Wk 26 - Heroin Flashcards
What is heroin?
- Diamorphine
- Powerful analgesic
What has similar effects to heroin?
Oxycontin + vicodin
Outline the pharmacokinetic of heroin
- IV: greatest intensity + rapid onset euphoria (7-8 sec)
- IM: slow onset euphoria (5-8 min)
- Sniffed/smoked: 10-15 min
What is IV heroin rapidly converted to?
6-monoacetylmorphine + morphine by esterases in liver, plasma + CNS
The onset of heroin’s effect is dependent on what?
Method of admin:
- Orally: 1st pass metabolism via deacetylation
- Injected: avoids 1st pass + crosses BBB rapidly
In the brain what is heroin metabolised to?
- 3-monoacetylmorphine
- 6-monoacetylmorphine (u opioid agonist that bind to opioid receptor)
How is morphine excreted?
Glucuronide conjugate
Which major enzyme systems metabolize opioids?
- CYP450
- UGTs: forms glucuronides
Why do addicts use heroin?
- Euphoria w/in 1-2 mins + high for 5hrs
- Relief from w/drawal symptoms
What are the w/drawal symptoms of heroin?
Peak: 48-72hrs + last a week
- Drug craving
- Restlessness
- Muscle + bone pain
- Cold flashes
What is cross tolerance?
Codeine, opium + morphine relieve w/drawal symptoms of heroin
What do endogenous opioids + exogenous opiates produce?
- Pain relief, respiratory depression, miosis
- LT: collapsed veins, abscesses, cellulitis, liver disease
- CNS depressant
What opiate-like substances does the brain produce?
- Pro-opiomelanocortin, pro-enkephalin + pro-dynorphin
- Cleave to form: endorphin, dynorphin, leu-enkephalin + met-enkephalin
Naloxone + naltrexone are antagonists all which receptor sites
u, k + d
Opioid receptors have high concentrations of what?
- NTS
- PAG
- Cerebral cortex
- Thalamus
- Substantia gelatinosa
How do opioids work on channels?
- Open K channels
- Close Ca channels
- Inhibit adenylyl cyclase activity
What is the overall effect of opiates on nerve cell functions?
- Red membrane excitability
- Slow cell firing
- Inhibit NT release
What is the mechanism of action of heroin in the reward system?
- Opioids + endogenous opioid NT activate presynaptic u opioid receptor on GABA neurons
- Inhibit release of GABA in VTA
- Allows dopaminergic neurons to fire more
- Release of DA in nucleus accumbens = pleasure
What is unassisted treatment?
Cold turkey
What is assisted treatment?
Use clonidine or long acting opiate drug (methadone/buprenorphine)
What are clonidine, lofexidine + guanfacine?
a2 adrenergic agonist:
- Act on central + peripheral ANS
- Red release of AD + NA
What is clonidine?
- Partial a2A agonist
- High efficacy for opioid w/drawal
- Fall in BP if non-hypertensive
- Indication: HT
What is lofexidine?
- Short acting selective a2A agonist
- Indication: symptom management of opioid w/drawak
- Cause drowsiness, dry mouth, throat + nose, hypotension + bradycardia
What is guanfacine?
- Selective a2A agonist
- Efficacy for opioid w/drawal + anxiety
- Less effect on BP
- Indication: ADHD
What is methadone?
- Slow acting opioid agonist
- Binds to u-opioid receptor
- Prevent heroin w/drawal for 24 hrs
- Respiratory depression, QT prolongation + hypotenso
What is naloxone?
- Short acting opioid antagonist
- High affinity at u-opioid receptor + low k + g
- Poorly abs orally
- IM/IV
- Heroin OD
What is naltrexone?
- Non-selective competitive antagonist at u-opioid receptor
- Displaces heroin + methadone in mins
- Used after opioid w/drawal to prevent relapse
- Vivitrol = injectable long acting naltrexone
- Hepatotoxicity from chronic use
What is buprenorphine?
- Partial u-opioid receptor agonist
- Taken 6-12hrs of heroin, 24-28hrs of methadone, will precipitate w/drawal
- Max dose: 32mg
- Antagonist at k + g opioid receptor red tolerance, dependence + attenuate dysphoria
What is suboxone?
- Buprenorphine + naloxone (4:1)
- Sublingual: bup = partial antagonistic effect
- Injected: 100% bioavailability
- Role: alleviate w/drawal symptoms + deter IV use
