Flashcards in Exam 2 Questions (Part 2) Deck (33):
1
Procaine (Novocain)
- Rapidly metabolized by blood cholinesterase to an allergen
- Allergic reactions occur
- Intermediate onset, short duration
2
Bupivacaine (Marcaine)
- Slow to intermediate onset, long duration of action
- Metabolized by CYP450 enzymes in liver
a. Slower rate than for esters
b. Good alternative if patients allergic to esters
- Duration prolonged if liver function impaired
3
Levobupivacaine (Chirocaine)
- active optical isomer of Bupivacaine (Marcaine)
4
Exparel
Long acting liposomal suspension approved for post surgical pain management
5
Lidocaine (Xylocaine)
- Rapid onset, intermediate duration of action
- Same metabolism pathway as bupivacaine
- Transdermal patch: Lidoderm
6
Peripheral Nerve Block
- Injection near nerve trunk
- Common for dental procedures, surgery on single extremity, etc
7
Epidural
- Space between bone and dura mater
- Large and accessible, route common for obstetrics
-Type of central neural block
8
Intrathecal
- Spinal Nerve Blockade: Subarachnoid Space
- Most effective
- Most dangerous
- Patient position and solution density determine area blocked
9
Central Nerve Blocks (General)
- Two types: Epidural and Intrathecal
- Postural headaches most common complaint
- Risk of hematoma if LMWH anticoagulants given concurrently
10
Sympathetic Block
- Sympathetic activity increases with complex regional pain syndrome
- Block usually occurs with central neural block, but can specifically inject area surrounding nerve chain ganglia
11
Diazepam (Valium): Skeletal Muscle Relaxant
- Increased GABA inhibition (via BZ and GABAA receptors) of 1a afferents (presynaptic) thus inhibiting hyperactive reflex arcs; of supra spinal center (sedation)
- Used for spasticity and muscle spasm
- Broadest spectrum of BZDs
- Sedation is a therapeutic benefit and side effect
- Long term concerns: dependence and withdrawal
12
Carisoprodol (Soma, Vanadem)
Cyclobenzaprine (Flexeril)
- Polysynaptic inhibitors (other centrally acting compounds)
- MECHANISM: spinal cord reflex inhibition and sedation
- USES: Often in combo with acetaminophen and aspirin
- ADVERSE: Drowsiness, dizziness, dependence, tolerance.
- Carisoprodol has an active metabolite, Meprobamate (Schedule IV)... avoid abrupt withdrawal
13
Baclofen (Lioresal)
- Used to treat spasticity
- Structurally similar to GABA
- GABA-B receptor agonist... inhibits release of excitatory neurotransmitters. Results in inhibition of alpha motor neuron activity in spinal cord and pain pathways. Relaxation of skeletal muscle and some analgesia
- Drug of choice for MS
- ADVERSE: Drowsiness, muscle weakness, withdrawal syndrome
14
Intrathecal Administration for Baclofen (Lioresal)
- Injection in subarachnoid space surrounding spinal cord
- Programmable pump system
- Maximize benefit (including analgesia), minimize side effects
- Drawbacks
a. Malfunction of pump system
b. Tolerance require dose increase over time
c. Severe withdrawal syndrome possible: merits black box warning
15
Dantrolene (Dantrium)
- Inhibits Calcium release from sarcoplasmic reticulum in skeletal muscle cells (RyR Antagonist); inhibits muscle contraction
- Indicated for severe spasticity regardless of cause, CVA, CP, spinal cord lesions, MS, malignant hyperthermia
- Adverse Effects: Generalized muscle weakness, hepatotoxicity
16
Gabapentin (Neurontin)
- Mechanism: Enhances GABA activity (antiseizure)
- Uses: Good in combination with others; also indicated fro chronic pain
17
Tizanidine (Zanaflex)
- Mechanism: Alpha 2 receptor agonist
- Related to clonidine, but less BP effects
- Inhibitory actions in spinal cord
a. Presynaptic inhibition of excitatory interneurons
b. Decreased activity of alpha motor neurons
- Sedation and dry mouth similar to clonidine
18
Botulinum Toxin
- Mechanism: Binds to presynaptic vesicles and inhibits release of ACh; produces paralysis rather than relaxation
- Uses: Indicated for dystonias and other specific muscle spasms; local injection paralyzes specific muscles
- Also approved to treat excess sweating, wrinkles, chronic migraine, and urinary incontinence in patients with spinal injuries
- Drawbacks: effects wear off in 2-3 months; limited number of muscles may be treated in a given session
- CAUTION: May spread from injection site
19
Tubocurarine (Curare)
- Nondepolarizing blocker (receptor antagonist)
- Competitive, reversible Nm receptor antagonist.
a. physically blocks ion channels associated with N receptors
b. actions can be reversed by ACh
c. No effect on M receptors
- Muscle Paralysis Order: Head and neck, limbs, respiratory muscles
- Adverse effects: Histamine release, hypotension, inhalation anesthetics and certain antibiotics enhance NMJ blockade
20
Antidotes to Curare
- AchE Inhibitors
- Sugammadex (Bridion)
21
Endogenous Opioid Peptides
- Inhibitory transmitters which modify most aspects of pain transmission and perception.
- Modulate hormonal fluctuations, thermoregulation, stress, anxiety, GI function, pain
- Three families of peptides have been identified
a. Pentapeptides (met and leu-enkephalin)
b. Dynorphins
c. Endorphins
22
Opioid Mixed Agonists/Antagonists
PROTOTYPES
- Butorphanol (Stadol)
- Buprenorphine (Buprenex, Butrans)
GENERAL
- Analgesia due primarily to Kappa receptor activity
- Only partial agonists or antagonists at mup receptor
a. may displace stronger agonists from mu receptor sites
b. may precipitate withdrawal in addicts
- Mized receptor activity results in "ceiling" (less efficacious) analgesic and respiratory depression with decreased dependence liability
ADVERSE SIDE EFFECTS
- Dysphoria
- Anxiety
- Hallucinations
23
Opioid Antagonist Prototypes
PROTOTYPES
- Naloxone (Narcan) iv
- Naltrexone (ReVia) po
GENERAL
- Pure competitive antagonists: highest affinity for mu receptors
- Used to treat overdoses, accelerate postop recovery, or treat dependence
- Precipitate withdrawal syndrome in opioid addicts
24
Prototype Opioid Analgesic
Prototype: Morphine
PHARMACOLOGICAL ACTIONS: CNS
- General
a. With Pain: Analgesia, euphoria, drowsiness, mental clouding
b. Without Pain: Nausea, apathy, dysphoria prominent
- Analgesia
- Pupillary Constriction (good indicator of abuse; no tolerance)
- Respiratory Depression
- Suppression of Cough Reflex
- Nausea and vomiting via stimulation of chemoreceptor trigger zone in brainstem
GI TRACT
- Decreases glandular secretions
- Decreases propulsive peristalsis, increases non-propulsive contractions
- Increase biliary tract pressure
GENITOURINARY TRACT
- Increase bladder detrusor and sphincter tone: urinary retention and exacerbation of pain due to kidney stones
- May prolong labor
PHARMOKINETICS
- Erratic po absorption: extensive first pass metabolism
- easily crosses placental barrier and fetal BBB
- Hepatic Metabolism: active metabolite
ADVERSE EFFECTS
- Tolerance: lack of effectiveness after repeated dosing
- Dependence: Higher doses required for sufficient pain relief: lacrimation, chills, goosebumps, hyperthermia, mydriasis, anxiety, hostility
- Overdose: Stupor, coma, respiratory depression, hypotension
25
Naloxone (Narcan, iv)
- Opioid antagonist
- Occupy opioid receptor without producing a pharmacological effect
- Reverse CNS and GI effects of morphine
- Several injections may be required (1 hr half life)
- May precipitate sudden and intense withdrawal in opioid addicts
26
Naltrexone (Vivitrol)
- Opioid antagonist
- Given po, longer half life (10 hours)
- Indications: opioid dependence, apnea in children, alcohol dependence
27
Methadone
- Similar to morphine, with longer duration of action and a longer, but less intense withdrawal syndrome
- Used primarily in heroin detoxification and maintenance programs
28
Meperidine (Demerol)
- More consistent oral absorption than morphine
- Primary Metabolite: Normeperidine
a. May produce CNS excitation and convulsions
b. Less respiratory depression than morphine
- Fewer GI and GU tract effects
- Indicated for labor pain
29
Fentanyl (Sublimaze)
- Anesthesia
a. Adjunct: Sedative, anxiolytic and analgesic properties
b. Used alone for certain types of CV surgery
c. Regional analgesia via direct injection into epidural spaces of the spinal cord (morphine also used)
- Transdermal system available for chronic pain (Duragesic)
- Iontophoretic system (Ionsys)
- Buccal/Transmucosal Admin: Lollipop (Actiq)
30
Partial Mu Agonists with Lower Maximum Efficacy
Codeine
- metabolized in part to morphine
- genetic variation in the P450 enzyme producing morphine result in decreases or increases in analgesic and respiratory depressant effect
31
Oxycontin
- Oxycodone controlled release form
- To be swallowed whole to release drug over 24 hour
- Extensive abuse
32
Targiniq ER
- Oxycodone + naloxone
- Designed to prevent abuse via inhalation or injection
33