl and sufentanil
Morphine, meperidine, fentanyl, sufentanyl, alfentanil and remifentanil. Which has the least protein binding?
Morphine
Morphine, meperidine, fentanyl, sufentanyl, alfentanil and remifentanil. Which has the most protein binding? (2)
Sufentanil and alfentanil
Morphine, meperidine, fentanyl, sufentanyl, alfentanil and remifentanil. Which has the most non-ionized fraction?
Fentanyl and meperidine
What properties of fentanyl and alfentanil hasten onset and decrease duration of action?
High lipid solubility
Alfentanil is less lipid soluble than fentanyl, but it has a more rapid onset and shorter duration of action. Why?
It has a high non-ionized fraction and lower volume of distribution, therefore more (percentage) of the drug is available for receptor binding
What major organ system can serve as reservoir for opioids?
Lungs
What characteristics decrease opioid binding in the lungs?
Tobacco use
Prior accumulation of other drugs
What terminates the effects of lipid soluble opioids (fentayl, sufentanil) drugs at lower doses? Higher doses?
Lower doses? Redistribution
Higher doses? Biotransformation
The time required for fentanyl and sufentanil concentrations to decrease by half is context sensitive. Why?
Because the half life depends on what amount of drug was administered, varies based on high or low dose
What is the major site of Metabolism of opioids? What drug is the exception?
Liver, by cytochrome C
Exception is remifentanil
Opioids have a [high/low] hepatic extraction ratio, therefore their clearance depends on ____.
High hepatic extraction ratio, Therefore clearance depends on blood flow to the liver.
What are the hepatic metabolic products of morphine (2)and hydromorphone (1)?
Morphine 3-glucuronide, Morphine 6 glucuronide and hydromorphone 3-glucuronide
What is the biotransformation product of meperidine and what is its significance?
Normeperidine, associated with seizures
True or false, the metabolic products of fentanyl, alfentanil and sufentanil are active?
False, these are inactive
What is the significance of norfentanyl?
Metabolic product of fentanyl, present in the urine long after fentanyl use, can be used to detect fentanyl abuse (chronic)
What do codeine and tramadol have in common re: hepatic metabolism?
Both have to be metabolized by CYP enzymes to become active compounds, morphine and O-desmethyltramadol, respectively
What makes remifentanil unique re: metabolism? Site?
Ester structure makes it suceptible to hydrolysis by non-specific esterases in RBCs and tissues. Half life of less than 10 minutes
True or false, a dose adjustment is needed for patients with a pseudocholinesterase deficiency if treatment with remifentanil (or even esmolol) is desired.
False. These drugs are metabolized by non-specific plasma esterases, not pseudocholine esterases
Significance of renal dysfunction on morphine and meperidine use?
Metabolites are excreted in urine. morphine 6 glucuronide is even more potent than morphine, therefore more chance of narcosis if renal failure is present, Accumulation of normeperidine is associated with seizures
True or false, seizures from normeperidine can be prevented / reversed with naloxone?
False
What opioid is unique in being able to cause tachycardia? Why?
Meperidine, structurally similar to atropine
Opioids [do/don’t] directly depress cardiac contractility?
Opioids do not depress contractility
Opioids [do/don’t] cause brady cardia?
Opioids cause brady cardia by stimulation of the vagus nerve
True or false, opioids can cause decreased BP?
True, usually from brady cardia, venodilation and depressed sympathetic reflexes
What class of drugs, when administered with opioids, are most likely to cause profound drop in BP?
Benzos
What 3 opioids are associated with histamine release? Significance?
Meperidine, morphine and hydromorphone, This can cause significant drop in SVR
True or false, large boluses of opioids can cause HTN? What is the reason?
True, this is typically attributed to not enough anesthetic depth
What are the mechanisms by which opioids depress ventilation?
Increase partial pressure of CO2 (PaCO2) and blunt the response to increasing CO2. This increases the apneic threshold (the greatest Paco2 at which pt remains apneic) and decreases hypoxic drive
What opioids are associated with bronchospasm? mechanism?
Morphine and meperidine. Mechanism is histamine induced bronchospasm
Rapids administration of what 4 opioids are associated with chest wall rigidity? How is this treated? centrally or peripherally mediated?
Fentanyl, alfent, sufent and reminfent
Treatment is neuromuscular blockers
Centrally mediated
What is the overall effect of opioids on intracranial pressure? cerebral perfusion? cerebral oxygen consumption?
Decreases all these parameters
What is the effect of opioids on EEG?
No effect
True or False, large doses of remifentanil Intraoperatively can produce acute tolerance?
True - will subsequently require larger doses of opioids to achieve the same effect
Best opioid for post op shivering is?
Meperidine
Opioids can cause biliary colic by causing contraction of ____ structure. What is the treatment?
Sphincter of oddi
Treatment is naloxone or glucagon
Chronic opioid use will result in tolerance to most side effects except? What are 2 drugs used to treat this side effect?
Constipation
Methylnaltrexone and almivopan
Why avoid NSAIDs in certain types of surgeries?
Bleeding risk Is the major issue.
Cox-1 and Cox-2, which is constitutive and which is induced?
Cox-2 is induced, Cox-1 is constitutive
Why is it possible to have cox-2 specific drugs, but generally speaking not cox-1?
Cox-2 binding site is larger, can accomodate larger molecules that cannot bind cox-1
True or false, acetaminophen acts as a cox-2 blocker?
True
Most Cox inhibitors are well absorbed orally. What is the exception?
Ketorolac
True or false, Cox inhibitors are lipid soluble?
True, This is how they centrally mediate analgesia and antipyresis
What is the major organ for biotransformation of the COx inhibitors?
Liver
