PO Pain Flashcards
(72 cards)
1
Q
What are the 3 majors sites of action of opioids?
A
- Brain (supraspinal)- opioids work prea nd post synaptically to activate descending inhibitory pathways
- Spinal cord (spinal)- directly on the dorsal horn of the SC
- Periphery- peripheral terminals of nociceptive neurons
2
Q
What are opioids are used for in anesthesia?
A
- Attenuate the SNS response to noxious stimuli
- Adjunct to inhaled agents during anesthesia
- Sole anesthetic (fentanyl/sufent/morphine- cardiac anesthesia only high doses, critically ill pateints
- perioperative and post op control of pain
3
Q
What are opioid characteristics that set them apart from other analgesics?
A
- Moderate to severe pain
- no max dose or ceiling effect
- tolerance can develop with chronic use
- tolerance associated with physical dependence but not necessarily with psychological dependence
- cross-tolerance- tolerant to one opioid, will be tolerant to others
- produce analgesia wihtout loss of
- touch
- proprioception
- consciousness (in smaller doses)
4
Q
What are some opioid classifications by class?
A
- Naturally occuring
- morphine and codein
- Semisynthetic: analogs of morphine
- heroin and dihydromorphone
- Synthetic
- exogenous 4 groups
5
Q
What are opioid classifications by action at receptor?
A
- Agonist- full activation
- Partial agonist
- Mixed agonist/antagonis- less activation
- Antagonist- prevents activation
6
Q
What is mechanism of action of opioid?
A
Activate sterospeicfic G protein coupled receptors
- post synaptic- directly decrease neurotransmission
- increased K conductance (hyperpolarization)
- Ca channel inactivation (decreased NT release)
- Modulation of phosphoinositide- signaling cascade and phospholipase C
- Inhibition of adneylate cyclase (decreased cAMP)
- pre synaptic- inhibits release of excitatory NT
- decrease acetylcholine, dopamine, norepinephrine, substance P release
7
Q
What are the main opioid receptors?
A
- Mu, kappa, delta
- theory- synthetic opioids mimic action of endogenous opioids by binding to opioid receptors
- activate endogenous pain modulating systems
- variable affinity and efficacy at different receptors types among the different drugs in this class
8
Q
What are the Mu receptos?
A
- Subtypes mu-1 and mu-2 (all opioids interact with these 2 receptors)
- Mu-3 receptors thought to be involved in immune process
- All endogenous and exogenous agonists act on mu receptors
- Mu receptors in brain, periphery and spinal cord
9
Q
What does Mu-1 cause?
A
- Supraspinal (most), spinal and peripheral analgesia
- euphoria
- miosis
- bradycardia
- urinary retention
- hypothermia
- all endogenous and synthetic opioid agonists work on these receptors
10
Q
What does Mu-2 cause?
A
- Hypoventilation
- Physical depedence
- spinal analgesia (also some supraspinal)
- constipation
- all endogenous and exogenous agonists act on these receptors
11
Q
What does Kappa receptor cause?
A
- Suprasinal, spinal and peripheral analgesia
- dysphoria
- sedation
- miosis
- diuresis
- dynorphins act on these receptors
- opioid agonist-antagonists often have principle actions at the kappa receptor
12
Q
What does delta receptor cause?
A
- Peripheral, supraspinal and spinal analgesia
- Hypoventilation
- Constipation
- Urinary retention
- Physical dependence (on chart)
- Enkephalins work on these receptors
13
Q
What are some genetic influencings on cyp 450 system and influence on opioids?
A
- CYP2D6 has 5 common mutations that can alter metabolism of
- codeine, oxycodone, hydrocodone and methadone
- can have unpredicatable pharmacokinetics and 1/2 lives
- Fentanyl metabolism least likely to be impaced by genetic variability in surgical population= has predictable pharmacokinetics (most immune to variances in metabolism
- Rate of metabolism may influence side effect rate
- studies indicate ultra rapid metabolizers at increased r/f PONV
- Believe someone if they say morphine makes them really nausous and avoid morphone analogs (fentanyl ok)
- studies indicate ultra rapid metabolizers at increased r/f PONV
14
Q
What are some systemic effects of opioids?
A
- Many systemic effects similar among opioids
- althought diff opioids are active at diff receptors to diff degress
- variable s/e and efficacy profiles
- makes sense if you consider the variance in chemical structures
- morphine as prototype
15
Q
What are some CNS effects of opioids?
A
- Analgesia
- Euphoria
- Drowsiness/sleep
- miosis (pupillary constriction)
- nausea- chemoreceptor trigger zone
- does NOT produce amnesia
16
Q
Pulmonary effects of opioids?
A
- Decreased RR and increased TV
- at higher doses, decreased RR and TV, leading to apnea
- decreased response to CO2/hypoxia
17
Q
What are some GI effects of opioids?
A
- Decreased gastric emptying
- direct stimulation of chemoreceptor trigger zone on the floor of 4th ventricle
- partial dopamine agonist?
- balanced by depression of the medullary vomiting center
18
Q
What causes pruritis by opioids?
A
- Cause unknown
- occurs primarily on face, particularly nose
- “fenatnyl nose itch”
- histamine release most probably cause with some i.e. MSO4 (also demerol)
19
Q
What is morphine?
A
- Naturally occuring opioid
- Severe acute pain almost always IM or IV admin
- PO used for chronic pain and cancer pain
- slow release formulations available- delayed onset 3-5 hours (not used preop/intraop much)
- considerable first pass effect
- 1/2 life 3-4 hours converted to active metabolite (morphine 6 glucuronide)
LAST SEMESTER STUFF (JUST IN CASE):
- Poor lipid solubility, PB= 35% (dr e syas this is high…) hightly ionized
- histamine release
- IM peak effect 45 min; IV 15-30 MIN
- DOA 4 hours
-
BRADYCARDIA VIA DIRECT STIMULATION OF VAGUS NERVE
- Inhibition of SA node as well
- metabolized by liver
- active metabolite M6G > potency than MSO4
- Kidneys play role in extrahepatic metabolism
- renal failure will have prolonged effects d/t M6G- AVOID!!
20
Q
What is codeine?
A
- Mild pain relief
- PO
- e1/2 t= 3 hours
-
prodrug: 10% is metabolized by cyp2D6 to its active form
- remaining drug is demethylated to inactive metabolite
- active form= morphine
- 10% caucasians, 30% asians lack 2D6– no analgesic effect
- antitussive effect remains even without conversion
- better for cough (lower dose) than pain relief
21
Q
What is hydrocodone?
A
- Vicodan
- PO
- Always combinesd with either ASA, ibuprofen, antihistamine, acetaminophen
- analgesic and antitussive
- used for chronic pain
- high abuse potential
22
Q
What is oxycodone?
A
- PO
- AKA oxycontin, percocet, percodan
- available in sustained release preparation (oxycontin)
- mod to severe pain; useful for chronic pain, postop pain
- also in combo with ASA or tynelol
- no active metabolites- safer in patients with renal dysfunction
- high abuse potential
23
Q
What is methadone?
A
- PO, IV, Sub q
- synthetic
- long plasma half life 8-59 hours or 13-100 hours (sources vary with range)
- opioid addiciton treatment (maintenance) dosed QD
- No active metabolites- safer in patients with renal dysfunciton
- chronic pain syndrome treatment: doses BID or TID q 4-8 hours
- neuropathic pain
- at risk for severe respriatory depression secondary to prolonged and unpredictable e1/2t
24
Q
Tolerance to opioids?
A
- Tolerance is common with chronic use of opioids (after 2-3 weeks of use)
- pt first notices a reduction in adverse effects
- shorter duration of analgesia
- followed by decrease in effectiveness of each dose
- tolerance to most adverse effects include
- respiratory and CNS depression
- can be surmounted by increasing the dose
- cross tolerance exists amojng all full agonists but is not complte
- when switching to another opioid, start with half or less of the customary equianalgesic dose
- switching opioid tolerant patients to methadone may improve pain relief
- tolerance ot sedative and emetic effects develop rapidly but not constipation
- a stimulant laxative with or without a stool softener should be started early in tx
- senna/docusate
25
What is dependence?
* physical dependence causes abstinence symptoms upon sudden d/c
* clinically significant dependence develops only after several weeks of chronic tx
* addiction involves psychological dependence and biologic and social factors
* cancer pain and acute pain patients rarely experience euphoria an deven more rarely develop psychologicla dependence or addiction
26
Dosage of opioids?
* Dose vary widely from one pt to another
* no minimum or max dose except limitation by the dose of acetaminophen or aspirin
* dose required to maintain optiumum pain relief with tolerable side effects must be used
* after intiial titration with short-acting opioid in first 12-24 hours, dose determination by around the clock dosing is recommneded
* a sustained release forumlation should be used in chronic pain
* immediate release doses that are 10-15% of the total daily dose should be used for breakthrough pain
* PCA given IV, SQ, or other routes are now widely used when the oral route are not feasible
27
Equianalgesic doses for control of of chronic pain?
If pain is well controlled and switching opioids, calculate equivalent dose and reduce by 25% for dose of new drug
28
What is equianalgesic dose of meperidine (PO and SQ/IV?)
PO= 150 mg
SQ/IV= 50 mg
29
What is equianalgesic dose for codeine (po and sq/iv?)
PO= 100 mg
sq/iv= 60 mg
30
PO equianalgesic dose for hydryocodone?
15 mg
31
Morphine equianalgesic dose (PO and SQ/IV?)
PO= 15 mg
SQ/IV= 5 mg
32
Equianalgesic dose of oxycodone (PO)
10 mg
33
Equianalgesic dose methadone? PO and SQ/IV?
10 mg PO
5 mg SQ/IV
34
Hydromorphone equianalgesic dose (PO, SQ/IV?)
PO= 4 mg
SQ/IV= 1.5 mg
35
What are some consideratiosn for non-opioid analgesics?
* First line agents for mild to moderate pain
* ceiling effect of ASA and acetaminophen b/w 650 and 1300 mg
* NSAIDS other than aspirin- analgesic ceiling may be higher
* Exceeding the ceiling dose of any of these drugs will result in increased adverse effects with no added efficacy
* tolerance does not develop to the analgesic effects of these drugs
36
What is acetaminophen?
* Central antiprostaglandin effect *(unsure how)*
* antipyretic
* pain reduced via blockade of:
* NMDA receptor activation in CNS
* Substance P in spinal cord
* may also be cannabinoid
* Lacks peripheral activity- weak antiinflammatory action (not a true NSAID)
* good choice in:
* peptic ulcer disease
* ped patients
* patients who need well functioning platelets
* *also good for pt with asthma because increase risk for NSAID reaction*
37
Dosing for acetaminophen?
* PO similar potency as ASA (in single analgesic doses, has same time-effect curve)
* PO dose= 325 mg-650 mg q 4-6 hours
* IV formulation just FDA approved in US in 2010
* IV dose 1 gram over 15 minutes infusion only q 4-6 hoursnot to exceed 4000 mg in 24 hours
38
How is tylenol metabolized?
conjugated and hydroxylated to inactive metabolites; very little excreted unchanged in kidneys
39
Issues with acetaminophen?
* Overdose can cause serious or fatal hepatic injury
* liver can only metabolize a limited amount of hepato-toxic metabolite **N-acetyl-p-benzoquinone** with **glutathione**
* when glutathione outnumbered by OD of acetaminophen, hepatic injury occurs
* **max safe dose 4 grams/day**
* safe dose even lower in ETOH abuse (use caution) (*also in pancreatitis)*
* also **increased** risk of **toxicity** in patients taking **isoniazid**
* **acetylcysteine** can substitute for **glutathione** and **prevent** **hepatic** injury if given within **8 hours fo OD**
40
Renal toxicity with acetaminophen?
* Renal papillary accumulation of metabolites can cause renal cell necrosis
* may be responsible for devleopment of some cases of ESRD
* *Even though liver saved, can end up with ESRD from toxicity damag*
* however, NSAIDS higher risk of renal toxicity than acetaminophen
41
What is the metabolism of arachidonic acid?
* Arachidonic acid is released from phospholipids by enzyme phospholipase A2
* Arachidonic acid is immediately metablized by either
* **cyclooxygenase** lead to formation of
* prostaglandin
* prostacyclin
* thromboxane
* **lipoxygenase** leads to formation of
* leukotrienes
* lipoxins
* **Epoxygenase** leads to formation of
* epoxyeicosatetraenoic acoid (4 types)
* regulated inflammation further researhc necessary to determine precise role
42
How do NSAIDS work?
Inhibit cyclooxygenase
43
How are phospholipase's generated?
by inflammatory process, released from cell membrane
44
What is Cox-1 and Cox 2?
Cyclooxygenase 1 and 2
* Cox 1 - (constitutive= always working)
* makes prostaglandins which:
* protect gastric mucosa
* endothelial function
* (production of proaggregatory thromboxane A2 IN PLT-- from book)
* Cox 2- inducible (by cytokines IL-1 and TNF which are all inflammatory mediators)
* makes prostaglandins which:
* involved in pain, inflammation and fever
* endothelial function
Non selective COX inhibits attack COX1 and 2 and can lead to severe GI bleeding and pt demise. Now have drugs that are more selective to COX2 and are more helpful
45
What is aspirin?
salicylate class
* aspirin effect in most mild to moderate pain
* HA, muscle pain, arthritis
* antipyretic
* MI/storke prevention; protection during MI (antiplt)
* Unlike other NSAIDs irreversible inhibition of cox
* single dose inhibits PLT function for lifetime of platelet 8-10 days
46
Effect of ASA on pt with ESRD?
* ESRD not induced by chronic ASA (in contrast with other NSAIDS)
* Prolonged bleeding (up to 15 minutes) in these patients with ASA
* *concern with ESRD pt taking ASA, falling, hitting head, can have huge risk for hematoma*
* *usually don't recommend ESRD to take ASA- because of bleeding, not necessarily an increase risk for ESRD issues*
47
ASA and Asthma?
* Single dose can precipitate asthma in aspirin-sensitive patients
* cross-sensitivity with other NSAIDS
* *if allerge to ASA, avoid other NSAIDS*
48
How can ASA affect LFT? GI? CNS?
* asa can increaes LFT (usually reversible
* like other NSAIDs, can cause GI bleeding and PUD
* CNS stimulation
* *perhaps via NMDA receptor, not well described and not clinically relevant*
49
Dosing of ASA?
* Analgesic vs anti-inflammatory dosing
* analgesic/antipyretic 325-600 mg
* anti inflammatory 1000 mg (3-5 g/day)
* *such a high dose and it can cause severe GI side effects*
* *tend to avoid using ASA as antiinflammatory*
* increase dose gradually
* follow serum salicylate levels
* rarely used d/t GI side effects
50
How is ASA cleared?
* Hepatic clearance
* E1/2 t is 15-20 minutes for ASA and 2-3 hours for active metabolite salicylic acid
* Salicylate overdose: metabolic acidosis, tinnitus
51
Can ASA be used in kids?
What type of salicylate acid has more favorable toxicity profile?
* Should not be used during viral syndromes in children and teenagers because of risk of reye's syndrome- (which causes encephalopathy)
* Non acetylated salicylates have more favorable toxicity profile
* do not interfere with PLT aggregation
* rarely associated with GI bleeding
* well tolerated by asthmatic patients
52
What are nsaids?
non-steroidal anti-inflammatory drugs
* Analgesic efficiacy
* helpful for arthritis related pain, MS pain, HA and dysmenorrhea--\> ceiling effect wiht post op pain
* *will decrease pain a litte, but not as much as opioids*
* more effective than full doses of ASA or acetaminophen
* equal or greater than usual doses of an opioid combined with acetaminophen
* Different NSAIDS have:
* similar efficacy at equipotent doses
* patient- to patient differences (*depends how pt metabolizes drug and genetic profile)*
* toxicity difference
* Anti-inflammatory
53
MOA of NSAIDS?
* Cyclooxygenase (COX) inhibiotr
* Blocks conversion of arachidonic acid to prostaglandins (PGs)
* decreases production and release of PGs
* analgesic, anti-inflammatory, antipyretic activity
54
Pharmacokinetics of NSAIDS?
* Weak acids- well absorbed
* Highly protein bound \>95%
* *longer DOA*
* small Vd (non-speicifc NSAIDS)
* extensively metabolized and excreted in urine
* most of the drug is metabolized and never reaches patient
* *metabolized by cyp450 in liver*
* Half-life varies from \<6 hours to \>12 hours
55
S/E NSAIDS?
* Asthma and anaphylactoid rection in aspirin-sensitive patients
* *always double chekc hx*
* *ask what precipitates asthma*
* *exercise induced- if asked on exam, don't give toradol, but clinically, would give it*
* reversible inhibiton of PLT aggregation
* inhibition of COX-1 blocks synthesis of thromboxane A2 which inhibits PLT aggregation
* Unlike opioids, no physicla dependence
* rare adverse effects
* hepatic injury
* aseptic meningitis
56
Pregnancy and use of NSAIDS?
* best avoided but cat B if necessary
* avoid in 3rd trimester, CAT D, due to premature closure of DA
57
Overview of common side effects of NSAIDs?
* Aseptic meningitis
* antipyretic effect
* impaired bone fusion (controversial)
* hepatotoxicity (certian nsaids RARE)
* decrease renal perfusion
* decrease GFR
* Decrease sodium transport
* angioedema (rare)
* HTN/increased CV risk
* bronchoconstriction
* rash/urticaria
* anti-plt effect (cox 1 and asa only)
* gastric ulceration (cox 1\> cox2)
* antiinflammatory effect
58
GI adverse effects of NSAIDS? Risk factors for GI s/e?
* Dyspepsia, GI bleeding PUD
* *Can see red dots on colonoscopy, not necessarily bad*
* Inhibiton of PGs that maintain normal gastric and duodenal mucosa
* increases acid production
* decreases mucus produciton, gastric blood flow
* Local irritaiton
* lipid soluble at low pH- enter gastric mucosal cells- lose lipid solubility- become trapped in cell
**Risk factors**
* high doses, prolonged use, previous GI ulcer or bleeding
* excessive ETOH intake
* elderly
* corticosteroid use
59
What are specific GI risks for various NSAIDs? (low, med, high risk)
Low risk
* Ibuprofen and naproxen at low doses
* etodolac, sulindac
* celecoxib
medium risk
* ibuprofen and naproxen at mod-high doses
* diclofenac, oxaprozin, meloxicam, nabumetone
High risk
* tolmetin, piroxicam, ASA, indomethacin, ketorolac (only get toradol 3-4 days in a row)
60
NSAID renal adverse effects?
* Decreased synthesis of renal vasodilator (PGs) (PGE2)
* leads to decreased renal blood flow
* fluid and sodium retention
* may cause renal failure or HTN
* Intersitital nephritis (rare)
* **in healthy people, rarely of clinical significance**
* risk factors (people who require prostaglandins for renal perfusion)
* old age (*even if older pt is otherwise healthy, still have decline in GFR)*
* CHF
* HTN
* DM
* Renal insufficiency
* ascites
* volume depletion
* duiretic therapy
61
Renal risk of speicifc nsaids?
* Can occur with all NSAIDs
* Increased risk
* longer half life
* highly potent COX inhibitors
* ketorolac, indomethacin
* higher doses
* "renal sparing"- lower risk, but not devoid
* sulindac, nabumetone
* celecoxib
62
Drug interactions of NSAIDS?
* Displaces other highly protein bound agents
* increases levels of warfarin, phenytoin, sulfonylureas, sulfonamids, digoxin
* Reduces effect of diuretics, beta blocker,s ACEIs, via suppression of renal PGs
* Increases lithium levels- *competing for protein binding sites*
* increased risk of GI bleed when combined with anti-coagulants
* probencid increases levels of most NSAIDS
* avoid with ketorolac
63
What is ketorolac?
* Non-selective cox inhibitor
* Only IV NSAID available in US
* IM or IV comparable to mild opioids
* double blind single dose study suggested similar time to pain relief with ketorolac or morphine
* *comparable to mild opioids*
* advantage: no vnetialtory or cardiac depression
* adverse effects similar ot typical NSAID
* increased bleeding time and periop blood loss
* serious GI bleeding, ulceration, perforation and/or renal toxicity can occur (especially in elderly or hypovolemic)
* potential for life-threatening bronchospasm
64
Ketorolac pharmacokinetics?
* Do not exceed 5 days of use
* IV onset ~10 min
* E1/2 t 5 hours (prolonged in elderly 30-50%)
* DOA 6-8 HOURS
* 99% protein bound
* conjugated in liver
* Dose IV:
* 30 mg IV x 1 or q 6 hours
* Daily max 120 mg
* elderly : if you use it at all, cut dose in 1/2
65
What are some selective NSAIDs?
* Celecoxib (celebrex) only agent available today
* withdrawn from market d/t increased MI risk
* rofecoxib (vioxx) valdecoxib (bextra)
* *removed d/t risk storke/MI*
* Selectively inhibit COX2 (nonselective NSAIDs inhibit COX 1 and 2)
* cox 1: gastric protection and produciton of TxA2
* vasoconstrictor, plt aggregation
* cox 2: produciton of prostacyclin (vasodilator, plt inhibitor)
* No more effective at reducing pain and inflammation
* same risk fo renal adverse effects
66
What is celecoxib?
celebrex
* Use the lowest effective dose
* \<200 mg/day
* 200 mg/day= naproxen 500 mg BID
* **BLACK BOX WARNING**
* Consider pt risk for CV events
* consider pt risk for GI events
* weight risk vs benefit
* PO
* Should be taken with food
* avoid in pt with sulfonamide allergy
67
Black box warning for NSAIDs?
* CV risk
* increased risk of serious CV thrombotic events, MI, stroke, which can be fatal
* GI risk
* increased r/f bleeding, ulceration, perforaiton of stomach or intestines, which can be fatal
* selective and non-selective NSAIDs
68
What are some adjuvant analgesics?
Antidepressants and anticonvulsants- drugs of choice for neuropathic pain
* **TCA** (amitriptyline, nortiptyline)
* diabetic neuropathy, postherpetic neuralgia, polyneuropathy, and nerve injury or infiltration with Ca
* may also improve underlying depression and insomnia
* **Venlafaxin**- (EFFEXOR) SSNRI
* neuropathic pain, HA, fibromyalgia, postmastectomy pain
* **Duloxetine** (cymbalta) SSNRI
69
What are some anticonvulsants that are used as adjuvant analgesics?
* **Gabapentin** (Neurontin) –mechanism not well understood
* Diabetic neuropathy, postherpetic neuralgia
* **Pregabalin** (Lyrica) –gabanergic, analogue of GABA
* Diabetic neuropathy, postherpetic neuralgia, fibromyalgia
* Analgesic effects may be related to **calcium** influx inhibition as well as **inhibition of the release of excitatory neurotransmitters** in spinal and supraspinal pathways via binding to α 2 δ-1 subunit of presynaptic voltage-gated calcium channels in the CNS.
* **Carbamazepine** (Tegretol)-Na channel blocker, and GABAnergic
* FDA approved for trigeminal neuralgia
* **Phenytoin (Dilantin), Sodium Valproate (Depakote), Clonazepam (Klonopin), and Topiramate (Topamax)**
* May relief neuropathic pain
* **Lamitrogen (Lamictal)-Gabanergic**
* Effective for central post-stroke pain and HIV-associated painful sensory neuropathies
70
How can hydroxyzine help with pain?
* Low dose IV/IM add analgesic effect to opioids in Ca and postop pain while reducing incidience of N/V
* is a histamine blocker
71
How can corticosteroids help with pain?
Can produces analgesia in some patients with inflammatory diseases or tumor infltration of nerves
72
Other analgeisc agents and topical analgesics?
* Topical
* 5% lidocaine approved for post herpetic neuralgia
* topical EMLA useful for cutaneous anesthesia
* capsaicin cream (zostrix) for neuropathic and osteoarthetiic pain
* transdermal clonidine patch may improve pain and hyperalgesia in sympathetically matained pain
* THC/CBD
* Ketamine
* Magnesium
