Analgesics

Question 0

Anaesthesia

Answer 0

Lack of sensation. Also ends in lack of pain but causes numbness.
Local anaesthetics can also cause muscle weakness or rlaxtion

Question 1

Analgesia

Answer 1

Reduction or relief in pain.

Does not inply that all pain is taken away.

Question 2

Analgesics work by

Answer 2

Blocking signals that go to brain

Interfere with brains interpretation of signals

Question 3

3 classes of analgesics

Answer 3

NSAIDs
COX-2 inhibitors
Opioids (narcotics)

Question 4

NSAIDs

Answer 4

Nonsteroidal anti inflammatory drugs provide analgesic and atipyretic (fever reducing) effects and in higher doses, anti inflammatory.
E.g. Aspirin (irreversible), ibuprofen, naproxen

Act as non selective inhibitors of enzyme cyclooxygenase (COX) by inhibting both COX1 and COX2 isoenzymes. Most are reversible. COX catalyses formation of prostaglandins and thromboxane from arachadonic acid. Prostaglandins act as messengers in inflammatory response.

Question 5

COX2 inhibitors

Answer 5

Form of NSAID that directly acts on COX2 isoenzyme. Doesnt inhibit production of thromboxanes.
This selectivity reduces risk of peptic ulceration
E.g. Paracetamol

Question 6

Paracetamol

Answer 6

Metabolised by liver and is hepatotoxic.
Prolonged use may lead to upper gi complications (stomach bleeding, kidney or liver damage)
Not antithrombotic (so can use in patients w coagulation probs)
Doesnt help with inflammation (as high levels of peroxides present in inflammatory lesions)

Question 7

How many tablets in OTC paracetamol

Answer 7

Pack of 16 to reduce suicides

Question 8

Opiods (brief)

Answer 8

Vey strong analgesics used to treat chronic pain.
Block opioid receptors in the brain to decrease perception, reaction and increase tolerance to pain.
E.g. Morphine and opium

Question 9

Lidocaine

Answer 9

Local anaesthetic and cardiac depressant used as antiarrhythmic agent. Stabilizes neuronal membrane by inhibiting ionic fluxes required for initiation and conduction of APs.
Blocks the Na+ channels so will not depolarise. Prevents pain signals from happening.
Used to relieve burning, itching, inflammation

Question 10

Opiods

Answer 10

Any type of substance (endogenous or chemical) that has morphine like effects and antagonised by naloxone
Can be morphine analogues (similar and derived from morphine like morphine, diamorphine, codeine)
Or synthetic derivative (structures unrelated to morphine like methadone)

Question 11

Morphine structure

Answer 11

Phenanthrene derivative with two plantar rings and two aliphatic rings which occupy a plane roughly at right angles with rest of molecule.

Question 12

Brains endogenous opiods

Answer 12

Enkephalin and endorphins

Question 13

Types of opiod receptor

Answer 13

• delta 1,2: more imp in peripheries but also contribute to analgesia through sc
• mu 1,2,3: responsible for MOST analgesic effects and some unwanted side effects (respiratory depression, euphoria, sedation and dependance)
• kappa 1,2,3: contribute to analgesia in spinal level and may elicit sedation and dysphoria but doesn’t contribute to dependance.

Question 14

Action of opioid receptors

Answer 14

All opioid receptors are g protein linked for inhibition of adenylate cyclase, thus reducing cAMP amount in cell.
Direct g coupling to the ion channels causing:
They also facilitate opening of K+ channels causing hyper-polarisation.
Inhibit opening of Ca2+ channels inhibiting transmitter release.

Question 15

Categories of opiates and examples

Answer 15

• pure agonists: high affinity for mu receptors and low for the delta and kappa. Most of the typical morphine like drugs.
• partial agonists: combine agonist and antagonist effects. Most of these drugs cause dysphoria by acting on k receptors

Question 16

Opiate antagonists

Answer 16

Block effects of opiates. These are naloxone and naltrexone

Question 17

Other ways opioids cause pain relief

Answer 17

In nociceptive pathway Opiods act on receptors in the PAG stimulating NRM to release 5-HT and enkephalins to dorsal horn, inhibiting post synaptic transmission. So no nociceptive impulses coming up.

Opioids also inhibit firing of nociceptive afferents in periphery under conditions of inflammation (as there are more opioid receptors on sensory neurones)

Question 18

Side effects of opioids

Answer 18

Euphoria, sedation, nausea, vomiting, constipation, decreased respiration

Question 19

1 theory of opioid tolerance

Answer 19

Receptors undergo changes causing decreased receptor activation (desensitisation) with prolonged exposure to opiods.
In animal models, this occurs when intracellular enzymes (GPCR kinases, -arrestins, and adenyl cyclase) activated by opioids so they ‘decouple’ the opioid receptor from Gprotein. Decreases analgesia

Question 20

Second theory of opiod tolerance

Answer 20

Through internalisation of opioid receptor from cell membrane. Endocytosis causes the cell membrane to form a bubble around the receptor, drawing it in. Receptor can no longer function and is down regulated.

Question 21

Physical dependance

Answer 21

Seen with abrupt withdrawal: Increased irritability, weight loss, shaking, writhing, jumping, aggression.
Much less intense if opites withdrawn slowly.
Craving lasts for months or years

Question 22

Treating opiod dependance

Answer 22

Detoxification 
Relapse prevention (by giving small amounts of the different drugs or naltrexone)
Lifestyle and behavioural change

Question 24

Co-codamol

Answer 24

Compound analgesic of codeine phosphate and paracetamol.

Used for relief when paracetamol and other NSAIDs are insufficient.

Question 25

Gabapentin

Answer 25

GABA analog. Originally to treat epilepsy but also in neuropathic pain. Interacts with T type voltage gated Ca2+ channels in cortical neurones.
Increases synaptic conc of GABA, enhances GABA responses at non synaptic sites in neuronal tissues and reduces release of glutamate.

Question 26

Mechanism implicated by gabapentin

Answer 26

Binding to presynaptic NMDA receptor causes reduction of axon excitability measured at presynaptic fibre volley in the CA1 area of hippocampus.

Question 27

Drugs that increase dopamine levels

Answer 27

Cocaine
Amphetamines
Alcohol
Opiates
Nicotine
Cannabinoids
MDMA

Question 28

How do drugs increase dopamine levels

Answer 28

Increased dopamine in nucleus accumbens of mesolimbic system.
The drugs block reabsorbtion of dopamine by binding to transporter.

Question 29

Treatment of alcohol dependance

Answer 29

Detoxification
Substitution (benzodiazepines?) 
Abstinence/ harm reduction
          - naltrexone
          - baclofen
          - acamprosate
          - disulfiram

Question 32

Acamprosate

Answer 32

Modulates (reduces) release of glutamate
Improves abstinence in alcohol dependance
Reduces craving for alcohol
Diesnt cause sickness

Question 33

Disulfiram

Answer 33

Inhibits aldehyde dehydrogenase to allow acetaldehyde accumulation.
Causes sickness when alcohol ingested
Doesnt reduce craving

Question 34

Naltrexone and baclofen

Answer 34

Blocks brain opiod receptors to reduce dopamine in nucleus accumbens.
Eliminates euphoria, reduces craving and doesnt cause sickness if alcohol ingested.
50mg daily oral.