Session 7 Flashcards Preview

Han's Pharmacology > Session 7 > Flashcards

Flashcards in Session 7 Deck (30):
1

What are autacoids and give three examples.

They are local modular mediatorys and signalling agents. For example, bradykinins, histamine, cytokines, leukotrienes and nitric oxide.

2

How are prostaglandins synthesised?

Arachidonic acid is converted via COX-1 and COX-2 to PG-H. This can then be converted to a range of prostaglandins, in particular PG-E. This is important in mediating the inflammatory response.

3

What are the roles of prostaglandins?

Bind with GPCRs and have specific actions depending on the receptor type present.

4

Describe the role of prostaglandins in sensitising afferent nociception.

Painful stimuli are carried by afferent 'C' fibres. PGE2 binds with 'C' fibre neuronal EP1 GPCRs. This inhibits potassium channels, increases sodium channel sensitivity and increases neuronal sensitivity to bradykinin.
This increases C-fibre activity.

5

Describe the role of prostaglandins in sensitising central nociception.

Increased cytokine levels in the dorsal horn causes increased COX-2 and PGE2 synthesis. PGE2 then increases sensitivity of secondary interneurones, leading to increased pain reception.

6

Describe the role of prostaglandins in pyrexia.

In infected/inflammatory states, bacterial endotoxins stimulate production of IL-1. This stimulates PGE2 synthesis, which results in both increased heat production and reduced heat loss via GPCRs.

7

What is the role of COX-1?

Constitutively expressed, and PG synthesis involved in cytoprotective role of gastric mucosa, myocardium and renal parenchyma. Also ensures optimal local perfusion. PG has a half life on 10 mins so needs constant synthesis.

8

What is the role of COX-2?

Expression induced by inflammatory mediators hence only expressed during injurious stimuli. .

9

What causes the therapeutic and adverse effects of NSAIDs?

COX-1 inhibition = ADRs
COX-2 inhibition = therapeutic effects.

10

Give three examples of NSAIDs ADRs.

Stomach ulceration and perforation, hypertension, bruising, risk of haemorrhage, skin rashes.

11

Give 2 DDIs of NSAIDs.

Aspirin, warfarin, sulphonylurea, methotrexate.

12

Describe the role of aspirin.

An NSAID that irreversibly inhibits COX enzymes by acetylation.
-Athero-thrombotic disease prevention
-GI cancer prophylaxis.

13

Describe the pharmacokinetics of Aspirin.

Rapidly hydrolysed in the plasma to salicylate. This is dose dependent: at lower doses it is first order, at higher doses it is zero order.

14

Describe the role of paracetamol.

No anti-inflammatory action (NOAD). It is a simple analgesic, and has antipyretic properties. Appears to selectively inhibit COX-1/2/3 activity in the CNS.

15

What happens when high doses of paracetamol have been taken?

PK becomes zero order. Phase 2 metabolism becomes saturated, causing increase in NAPQI. This depletes the glutathione levels until there becomes an increase in unconjugated NAPQI. This causes hepatic cell death and renal failure.

16

What is the treatment for paracetamol overdose?

Activated charcoal or N-acetylcysteine. This increases glutathione levels.

17

Describe the pain pathway.

Nociceptor to afferent pain fibres, to dorsal root on spinal cord, to the substantia gelatinosa, to the thalamus and primary sensory cortex.

18

What are the three main endogenous opioid peptides?

Enkephalins (from proenkephalin), Endorphins (from POMC) and dynorphins (from prodynorphin).

19

Name the three opioid receptor classes.

- MOP (supraspinally)
- DOP (widely distributed)
- KOP (spinally)

20

How do opiates work to reduce pain?

-Increase outward flow of potassium ions
-Decrease excitability of the neurone
-Decrease influx of calcium
-Reduce cAMP synthesis
-Reduced release of neurotransmitter.

21

Name the four types of opioids and give an example of each.

1) Agonists: morphine, codeina, methadone (bind to MOP)

2) Partial agonists: buprenorphine

3) Agonist/antagonist: nalbuphine (antagonist at MOP, partial at KOP and agonist at DOP)

4) Antagonist: naloxone (binds to MOP).

22

Describe the PKs of morphine.

25% oral bioavailability, 35% protein bound, half life of 1.3-6.7 hours. Glucuronidised to M6G and M3G, and M6G is the main active metabolite.

23

What must happen to diamorphine for it to exert it's therapeutic effects?

Acted on by pseudocholinesterases to convert it to morphine.

24

What is used to maintain opioid dependence?

Methadone

25

Why might codeine not work as well in 10% of Caucasian individuals?

Genetic polymorphism to CYP2DP enzymes, hence it is not broken down to morphine.

26

Give two uses of opioids.

To relieve moderate to severe pain, care of terminally ill patients, anaesthetics and in labour.
Also to treat diarrhoea, heroin addition and following an MI.

27

Which opioid can cross the placentra?

Pethidine.

28

Give three ADRs of opioids.

Respiratory depression
Euphoria
Constipation
Hypotension
Vomiting and diarrhoea
Confusion, miosis and coma
Anaphylactic response.

29

How do you resolve opioid overdose?

Give the opioid antagonist naloxone which reverses respiratory depression.

30

What information is required to be noted when prescribing opiates?

Name and address
Form and strength of the preparation
Total volume in ml
The dose