Exam 2 Questions (Part 2)

Question 1

Procaine (Novocain)

Answer 1

• Rapidly metabolized by blood cholinesterase to an allergen
• Allergic reactions occur
• Intermediate onset, short duration

Question 2

Bupivacaine (Marcaine)

Answer 2

• 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

Question 3

Levobupivacaine (Chirocaine)

Answer 3

• active optical isomer of Bupivacaine (Marcaine)

Question 4

Exparel

Answer 4

Long acting liposomal suspension approved for post surgical pain management

Question 5

Lidocaine (Xylocaine)

Answer 5

• Rapid onset, intermediate duration of action
• Same metabolism pathway as bupivacaine
• Transdermal patch: Lidoderm

Question 6

Peripheral Nerve Block

Answer 6

• Injection near nerve trunk

- Common for dental procedures, surgery on single extremity, etc

Question 7

Epidural

Answer 7

• Space between bone and dura mater
• Large and accessible, route common for obstetrics
• Type of central neural block

Question 8

Intrathecal

Answer 8

• Spinal Nerve Blockade: Subarachnoid Space
• Most effective
• Most dangerous
• Patient position and solution density determine area blocked

Question 9

Central Nerve Blocks (General)

Answer 9

• Two types: Epidural and Intrathecal
• Postural headaches most common complaint
• Risk of hematoma if LMWH anticoagulants given concurrently

Question 10

Sympathetic Block

Answer 10

• Sympathetic activity increases with complex regional pain syndrome
• Block usually occurs with central neural block, but can specifically inject area surrounding nerve chain ganglia

Question 11

Diazepam (Valium): Skeletal Muscle Relaxant

Answer 11

• 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

Question 12

Carisoprodol (Soma, Vanadem)

Cyclobenzaprine (Flexeril)

Answer 12

• 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

Question 13

Baclofen (Lioresal)

Answer 13

• 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

Question 14

Intrathecal Administration for Baclofen (Lioresal)

Answer 14

• 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

Question 15

Dantrolene (Dantrium)

Answer 15

• 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

Question 16

Gabapentin (Neurontin)

Answer 16

• Mechanism: Enhances GABA activity (antiseizure)

- Uses: Good in combination with others; also indicated fro chronic pain

Question 17

Tizanidine (Zanaflex)

Answer 17

• 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

Question 18

Botulinum Toxin

Answer 18

• 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

Question 19

Tubocurarine (Curare)

Answer 19

• 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

Question 20

Antidotes to Curare

Answer 20

• AchE Inhibitors

- Sugammadex (Bridion)

Question 21

Endogenous Opioid Peptides

Answer 21

• 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

Question 22

Opioid Mixed Agonists/Antagonists

Answer 22

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

Question 23

Opioid Antagonist Prototypes

Answer 23

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

Question 24

Prototype Opioid Analgesic

Answer 24

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

Question 25

Naloxone (Narcan, iv)

Answer 25

- 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

Question 26

Naltrexone (Vivitrol)

Answer 26

- Opioid antagonist - Given po, longer half life (10 hours) - Indications: opioid dependence, apnea in children, alcohol dependence

Question 27

Methadone

Answer 27

- Similar to morphine, with longer duration of action and a longer, but less intense withdrawal syndrome - Used primarily in heroin detoxification and maintenance programs

Question 28

Meperidine (Demerol)

Answer 28

- 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

Question 29

Fentanyl (Sublimaze)

Answer 29

- 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)

Question 30

Partial Mu Agonists with Lower Maximum Efficacy

Answer 30

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

Question 31

Oxycontin

Answer 31

- Oxycodone controlled release form - To be swallowed whole to release drug over 24 hour - Extensive abuse

Question 32

Targiniq ER

Answer 32

- Oxycodone + naloxone | - Designed to prevent abuse via inhalation or injection

Question 33

Tramadol (Rybix, Ryzolt, Ultram)

Answer 33

- Weak mu agonist, strong inhibitor of NE/5HT reuptake - Unique adverse effect: seizures - Caution: May cause respiratory depression in children