Pain killing Meds

Question 1

Do prostaglandins produce pain?

Answer 1

NO, but they potentiate the pain caused by other mediators of inflammation (e.g. histamine, bradykinin).

Prostaglandins sensitize sensory nerve endings to nociceptive stimuli.

Question 2

Do NSAIDs have an antipyretic action?

Answer 2

Indirectly, yes.

Fever - endogenous pyrogen (interleukin I) released from leucocytes - these act on thermoregulatory centre in hypothalamus.

This effect also causes a rise in hypothalmus prostaglandins which are pyogenic.

Question 3

Can you use aspirin for gout?

Answer 3

No because they raise plasma urate levels at low doses by inhibiting uric acid secretion in the renal tubules.

Question 4

Do prostaglandins cause inflammation?

Answer 4

Yes;

they are released from cells in response to chemical/ physical trauma.

they stimulate inflammatory cell chemotaxis (vasodilation, >> permeability >> oedema

• they sensitize sensory nerve endings to nociceptive stimuli.

Question 5

Relationship of COX (cyclooxygenase Isozymes)

and NSAIDs

Answer 5

NSAIDS are non-selective inhibitors of COX-1 and COX-2.

COX-1 has a protective effect on GI tract. COX1 is involved with synthesis of prostaglandins that are cytoprotective.

COX-2 - normally levels are low, it is up-regulated in the inflammatory process by substances such as cytokines, endotoxins.

Question 6

Relationship between NSAIDs and lithium

Answer 6

NSAIDs inhibit the renal excretion of lithium and can increase lithium levels and toxicity.

Question 7

Can you combine Spironolactone with NSAIDs?

Answer 7

Not advisable due to increased risk of hyperkalaemia.

Question 8

Why is it advisable for children not to have salicylates?

Answer 8

Increase risk of Reye’s syndrome

(salicylates; aspirin - salicyclic acid)

Question 9

Relationship of aspirin levels to pharmological and toxic effects

Answer 9

Question 10

Adverse effects of aspirin

Answer 10

Reye’s syndrome

GI bleeding

>> does; tinnitus, hyperventilation, fever, dehydration, metabolic acidosis, organ failure, death

hypoprothrombinaemia - impairment of haemostasis.

Question 11

Tx of salicylate overdose

Answer 11

induce vomiting

IV Sodium bicarbonate

dehyration support

Question 12

Celecoxib - what’s special about this NSAID?

Answer 12

Is the first selective COX-2 inhibitor (therefore doesn’t affect cytoprotective effects of COX-1).

Less risk of GI bleeding.

>>> risk of cardiovascular events

Question 13

NSAIDs has two unusual indications, what are they?

Answer 13

Alzheimer’s

(neurogeneration is accomopanied by inflammatory COX mechanisms)

Colon cancer

(angiogensis of tumour growth requires COX-2 activity)

Question 14

antidote to acetaminophen overdose

Answer 14

acetylcysteine

Question 15

what is >>>> acetaminophen toxic?

Answer 15

due to depletion of hepatic glutathione that converts the hepatotoxic quinone intermediate.

Question 16

Adverse effects of acetaminophen?

Answer 16

long term use is associated with an increased risk of renal dysfunction.

Question 17

What is COX?

cyclooxygenase

Answer 17

an enzyme that catalyzes the first step in the synthesis of prostaglandins from arachidonic acid

Found in endoplasmic reticulum

Question 18

How do NSAIDS work?

Answer 18

decrease COX activity by competitive inhibition.

(non-selective, therefore affects the cytoprotective GI aspect of COX-1)

Except aspirin; forms a covalent, irreversible inhibition of COX.

Net effect << prostaglandin production

Question 19

Why does APAP (acetaminophen) only have a WEAK anti-inflammatory effect?

Answer 19

Because it inhibits COX-3 only.

Question 20

Can you give NSAIDs in pregnancy?

Answer 20

NO, especially in the second half of pregnancy.

Acetaminophen can be safely given for analgesia and antipyresis.

Question 21

What are the two groups of analgesics?

Answer 21

• opiods
• nonopiods (also called NSAIDs because of significant anti-inflammatory effect)

Question 22

MOA of opioids?

Answer 22

Act primarily in the spinal cord and brain to inhibit the neurotransmission of pain.

Question 23

MOA of nonopioids?

Answer 23

Act primarily on peripheral tissues to inhibit the formation of algogenic or pain-producing substances such as prostaglandins?

Question 24

Three origins of pain, what are they?

Answer 24

somatic

visceral

neurogenic

Question 25

Why are drugs like codeine (moderate opiod agonist) best combined with acetaminophen or a NSAID?

Answer 25

Moderate opioid agonists cause intolerable adverse effects if given in high doses for severe pain.

Therefore best given submaximally with another drug for best clinical effectiveness.

(NB. strong opioid are better tolerated, therefore use for severe pain)

Question 26

Strong Opioid Agonists include:

Answer 26

Morphine

Methadone

Oxycodone

Fentanyl

Meperidine

Question 27

CNS effects of Morphine (7)

Answer 27

1. analgesia
2. sedation
3. euphoria/ dyphoria
4. miosis
5. nausea/ vomiting
6. respiratory depression
7. inhibition of cough reflex

Question 28

What is the importance of miosis if a patient has taken opioids?

Answer 28

It’s a diagnositic sign of opioid overdose because little/ no tolerance developes to miosis

Question 29

What is the cardiovascular effect of morphine (and other opioids)?

Answer 29

VASODILATION

• orthostatic hypotension (careful with this)
• it would helps patients with coronary artery disease due to << peripheral resistance

Therefore: << Cardiac work, << myocardial oxygen demand.

Question 30

How do opioids depress respiratory function?

Answer 30

Reduce hypercapnic drive

Reduce tidal volume and rate

IMP. cerebral circulation is very sensitive to CO2 levels and responds with incrase in cerebral blood flow, therefore >> pressure.

DON’T use opioids with closed-head injuries.

Question 31

What’s the antidote to opioid overdose?

Answer 31

Naloxone

Question 32

Other effects of opioids (except CV and cns):

Answer 32

nausea and vomiting (opiods stimulate chemoreceptor trigger zone in the medulla)

Pruritus (due to release of histamine)

Flushing and warmth of upper torso (due to histamine)