opioids

Question 1

opiates vs opioids

Answer 1

opiates are natural products coming from the plant ie morphine/codine, opioids is anything which has opiate-like activity, including synthetic material

Question 2

DIAGRAM opiate comparison of structures- hydroxyl and nitrogen groups + agonist vs antagonist

Answer 2

morphine has a nitrate group- important for binding to receptor, as if made LONGER, becomes ANTAGONIST rather than AGONIST: aromatic ring and 3rd OH group also important for binding also has 2 hydroxyl groups- these are replaced by acetyl groups to form heroin, or by 1 methyl group to form codeine

Question 3

which binds best to receptor out of the 3

Answer 3

morphine, as heroin and codeine don’t have both hydroxyl groups, so are PRODRUGS

Question 4

how to make morphine more lipophilic

Answer 4

replace hydroxyl group at position 6 with acetyl group

Question 5

is heroin or morphine more lipid soluble

Answer 5

heroin as has acetyl group, so even though less binding to receptor, can access tissues better

Question 6

how opioids are taken

Answer 6

ingestion or intravenous

Question 7

absorption of opiods- pkas in different areas

Answer 7

is a basic drug- so very ionised in stomach, a bit better in intestine, a bit better in blood however even in blood has PKA of 8, and blood pH 7.4, so not absorbed well in blood as well

Question 8

comparison of pharmacokinetics- potency, duration+clearance and lipid solubility

Answer 8

heroin, methadone and fentanyl more potent than morphine, codeine least methadone longest acting, the rest have similar duration- thus methadone has least CLEARANCE, the rest are similar methadone and fentanyl MUCH MORE lipid soluble, heroine and codeine slightly more than morphine- the more lipid soluble, the more potent (EXCEPT codeine)

Question 9

comparison of active metabolites

Answer 9

morphine has most active metabolites (GLUCORONIDES)- these cause euphoria, but NOT respiratory depression active metabolites of heroin/codeine are morphine methadone/fentanyl has no active metabolites

Question 10

difference between methadone/fentanyl

Answer 10

clearance rates ie metabolism

Question 11

why codeine less potent than morphine even though more lipid soluble

Answer 11

only 10% converted to morphine

Question 12

what opioids act on, and what else acts on this

Answer 12

act on opioid receptors- endorphins, enkephalins and dynorphins (opioid peptides produced by body) also act on receptors

Question 13

types of opiate receptors and main receptor

Answer 13

endorphins act on Mu receptors, enkephalins act on delta receptors, dynorphins act on kappa receptors Mu is MAIN receptor

Question 14

what type of drugs are opiates and why (mechanisms)

Answer 14

DEPRESSANTS- reduce activity of cell by causing hyperpolarisation, less Ca2+ influx, and less adenylate cyclase activity

Question 15

effects of opioids

Answer 15

analgesia, anti-tussive and euphoria

Question 16

side effects of opioids

Answer 16

respiratory effects, nausea/vomiting, pupil constriction, and GI issues

Question 17

DIAGRAM pain pathway- perception, tolerance effect of hypothalams/LC, and substantia gelatinosa

Answer 17

PAIN PERCEPTION- peripheral stimuli go to dorsal horn, which go to thalamus- thalamus sends signal to cortex, and cortex processes pathway PAIN TOLERANCE- cortex (memory of previous pain) and thalamus affects integrating centre for pain tolerance called PAG, which sends impulses to NRM, which sends inhibitory impulses to spinal cord ie increases tolerance ie decreases pain NRPG also part of pain tolerance- an automatic response to pain by sending impulses to NRM hypothalamus sends impulses to PAG depending on health- if unhealthy, pain tolerance decreases, so more pain, and if healthy, there’s less pain LC (SNS part of brain) increases pain tolerance to help you flee substantia gelatinosa part of spinal cord- receives impulses from NRM, and modifies pain tolerance

Question 18

how opioids affect pain pathway

Answer 18

act on nociceptors in periphery, effect spinal cord, but also depress activity in PAG and NRPG

Question 19

how opioids cause euphoria- comparsion to cannabis and difference

Answer 19

like cannabis, they inhibit GABA effect on VTA (GABA inhibits VTA, so opioids inhibit the inhibition), thus more dopaminergic neurones fire to NA= more dopamine difference- act on Mu receptor unlike cannabis

Question 20

coughing pathway

Answer 20

mechano/chemoreceptors send impulses to cough centre in medulla, which send impulses to diaphragm/intercostal muscles to cause contraction= cough

Question 21

how opioids are anti-tussives ie less coughing including vagus/receptor

Answer 21

receptors send impulse to medulla via ACH vagus, and medulla sends impulses to muscles via 5HT1A receptors opioids inhibit both

Question 22

opioids and respiratory depression

Answer 22

they affect central chemoreceptors that respond to PaCO2 levels, thus the urge to breathe by the medulla is affected

Question 23

opioids and vomiting

Answer 23

GABA inhibits chemoreceptor trigger zone which activates medullary vomiting centre opioids inhibt GABA aka DYSINHIBITION

Question 24

opioids and miosis, and significance

Answer 24

GABA inhibits PNS- opioids inhibit GABA aka DYSINHIBITION, causing pupil constriction- often DIAGNOSTIC

Question 25

opioids and GI disturbance

Answer 25

there are many opioid receptors in gut- opioid is a depressant so it slows gut motility

Question 26

opioids and urticaria

Answer 26

causes large histamine release= allergic reaction

Question 27

tolerance of opioids

Answer 27

increase arrestin (proteins that internalises receptors)- thus downregulation of opioid receptors occur, as more internalised

Question 28

dependence of opioids

Answer 28

there’s a mental craving, as well as a PHYSICAL WITHDRAWAL (flue like symptoms)

Question 29

treatment of opoid overdose

Answer 29

naloxone (opioid antagonist) given, as has longer nitrate chain