Acute Pain - Drugs - Exam 2 Flashcards
1
Q
A
2
Q
What are long-term Opioid options? (7)
A
- codeine (Tylenol #3)
- fentanyl (duragesic patch)
- hydrocodone (lortab, vicodin)
- hydromorphone (dilaudid)
- methadone (dolophine)
- morphine (MSIR, MScontin, Kadian)
- oxycodone (OxyIR, Percocet, Percodan, Oxycontin)
3
Q
Codeine
What is the chemical name?
What is it derived from?
It has a substitution of ____ group for ____ group on #3 carbon of morphine.
A
3-methyloxymorphine
- derived from opium poppy plant (papaver somniferum)
- methyl group for hydroxyl group
4
Q
Codeine
Receptors:
A
- Mu opioid
- weak kappa/delta
5
Q
Codeine
Codeine is more reliably ________ ________ than morphine.
A
absorbed orally
6
Q
Codeine
Codeine is admin as a ________.
It is metabolized by what enzyme? (active state)
what enzyme metabolizes codeine to the inactive state?
A
- prodrug
- CYP2D6 = morphine (active)
- CYP3A4 = norcodeine (inactive)
7
Q
Codeine
Why is there variability in analgesic effects w/ codeine?
A
- > 50 polymorphisms in CYP enzymes
- don’t give to children < 12y/o - they will only get the SE and no pain relief
8
Q
Codeine
Adult dose:
max dose:
How much codeine does Tylenol # 3 have?
Tylenol # 4?
A
- 15-60 mg q4h
- max: 360mg/d (4-6 doses)
- # 3 - 30mg
- # 4 - 60mg
9
Q
Codeine
Pedi dosing
max:
A
0.5-1mg/kg
Max: 60mg
try to avoid giving
10
Q
Codeine
At what dose of codeine do you get the max analgesic effect?
What med & dose is this comparable to?
A
60 mg
Aspirin 650mg
11
Q
Codeine
Half-life
A
3-3.5hrs
12
Q
Codeine
Drug Interactions
A
- opiods
- alcohol
- anticholinergics
13
Q
Codeine
Adverse/SE (8):
A
- n/v
- brady
- hypotension
- resp. depression (lg. doses)
- urinary retention
- constipation
- dizziness
- miosis
14
Q
Codeine
Contraindications
A
- hypersensitivity
- acute/severe asthma (histamine release = bronchoconstriction)
- paralytic ileus
15
Q
Tramadol
What is the chemical name?
- composed of a racemic mixture w/ a ____ and ____ enantiomer.
A
- Synthetic 4 phenylpiperidine analogue of morphine & codeine
- + and - enantiomer
16
Q
Tramadol
MOA of the + enantiomer:
A
- centrally acting opioid agonsit
- mod. affinity @ Mu
- weak Kappa/delta
- opposes serotonin reuptake
17
Q
Tramadol
MOA of the - enantiomer:
what are the effects of this?
A
- inhibits NE reuptake
- stimulates a2 receptors
- effects: BP issues, potentiate precedex
18
Q
Tramadol
Metabolism:
active metabolite:
potency:
A
- CYP2D6 & CYP3A4
- O-desmethyltramadol
- 2-4x potent as tramadol (less potent than morphine)
19
Q
Tramadol
Potency compared to morphine
A
1/5-1/10 as potent as morphine
20
Q
Tramadol
Onset:
A
1-2 hrs
21
Q
Tramadol
Half-life:
A
- tramadol: 6.3hrs
- metabolite: 7.4hrs
22
Q
Tramadol
PB:
A
20%
23
Q
Tramadol
Vd:
A
2.6-2.9L/kg
24
Q
Tramadol SE/Precautions
Major Contraindication:
high incidence of:
A
- do NOT give in pts w/ seizure disorders
- high incidence of n/v
25
# Morphine
Who was morphine named after?
Morpheus the Greek God of Dream
26
# Morphine
What preparations is Morphine available in?
* immediate and sustained release
* elixir
* suspension
* tablets/capsules
* epidural/intrathecal
27
# Morphine
Oral dose:IM/IV dose
* oral dose 3x more
* oral - 30 mg
* IV/IM - 10 mg
28
# Morphine
Receptor Effects:
Mu 1 & Mu 2
29
# Morphine
Metabolism:
active metabolites and effects
* conjugation (glucuronic acid) w/ hepatic & extrahepatic sites (kidneys)
* **morphine-6-glucuronide: analgesia**
* **morphine-3-glucuronide: neurotoxicity & hyperalgesia**
30
# Morphine
What are the 3 reasons why morphine has **minimal absorption into the CNS**?
1. poor lipid solubility
2. high PB%
3. high degree of ionization @ physiologic pH
31
# Morphine
PO dose & onset:
* PO: 30-60mg
Onset: 30min - 1hr
32
# Morphine
IV dose & onset:
* IV dose: 2.5-15mg
* IV onset: 15 min
33
# Morphine
IM dose:
IM onset:
IM dose: 10-15 mg
IM onset: 20 min
34
# Morphine
Peak:
Duration:
* peak: 45-90 min
* duration: 4-5 hrs
35
# Morphine
E 1/2 time:
1.7-3.3 hours
36
# Morphine
Does morphine have greater analgesia potency and slower offset in men or women?
Women
37
# Morphine
% PB
Vd
* % PB - 35%
* Vd - 224L/kg
38
# Morphine
What pt population should morphine be **avoided in** and why?
* renal impairment
* morphine-6-glucuronide accummulation = resp. depression
39
# Morphine
Side Effects:
* sedation
* resp. depression
* constipation, n/v
* **HISTAMINE RELEASE - acute use**
* euphoria
* tolerance/dep.
40
# Oxycodone
What 2 formulations is it available in?
* intermediate release
* controlled release
41
# Oxycodone
Science:
It is a ________ derivative of ________.
Made alone or in combo with ________, ________, or ________.
* semi-synthetic derivative of thebaine
* Acetaminophen, aspirin, ibuprofen
42
# Oxycodone
What 2 main conditions is oxy used for?
* neuropathic pain
* chronic pain
43
# Oxycodone
Metabolism:
Admin as a ________.
Metabolites (2)
Oxy has an extensive ________, and is excreted in the ________.
* metabolized in liver (CYP2D6)
* admin as a prodrug
* Metabolites:
**oxymorphone - active**
**noroxycodone - inactive**
* extensive 1st pass effect
* excreted in urine
44
# Oxycodone
What receptors does oxy work on?
* Mu & Kappa in CNS
45
# Oxycodone
Dosing:
morphine equivalence:
5mg PO
* 10-15mg of Oxy = 10mg morphine
46
# Oxycodone
Onset:
Duration:
* Onset: < 1 hr
* Duration:
**IR: 3-4hrs
CR: 12 hrs**
## Footnote
allows pt to get to steady state and remain there
47
# Oxycodone
Half-life
IR:
CR:
* IR: 3 hrs
* CR: 4.5hrs
48
# Oxycodone
PB %
Vd
* % PB - 45%
* Vd - 2.6L/kg
49
# Oxycodone
Interactions/SE
**additive effects w/ other CNS depressants**
* sedation, resp. depression
* constipation, n/v
* **histamine release**
* euphoria
* tolerance/dep. (less)
50
# Methadone
Methadone is a synthetic ________ opioid and mixed ________ - ________.
* synthetic broad-spectrum opioid
* mixed agonist/antagonist
51
# Methadone
MOA/receptors:
* weak, non-competitive NMDA receptor antagonist
* serotonin reuptake inhibitor
* monoamine transmitter reuptake inhibitor
* mu receptor activity
52
# Methadone
what is methadone most commonly used for?
What drug properties make it ideal for this use?
* maintenance drug for opioid addiction
1. oral bioavailability (60-95%)
2. high potency
3. long DOA
53
# Methadone
Metabolism
Increased by:
Decreased by:
Excretion:
* liver - CYP3A4, CYP1A2, CYP2D6
* increased - inducers (carbamazepine)
* decreased - antiretrovirals & grapefruit juice
* excretion - urine & bile
**safe for elderly - hepatic/renal impairment don't influence clearance much**
54
# Methadone Dosing
How long will it take to reach steady state?
Half-life:
* up to 10 days
* half-life **variable 8-80hrs**
55
# Methadone
Dose:
Routes:
* 2.5-10mg
* PO, IM, SQ
* q4-12hrs
**10mg go to dose = 12 to 24hrs pain control for 1 dose**
56
# Methadone
What 3 things can increase the concentration/effects of methadone?
1. ciprofloxacin
2. diazepam
3. ethanol (acute)
57
# Methadone
What 4 things can decrease the concentration/effects of methadone?
1. amprenavir
2. phenobarbital
3. phenytoin
4. rifampin
**severe, unpredictable reactions w/ MAOIs**
58
# Methadone
SE
* similar to others
* resp. depresison
* hypotension
* confusion/sedation
**rare: brady, QT prolongation, torsades de point**
59
# Fentanyl Science
A ________ derivative synthetic opioid.
Structurally r/t what drug?
* pheynylpiperidine
* Meperidine
60
# Fentanyl
Metabolism:
Metabolites (3)
* metabolism: CYP450 - N-demethylation
* Metabolites:
**Norfentanyl, hydroxyproprionyl-fentanyl, hydroxoyproprionyl-norfentanyl**
61
# Fentanyl
How long can **norfentanyl** be detected in the urine after a single dose?
72 hrs
62
# Fentanyl Dosing
IV dose:
IV onset:
IV half-life:
* dose: 50-100mcg
* Onset: 5-10min
* Half-life: 30min-1hr
63
# Fentanyl Dosing
PNB dose:
10mcg
64
# Fentanyl Dosing
Transdermal Dose:
TD onset:
TD half-life:
* dose: 12.5-100mcg
* onset: 12-24hr
* half-life: 20-27hr
65
# Fentanyl Dosing
Transmucosal Dose:
TM onset:
TM half-life:
* Dose: 200-1600mcg
* onset: 6-15min
* half-life: 2-12hr
66
# Fentanyl
E 1/2 time:
* 3.1-6.6 hours
67
# Fentanyl
Why does **Fentanyl** have a greater potency & more rapid onset compared to **morphine?**
* greater lipid solubility of Fentanyl
68
# Fentanyl
Why does **fentanyl** have a shorter DOA w/ a single dose?
1. rapid redistribution to inactive tissue (fat, skel. muscle)
2. 75% of initial dose undergoes 1st pass pulmonary uptake
69
# Fentanyl
PB % -
Vd -
* % PB - 84%
* Vd - 335L
70
# Fentanyl
Interactions/SE
**additive effects w/ other CNS depressants**
* sedation/resp. depression
* constipation/n/v
* histamine release
* euphoria
* tolerance & dependence
71
# Hydromorphone Science
A synthetic drug and ________ ________ of analogue of morphine.
Can be formed by N-demethylation of ________.
* hydrogenated ketone
* hydrocodone
72
# Hydromorphone
What forms is hydromorphone available in?
What are their potencies compared to morphine?
* PO 3-5x more potent
* IV 8.5x more potent
* rectal
73
# Hydromorphone
Metabolism:
Metabolites & effects
What pt population are these effects worse in?
* metabolism: liver
* Metabolites
**hydromorphone-3-glucuronide - neurotoxicity** (allodynia, myoclonus, seizures)
***worse in renal insuff. pts***
74
# Hydromorphone Dosing
IV post-op dose:
reg IV dose:
Onset:
* 0.2mg IV q 3-5min
* usually under 2mg
* 0.2-1mg (reg. IV dose)
* Onset: 10-15min
75
# Hydromorphone Dosing
Oral dose:
Onset:
* dose: 2-8mg
* onset: 30min-1hr
76
# Hydromorphone
DOA:
Half-life:
* DOA: 3-4hrs
* half-life: 2.3hrs
77
# hydromorphone
Interactions/SE
**additive effects w/ CNS depressants**
* sedation/resp. depression
* constipation/n/v
* histamine release
* euphoria
* tolerance/dependence
78
# Hydrocodone Science
A semi-synthetic opioid which is a ________ derivative.
* Codeine
79
# Hydrocodone
How much more potent is hydrocodone than codeine?
6-8x more potent
80
# Hydrocodone
Metabolism:
Metabolites:
* CYP2D6 - hydromorphone
* CYP3A4 - Norhydrocodone (inactive)
81
# Hydrocodone Dosing
What is the hydrocodone:morphine equivalence dosing?
* 10 mg Morphine = 30 mg hydrocodone
82
# Hydrocodone Dosing
PO dose:
onset:
* 2.5-10mg hydrocodone w/ 300-750 mg acetaminophen q 4-6hr
* onset: 30min
83
# Hydrocodone
Peak:
E 1/2 time:
* peak: 1.3 hrs
* E 1/2 time: 3.8 hrs
84
# Hydrocodone
What forms are hydrocodone available in?
What other drugs is hydrocodone put in combo with?
* tablet/capsule, syrup/solution, XR suspension, XR tablet
* combo drugs: tylenol, ASA, guaifenesin, various anti-histamines
85
# Hydrocodone
What other drug:drug interactions are there w/ hydrocodone?
* CYP inhibitors/inducers
* sedation - opioids/benzos
* barbs - hypotension
* IV Mg & CCB - increased opioid effects (sedation/HoTN)
86
# Hydrocodone
SE:
* miosis, histamine release pruritis
* decreased hypercapnic drive/RR/airway reflexes
* brady, HoTN
87
# Hydrocodone
What 3 things needs require caution w/ hydrocodone?
1. alcoholism
2. drug abuse
3. drugs w/ tylenol
88
# Buprenorphine Science
A semi-synthetic ________ - ________ opioid.
Derived from the opium alkaloid ________.
* agonist-antagonist
* thebaine
89
# Buprenorphine
MOA/receptors
**used for tx of opioid abuse disorder and cancer/chronic pain**
* pt agonist Mu receptors
* kappa antagonist
* weak delta receptor agonist
90
# Buprenorphine
What are 4 advantages to using Buprenorphine in cancer and chronic pain tx?
1. less resp. depression
2. less immune suppression
3. reduced constipation
4. no accumulation in pts w/ impaired renal function
91
# Buprenorphine
What 5 preparations is Burprenorphine available as?
1. Cizdol
2. Subutex
3. Suboxone
4. Zubsolv
5. Bunavail
**IV, patches, PO, SL**
92
# Buprenorophine
Metabolism:
Metabolite & effects:
* CYP3A4
* Metabolite: Norbuprenorphine
**full agonist - mu, delta, ORL-1 opioid receptors
pt agonist - kappa**
*little anti-nociceptive potency, **markedly increased resp. depression***
93
# Buprenorphine
* Buprenorphine - Morphine Equivalence
0.3mg IM Buprenorphine = 10mg Morphine
94
# Buprenorphine
SL onset:
SL DOA:
TD patch Dose:
* SL onset: 30 min
* DOA: 6-9hrs
* TD patch: 5-70 mcg/hr for 4-7 days
95
# Buprenorphine
E 1/2 time:
* 20-73hrs
96
# Buprenorphine
SE:
* drowsiness
* n/v
* ventilation depression - **prolonged/resistant to antagonism w/ naloxone = pulm. edema**
