Opioids Flashcards
Morphine
Naturally occurring Opioid
Analgesis
Uses;
- analgesia
- anesthesia adjunct for induction or maintenance
- Acute or chronic severe pain
MOA;
- Binds to Mu opioid receptors and inhibits pain pathways and alters perception and response to pain
- mimics endogenous substances (enkephalins, endorphins and dynorphins at opioid receptors and cause decreased NT release (substance P), Increases K conductance (hyper polarizes)
- At the SC morphine de creases the release of substance P decreasing the transmission of nociceptive impulses
Dose;
- “Pain 1 - 5 mg q 2 -5 min” Dr. Bowman
- Analgesic; 0.01 - 0.02 mg/kg
- Adjunct anesthesia; up to 2mg/kg
- infusion; 0.8 - 10 mg/hr
Pharmacokinetics;
- onset; 15 - 30 min
- E1/2time; 1.5 - 3 hrs
- DOA; 4 hrs
- Vd; 3 - 4 L/kg
- Pb; 35%
- 23% nonionized
metabolism;
-kidneys play a role in metabolism (increased rates of renal metabolism can be seen with impaired liver metabolism)
-conjugated in the liver into
metabolites
-ACTIVE metabolite; Morphine 6-glucuronide (5 -10%) which is more potent than morphine
elimination;
- 1 - 10% excreted unchanged in urine by kidneys
- 7 - 10% in feces
Side Effects; CV; -histamine release -hypotension -bradycardia (direct action on vagus nerve)
Resp;
- Resp depression (delayed)
- depressed cough reflex
CNS;
- sedation/ drowsiness/confusion
- skeletal muscle weakness
- miosis (decreased pupil size)
GI/GU;
- N/V/ constipation
- urinary retention
Contraindications;
- hypersensitivity
- severe respiratory depression
- severe asthma (histamine release)
- increased ICP
- ileus
- Avoid in renal dysfunction
caution; delayed respiratory depression possible, particularly with epidural and intrathecal administration; monitoring is important
Meperidine (Demerol)
Synthetic Opioid Phenylpiperidine derivative Analgesic Narcotic 1/10th the potency of morphine
Uses;
- moderate/ severe pain
- anesthesias adjunct
- pre-op sedation
- post-op shivering
- analgesia after surgery (weak LA properties when injected perineurally, cause analgesia)
- antispasmodic effects
MOA;
-Agonist at Mu & Kappa opioid receptors, inhibitor of pain pathways, alters perception and response to pain, and causes generalized CNS depression
Dose; 75 - 100 mg
post op shivering; 12.5 - 50 mg IV
Pain; 5mg IV q 5min
*do not exceed 1000mg/24 hrs r/t increased risk of seizures (normeperidine)
Reversal; Naloxone (Narcan)
2mg IV up to 10mg
Pharmacokinetics;
- onset; 10 min?
- E1/2 time; 3 -5 hours
- DOA; 2 - 4 hours
- Pb; 70%
- Vd; 3.5 - 5 L/kg
- 7% nonionized
metabolism;
- 90% metabolized by hepatic enzymes into
- active metabolite Normeperidine
- first pass uptake by lungs is 65%
elimination;
-pH dependent urinary excretion; lower urine pH more excreted unchanged
Side Effects CV; -orthostatic hypotension -increased HR -histamine release; and higher doses can cause more hemodynamic instability
Resp;
-respiratory depression (may be more severe than morphine)
CNS;
- fatigue/ drowsiness/sedation
- confusion/ hallucinations
- increased ICP
- risk of seizure (normeperidine)
- skeletal muscle weakness
GI;
- N/V/constipation
- biliary spasm
GU;
-urinary retention
Contraindication;
-MAOis
Caution;
- repeated doses of meperidine is not recommended
- crosses placenta
Hydromorphone (Dilaudid)
Opioid
Uses;
- adjunct anesthetic to provide analgesia for induction and maintence
- Post-op pain relief
MOA;
-mimics endogenous opioids at the Mu 1 and 2 opioid receptor alters pain pathways and perception of pain to produce analgesia
Dose; -0.5 - 2mg IV q 2 - 6 hours -"0.25 - 0.5 mg q 2-5 min for pain" Dr. Bowman *5x more potent than morphine (more sedation, less euphoria) Pharmacokinetics; -onset; <30 min -peak; 5 - 10 min -E 1/2 time; 2.3 hours -DOA; 2 - 4 hours -Vd; 302.9 L -Pb; 8 - 19%
metabolism;
in the liver by glucuronidation
eliminated;
excreted inuring by kidney only small amounts excreted unchanged
Side Effects;
- Respiratory depression
- decreased respsone to hypercarbia and hypoxia
- decreased cough reflex
- Decreased BP
- dose dependent bradycardia
- decreased CBF and ICP
- N/V/ constipation
- urinary retention
- sphincter of oddi spasm
Contraindications;
- hypersensitivity
- pregnancy
caution with respiratory depression
Fentanyl
Synthetic phenylpiperidine
opioid agonist
analgesic
100x more potent than morphine
Uses;
- intra and post-op analgesia
- blunt SNS response to airway manipulation
- reduce MAC of VA
- GA; as sole agent or in combo
- Regional anesthesia
MOA;
-binds to Mu opioid receptors in the brain and spinal cord producing analgesia and mimics endogenous opioids (endorphins, enkephalins and dynorphins) activating the antinociceptive system; hyper-polarizes the cell and blocking release of NT
Dose; 100x more potent than morphine -Premed; 25 - 100 mcg -GA; alone; 50 - 150 mcg/kg -TIVA; mild/moderate stim; 1 - 5 mcg/kg mod/severe (plan to extubate) 5 - 10 mcg/kg (stay intubated) 5 - 50 mcg/kg
Narcan 2mg IV; max 10mg to
Pharmacokinetics; -onset; 5 - 10 min (effect site equilibrium 6.8 min) -E1/2t; 3 - 6.5 hrs -DOA; 60 min (contact sensitive 1/2 time 260 min; turn got off 45 min before case ends) -Vd; 4 L/kg -Pb; 80% -8.5% nonionized
metabolism; by liver and is dependent on blood flow
75% first pass pulmonary uptake
excretion; <10% excreted unchanged in urine
-can be detected in urine 48-72 hrs after administration
Side Effects; CV; -bradycardia -hypotension -arrhythmia Resp; -resp depression -depressed airway reflex -decreased response to hypercarbia and hypoxia CNS; -risk of increased ICP in head trauma if respiration not controlled -muscle rigidity -miosis -sedation/ confusion/ CNS depression GI; -N/V/ delayed gastric emptying
Contraindications; -hypersensitivity -fast push; can cause right chest Caution; -impaired liver/ kidney function -head trauma/ increased ICP -bradyarrhythmias -N20 CV depression with large doses of fentanyl
Remifentanil
Synthetic opioid
phenylpiperidine derivative with an ester link (ultra rapid metabolism)
100x more potent than morphine
(potency similar to fentanyl)
Uses;
- analgesia during GA for quick on and off desired effect
- Blunt SNS response (intubation, airway manipulation, tourniquet pain)
MOA;
-Binds to opioid receptors and mimics endogenous opioids (endorphins, enkephalins and dynorphins) hyperpolarizing (increased K conductance) and decreasing release of NT (substance P, epi, NE, acetylcholine) alters pain pathways and interpretation pain, increases pain threshold
Dose;
induction; 0.5 - 1 mcg/kg over 1 min
infusion; 0.05 - 2mcg/kg/min (in combo with VA or propofol)
Narcan 2mg to reverse
Pharmacokinetics;
- onset; 1 - 3 min
- E1/2t; 10 min
- DOA; 7 -12 min
- Vd; 0.3 - 0.5 L/kg
- Pb; 60- 90%
- 60% nonionized
metabolism; rapid metabolism by nonspecific plasma and tissue esterase
elimination; excreted by kidneys
accumulation is rare internal or liver dysfunction
metabolism NOT effected by cholinesterase deficiency
Side Effects;
- dose dependent respiratory depression
- slight hypotension and bradycardia
- decrease CBF and CMR02 at higher doses
- dizziness/ headache/agitation
- N/V
- delayed gastric emptying
Contraindications;
- Pregnancy (class C)
- hypersensitivity
Caution;
decrease dose in Elderly by 50% (decreased clearance and Vd and increased potency)
Alfentanil
Synthetic Opioid Tetrazole derivative of Fentanyl (rapid onset analgesic) 10 - 20x more potent than morphine 1/5th the potency of morphine
Uses;
-Analgesia for noxious stim thats acute and transient
(intubations, performance of retrobulbar block)
-Analgesic adjunct in maintenance of anesthesia
-Induction and maintenance of cardiac anesthesia at high doses
MOA;
-Binds to Mu opioid receptors and hyper-polarizes the cell, decayers release of NT and blocks nociceptive (pain) pathways, alters response to pain and increases threshold for pain
Dose; analgesic; 5 - 30 mcg/kg induction; 50 - 200 mcg/kg (cardiac OR) Maintenance infusion with VA; 25 - 150 mcg/kg/hr
Reversed with Narcan 2mg IV
Pharmacokinetics;
- onset; RAPID (1.4 min)
- E1/2t; 90 min
- DOA; 30 - 60 min
- context sensitive 1/2 time 60 min
- Vd; 0.45 L/kg
- Pb; 92%
- 90% nonionized
-context sensitive 1/2 time (60 min) can be longer for infusions up to 8 hrs, despite short E1/2 time; might not be best choice for infusions for ambulatory surgery sedation
metabolism; by the liver
(96% of alfentanil cleared from plasma within 60 min of administration)
Elimination; <0.5% excreted unchanged by kidney
Side Effects;
- respiratory depression
- more hypotension then fentanyl; administers slowly
- HR generally unchanged
- muscle rigidity
- generalized slowing of EEG
- increased CSF fluid pressure in pt with brain tumors
- N/V
Contraindication;
- Rapid administration can cause skeletal muscle and chest wall rigidity, impairing ventilation
- Increased ICP
- Severe respiratory depression
Caution;
Parkinson’s disease; can decrease central dopaminergic transmission
Sulfentanil
Synthetic Opioid
Phenylpiperidine derivative
1000 x more potent than morphine
10x more potent than fentanyl
Uses;
- analgesia adjunct for anesthesia
- can be used as sole anesthetic or in combo
Dose;
- analgesia; 0.1 -1 mcg/kg
- > 2mcg/kg not compatible with immediate post op extubation
- 8 - 50 mcg/kg with 100% O2 with muscle relaxant produces anesthesia sole anesthetic
Reversed with Narcan 2mg
MOA;
Binds to opioid receptors and mimics endogenous opioids (endorphins, enkephalins, dynoprhins) and hyper polarizes and deceases release of NT. Blocks the nociceptive (pain) pathway, alters response to pain and increases threshold, also causes sedation
Pharmacokinetics;
- onset; 1 - 3 min
- E1/2t; 2.5 - 4 hours
- DOA; 30 min
- Vd; 3 L/kg
- Pb; 93%
- 20% nonionized
metabolism occurs in liver and small intestine
excreted only 2%unchanged by kidney
Side Effects;
- respiratory depression
- bronchospasm
- CV effects vary; can have hyper/hypotension, Brady or tachycardia
- confusion/ sedation
- chest wall rigidity
- N/V/constipation
- biliary spasm
- urinary retention
Contraindications;
- hypersensitivity
- paralytic ileus
caution;
- severe respiratory disease/ airway obstruction
- renal and liver disease
Reduce dosing in elderly
Naloxone (Narcan)
Nonselective Competitive Opioid receptor antagonist
Uses;
-Reversal of opioid induced respiratory depression
MOA;
-blocks all opioid receptors and displaces all opioids from receptors
Dose;
0.1 - 2mg IV up to 10mg
Pharmacokinetics;
- onset; 1 - 2 min
- E1/2t; 1 - 1.5 hrs
- DOA; 30 - 60 min
metabolized by the liver
excreted by the kidneys
Side Effects;
- PULMONARY EDEMA
- hypertension
- tachycardia
- pain
- irritability/restless/seizure
- N/V/ diarrhea
Contraindications;
-pregnancy
Caution;
-CHF (r/t pulmonary edema)
