OPIOIDS and NonOP EXAM REVIEW Flashcards
What are some of the causes of Nausea and vomiting associated the use of opioids?
DPG
- Opioid induced N/V are caused by direct stimulation of the chemoreceptor trigger zone in the floor of the fourth ventricle
- Opioids may act as a partial dopamine agonist at
the chemoreceptor trigger zone - Morphine may also cause N/V by ↑ GI secretions
and delaying passage of intestinal contents
Which opioid agonist is contraindicated in a patient taking a MAOI?
Meperidine
MAOI( phenelzine, Selegine)
How do opioid agonist affect bile duct pressure? Which agents have the greatest/least effect?
• Equal analgesic doses of opioids ↑ bile duct pressure above pre drug levels Greatest effect --> FENTANYL Intermediate ---> MORPHINE Least ---> MEPERIDINE
What is the drug of choice to reverse biliary spasms in a patient taking chronic narcotics?
Glucagon (2mg IV) may reverse opioid induced biliary
smooth muscle spasm
How are opioid receptors classified? What endogenous neurotransmitter affects each receptor?
OPIOD receptors (3) Mu , Delta, Kappa (ALL G-COUPLED ) antagonize adenylate cyclase, decrease CAMP
Opioid receptors on primary afferent neurons are
activated by 3 endogenous peptide opioid receptor ligands
Endorphins:
Mu 1–> endomorphins and B-endorphins (also morphine itself and synthetic opiods
Mu 2 –> endomorphins and B-endorphins (also morphine itself and synthetic opiods
Enkephalins –> DELTA
Dynorphins –> KAPPA
What endogenous neurotransmitter affect Mu receptors? Think mEN!
ENDORPHINS
What endogenous neurotransmitter affect KAPPA receptors? (KevinDurant KD)
DYNORPHINS
What endogenous neurotransmitter affect DELTA receptors? DELTA –think DeK
ENKEPHALIN
What narcotic is associated with first past lung effect? What concern is this to the clinician?
75% of initial fentanyl dose undergoes first pass
pulmonary uptake
Limits the initial amount of drug that reaches the systemic circulation
What is expected with the use of IV induction doses of morphine?
DROP in BP and SVR (histamine release)
Exaggerated HYPOTENSION on induction
May prevent drop by giving H1/H2 antagonist.
• Opioids given prior to induction may slow heart rate during exposure to VA with/without surgical stimuli
What is the reversal agent for benzodiazepines?
which part?
FLUMANEZIL
Flumenazil only REVERSES the BENZODIAZEPINES COMPONENT OF VENTILATORY DEPRESSION
Does not work for OPIOD ventilatory depression
What is the reversal agent opioid agonist
NARCAN
What is the reversal agent for anticholinergics (look it up)?
Physostigmine
What opioid agonist has the greatest context sensitive half life?
FENTANYL 260 min
Potency of Meperidine
1/10th as potent as morphine
Potency of Fentanyl
100 times more potent than morphine
Potency of SUFENTANYL
• 5-10 times more potent than fentanyl
Hydromorphone potency
8 times more potent then morphine
Tramadol Potency
5-10 times less potent analgesic than morphine
Alfentanyl Potency
1/5-1/10 less potent than fentanyl
Effect equilibration time of each opioid agonist?
Which one is fastest
FSAR (6.8,6.2,1.4,1.2) Fentanyl (6.8) Sufentanyl (6.2) Alfentanyl (1.4) Remifentanyl (1.1) FASTESt
Which opioid agonist can cause bradycardia? MFAS
Morphine
FENTANYL
Alfentanyl
Sufentanyl
Which opioid agonist can cause Tachycardia?
MEPERIDINE
What receptor is responsible behind the anti-shivering effects of opioid agonist?
KAPPA RECEPTORS (10% of drugs activity) (Dynorphins goes there FYI)
What area of the spinal cord has the greatest concentration of Mu receptors?
substantia gelatinosa (dorsal horn)
Morphine Metabolism
LIVER: Principle pathway is conjugation with glucuronic acid in hepatic and extra hepatic sites, MAINLY by the KIDNEYS (renal has significant metabolism)
Principle metabolites
Morphine -3-glucuronide (75-80%)Pharmacologically
inactive
Morphine Metabolite (POTENT)
Morphine-6-glucuronide (5-10%)-pharmacologically active more potent and longer duration of action than morphine
MEPERIDINE METABOLISM
LIVER:Hepatic metabolism is extensive, 90% metabolized to NORMEPERIDINE (demethylation) and meperidinic acid (hydrolysis)
Better excretion with acidic urine
Decrease renal function, may LEAD TO ACCUMULATION Of Meperidine and metabolites MAY INCREASE RISK OF SEIZURES
FENTANYL METABOLISM
Is metabolites pharmacologically active?
LIVER• Metabolized by N-demethylation, producing NORFENTANYL, which is structurally related to normeperidine
• Norfentanyl is excreted in the urine and
detectable for 72 hours after a single IV dose
–>NO
REMIFENTANYL- METABOLISM
Only opiod____________
Not affected by
UNIQUE metabolism
–> Only opioid NOT METABOLIZED IN THE LIVER
—> RENAL FAILURE
Ester linkage makes drug susceptible to hydrolysis by nonspecific plasma and tissue esterase’s
UNIQUE METABOLISM results in
1. Brevity of action
2. Rapid onset and short duration of action = precise and titratable effect
3. Non-cumulative effects
4. Rapid recovery after discontinuation of infusion
What are the different chemical groups for the opioid agonist?
SEMISYNTHETIC – From modified Morphine molecule: Codeine, Heroin, Hydromorphone, Oxycodone
CHHO
SYNTHETIC OPIOIDS -Contain nucleus of morphine but are manufactured by synthesis - rather than
modified morphine molecule: Fentanyl, Sufentanil, Alfentanil, Remifentanil, Methadone, Meperidine,
Tramadol
What are the different water solubilities of each opioid agonist?
water soluble is MMRCHT
Lipid solule is FAS
Morphine, Meperidine, Remifentanyl, Codeine, Hydrocodone, Tramadol, (WATER SOLUBLE)
Fentanyl, Alfentanyl, Sufentanyl (LIPID SOLUBLE)
Match each opioid agonist with the most likely receptor?
Mu 1, Mu2 agonist –>Endorphins, Morphine, Synthetic opioids
Meperidine- Demerol – Synthetic opioid agonist at mu & kappa opioid receptors
Morphine, Fentanyl – Mu receptors (1 and 2)
Sufentanil –active at Mu, also binds at delta and kappa
Remifentanil – selective Mu agonist
Tramadol - Centrally acting analgesic with a moderate affinity for mu receptor, weak kappa &
delta opioid receptor affinity
What are risk of naloxone administration?
What decreases risk of N/V?
–>N/V appear to be related to rate and dose given
Fortunately vomiting occurs simultaneously with
awakening which allows for pt to protect their
airway
–>Administration over 2-3 minutes
What is the time to peak for morphine IV/IM
• IV-15-30 minutes – rapid onset
• IM 45-90 minutes for peak effect
Remifentanil IV = 1.1 min (fastest onset)
Alfentanil: IV = 1.4 min, rapid onset
Sufentanil: IV = 6.2 min
Fentanyl: IV = 6.4-6.8 min (Stoelting says 6.8 min)
Analgesia, euphoria, respiratory depression associated with morphine are probably mediated mainly through this opioid receptor type:
Mu receptor
Tolerance develops to analgesia, euphoric, sedative,
depression of ventilation and emetic effects but not to
effects on
Miosis and constipation
What are common side effects of neuraxial narcotics?
- Pruritus (MOST COMMON face, neck upper thorax) Cephalad migration into CSF)
- Nausea/vomiting
- Urinary retention (most common in young males)
- Depression of ventilation
What is a metabolite of meperidine? Half time? what about patient with renal failure? Potency? What does it cause?
NORMEPERIDINE
• Elimination Half time of 15 hours
• Pt with renal failure half life may be >35 hours (can be detect in urine for 3 days)
Normeperidine is ½ as potent as meperidine as an
analgesic
Normeperidine causes CNS stimulation- toxicity manifests
as myoclonus and seizures- most likely during prolonged
meperidine administration as during PCA, especially with
renal function
What is a disadvantage of high dose fentanyl? 2 Ps
Possible awareness, postop ventilation depression
What are expected cardiovascular effects of morphine?,
BBOH
- ↓ BP can occur due to morphine induced bradycardia or
histamine release - Bradycardia due to ↑ activity over vagal nerves, stimulation of vagal nuclei in the medulla, also depressant effect on SA node and slowed conduction through AV node
- Opioids given prior to induction may slow heart rate during exposure to VA with/without surgical stimuli
- Histamine release and hypotension can be minimized by limiting the rate of administration to 5mg/minute IV,
maintain pt supine and well hydrate
What are expected cardiovascular effects of meperidine?
ROHM?
-Rarely causes bradycardia, may ↑ HR- good for pt
with bradycardia
- Orthostatic hypotension
- Hypotension more frequent and more profound
than with morphine
- More ventilatory depression than morphine
What are expected cardiovascular effects of Fentanyl? (NCCB)
1.No histamine release-no dilation of venous vessels to
cause hypotension
2. Carotid sinus baroreceptor reflex control of heart rate is
depressed by fentanyl
3. Chest wall rigidity
4. BRADYCARDIA more prominent than with morphine
What are expected cardiovascular effects of Alfentanyl?
Bradycardia
What are expected cardiovascular effects of Sufentanyl?
Chest wall rigidity, Bradycardia
Extra Morphine does not sensitize the heart to catecholamines or predispose to dysrhythmias as long as
hypercarbia or arterial hypoxemia doesn’t result from ventilatory depression
***Extra Morphine does not sensitize the heart to catecholamines or predispose to dysrhythmias as long as
hypercarbia or arterial hypoxemia doesn’t result from ventilatory depression
***EXTRA Rapid IV administration of opioids can cause
• Risk greatest with
Sufentanil may cause
skeletal muscle rigidity, especially the abdomen and thoracic area- leading to difficult ventilation
Fentanyl than remifentanil, than morphine
laryngospasm & ⇧ difficulty to ventilate
EXTRA Very short-acting;
REMIFENTANYL
eXtRA Principal alkaloid in opium (derived from opium poppy)
MORPHINE
What are signs symptoms of narcotic overdose
(MHC) ?
Triad of
Miosis
Hypoventilation
Coma should suggest NARCOTIC OVERDOSE
What are the TWO principal metabolites of MORPHINE? % and which active/inactive?
Morphine -3-glucuronide (75-80%)Pharmacologically
INACTIVE
• Morphine-6-glucuronide (5-10%)-pharmacologically ACTIVE more potent and longer duration of action than morphine
What are the principal metabolites of MEPERIDINE? active/inactive?
NORMEPERIDINE –> Active
What are the principal metabolites of FENTANYL? active/inactive?
NORFENTANYL –> Minimal pharmacological activity
Extra : Mixed agonist-antagonist:
NALBUPHINE
BUTORPHANOL
EXTRA Elimination of morphine glucuronide may be
impaired in_______ leading to_______
renal failure
accumulation of metabolites and unexpected
respiratory depression with small doses
EXTRA How does Meperidine reduce SHIVERING
Meperidine, through acting on an alpha type 2 adrenergic receptor, appears most effective among opioid agonists in reducing shivering.
EXTRA Repeated administration of this/these opioid may lead to seizures and tremor.
MEPERIDINE
EXTRA Only________ forms of the opioid exhibit
agonist activity
levorotary
EXTRA: Opiods Agonist MOA
Leads to
⇩intracellular cAMP concentration
⇩ Ca+ + ion influx and inhibits the release of excitatory
neurotransmitters (Glutamate, substance P)
DECREASE cAMP (both presynaptic and post synaptic)
EXTRA: All 3 classes of receptors
• All 3 classes couple to G proteins and subsequently inhibit adenyl cyclase,
⇩ conductance of voltage gated calcium channels or
open potassium channels
EXTRA The principal metabolic pathway associated with morphine metabolism is
conjugation (phase II metabolism)
Characteristics of Mu-1 receptors (MUHLE) Produces \_\_\_\_\_\_\_(\_\_\_\_and \_\_\_\_\_\_)
Mu1 – produces analgesia(Supraspinal & spinal) • Miosis • Urinary retention • Hypothermia • Low abuse potential • Euphoria
Agonists of Mu1 and Mu2 –> MES
Morphine
Endorphins
Synthetic opioids
Extra Characteristics of Mu-2 receptors (CHAsP)
Responsible for
Where is analgesia?
Mu2 –responsible for • Constipation- marked • Hypoventilation • Analgesia (spinal) • Physical dependence (addiction)
EXtRA Characteristics of Kappa Receptors
______ (__________and ______)
LADS -MD
- Low abuse potential
- Analgesia (supraspinal & spinal)
- Dysphoria
- Sedation
- Miosis
- Diuresis
Extra: Agonist of KAPPA is______
cause Inhibition of _________Via -________which resuts in ____
less________ but may cause _____And ______
What may be resistant to the analgesic effect of Kappa receptors?
Dynorphins- cause inhibition of neurotransmitter release via type N calcium channels which results in analgesia
•Less respiratory depression, but may cause diuresis and dysphoria
• High intensity painful stimulation may be resistant to the analgesic effect of kappa receptors
Extra: Where does Opioid agonist-antagonists often act principally ?
on kappa receptors
EXTRA Delta Receptors (PAVACU)
Analgesia where?
- Physical dependence
- Analgesia (supraspinal & spinal)
- Ventilatory depression
- Antidepressant effects
- Constipation- minimal
- Urinary retention
EXTRA -Inhibits release of excitatory neurotransmitters
Endorphins
FY*I Spinal cord ends at
L-1
Relieve PRURITIS with
Can relieve with opioid antagonist
EXTRA Risk of ventilatory depression with opiods increase with __________intrathoracic pressure
Increased intrathoracic pressure
EPIDURAL MORPHINE SHOULD BE
PRESERVATIVE FREE
Morphine is better for _____than ____pain
dull pain; sharp pain
X_TRA: MORPHINE Respiratory acidosis(hypoventilation) will decrease the
non ionized portion but may lead to
higher CNS concentrations due to ↑ cerebral blood
flow due to the ↑ carbon dioxide levels
Morphine vs Fentanyl
Morphine accumulates rapidly in the (3) and unlike fentanyl does
kidneys, liver and skeletal muscles
not undergo significant first pass effect into the lungs
XTRA important• CV- high doses (_______)to supine
normovolemic patient is UNlikely to cause a_________
• Change from supine to standing may cause
• Caused by impairment of______
• Decrease in vasomotor tone leads to ________ ,_______ and ________
(1mg/kg IV)
direct myocardial depression or hypotension
hypotension and syncope
compensatory sympathetic nervous system response
decreased preload,
cardiac output and blood pressure
eXTRA • Ventilatory depression can result in the baby as a
result of giving mom opioids- so give ________
• Morphine causes greater neonatal depression in
the neonate then Meperidine
• May be a result of an____________
• Chronic opioid use by the mom may result in__________________
give after delivery
immature BBBphysical dependence (intrauterine addiction)
• Administration of naloxone may cause life
threatening
neonatal abstinence syndrome
Initial symptoms of withdrawal include (IRDYL)
•
Insomnia Restlessness Diaphoresis Yawning Lacrimation, or coryza
Prevention of Withdrawal
CLONIDINE
Best suited for providing analgesia especially for short surgical procedure and also when rapid recovery is beneficial.
REMIFENTANYL
OPIODS OD and eyes
MIOSIS
Unless hypoxemia –> MYDRIASIS
Narcan dose
Naloxone 0.4-2mg every 2-3 minutes as needed
____ , ____,____,_____are analogues of Meperidine (FARS)
Fentanyl
Alfentanil
Remifentanil
Sufentanil
• Principally for analgesia during labor and delivery
and after surgery
MEPERIDINE
Fentanyl
Single IV dose-more rapid onset and shorter
duration of action than morphine due to its rapid
redistribution to inactive tissues ( fat, skeletal
muscle)
Low dose fentanyl
• Low dose 1-2 mcg/kg
High dose fentanyl
50-150mcg/kg SURGICAL ANESTHESIA
Doses of SUFENTANYL
0.1-0.4 mcg/kg
Metabolism of this opioid is dependent neither on liver metabolism or renal excretion:
REMIFENTANYL
FASTER ONSET Of activity
REMIFENTANYL
Inappropriate for POST OP analgesia control
REMIFENTANYL
REMIFENTANYL Anesthesia induced with_______over 60-90 seconds or with gradual initiation of infusion at________
for about 10 minutes, before a hypnotic prior to tracheal
intubation
1mcg/kg IV ;0.5-1.0 mcg/kg IV
Meperidine causes
Mydriasis and elevated HR
What is the reason there is rapid effect site equilibration of ALFENTANYL?
due to low pKa90% of drug is non-ionized at physiologic pH
Effect equilibration time of Alfentanyl
1.4 min
Opioid more susceptible to CYP450 function
Alfentanyl
