Analgesia Pharmacodymanics Flashcards
1
Q
Opioid CVS effect:
A
- CNS-Dose dependent BradyC (like atropine);
- May cause Compensatory sympathetic response.
- Less Sympathetic Outflow -> Dec BP
2
Q
Opiod Central Resp effect:
A
- RR: Decrease alot, may breath on command;
- Increased resting pCO2;
- Hypercarbia (alot, lasts past analgesia)/Hypoxia; Decreased Airway Reflexes (Central antitussive effect).
3
Q
Opioid External Response:
A
- chest wall rigidity,
- vocal cord closure with high bolus doses (impairs ability to ventilate).
4
Q
Opioid Neurolog effect (CMRO2, CBF, ICP):
A
- CMRO2: Modest Dec;
- CBF: Dec when administered with N2O;
- ICP: Decreased. [ CBF and ICp can inc with hypercarbia),
- no effect on SEP
5
Q
Opioid GI effect:
A
- Decreased Motility -> dec gastric emptying and peristalsis -> Inc Ileus;
- Increase Chemotrigger Zone Trigger, Inc Vestibular Sensititivity;
6
Q
Opioid GU effect:
A
Inc urinary Retention especially with spinals
7
Q
Meperidine Benefit and AE:
A
Benefit: Can be used for postop shivering,
AE:
- Direct myocardial depressant (may also become tachyc due to atropine like effect),
- in CKD, Meperidine can lead to seizure (focal neuroexcitation after inc doses);
- causes Histamine release -> Hypotension + tachycardia,
- CBD pressure inc,
- Serotonin Syndrome: Delirium + hyperthermia
8
Q
Fentanyl: Benefit, AE
A
Benefit:
AE:
- peak respiratory depression at 5-15 min (lag behind analgesics),
- less emetic vs morphine;
- Fast distribution and inc with large and repeated doses,
9
Q
Alfentanil Benefit; AE:
A
Benefit: Rapid Peak effect useful for blunting response to single, brief stimulus;
AE: CYP3A4, inhibited by erythromycin, Navir, can inhibit clearance,
Use Ideal Body weight for High BMI
10
Q
Morphine: Benefit; AE:
A
Benefit: Peak effected may be delayed 10-40 min
AE:
- Adjust in CKD,
- Histamine release,
- slow crossing of blood brain barrier (10-40 min)
11
Q
Hydromorphone Benefit, AE:
A
Benefit:
- Less histamine release,
- safer in renal impairment,
- shorter time to peak effect
AE
12
Q
Methadone MOA; AE:
A
MOA:Opiate agonist and NMDA R antagonist;
AE:
- Respiratory depression, long half life but usaully need q6-8h dosing.
- Can lead to QT prolongation (esp >200mg/d, try to use EKG prior to iniating/titrating).
13
Q
Oxycodone AE, warning
A
AE
- Cannot Crush/NGT use,
- Rapid metabolizer may have high toxicity,
- Highly abusive,
- Poor metabolier (CYP2D6) may need higher dose
14
Q
Codeine MOA, AE
A
MOA: Raises Pain Threshold without change to pain.
AE:
Ultrametabolizers esp in children can lead to OD from coedine (do not give to kids esp after tonsillecvtomy/adenoidectomy)
15
Q
Butorphanol (MOA, Benefit, AE):
A
MOA:
- partial agonist to mu receptor or compeititve antagon,
- agonism of kappa and delta;
AE:
- HTN, pulm-HTN,
- Inc CO,
- Mild GI and Billiary System, used on OB
16
Q
Tramadol (MOA)
A
MOA:
- Opiate agonist and TCA-Like Spinal inhib of pain (similar to SNRI)
- M1 metabolite has 200x more afinity to mu opioid receptor
17
Q
Tramadol (Benefit, AE)
A
Ben: Less Resp and GI effect.
AE:
- in CKD, ETOH, CVA, TBI may lead to Seizures,
- poor antagonist by naloxone
18
Q
NSAID MOA:
A
- Inhibs Cyclooxygenase (COX)
- decrease inflammatory mediator (prostaglandins)
- dec pain, temp, inflam
19
Q
NSAID COX1 AE:
A
- GIB/Ulcers,
- Decreased Renal perfusion (esp in hypovolemia,
- Decrease Platlet Aggregation,
- Dec Prostaglandin -> nsaids induced bronchospasm
20
Q
NSAID COX2 AE:
A
Increase CVA and MI risk
21
Q
NSAID Benefit limited?
A
Limited by maxing out pain reliefs but ae continues
22
Q
Max Dose of Ibuprofen, Naproxen, Diclofenac
A
- Ibuprofen 3200;
- Naproxen 1250 mg;
- Diclofenac 200mg
23
Q
Tylenol Onset, Elim
A
- 5-10 min,
- rectal absoprtion is rapid but sporadic
- cleared only by liver
24
Q
Tylenol Benefit
A
- Can be used in preggers,
- does not affect inflammation, only temp and pain,
- No GI-tract problems,
- No platelet problems
25
Tylenol AE
1. Can OD (both single or cummulative);
2. Hepatic Necrosis due to depletion of antioxidant glutathione
3. N acetyl-p-benzoquinone;
Tx with NAC within 8 hours. Rectal tylenol is slow and erratic
26
Toradol Benefit/AE:
Ben:
## Footnote
* IV provide more analgesic vs inflam
* no resp dep;
* no cbd spasm,
* roughly ~10 mg morphine .
AE
* prolong bleeding,
* platelet dsfxn only in spinal anesthesia not ga. can trigger renal dsyfxn
27
ASA Benefit/ AE:
Ben:
AE:
* stop 10 days prior surgery stop/caution in gib,
* hemorrhage,
* low plt,
* Caution in hemophilia, uremia or vWF, asthma
28
Celecoxib Benefit/AE:
AE:
## Footnote
* relies on hepatic metabolism (reduce if liver dysfxn)
* associated with ACS,
* LFT inc,
* htn,
* edema,
* ckd,
* sulfa/asa allergy
29
MOA of NSAIDS
Blocks conversion of arachidonic acid to Prostagladins
30
Gabapentin moa, indicates, ae
MOA:binds voltage gates ca chan,
Indic: neuropathic pain, fibromyalgia, spinal stenosis,
AE: dizzy, sedate, weight inc, n/v
31
Pregabalin Moa, indicate, ar
MOA: binds to ca voltage gates,
Indicate: neuropathic, fibromyalgia,
AE: dizzy, sedate, edema ha
32
Topiramate moa, indicate, ae
MOA:na, ca chan enhance gaba.
Indic:Neuropathic chronic lumbar,
AE: sedation, weight loss
33
cyclobenzaprine indicate, ae
Indic: Spastic pain/Muscle Spasm;
AE: Dry mouth, drowsiness, headache, confusion
34
Carisoprodol, MOA, Indicate, AE
MOA: Interneural inhibition,
Indic: Acute MSK pain,
AE: Dry mouth, drowsiness, headache, ams
35
Baclofen, MOA, indicate, AE
MOA: Binds Gaba-B, inhibits Neuro transmitter release;
Indic: Spine origin spasticity, UMN dz, acute back pain, CN5 Neuralgia;
AE: Drowsiness, dizziness, nausea, ams
36
Amitripyline MOA, Indicate, AE
MOA: TCA SNRI; AntiHis, AntiCholin,Anti 5HT
Indicate: Tension Headache, TMD, Facial-Myofascial pain;
AE: Ache: Dry mouth, constipation, Weight gain, drug interactions
37
Duloxetine MOA, Indicate, AE
MOA: SNRI;
Indicate Neuropathic pain, fibromylagia.
AE: Nausea, drowsy, dry mouth constipation
38
Tizanidine MOA, Indicate, AE
MOA: A2, Presynaptic inhibition of motor neurons;
Indicate: spasticity, paravertebral spasms;
Ae: dry mouth, somnolence, asthenia, dizziness
39
Meperidine AE
Long 1/2 Life of Active Metabolite (normepeidine) esp Renal Pt is a proconvulsant
40
Meperidine MOA
Affecting K receptor taht leads to Anti-shivering
41
Meperidine Use
shivering from multiple causes including GA, Epidural, fever, transfusionRXN , and amphotericin B.
42
Opioid Receptors Types
Mu, Kappa, Delta
43
Mu Receptor effects
µ1: analagesia + Dependence. µ2: Resp Depression, Miosis, Euphoria, Dec GI Motil, Physical Dependence, µ1: analagesia + Dependence. µ3: Unknown
44
Kappa Receptor Effect
Analagesia, Dysphoria, Sediation, Misosi, anti ADH
45
Delta Receptor Effects
Analalgesia; Dependence, Antidepressant
46
Methadone MOA and effects
Mu agonist, antagonism of NMDA and SSRI (leading to chronic neuropathic pain control with psych helping also). May lead to upregulation of NMDA receptors + NO release -\> Hyperalgesia. Can still cause respiratory depression; QTc prolong [needs ekg monitoring]
47
Naloxone AE
P-Edema, hyperalgesia
48
NSAID MOA and limitation
Inhibit COX affecting synthesis of prostaglandin. [PGE2: sensitization nociceptors +hyperalgesia]; Has Ceiling effect.
49
NSAID Benefit
Less opioid usage that leads to less N/V and sedation
50
NSAID AE and rf of these
Plt Dysfxn, GI ulcer, Nephrotoxicity [esp with hypovolemia, CHF, CKD]
51
COX2 inhibitor AE
Fluid retention and HTN
52
COX 1 vs COX 2
1: Consitutive enzyme that produce prostaglandin for house keeping (gastric protection + hemostasis); 2: Inducible form of enzyme that produces prostaglandin that mediate pain, inflam, fever and carcinogenesis
53
PGE2 effect
Sensitizing nocioreceptor to His + bradykinin; Enhance pain ntrainsmission at dorsal horn via inc release of substance P and glutamate from first order pain neurons. along with inhibiting neurotrans from descending pain modulating pathways
54
Opioids with ceiling effect
Mixed agon/antagon such as nalbuphine
55
Buprenoprhine Duration, MOA and effects
10 hours duration; Partial Mu agonism -\> Ceiling Effect of Rep Depression [max resp depression 50% + Reduce w/d.
56
Buprenoprine combined with what and why
Naloxone; which does not affect theraputic dose of buprenorphine to avoid abuse.
57
Tx of acute opioid w/d
Clonidine (sx only : N/v sweating, diaphoresis, restlessness)
58
Naltrexone OA and use
Opioid Antagonist that is used towards the end of opioid period diminished.
59
Morphine 3 glucuronide Metabolite Effect
Majority of Metabolite from Liver 60%, Hyperalgesia; agitation, myoclonus, delirium
60
Morphine 6 glucuronide
Drowsiness, n/v, coma, respiratory depression
61
Codeine In peds
Neonates have Decreased CYP2D6 x 2 wks (which converts to active form, morphine) -\> Less sensitivity to codeine vs kids
62
Morphine in Peds
Neonates are more sensitive to morphine -\> Decrease in ventilatory response at lower CO2 vs adults
63
Metabolism of Morphine Which enzyme
UGT2B7 (UDP-Glucuronosyltransferase-2B7)
64
Metabolism of Fentanyl and tramadol and effects on peds
to Norfentanyl and Nortramadol; CYP3A4 (also affects Methadone). premmies+Neonates Less of this enzyme -\> more suscpetible
65
Methadone Cardiac AE and CoRF
QT Prolongation esp with CYP3A4 inhbiitors.
66
Best analgesic effectiveness of continuous epidural infusion; PC epidural analgesia; PCA and PRN
CEI\>PCEA\>PCA\>PRN
67
Why Epidural \> Opioids
Less Mortality; PNA, Ileus, Less time before ambulation
68
Fentanyl premedication effect
Sensitize pt to pain postop
69
effect of ssri on opioids metabolism
inhibit cyp2d6, leading to slower onset for any codone derivative to morphine
70
Opioid Effect CVS
Decreases sympathetic tone/inc muscarinic -\> dec MAP, dec VR
71
Opioids and LFT
Hypoalbuminemia increases free opioids in the blood, decreasing total requrirement
72
Fastest Onset Opioid and why
Alfentanil (acceleration; 1.1min) due to low pka (6.5) -\> low lipid solubility; 4s: 4x faster onset; 1/4 duration, 1/4 potency
73
Strongest Opioid
Sufenanil (super)
74
Opioid Onset of action Key Factor
Unionized Fraction/ Low Lipid solubility
75
Opioid Duration Factor
Low solubility means longer
76
CYP of Opioids (i1)
77
Opioid Metabolism (i1)
78
Opioid Table i1
79
Schedule Drugs List
80
