Physiology Analgesia and Analgesic Drugs Flashcards Preview

Neurology > Physiology Analgesia and Analgesic Drugs > Flashcards

Flashcards in Physiology Analgesia and Analgesic Drugs Deck (55):
1

what are the different mechanisms for analgesics reducing nociception

acting at site of injury (decrease nociceptor sensitisation in inflammation by blocking synthesis of prostaglandins)

suppressing nerve conduction (blocking/ inactivating v-activated sodium channels) (local anaesthetics)

suppressing synaptic transmission of nociceptive signals in dorsal horn (opioids and some antidepressants)

activating descending inhibitory controls (opioids and tricyclin ADs)

targeting ion channels upregulated in nerve damage (gabas)

2

what is the who analgesic ladder

NSAID (aspirin, diclofenac, ibruprofen, naproxen) and/or paracetamol

weak opioid (codeine, tramadol, dextropropoxyphene)

strong opioid (morphine, oxycodone, hydromorphone, heroim, fentanyl)

3

whats the difference between opiates and opioids

Opiates – substances extracted from opium, or of similar structure to those in opium
Opioids – any agent (including endogenous peptides, known collectively as endorphins/enkephalins) that act upon opioid receptors

4

does paracetamol have anti inflammatory effects

no

5

what mediates supraspinal anti-nociception

descending pathways from the brainstem:
-brain regions involved in pain perception (cortex, thalamus, hypothalamus) project to specific brainstem nuclei
-neurones of brainstem nuclei give rise to efferent pathways that project to spinal cord to moderate afferent input
(the gate theory)

6

what areas of brain stem are important in supraspinal nociception

the periaqueductal grey (midbrain)
locus ceruleus (pons)
nucleus raphe magnus (medulla)

7

what activates PAG

electrical stimulation
endogenous opioids (enkephalins)
morphine/ related compounds (excite it by inhibiting inhibitory GABA interneurones)

8

what does PAG activation cause

profound analgesia

9

how doe PAG neurones work

activated PAG neurones project to the nucleus raphe magnus and excite serotonergic and enkephalinergic neurones
+ also project to dorsal horn causes suppressed nociceptive transmission

10

what do locus coeruleus noradrenergic neurones do

project to the dorsal horn and inhibit nocicpetive transmission

excited by PAG neurones

11

opioids also activate NRM neurones, what do these release

5-HT and enkephalins

12

how do opioids suprpress pain

activate descending pathways which suppresses pain:
-excites PAG and NRM by disinhibition

13

what are the resp adverse effects of opioids

apnoea:
-blunts medullary resp centre to CO2

14

what are the cardio adverse effects of opioids

orthostatic hypotension:
-reduced sympathetic tone and bradycardia
-histamine evoke vasodilation

15

what are the GI adverse effects of opioids

nausea
vomiting
constipation
increased intrabiliary pressure

-acts on chemoreceptor trigger zone
-increased smooth muscle tone
-decreased motility

16

what are the CNS adverse effects of opioids

confusion, euphoria, dysphoria, hallucinations, dizziness, myoclonus, hyperalgesia (with excessive use)

17

what are the agonist types of opioids and how do they work

morphine
diamorphoine
codeine
fentanyl
pethidine
buprenophine
tramadol
methdone

prolonged activation of μ-opioid receptors

18

how is morphine metabolised

metabolised in the liver
excreted by the kidney

19

how can morphine be administered

IV, IM, SC or orally
epidural, intrathecal

20

what is oral morphine good for

immediate breakout pain

21

what is morphine not good at

reducing neuropathic pain

22

what is diamorphine used for

rapid onset- used in severe post op pain

23

what is codeine used for

mild/ moderate pain

24

how is codeine metabolised

in liver (metabolised into morphine)

25

how is codeine administered

orally (not IV)

26

what are the extra effects of codeine

anti diarrhoeal (constipation) and antitussive

27

what is fentanyl

agonist opioid
more potent that morphine

28

what for and how is fentanyl used

maintenance anaesthesia
IV (in acute), transdermal (in chronic pain states)

29

what for and how is pethidine used

acute pain (labour)
IV, IM, SC
not suitable for chronic pain
should not be given with MAO inhibitors

30

what for and how is buprenophine used

chronic pain
patient controlled injection systems
long duration
can be given via injection or sublingually

31

how is tramadol given

orally
avoid in epilepsy can cause seizures

32

what for and how is methadone given

orally
has long duration of action so used in opioid withdrawal
used in chronic cancer pain

33

what are the antagonist opioids and how do they work

naloxone
naltrexone
alvimopan
methylnaltrexone

competitive antagonist at μ-opioid receptors

34

what are antagonist opioids used for

to reverse opioid toxicity associated with strong opioid overdose

35

how are antagonist opioid given

incrementally IV. IM and SC routes are alternatives if IV is not practical

36

why is the half life of naloxone important

short half-life – very important since opioid toxicity can recur to ‘strong opioid’ agonists with a longer duration of action. Clinically, you must monitor the effect of naloxone very carefully, titrating the individual dose, and frequency, to that required to reverse opioid toxicity and do not leave the patient unattended

37

what is the advantage of naltrexone

oral availability and a much longer half-life

38

what is the advantage of alvimopan and methylnaltrexone

do not enter CNS, reduce G.I. effects of surgical and chronic opioid agonist use

39

how do NSAIDs work

diminish nociceptor sensitisation by inhibiting the synthesis and accumulation of prostaglandins (cause hyperalgesia, allodynia and pain) by COX enzymes 1 and 2

suppress the decrease in the activation threshold of the peripheral terminals of nociceptors that is caused by prostaglandins
decrease recruitment of leukocytes that produce inflammatory mediators
if they cross the BBB, suppress the production of pain-producing prostaglandins in the dorsal horn of the spinal cord (that, for example, reduce the action of the inhibitory neurotransmitter, glycine)

40

what are all the effects of NSAIDs

analgesic
antipyretic
anti inflammatory

41

what are the non specific NSAIDs

aspirin
ibruprofen
naproxen
diclofenac
indometacin

42

what are the specific COX 2 NSAIDs

ones ending in ib
etoricoxib
celecoxib
lumiracoxib

43

when are COX enzymes active

COX-1 is constitutively active, COX-2 is induced locally at sites of inflammation by various cytokines

44

does paracetamol act peripherally or centrally

only centrally

45

what can long term administration of non selective NSAIDs cause

GI damage
(PGE2 produced by cox-1 protects against acid/ pepsin environment(

46

what can paracetamol damage

kidney- cox 2 inhibition here can compromise renal hemodynamics

47

what is the downside of selective cox 2 NSAIDs

are prothrombotic

48

does neuropathic pain respond to NSAIDs

no

49

what is used to treat neuropathic pain

gabapentin and pregabalin (antiepieptics)
amitriptyline, nortyptiline and desipramine (tricyclic antidepressants)
carbamazepine

50

how do gabapentin and pregabalin work

DO NOT WORK VIA GABAERGIC SYSTEMIC

reduce the expresison of V activated Ca2+ channels which are upregulated in damaged sensory neurones

this causes a decrease in neurotransmitters (glutamate and substance P) from central terminal of nociceptive neurones

51

what is gabapentin used in

migraine prophylaxis

52

what is pregabalin used in

diabetic neuropathy

53

how do tricyclic antidepressants work

work centrally
decrease the reuptake of noradrenaline

54

how does carbamazepine work

blocks subtypes of v activates Na+ channels that are upregulated in damaged nerve cells

55

what is the first line Tx to control pain intensity and frequency of attacks in trigeminal neuralgia

carbamazepine