Opioids (Dr. E's Lecture) Flashcards Preview

Drug Cards > Opioids (Dr. E's Lecture) > Flashcards

Flashcards in Opioids (Dr. E's Lecture) Deck (71)
Loading flashcards...
1

What does the word "opioid" refer to?

all substances, natural and synthetic, that bind to opioid receptors and produce an agonist effect

2

What are the naturally occurring opioids?

Morphine

3

What are the Semisynthetic opioids?

Analogs of morphine
Heroin, Hydromorphone, Codeine

4

What are the 4 subdivisions of the synthetic (exogenous) opioids?

1. Morphinan derivatives
2. Diphenyl derivatives
3. Benzomorphans
4. Phenylpiperidines

5

What are the synthetic opioids of morphinan derivatives?

Levorphenol
Butorphenol

6

What are the synthetic opioids of Diphenyl derivatives?

Methadone

7

What are the synthetic opioids of Benzomorphans?

Phenazocine
Pentazocine

8

What are the synthetic opioids of Phenylpiperidines?

Meperidine
Fentanyl
Alfentanil
Sufentanil
Remifentanil

9

how does a partial agonist work?

regardless of the dose the drug cannot produce full mu receptor effects like morphine

10

How do agonist/antagonists work?

agonist at one receptor, kappa and antagonist at mu reversing respiratory depression

11

What are the 3 endogenous agonists?

Enkephalins, Endorphins, Dynorphins

12

Opioid receptors are activating pain _____________ systems. which are?

-Antinocioceptive
-Inhibiting excitatory Neurotransmitters (ie substance P)

13

Where are mu receptors primarily?

in the brain and spinal cord

14

Tell me all about the mu-1 receptor

-Analgesia
-Euphoria
-Supraspinal (and spinal to lesser degree)
-Miosis
-Bradycardia (direct central vagal activity)
-Urinary retention
-All endogenous and synthetic agonists act on these receptors

15

Tell me all about the mu-2 receptors

-Hypoventilation
-Physical dependence
-Spinal analgesia (and some supraspinal)
-Constipation (marked)
-all endogenous and synthetic agonists act on these receptors

16

tell me about the kappa receptor

-Supraspinal and spinal analgesia
-Dysphoria
-Sedation
-Miosis
-Only DYNORPHINS act on these receptors
-some agonist/antagonist such as Butorphenol also act there

17

Tell me about the delta receptor

-Supraspinal and spinal analgesia
-Hypoventilation
-Physical dependence
-Constipation (minimal)
-urinary retention
-Only ENKEPHALINS act on these receptors

18

In a nutshell, tell me all of the effects of Mu-1

-supraspinal
-bradycardia
-euphoria
-sedation, prolactin release
-hypothermia
-catalepsy
-Indifference to environmental stimulus
-miosis
-urinary retention
-low abuse potential

19

In a nutshell, tell me all of the effects of Mu-2

-spinal
-bradycardia
-resp. depression
-euphoria
-pruritis
-dopamine turnover
-possible growth hormone release
-miosis
-inhibition of peristalsis
-n/v
-urinary retention
-Can cause physical dependence

20

In a nutshell, tell me about the effects of Kappa

-Supraspinal, spinal
-possible resp. depression
-sedative dysphoria
-psychotomimetic reactions (hallucinations, delirium)
-miosis
-diuresis (inhibition of vasopressin release)
-low abuse potential

21

In a nutshell, tell me about the delta receptor

-supraspinal, spinal
-modulate mu receptor activity
-Resp. depression
-Urinary retention
-pruritis
-physical dependence

22

What type os receptor is the opioid receptor?

G protein coupled- G-alpha-i and G-alpha-o

23

What are the effects of an opioid binding to the receptor? (4)

-(+) K channel inward rectifier (increases outward K flow to hyperpolarize cell)
-(-) decreases conversion of adenyl cyclase to cAMP
-(+) MAPK cascade: 1. gene expression and 2. Phospholipase A2 (production of prostaglandins and leukotrienes)
-(-) Voltage-dependent Ca channel (N-type)->suppression of neurotransmitter release (sub. P)

24

What is the MOA of the opioids on the receptors?

-opioid receptors exist on the peripheral ends of primary afferent neurons
-activation of receptors either
1. directly decreases neurotransmission or
2. inhibits the release of excitatory neurotransmitters (ie. Substance P)

25

What are the pharmacokinetic features of the opioids regarding the onset of action?

-Weak Bases
-Only unionized & unbound opioids can diffuse from blood to target tissue thus:
~higher % unionized the higher diffusible fraction and the faster the onset
~higher % unbound the faster the onset

26

Why does morphine have a slower onset of action?

because its % nonionized at physiologic pH is only 23%

27

Why does Alfentanil have a very rapid onset of action?

b/c it has a high % unionized (89%) at pH 7.4

28

What are the pharmacokinetic features of the opioids regarding the volume of distribution?

-Vd= dose of drug at time 0/ plasma [ ] b4 elimination occurs
-Larger Vd equates to a longer duration of action
-Vd related to lipid solubilty (1st, most important parameter), protein binding (2nd), (and 3rd molecular size/structure)
-higher lipid solubility=Larger Vd, longer DOA!
~more lipid soluble the more potent these drugs are
-Redistribution and fast termination of effect b/c of drug redistributing to other sites and is gone from the effect sites

29

What is the pKa, %non-ionized, Protein binding(%), Vc, Vd, Clearance, E 1/2 life (hr), partition co-ef (o/w) of MORPHINE?

pKa= 7.9
%nonionized= 23
Protein binding=35%
Vc=0.23 L/kg
Vd=2.8 L/kg
Clearance=15.5 ml/kg/min
E 1/2L= 1.7 - 3.3hr
o/2 partition coe= 1

30

What is the pKa, %non-ionized, Protein binding(%), Vc, Vd, Clearance, E 1/2 life (hr), partition co-ef (o/w) of MEPERIDINE?

pKa= 8.5
% nonionized= 7
protein binding= 70%
Vc= 0.6 l/kg
Vd=2.6 l/kg
Clearance=22.7 ml/kg/min
E1/2L= 3-5hrs
o/w partition coe= 21