Slattery

Question 1

Opiate

Answer 1

drug derived from opium poppy

Opium, morphine, codeine

Question 2

Opioid

Answer 2

more generic term; all substances, endogenous and exogenous, that bind opioid receptors

Endorphins (endogenous)
Morphine, also an opiate
Fentanyl, synthetic so not an opiate

Question 3

Narcotic

Answer 3

originally meant sleep inducing (Greek “narcos”)

Now a legal term encompassing illicit drug use

Includes opioids, cannabinoids, stimulants, etc.

(avoid use of this term…)

Question 4

Opioid Receptors

Answer 4

Mu (μ)
Analgesia
Respiratory depression
Decreased gastrointestinal motility
Physical Dependence

Kappa (κ)
Analgesia
Sedation
Decreased gastrointestinal motility

Delta (δ)
Modulates μ activity

Question 5

Endogenous Opioids

Answer 5

Peptide ligands generated from pro-hormone precursors

Mu (μ) ligands
Endorphins
Endomorphins

Kappa (κ) ligands
Dynorphins

Delta (δ) ligands
Enkephalins

ORL1 ligands
Nociceptin
Orphanin

Question 6

Opioid Receptor Signal Transduction

Presynaptic inhibition of afferent neurons

and

Postsynaptic inhibition

Answer 6

–presynaptic–

Receptor activation blocks voltage-gated Ca2+ channels

Reduced release of glutamate and substance P

–postsynaptic–

Receptor activation opens K+ channels
Inhibit excitation of postsynaptic neuron

Question 7

Opioid Receptor Signal Transduction

Descending inhibitory pathway

Answer 7

Pain inhibitory neuron indirectly activated

Opioid receptor activation blocks release of GABA from inhibitory interneuron (inhibitory of inhibition!)

Greater inhibition of nociceptive processing in dorsal horn of spinal cord

Putative sites of action:
Midbrain
Medulla
Spinal cord

Question 8

Acute overdose treatment for opiod use…

Addiction treatment for opiod use…

Answer 8

Naloxone
Short duration of action
Need multiple doses: single dose could cause relapse after 1-2 hrs

Injection to avoid first pass

Naltrexone
Orally effective
Single dose, alternate days blocks heroin effects
Prevent relapse in opioid addiction and alcohol addiction

Question 9

Arachidonic acid is acted upon by one of two enzymes:

Answer 9

1. Lipoxygenase to generate leukotrienes (inflammatory/alergic)
2. **Cyclooxygenase **to generate:
   - Prostaglandins
   - Thromboxane
   - Prostacyclin

Question 10

Cyclooxygenase (COX)

Answer 10

Target of NSAIDS

Two isoforms
COX1: normal physiology
Gastric cytoprotection, vasodilation, platelet aggregation

COX2: inducible; Induced by acute inflammation
Inhibited by glucocorticoids

Question 11

Reye’s Syndrome

Answer 11

Associated with aspirin use in presence of viral infection (varicella, others)

Rare, often fatal

Children at highest risk

Question 12

Indomethacin

Answer 12

Analgesic, antipyretic, anti-inflammatory (NSAID)

most potent COX inhibitor

Significant toxicity

Used to treat patent ductus arteriosus
Congenital disorder, ductus arteriosus fails to close after birth
Possibly mediated by effect on PGE2

Question 13

Ketorolac

Answer 13

NSAID, can be injected (IM, IV)

Can replace morphine if opioid addiction is an issue

When combined with opioid, can decrease opioid requirement by 25-50%

Question 14

Celecoxib

Answer 14

A selective COX2 inhibitor

physiology

COX1: normal physiology, constitutive activity
COX1 inhibition responsible for NSAID side effects

COX2: induced during inflammation
COX2 inhibition responsible for NSAID therapeutic effects

**watch for increased risk of MI and stroke (past associated with Rofecoxib and Valdecoxib)

Question 15

Acetaminophen

Answer 15

Tylenol

Not anti-inflammatory
Analgesic and antipyretic

mechanism unclear

Toxic, free radical metabolite in liver
_Hepatic necrosis_ (alcohol exacerbates)

Advantages

Minimal GI irritation
No effect on bleeding
No effect on respiration

Question 16

“aspirin hypersensitivity”

Answer 16

Allergy- or anaphylaxis-like symptoms: Rhinitis, profuse watery secretions, bronchial asthma, bronchoconstriction, hypotension, vasomotor collapse, coma

Not immune (immunoglobulin) mediated…

Likely due to shunting of arachidonic acid into leukotriene pathway

Treat with epinephrine

Question 17

How do you treat acetaminophen toxicity?

Answer 17

Use N-acetylcysteine as scavenger drug

Exogenous equivalent of glutathione

Question 18

Local anesthetics block ________ and, therefore, conduction of action potential.

Drug ionization and pK?

Answer 18

sodium channels

only the ionized form of drug interacts with and blocks Na+ channel

Lower pK drugs have more rapid onset of action

Question 19

opioid overdose symptomes

Answer 19

Euphoria, drowsiness, slurred speech, and pupillary constriction (miosis)