Lecture 3 - NSAIDs and Opioids Flashcards Preview

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Flashcards in Lecture 3 - NSAIDs and Opioids Deck (27):
1

Opioid agonists:
- what is the natural ligand to opioid receptors ?
- where in the brain are opioid receptors found?
-

Natural Ligand: Endorphins


Locations of Receptors:
Brain -- PAG, Amydala, Hypothalamus, corpus stiratum
Spinal cord

2

Mu Opioid Agonists --
what is the mechanism of action of most opioid agonists ?

Receptors are both pre and post synaptic:

• Pre synaptic: When Mu agonist binds, decreased conductance of voltage gated calcium channels/less likely for the vesicles to merge and release contents to synaptic cleft

• Post Synaptic level -- Increase in K conductance; hyperpolarization of the post synaptic membrane; less likely to reach action potential

3

what are the three different classes of opioid receptors? which is most likely to cause side effects?

• Mu -- the workhorse for pain relief; also most of the associated unwanted side effects from these drugs (respiratory depression, for example)

• Kappa -- contribute to spinal analgesia; also some unwanted side effects such as constipatin, miosis, sedation

Delta -- contribute to analgesia

4

Opioid agonist effects/side effects at the CNS level?

Analgesia
Sedation
Respiratory System -- Dost dependent depression (depressant effect on brain stem ventilation centers; loss of CO2 responsiveness)

Muscle rigidity

Miosis

5

Opioid agonist effects/side effects at the cardiovascular level?

-- describe the potential mechanisms for this

CVD-- Hypotension

Mechanism:
Bradycardia -- from decreased central sympathetic tone
Increased activity of vagal nerves --
Depressant at the SA node
Histamine Release -- vasodilation; decreased preload via venous pooling

6

Opioid agonist effects/side effects at the GI level?

constipation -- decreased peristalsis; increased sphincter tone; more water resorption

Nausea and Vomiting -- direct stimulation of chemo-receptor trigger zone on the 4th ventricle


7

side of effects of Mu agonists at the level of the GU, skin and placenta?


• The GU -- increased tone and peristalsis of the ureter; tone of vascular sphincter is enhanced; urinary retention
• The Skin -- histamine release, cutaneous vasodilation, urticaria
• Placenta -- No a barrier for transfer; neonatal ventilator depression or even neonatal dependence is a possibility

8

what three factors influence ability of a drug to cross the BBB

Lipid Solubility (higher lipid solubility, the easier the cross)
Charge
Drug is un bound to protein

9

MORPHINE

- - mechanism?
CNS penetration?
- Onset?
Peak effect?
Duration?
Metabolism/metabolites?
excretion?
be careful giving this drug to patients with....

Mu agonist

CNS Penetraton -- poor -- delay in the crossing BBB

• Onset -- 15 to 30 minutes;
• Peak effect: (Blood to brain); 45-90 minutes
• Duration: 4 hours

Metabolism via the Liver
15-25% M6G Metabolite -- still active; prolonged effects in the body;
Excreted via the kidneys
Becareful giving to patients with Renal insufficiency

10

• Meperidine (Demerol)
- Mechanism?
- potency compared to morphine/
- Duration?
- side effects?
- Metabolism/MEtabolites?
- Clinical uses?

- Synthetic opioid agonist that also has anti-muscarininc effects
- 10% as potent as morphine
- duration - 2-4 hours
- Metabolism: Normeperidine, which can cause clonus and seizures

- Side effcts: Antimuscarinics effects, histamine release, decreaed myocardial contractility


- Only current clinical use: Post operative shivering

11

Fentanyl
Potency compared to morphine? why?
onset vs dduration?
Metabolism?

100x more potent that morphine -- more lipid soluble, fast onset, long context sensitivehalf life

Fast onset --
Short duration -- redistributes quickly bc of thoses same properties

no active metabolites

No histamine release

12

which two opioid agonists can cause histamine release?

Morphine, Meperidine

13

Sufentanil
- potency compared to fentanyl
- onset?
- duration ?
- Metabolsim?
Clinical uses?

10x more potent than fentayl
Very lipopholic
very fast Onset
Short duration (rapid redistribution)
No active metabolites
Used for intra-operative infusions

14

Remifentanil
- potency compared to fentayl
- Chemical structure? what is the significance of this?
-peak effect?
- Duration?
-Metabolism?

Similar potency to fentanyl

Ester linkage -- metabolised by estase in the blood stream
therefore can be used in patients with liver or kidney failure
No toxic metabolites

Peak effect - 1 minute
extremely short, and very predictable, duration

15

Methadone
- mechanism?
- uses?
Metabolims?
considerations of dosaging?

Mu opioid agonist; also an NMDA receptor Antagonist; both help with pain modulation

• Used for chronic pain; used for weaning off heroin


• Half-life is unpredictable (16-120 hours?)
• The drug can accumulate; can result in respiratory arrest
• Have to start off on small doses;

16

• Hydromorphone (dilaudid)

- potency compared to morphine?
-

• 5x a potent as morphine
• Same side effect profile as morphine
• Safer in renal failure patients

17

Mixed Drugs: Opioid receptor agonists/Antagonists --

what are they ?
Mechanism? (which receptors)
Advantages?
who are they used for?

• Butorphanol, nalbuphine, buprenorphine
Mixed Mechanism
Partial agonists at one receptor (eg Mu)
Competitive antagonist at another (Delta, Kappa)

Advantages -- good analgesic, but avoid some of the side effects, such as respiratory depression

• Generally reserved for patients who cannot tolerate pure agonist

18

Opioid Antagonists:

what are they?
mechanism?
clinical use?
side effects?
metabolism/duration/

Naloxone, naltrexone
• High affinity for opioid receptor ---
• Will displace the agonist; used for rescue
side effects: Withdrawal; increased SNS activity; such as pain perception, tachy, HTN

naloxone --
Duration -- 30-45 minutes
Metabolized in theliver

19

NSAID
Mechanism
Therapeutic profile

Mechnaims -- COX Inhibtion



Therapeutic profile -- Analgesia, anti-inflammatory, anti-pyretic, Synergistc effect with opioids

20

what is the mechanism of anti-pyresis of NSAIDs

IL1 and IL6

21

NSAID side effect profile

Side effects
COX 1 -- GI mucos, renal parenchyma, platelets
COX 2 - pain and inflammation

Bleeding, Gastric Ulceration, Renal dysfunction,
Allergic Rx, Asthma, Hepatocellular injury, Tinnitus

22

• Non Selective COX Inhibition -- -
- what are they

ASA, Ibuprofen, Naproxen, Acetopminophen, Ketorolac

23

COX 2 selective inhibitor

- most often used clinically for...
- benefits ?

Celecoxib
○ Especially arthritis
○ Post-operative pain

- ○ Crosses BBB
○ Highly lipophilic
○ Lacks inhibition of platelet aggregation
○ Decreased GI side effects

24

Aspirin
- therapuetic profile
- side effects?

Analgesic, Anti-pyretic, Anti-inflammatory

Side effcts -- GI upset, dyspepside, bleeding, alergic rxn

25

• Ibuprofen, Naproxen
- therapeutic profile
- side effects
benefit of naproxen over ibu?

○ Analgesic, antipyretic, anti-inflammatory
○ Side effects:

GI irritation, dyspepsia, etc. but less than aspirin

Naproxen -- longer half life; can take BID

26

Acetominophen
- primary side effect?

HEPATOTOXIC --- NAPQI, treat with NAC

27

Ketorolac (Tordol)
therapeutic profile --
Side effects
Benefits
Metabolised by...

○ Potent analgesic effects --- good alternative to opioids
Moderate Anti-inflammatory
Potentiates actions of opiates

No Ventilatory or cardiac depression

Liver Metabolism

Side effcts -- Platelet aggregation inhibition, GI irritation, Renal toxicity, hepatic toxicity, GI irritation