Opioids/Pain Flashcards
Meperidine
Meperidine
Class: synthetic opioid agonist, phenylpiperidine derivative with 1/10 the potency of morphine.
MOA:
Agonist at mu and kappa and inhibits either cAMP or IP3, increasing the conductance of potassium to hyperpolarize the membrane or decreasing the condutance of calcium to prevent neuronal transmission. Presynaptically, will work to decrease exocytosis of excitatory neurotransmitters, post synaptically will hyperpolarize membrane. Overall increasing pain treshhold, altering pain perception, and inhibiting ascending pain pathways.
PK:
Onset: 10 minutes
DOA: 2-4 hours
E1/2T: 3-5 HOURS
PB: 70% - high
vD: 3.5 - 5 L/kg - large
pKa: 8.5 - low lipid solubility 10% nonionized in blood
metabolized by liver to active metabolite normoperidine (50% potency, longer E1/2t), and excreted in urine.
Normoperidine is a neuro irritant and can cause myoclonus and seizures with accumulation.
dose:
50-100 mg IV
12.5 mg IV for shivering
Max dose: 1g/24 hours
SE:
Meperidine is a HISTMAINE releaser -
tachycardia, hypotension, flushing, bronchospasm.
Meperidine also has an atropine like structure and can cause tachycardia via this method as well, but is a direct myocardial depressant.
Euphoria / Sedation
N/V/constipation
urinary retention, pruritus, dry mouth, biliary spasm
DOSE DEPENDENT RESP. DEPRESSION, decrease RR, increase tV
C/I:
Resp. depression
asthma / COPD / r/t r/f bronchospasm
caution with seizure hx
caution with renal failure. - decrease dose
caution with CAD r/t increase in HR
C/I in MAO-Is - r/f serotonin syndrome
Morphine
Morphine
Endogenous opioid agonist, naturally occuring.
MOA:
Binds to mu, kappa, delta receptors and inhibits adenylate cyclase and IP3. At presynaptic neurons it decreases condutance of calcium and prevents exocytosis of excitatory neurotransmitters. Post synpatically is increases potassium conductance to hyperpolarize membrane. Overall it increases pain threshhold, alters pain preception and inhibits ascending pain pathways.
Pk:
onset: reaches peach within 15 to 30 minutes.
DOA: 3 hours
E1/2t: 3-4 hours
PB: 30%
vD: 3L/kg
pKa: 7.9 - poorly lipid soluable, 23% nonionized at physiologic ph.
Metabolized by liver to morphine-3-gluconaride and morphine-6-gluconaride. M3G is less active, M6G is active, 65 more potent than original drug. Metabolites are excreted 10% unchanged in urine, feces.
Dose:
0.01 to 0.02 mg/kg IV for analgesia
SE:
Morphine is a histamine releaser, can cause bronchospasm, hypotension, flushing.
Morphine also inhibits SA/AV node and acts directly on vagal nerve to produce bradycardia.
Can also have dose dependent decrease in HR, BP, SVR.
Dose dependent respiratory depression with decrease rr and increase tv at low doses and decreases in both at higher doses.
Sedation/europhia
urinary retention/pruritus/dry mouth
N/V/constipation
C/I:
resp depression/sedation
Renal insufficiency r/t accumulation of M6G
COPD/ASTHMa r/t bronchospasm
paralytic ileus
has synergistic hypnosis and resp. depression effects with benzos and other CNS depressants
Fentanyl
Fentanyl
Synthetic opioid agonist with 100x the potency of moprhine.
Phenylpiperidine derivative.
MOA: Binds to opioid receptors mu, kappa, delta and inhibits adenylate cyclase or phospholipase C. Presynaptically decreases the conductance of calcium preventing exocytosis of excitatory neurotransmitters. post synaptically increases the condutance of potassium, hyperpolarizing the membrane. Increases pain treshhold, alters perception of pain, and inhibits ascending pain pathways.
Pk:
onset: fast, effect time 6.4 minutes
DOA: 1 hour
E1/2T: 3-6 hours
context sensitive half time - longer 260 minutes
PB: high 80%
vd: 4 L/kg
pKa 8.4 - 8% nonionized at physiological pH
75% first pass pulmonary uptake
metabolized by liver, has weak metbaolite of NORFENTANIL. Clearance is dependent on hepatic blood flow.
dose:
1-2.5 mcg/kg for analgesia, SNS attenuation
25-100 mcg PRN during surgery for stim
SE:
Chest wall rigidity, rigidity of chest wall muscles and of larynx
Bronchospasm
Urinary retention, dry mouth, pruritus, biliary spasm
N/V/Constipation
euphoria, sedation, analgesia*
dose dependent resp. depression -decrease rr increase tv at low doses, decrease both at higher doses.
Blunts SNS response to DVL
C/I:
sedation, resp. depression
hepatic disease
head trauma if not ventilated,
caution with gallbladder disease,
synergistic hypnosis and sedation with benzos and CNS depressants.
Sufentanil
Sufentanil
Onset: fast, effect time = 6.2 min
DOA: 30 minutes
E1/2t: 2 - 2.5 hours
context sensitive half time: 30 minutes
PB: 90%
VD: 3L/kg
pKa 8.0 – 20% nonionized at 7.4
regarded as highly lipid soluble
metabolized by the liver, small intestine, into weakly active desmethylsufentanil, excreted in urine also has 75% first pass pulmonary uptake and is subject to 2nd peak effect
dose:
0.1 to 0.3 mcg/kg IV
SE:
rigid chest wall, especially at high dose. Muscle rigidity of the chest muscles and also the larynx, bronchospasm.
euphoria, sedation, analgesia
dose dependent resp. depression, decrease in rr, increase in tv until higher doses than decrease in both.
N/V/Constipation / biliary spasm
urinary retention, dry mouth, pruritus,
dose dependent decrease in hR, BP, SVR
blunt SNS response to DVL
C/I:
resp. depression, sedatoin
caution in asthma - r/f bronchospasm
synergistic hypnosis, edation with benzos or other CNS depressants,
caution in hepatic and renal disease
Alfentanil
Alfentanil
Tetrazole derivative of fentanyl. Synthetic opioid agonist.
10-20x the potency of morphine. - weaker than fentanyl, sufentanil, remi
Pk:
onset: rapid 1.4 minute effect time
DOA: 30-60 minutes
E1/2T: 1.5 hours
context sensitive e1/2time - 60 minutes
PB: High 90%
vD: 0.4 l/kg- small
pKa: 6.5 - 90% noninoized which is why it has ar apid onset.
Metabolized by liver and small intestine and excreted in the urine.
dose:
50-200 mcg/kg
SE:
Can have rigid chest syndrome, less likely than sufentanil and fentanil
analgesia/euphoria/sedation
n/V/Constipation - biliary spasm.
dry mouth, urinary retention, pruritus
MINIMAL CHANGE IN HR, BP, SVR
dose dependent resp depression
C/I:
PARKINSONS - can decrease dopaminergic transmission
resp depressoin/sedation
increase ICP
synergistic hypnosis and sedation with other CNS depressants/benzos
Remifentanil
Remifentanil
Class: phenylpiperidine derivative, synthetic opioid agonist WITH ESTER LINKAGE.
MOA:
Opioid agonist at mu, kappa, delta. Mimics endogenous opioids, binds to receptors and presynaptically decreases calcium condutance, preventing exocytosis of excitatory neurotransmitters, postsynaptically increases potassium conductance hyperpolarizing membrane. Works to increase pain thresshold, alter pain perception, and inhibit ascending pain pathways.
Pk:
onset: immediate
DOA: 7-12 minutes - shortest
E1/2t: 10 minutes
metabolized by tisse and plasma esterases to inactive metboalites.
Dose:
1-2 mcg/kg
SE;
Analgesia, euphoria, sedation
dose dependent resp depression, decrease RR, increase TV then decrease in both
urinary retention, dry mouth, pruritus, SOO spasm.
Dose dependent decrase in HR, SVR, BP
c/i:
resp. depression, sedation
not used in epidurals r/t glycine in prep
can cause opioid induced hyperalgesia with d/c, must have post-op pain plan
synergistic hypnosis and sedation with other CNS depressants and benzos
Hydromorphone
Hydromorphone
class: semi-synthetic opioid agonist, derivative of morphine, 5x more potent than morphine
Mimics endogenous opioid action at mu receptors, binds to receptor, presynaptically decreases calcium conductance decreasing exocytosis of excitatory neurotransmitters. Post synaptically increases potassium conductance, hyperpolarizing membrane. Raises pain thresshold, alters pain perception, inhibits ascending pain pathways.
Pk:
Onset: immedate
peak: 5-10 minutes
DOA: 4-5 hour
E1/2T: 1-3 hours
Significant first pass when given PO. Metabolized by liver to hydromorphone-3-gluconaride, inactive metabolite. Excreted in urine.
DOSE:
1-4 mg IV q4-6
SE:
Analgesia, euphoria, sedation - more sedation and less euphoria than morphine
dose dependent resp. depression
dose dependent decrase in HR, BP, SVR
urinary retention/ pruritus / dry mouth.
N/V/constipation / biliary spasm
C/I:
resp depression/sedation
synergistic sedation/hypnosis with benzos/ other CNS depressants
Ketorolac
Ketorolac
Class: Non selective non-steroidal anti-inflammatory drug
MOA: Inhibits cycloxgenase 1 and 2, prevents the conversion of arachanidonic acid to prostaglandins, prostacyclin, and thromboxane. Anti-inflammtory, anti-pyretic, and provides analgesia. Only IV NSAID available.
Pk:
Onset: 10 minutes
DOA: 6-8 hours
E1/2T: 5 hours
PB: 99%
Metabolized by liver to glucuronic acid and 60% excreted in urine
Dose:
30 mg IV q 6 hours
MAx dose 120 mg / 24 hr
do NOT exceed 5 days of use
half dose in elderly population
SE:
Bronchospasm
Prolonged bleeding
GIB/ulcerations
renal toxicity, acute renal failure
impaired bone healing
reduces the effects of diuretics, BB, and ACE-I
increased risk of bleeding with other co-ags
C/I:
asthma
ASA allergy
renal failure
liver failure
GIB
co-agulopathies
pregnancy 3rd trimester
Acetaminophen
Acetaminopehn
Non-opioid analgesic, anti-pyretic, central anti-prostaglandin effects
MOA:
NMDA receptor antagonist in CNS
Substance P receptor antagonist in spinal cord
Desensitizes TRPA channels and blocks influx of Ca and Na
LAcks peripheral effects which is what make its a weak anti-inflammatory
Pk:
IV peak: 15 minutes
PO peak: 30-60 minutes
IV has a higher peak, occurs sooner
max rever reduction in 30 minutes
CONJUGATED IN liver and excreted unchanged in urine.
Dose:
IV: 1g over 15 mintues q 4-6 hours
PO: 325 - 650 mg q 4-6 hours
Do NOT exceed 4 g/day
SE:
OD = liver exhausts supply of glutathione -liver failure
increases r/f hepatoxicity with isoniazid
can lead to renal damage r/t cumulative build up of metabolites but still less toxic than NSAIDs for kidneys
C/I
liver dx
renal dx
hepatitis
alcoholic cirrhosis - must decrease dose
