Analgesic Drugs And Their Metabolism Of Action

Front 1

Opioids

Back 1

Drug with a morphine like action acts on opioid receptors

Front 2

Opiates

Back 2

drug with morphine like structure

Front 3

Opium

Back 3

extract from the juice of the oriental poppy Papaver somniferum

Produce euphoria, analgesia, sleep, combating diarrhoea

Front 4

2 groups of opioid

Back 4

morphine analogues: morphine, codeine, diamorphine, naloxone

Synthetic opioids: pethidine, fetanyl, methadone, pentacozine

Front 5

Opioids receptors

Back 5

mu, kappa, delta -Gi GPCR -> inhibit AC -> decrease cAMP -> open K channel, close Ca channel -> hyperpolarisation of neurones -> neurotransmitter can't be released

Front 6

Where is mu receptors?

Back 6

Mostly in the brain, spinal cord, periphery

Front 7

Where is delta receptors

Back 7

Periphery (increase expression in inflammation)

Front 8

Where is kappa receptor?

Back 8

mainly in the spinal cord

Front 9

Opioid effects on the CNS

Back 9

Analgesia: antinociceptive, decrease the affective component of pain

Euphoria: mainly mu mediated, offset by k mediated dysphoria

Respiratory depression: less sensitive of respiratory center to pCO2, all analgesics (can be fatal)

Cough suppression: antitussive, limited evidence

N&V

Pupillary constriction: central mediated

Front 10

Opioid effects on peripheral

Back 10

Decrease GI tone, motility -> constipation, decrease drug absorption

Histamine release from mast cell -> itching, urticaria, hypotension, bronchospasm

Front 11

Endogenous opioid peptides

Back 11

Endophins, enkedophins, dorphins, endomorphins

Front 12

NSAIDS

Back 12

Degree of inflammation: varies with drug: indomethacin > ibu > para

Inhibition of PGs, TXA formation from AA by COX

Front 13

COX-1

Back 13

Constitutive

Products involved in signalling and homeostasis

Front 14

COX-2

Back 14

Inducible

A part of inflammatory response

Front 15

Where do PGs act?

Back 15

On EP receptor

At the sensory nerves, PGs: not direct pain producers but potentiate the action of other agents at their receptors

PGs enhance the function of kinin receptors, TRPV1, P2X...

PGs decreases temperature required to open TRPV1 by phosphorylating channel proteins

Front 16

Unwanted side effects of NSAIDS

Back 16

GIT disturbance, skin reactions, renal damage, analgesic neuropathy, brochospasm

With COX 2, increase stroke, CV risk

Front 17

Sites of action of opioids and NSAIDs

Back 17

Opioids: descending inhibitory pathway (5HT, NA) -> negative excitation of transmission neuron)

Opioids: negative neuropeptide release ->( transmission of C fibre -> excitation )

NSAIDS: inhibit inflammation -> (mediatators released -> noxious stimulus to C fibre)

Front 18

NICE/WHO pain ladder

Back 18

Stage 1: non-opioids

Step 2: weak opioids

Step 3: strong opioids

Front 19

TRVP1 channels

Back 19

highly expressed in sensory nerves

Activated by inflammatory conditions (temp, heat, chemical modification)

Gated cations -> depolarisation of sensory nerves and excitatory mediator release

Stimulated by vanilloids (capsaicin)

Agonist: rapidly sensitise the channels -> burning sensation -> analgesia

Front 20

Cannabinoids

Back 20

Major active component: THC, act via CB1, CB2, mimic action of endocannabinoids anandamide, 2AG

Inhibits neurotransmitter release -> decrease excitation in pain pathway

Front 21

Where is CB1?

Back 21

spinal cord, brain, sensory nerve

Front 22

Where is CB2?

Back 22

immune cells, also inflammatory effects

Front 23

Tramadol

Back 23

Weak mu opioids receptor agonist, 5HT releaser, NA reuptake inhibitor

Metabolised to 0-desmethyltramadol -> much more potent than any opioids

Descending monoamine control of pain transmission effect

Not CD in UK

Antagonist at NMDA receptors, 5HT, NAChr, MAChr, TRPV1 receptor

Treatment of chronic pain, immediate pain

Risk of seizures (if overdose)

Long half life: decrease abuse potential

Front 24

Tapentadol

Back 24

Centrally acting analgesics with a dual mode of action: agonist at mu opioid receptor, NA reuptake inhibitor

Descending pain control: potentiated

Same effects to other opioids but have better SEs profile

Caution in seizure prone patient

Not CD in UK

Front 25

Clonidine

Back 25

alpha 2 AR agonist

act on pre-synaptic receptors: decrease neurotransmitter release

Analgesic effect: reduce excitatory transmitter release in brain, spinal cord pathways but lack of selectivity -> not use clinically

Except migraine prevention

Front 26

Neuropathic pain

Back 26

damage to neural tissue bc of trauma, herpes, infection, diabetes, chemo, central pain, HIV, alcoholism

Accompanied by allodynia

Caused by peripheral, central sensitisation of pathways

More difficult to treat than other forms of pain

Common therapy: tricyclic antidepressants, anti-epileptic

Front 27

Anti depressants

Back 27

Amitriptyline, TCAs.

enhance descending monoaminergic pain control

Dose less than for anti-depression

Front 28

Anti-epileptic drugs

Back 28

Pregabatin, gabapentin: 1st line treatment for diabetic neuropathy

GABA agonist, interact with voltage sensitive Ca channel, pre synaptic NMDA receptor, enhance descending NA pain control

Front 29

Anti-convulsants

Back 29

Carbamazepine

effective in treating trigeminal neuralgia

Acts on voltage gated Na channel

Lamotrigine: post-stroke pain, HIV/AIDS neuropathy in patient who received antiretroviral therapy

Efficacy of opioids, tramadol, morphine, oxycodone if other meds fail

Front 30

Capsaicin

Back 30

same evidence for relief with topical capsaicin (TRVP1 agonist)

Intense burning, pre treatment with EMLA cream necessary

Front 31

Acupuncture

Back 31

Placebo effect

70% report significant effect, 60% report with sham acupuncture (inappropriate needle placement)