Substance Abuse Flashcards
(55 cards)
Ok so starting off with the heavy stuff, let’s name the 1st two dopamine (DA) pathways from the ventral tegmental area (VTA) involved with reward
VTA–> nucleus accumbens
VTA–> prefrontal cortex
What’s the neural DA pathway from the substantia nigra? What is it associated with?
SN –> CPu
caudate/putamen)
A/w with habit and compulsions
What’s the neural NE pathway from the locus coeruleus (LC) and what is it associated with?
LC –> forebrain, cerebellum
A/w with arousal and attention
What’s the neural serotonin (5HT) pathway from the raphe nucleus and what is it associated with.
Raphe nuc –> forebrain, cerebellum
A/w mood and visual
On to the actual drugs. Starting with Opiates. Name 4 opiates
- Heroin
- Morphine
- Oxycodone
- Hydrocodone
What are the effects of opiates. Many many many options here.
nausea emesis “foam cone” euphoria (lasts~1hr), somnolence sedation (lasts 2-4hrs) dissociation analgesia resp depression LOC endocrine/immune disturbances constipation
What is the mechanism of opioids
- 1’ target: Mu opioid-R
- 1’ effect: Gi/o receptor that when stimulated causes hyperpolarization.
3: Result: disinhibition of DA release and euphoria.
What’s the most terrifying effect of opiates?
OD/Sudden Death: Profound respiratory depression, arrhythmia, cardiac arrest, severe pulmonary edema
What are the pulmonary effects of opiates?
- Pulmonary edema
- Septic embolism (from endocarditis)
- Lung abscess,
- Foreign body granulomas from Talc
- Opportunistic infections.
*Note, granulomas can be found elsewhere like spleen, liver and lymph nodes
Infections due to opiate use are likely to end up:
- Skin
- Heart valves (Right sided tricuspid - S. Aureus)
- Liver
- Lungs
What kind of skin shit happens when you take too many opiates?
- Cutaneous lesions from subQ injections
2. Hyperpigmentation over injection sites
What kind of kidney shit happens when you take too much opiate shit in your shit
- Amyloidosis from skin infections
- Segmental glomerulosclerosis
- Proteinuria
- Nephrotic syndrome
What will you see on labs when you have an opiate overdoser on your hands?
6-MAM
monoacetylmorphine
Talk me through the withdrawal process of opiates?
6-12h: lacrimation, rhinorrhea, yawning, sweating, goosebumps, anxiety
12-24h: restless sleep
16-96h: dilated pupils, goosebumps, tremor, weakness, anorexia, nausea, vomiting, intestinal spasms (cramps), diarrhea, muscle/back pain/spasms/jerks, CNS stimulation, depression, wt loss, acid-base change, dehydration, ketosis
Max sx at 48-72h; abate w/in 7-10d
What happens after detox of opiates?
- Relapse extremely common (80%)
- Craving for months-years
- Conditioned withdrawal syndrome – return to environment previously used shows features of withdrawal
What’s going on with drug tolerance?
- no change in opiate drug metabolism
- mu opioid receptor are desensitized (receptors are phosphorylated)
- NO/little reduction in # of receptors
- Signal transduction pathways are modified
- Gene expression altered
What’s going on with drug dependence?
- Compensatory changes are “unmasked” when drug is withdrawn aka there is withdrawal
- Withdrawal sx are often opposite to the acute drug effects
- Withdrawal is caused by giving a drug antagonist like naloxone or naltrexone for opiates
What is addiction?
Tolerance+Physical dependence+psychological dependance
May be considered a dz of maladapted learning
How do you treat a opiate addiction?
- Detox
- Maintenacne therapy
More detail in next cards
What does detox for opiate addiction look like
- Cold turkey – not recommended
- Methadone
- Clonidine: suppression of sx by α2 R activation (inhibits firing of locus ceruleus neurons)
- Antagonist-accelerated withdrawal: naltrexone-precipitated withdrawal induces rapid transition to non-dependent state
What’s the maintenance therapy like for opiate addiction?
- Heroin maintenance (not legal in US) – replace illegal w/legal heroin
- Methadone maintenance – dose increased progressively, blocks assoc of high w/heroin, maintained daily for months-years, decrease when stable, significantly dec relapse rate
- Antagonist or partial agonist – after detox give naltrexone to block effects of any self-administered opiate
- Buprenorphine – mixed agonist-antagonist – blocks opiate effects, but induces high by itself
- Buprenorphine/Naloxone (Suboxone) – naloxone has poor oral bioavailability, but if injected naloxone is activated
What is fentanyl
Short acting synthetic opiate
Used for anesthesia
What is the mechanism for benzodiazepines?
1’ target: Acts allosterically on GABA(a) receptors
1’ effect: potentiates GABA
Result: hyperpolarization, sedation, mild euphoria, DA release
Where do we get cocaine from?
Extracted from coca leaves → water soluble powder. Mixed with Talcum powder or lactose. Snort or dissolve in water and inject.
