D3 Opiates Flashcards
essential idea of opiates
potent med drugs prepped by chem modification of natural products
- can become addictive and substances of abuse
what are opiates
natural narcotic analgesics derived from the opium poppy
how do opitates prevent pain
preventing the transmission of pain impulses in the brain rather than at the source
where do analgesic properties of opitates come from
- humans possess opioid receptors in brain – temporary binding blocks transmission of impulses betw brain and pain signalling cells
- interferes with perception of pain w/o depression central nervous system
what are the effects of opiates
act on brain = change in behaviour and mood = a narcotic
- effective painkillers, but addictive properties + side effects
what is the blood brain barrier
a membrane that surrounds the brain to protect it
- hydrophobic, non-polar environment (not easily crossed by polar molecules)
what does the ability of the drug to cross blood brain barrier depend on
chemical structure and solubility in water and lipids
what solubility types are impt in where 2
chem structure determines solubility!
- aqueous solubility impt in blood
- lipid solubility impt in crossing blood brain barrier
side effects of using strong analgesics 4 (disadvantages)
- constipation
- suppresson of cough reflex
- contriction of pupil (Eye)
- narcotic effects (eg slowed breathing, nausea, drowsiness)
pain management: WHO 3 step analgesic ladder
- use mild analgesics
- add weak opioid eg codeine/tramadol
- severe pain: strong opioids eg morphine, methadone
synthesis of codeine
syn. from morphine thru methylation reaction
- one hydroxyl grp is methylated to prod. codeine
synthesis of diamorphine (heroin)
syn, from morphine thru acetylation reaction
- two hydroxyl grp acetylated
codeine vs diamorphine
synthesis: methylated vs acetylated
change 1 OH grp vs 2
- both from morphine
- both change hydroxyl (-OH) groups
why is diamorphine more potent than morphine 3
- increased lipophilicity from additional acetyl grps
- dia.m crosses blood brain barrier more rapidly = enhanced central nervous sytem effects, incr potency
- dia.m undergoes rapid hydrolysis in body into morphine (active metabolite) = incr potency
what derivative of morphine is most potent and why
6-acetylmorphine
- contains ester link at only one position
- does not need to undergo hydrolysis reaction (before interacting w brain cells)
- prod as a metabolite from heroin in body BUT
- high activity = extremely dangerous in pure form
morphine structure and functionla grps
the 2 -OH on top and bottom right
- arene
- ester
- alkenyl
- hydroxyl (2)
- tertiary amino (constant)
codeine structure and functional grps
-OH at top right,
- O - CH3 on bottom right
- arene
- ester 2
- alkenyl
- hydroxyl (1)
- tertiary amino (constant)
diamorphine structure and functional groups
-O-C = O
– CH3
on both top and bottom right
- arene
- ester
- alkenyl
- ester (ethanoate) 2
- tertiary amino (constant)
where is codeine obtained from
0.5% raw opium
usually prepped from morphine
where is morphine obtained from
raw opium 10%
where is diamorphine obtained from
found in opium BUT usually obtained thru reaction of morphine
theraputic uses of codeine
- sometimes used in prep with non-narcotic drugs (eg paracetamol/aspirin) in 2nd stage of pain management ladder
- used in cough meds + short term diarrhoea treatment
theraputic uses of morphine
- managemnt of severe pain eg advanced cancer
- can lead to dependence – must be regulated by a medical professional
theraputic uses of diamorphine
- medically used only in a few countries legally
- most rapidly acting, most abused
- initial euphoric effects, but high potetial for addiction and incr tolerance
- dependence –> withdrawl symptoms
