Pharmacology - Narcotics

Question 1

What are the three types of endogenous opioids?

Answer 1

enkephalins, endorphins, and dynorphins

Question 2

What accounts for “Stress analgesia” (e.g. in war etc.)

Answer 2

β-endorphin and ACTH share common precursor and are co-released with stress - result is release of cortisol + endogenous opioids

Question 3

3 common functions of endogenous and exogenous opiods:

Answer 3

inhibition of pain perception,

modification of
gastrointestinal/autonomic function

reward properties

Question 4

Name and function of 4th endogenous opioid discovered in 1995

Answer 4

nociceptin/orphanin FQ

drug reward and reinforcement, feeding, learning and memory

Question 5

4 types of opioid receptors and corresponding chromosomes

Answer 5

MOR - mu opioid receptor, chromosome 6)
DOR - delta opioid receptor, chromosome 1)
KOR - kappa opioid receptor, chromosome 8)
NOR - N/OFQ opioid receptor, chromosome 20).

Question 6

Common features of opioid receptors

Answer 6

All are G protein-coupled receptors, with extracellular,
transmembrane, and intracellular domains.

Classes have homology in the receptor types

Question 7

How are opioid receptors activated?

Answer 7

Ligands are recognized on the extracellular domain; G proteins bind to the
cytoplasmic aspect of the receptor, and activate/bind GTP

Question 8

Signaling pathway initiated by ligand binding to opioid GCPRs

Answer 8

• Adenylyl cyclase activity is inhibited
• Voltage-gated Ca2+ channels on the cell membrane close
• K+ current is stimulated through several channels
• PKC and PLCβ are activated

Question 9

How do mu opioid receptors influence neuronal excitability?

Answer 9

via “disinhibition” of presynaptic release of GABA

Question 10

What does activation of opioid receptors do?

Answer 10

agonists inhibit release of substance P and
ascending transmission of pain from dorsal horn neurons by activating pain
control circuits descending from the midbrain

Question 11

T/F exogenous opioids are alkyloids where as endogenous opioids are peptides

Answer 11

true

Question 12

binding site of peptides

Answer 12

extracellular loops in combination

with the core

Question 13

What accounts for different effects and side effects as well as metabolism of different ligands?

Answer 13

small chemical modifications of the

ligands result in changes in signal transduction sequences

Question 14

T/F tollerance toward and opioid over time results in decreased side effects

Answer 14

True

Question 15

tollerance is associated with:

Answer 15

decreased effectiveness, and decreased side effects,

with repeated administration

Question 16

Molecular basis for tolerance involves:

Answer 16

phosphorylation or receptor internalization

Question 17

Side effects of opioids

Answer 17

Analgesia
Mood alteration; stimulation of reward centers
Miosis
Convulsions
Decreased respiration
Cough suppression (antitussive)
Nausea and emesis
Constipation
Urinary retention
dermal vasodilatation and urticaria (hives)

Question 18

What causes opioid induced uticaria (itching/hives)

Answer 18

Opioids stimulate mast cell degranulation and release of histamine

can be managed with an antihistamine (non sedating are preferred to avoid synergy with analgesic e.g. loratadine, fexofenadine)

Question 19

What causes nausea and emesis

Answer 19

Direct stimulation of the
medullary trigger zone for emesis

Delayed gastric emptying

Question 20

T/F cough suppressant activity is unrelated to respiratory depression

Answer 20

True - may be mediated

through receptors unrelated to GPCRs

Question 21

Mechanism for opioid induced decrease in respiration

Answer 21

direct stimulation

of brainstem respiratory centers

Question 22

T/F Opioids lower seizure threshold

Answer 22

true

Question 23

What causes opioid induced miosis? What receptor is involved?

Answer 23

direct stimulation of oculomotor complex to effect papillary constricution (mimicking parasympathetic response)

Question 24

Mechanism for mood alteration/reward

Answer 24

opioids directly stimulate the dopamine pathway in the ventral striatum (VTA)
– stimulates limbic functions (e.g. motivation and affection)

Question 25

T/F opioid induced miosis and constipation lessen with tolerance

Answer 25

False

Question 26

T/F oral, sublingual, transmucosal, rectal absorption of opioids undergo significant first pass metabolism

Answer 26

True

Question 27

T/F opioid absorption is slow

Answer 27

False - rapid!

Question 28

Steps of opioid metabolism:

Answer 28

Occurs in liver - glucuronidation is primary metabolic pathway Opioids and their metabolites are then excreted by the kidney

Question 29

Factors that require dose adjustment to prevent overdose:

Answer 29

cirrhosis, chronic or acute renal insufficiency, dehydration

Question 30

Who should NOT have regular opioid dosing but can be treated on PRN basis?

Answer 30

oliguric or anuric patients

Question 31

Peak serum concentration times based on administration method (IV, subQ, intramuscular, oral)

Answer 31

5-10 minutes I.V. 30 minutes subQ or intramuscular administration, one hour for oral

Question 32

What is “bolus effect”? When does it occur?

Answer 32

swings in plasma concentration, with sedation occurring as a result of high blood levels and breakthrough pain when the serum levels are at trough most commonly with intravenous or intramuscular administration

Question 33

Pain medications for mild pain vs moderate pain vs severe pain (3 step-laddar from WHO) :

Answer 33

``` Step 1: mild ASA (aspirin) Acetaminophen NSAIDs +/- adjuvants ``` ``` Step 2: moderate A/Codeine A/Hydrocodone A/Oxycodone A/Dihydrocodeine Tramadol +/- adjuvants. ``` ``` Step 3: severe Morphine Hydromorphone Methadone Levorphenol Fentanyl Oxycodone +/-adjuvants ```

Question 34

T/F acceptable adjuvants to narcotics include acetaminophen, NSAIDS, tricyclics, anticonvulsants

Answer 34

True

Question 35

benefit of adjuvants

Answer 35

“spare” use of | higher dose opioids

Question 36

T/F morphine-6-glucuronide (M-6) is an active metabolite while morphine-3-glucuronide (M-3) is inactive

Answer 36

True

Question 37

T/F codiene itself is largely inactive but undergoes demethylation to active morphine

Answer 37

true

Question 38

T/F only 10% of the ingested dose of codeine is demethylated | to morphine

Answer 38

True

Question 39

Conversion of codeine to morphine is dependent on

Answer 39

the CYP2D6 pathway

Question 40

T/F 10% of Caucasions are unable to convert codeine to morphine and have nausea and vomiting instead of analgesia

Answer 40

true

Question 41

T/F antitussive effect of codiene involves | non-opioid receptors that bind codeine itself

Answer 41

true

Question 42

synthetic codeine analog, and a weak mu agonist, which has a demethylated metabolite that is a more potent analgesic developed to be less addictive but still has adictive potential less constipating than morphine effective for moderate pain

Answer 42

Tramadol

Question 43

highly lipid soluble, strong opioid used intravenously and in a transdermal patch.

Answer 43

Fentanyl

Question 44

T/F suspected MOA of tramadol is inhibition of | norepinephrine and serotonin uptake

Answer 44

True

Question 45

extended duration of action with 90% | bound to plasma proteins. accumulates in tissues - used as maintenance treatment for heroine addiction

Answer 45

Methadone

Question 46

Doing changes of methadone and fentanyl patches should be restricted to

Answer 46

1/week because of long half life

Question 47

opioid no longer in use due to toxic metabolite that causes mental status changes and seizures

Answer 47

Meperidine metabolite normeperidine

Question 48

2 most common opioid antagonists

Answer 48

Naloxone | Naltrexone

Question 49

approved for use in the treatment of alcoholism

Answer 49

Naltrexone

Question 50

useful in the treatment of acute opioid toxicity. Can only | be administered parenterally (IM, SQ, IV), and has a short half life

Answer 50

Naloxone

Question 51

MDD of acetaminophen

Answer 51

3000 mg in 24 hours

Question 52

Withdrawal symptoms brought about by abrupt discontinuation of opioids in tollerant patients ideal dose reduction paradigm?

Answer 52

``` yawning, sweating, piloerection, vomiting, pain shit-squirts muscle spasms ``` reduced by half every 2 to 3 days

Question 53

T/F With parenteral dosing half life is shorter and doses must be given MORE frequently and can result in bolus effect solution is continuous IV/intrathecal infusion

Answer 53

true

Question 54

Dosing paradigms for immediate vs extended release opioids vs transdermal fentanyl patches

Answer 54

immediate release preparations is every 4 hours extended release preparations is every 8-24 hours, usually every 12 hours every 72 hours

Question 55

T/F Oral breakthrough prescriptions should always be immediate release preparation, actual dose is calculated as 10% of the total 24 hour dose

Answer 55

True

Question 56

What is Equianalgesic dosing?

Answer 56

dose equivalent when switching from one opioid to another oral doses are usually two or three times higher than parenteral doses (e.g. I.V. /I.M) because of first pass metabolism

Question 57

T/F cross tolerance to another opioid is usually incomplete so dosing is adjusted downward by 25-50% of the calculated equianalgesic dose.

Answer 57

true

Question 58

T/F True opioid allergies are rare - history of urticaria alone probably side effect, not an allergy, but urticaria and bronchospasm might be

Answer 58

true

Question 59

T/F overdoses have quadupled in past 12 years

Answer 59

true

Question 60

What is I-STOP? What has it resulted in?

Answer 60

NYS Prescription Monitoring Program - Starting in 2015 prescribers must check a state database before writing prescriptions for opioids + pharmacies file data for prescriptions to central database less opioid prescribing