Lecture 3 - NSAIDs and Opioids Flashcards

1
Q

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

A

Natural Ligand: Endorphins

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Mu Opioid Agonists –

what is the mechanism of action of most opioid agonists ?

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

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

A
  • 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Opioid agonist effects/side effects at the CNS level?

A

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

Muscle rigidity

Miosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Opioid agonist effects/side effects at the cardiovascular level?

– describe the potential mechanisms for this

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Opioid agonist effects/side effects at the GI level?

A

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

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

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

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

MORPHINE

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

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

• Meperidine (Demerol)

  • Mechanism?
  • potency compared to morphine/
  • Duration?
  • side effects?
  • Metabolism/MEtabolites?
  • Clinical uses?
A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

which two opioid agonists can cause histamine release?

A

Morphine, Meperidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q
Sufentanil 
- potency compared to fentanyl  
- onset?
- duration ?
- Metabolsim? 
Clinical uses?
A
10x more potent than fentayl
Very lipopholic 
very fast Onset 
Short duration (rapid redistribution) 
No active metabolites 
Used for intra-operative infusions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Remifentanil

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

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q
Methadone 
- mechanism? 
- uses? 
Metabolims?
considerations of dosaging?
A

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;
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

• Hydromorphone (dilaudid)

  • ## potency compared to morphine?
A
  • 5x a potent as morphine
    • Same side effect profile as morphine
    • Safer in renal failure patients
17
Q

Mixed Drugs: Opioid receptor agonists/Antagonists –

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

A

• 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
Q

Opioid Antagonists:

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

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
Q

NSAID
Mechanism
Therapeutic profile

A

Mechnaims – COX Inhibtion

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

20
Q

what is the mechanism of anti-pyresis of NSAIDs

A

IL1 and IL6

21
Q

NSAID side effect profile

A

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
Q

• Non Selective COX Inhibition – -

- what are they

A

ASA, Ibuprofen, Naproxen, Acetopminophen, Ketorolac

23
Q

COX 2 selective inhibitor

  • most often used clinically for…
  • benefits ?
A

Celecoxib
○ Especially arthritis
○ Post-operative pain

  • ○ Crosses BBB
    ○ Highly lipophilic
    ○ Lacks inhibition of platelet aggregation
    ○ Decreased GI side effects
24
Q

Aspirin

  • therapuetic profile
  • side effects?
A

Analgesic, Anti-pyretic, Anti-inflammatory

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

25
Q

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

A

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

GI irritation, dyspepsia, etc. but less than aspirin

Naproxen – longer half life; can take BID

26
Q

Acetominophen

- primary side effect?

A

HEPATOTOXIC — NAPQI, treat with NAC

27
Q
Ketorolac (Tordol) 
therapeutic profile -- 
Side effects
Benefits
Metabolised by...
A

○ 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