Pharmacology - Narcotics Flashcards Preview

MS 2 - Unit 3 > Pharmacology - Narcotics > Flashcards

Flashcards in Pharmacology - Narcotics Deck (60):
1

What are the three types of endogenous opioids?

enkephalins, endorphins, and dynorphins

2

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

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

3

3 common functions of endogenous and exogenous opiods:

inhibition of pain perception,

modification of
gastrointestinal/autonomic function

reward properties

4

Name and function of 4th endogenous opioid discovered in 1995

nociceptin/orphanin FQ

drug reward and reinforcement, feeding, learning and memory

5

4 types of opioid receptors and corresponding chromosomes

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).

6

Common features of opioid receptors

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

Classes have homology in the receptor types

7

How are opioid receptors activated?

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

8

Signaling pathway initiated by ligand binding to opioid GCPRs

• 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

9

How do mu opioid receptors influence neuronal excitability?

via "disinhibition" of presynaptic release of GABA

10

What does activation of opioid receptors do?

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

11

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

true

12

binding site of peptides

extracellular loops in combination
with the core

13

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

small chemical modifications of the
ligands result in changes in signal transduction sequences

14

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

True

15

tollerance is associated with:

decreased effectiveness, and decreased side effects,
with repeated administration

16

Molecular basis for tolerance involves:

phosphorylation or receptor internalization

17

Side effects of opioids

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)

18

What causes opioid induced uticaria (itching/hives)

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)

19

What causes nausea and emesis

Direct stimulation of the
medullary trigger zone for emesis

Delayed gastric emptying

20

T/F cough suppressant activity is unrelated to respiratory depression

True - may be mediated
through receptors unrelated to GPCRs

21

Mechanism for opioid induced decrease in respiration

direct stimulation
of brainstem respiratory centers

22

T/F Opioids lower seizure threshold

true

23

What causes opioid induced miosis? What receptor is involved?

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

24

Mechanism for mood alteration/reward

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

25

T/F opioid induced miosis and constipation lessen with tolerance

False

26

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

True

27

T/F opioid absorption is slow

False - rapid!

28

Steps of opioid metabolism:

Occurs in liver - glucuronidation is primary metabolic
pathway

Opioids and their metabolites are then excreted by the kidney

29

Factors that require dose adjustment to prevent overdose:

cirrhosis,
chronic or acute renal
insufficiency,
dehydration

30

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

oliguric or anuric patients

31

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

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

32

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

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

33

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

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

34

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

True

35

benefit of adjuvants

“spare” use of
higher dose opioids

36

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

True

37

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

true

38

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

True

39

Conversion of codeine to morphine is dependent on

the CYP2D6 pathway

40

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

true

41

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

true

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

Tramadol

43

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

Fentanyl

44

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

True

45

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

Methadone

46

Doing changes of methadone and fentanyl patches should be restricted to

1/week because of long half life

47

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

Meperidine

metabolite normeperidine

48

2 most common opioid antagonists

Naloxone
Naltrexone

49

approved for use in the treatment of alcoholism

Naltrexone

50

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

Naloxone

51

MDD of acetaminophen

3000 mg in 24 hours

52

Withdrawal symptoms brought about by abrupt discontinuation of opioids in tollerant patients

ideal dose reduction paradigm?

yawning,
sweating,
piloerection,
vomiting,
pain
shit-squirts
muscle spasms

reduced by half every 2 to 3 days

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

true

54

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

immediate release preparations is every 4 hours

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

every 72 hours

55

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

True

56

What is Equianalgesic dosing?

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

57

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

true

58

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

true

59

T/F overdoses have quadupled in past 12 years

true

60

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

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

Decks in MS 2 - Unit 3 Class (45):