exam 3 Flashcards
1
Q
opioids are classified as
A
narcotic analgesics (pain relieving drug)
2
Q
narcotic analgesics
A
- produce pain without unconsciouness
- produces relaxation/sleep state
- produces state of euphora (not usually thru oral)
- high doses causes respiratory depression
3
Q
How are the narcotic analgesics made?; Opium, Opiate and Opioid
A
Opium - extract from poppy plant; morphine
Opiate - derived from poppy plant; morphin e
Opioid
- naturally derived molecules (morphine)
- semi-synthetics (heroin)
-synthetics molecules (fentanyl)
- endongonous peptides (endorphins)
4
Q
Heroin
A
- more potent than morphine (2-4x) through IV
- equipotent (produce same effect, but at different doses) when taken orally
5
Q
4 aspects of opioid intoxication
A
- rush
- high
- nod
- being straight
6
Q
adverse effects of opioids
A
- vomiting
- high doses effects (lethality)
- constipation (oic)
7
Q
opioid subtypes
A
mu, delta, kappa and NOP-R
all opioid receptors are gpcrss
8
Q
mu receptor
A
seems to be major subtype that produces analgesic effects, euphoria, addicition and respiratory addiction
9
Q
mu receptor KO mice
A
- do not self administer
- do not exhibit conditioned place prefernce (where they receive the drug)
- no dependence on drug after chronic use
- no side effects of constipation, respiratory depression or analgesia
10
Q
location of mu receptors (in the brain)
A
- expressed in analgesic area of the brain
- positive reinforment
- cough supressants, respiratory/cardiovascular depression, nausea, vomiting
11
Q
how opioids mediate effects
A
- postsynaptic inhibition
- axoaxonic inhibition
- presynapic autoreceptors
12
Q
opioids and pain
A
pain is subjective, varies in intensity and quality
first/early pain (immediate); Adelta fibers, large, myelinated, fast
second/late pain (dull, chronic); C fibers, thin, unmyleniated
13
Q
how opioid drugs mediate pain
A
- within spinal cord
- descending pathways from PAG (brain to spinal cord)
- higher brain sites (reducing emotional responses to pain)
14
Q
PAG and descending in modulation
A
-PAG is key to descending pain inhibition
-stimulating PAG created analgesic effect but tolerance develops
- IV morphine did not help, as cross-tolerance develops too
15
Q
GABAergic interneurons
A
GABAergic interneurons in the PAG normally inhibit descending pain-control neurons by releasing GABA, which acts as a “brake.”
Opioid Effect:
Opioids bind to μ-receptors on these GABA neurons and inhibit the inhibitor → lifting the brake → activating descending pain relief pathways.
16
Q
reinforcement + tolerance+ dependence
A
Mesolimbic DA pathway:
- injecting opioid causes stopping the GABAbrake, which causes feel goods (dopamine) to flood the nucleaus Accumbens
reinforcing properties
lowers icss threshold
17
Q
severity of withdrawal
A
- vary with paritculsr drug
- heroin (iv); 2-4 days after use
- complete in 7-10 days
- methadone: agonist of mu opioid receptor
18
Q
withdrawal = rebound hyperactivity
A
19
Q
Medication-Assisted Treatment (MAT) for opioid use disorder
A
- best approach for opioid use
Drugs: FDA approved
-methadone (opioid) - buprenorphine (opioid)
- naltrexone
20
Q
Methadone maintenance therapy
A
- given orally (not producing euphoria) but actiavtes just enough for them to operate in society
- cross dependenace with heroin: prevents severe withdrawal symptoms
- cross-tolerance: chronic methadone exposure, euphora of heroin is reduced
21
Q
Buprenorphine
A
- orally or dissolving strips
- longer duration
- lower risk of overdose
22
Q
Suboxone
A
-Buprenorphine and naloxone (opioid antagonist)
- when taken orally the Buprenorphine is absorbed, naloxone is not
but taken through IV, the naloxone (Narcan) will be activated and cause severe withdrawal
23
Q
Naltrexone (vivitrol)
A
- longer duration than naloxone
- effective when taken orally
- highly motivated individuals
24
Q
Psychomotor stimulants
A
increase motor activity and produce euphoria.
25
Cocaine
Erythroxylon coca plant, native to South America.
26
Basic Pharmacology of Cocaine
Turned into cocaine hydrochloride (HCl):
Water-soluble — can be snorted, taken orally, or injected IV.
Not heat-stable — cannot be smoked easily.
27
Smokable cocaine
Made by mixing cocaine HCl + baking soda + heat.
Produces freebase crystals that crackle when smoked.
Crack cocaine:
Can be smoked — leads to rapid brain entry → stronger high.
Much cheaper than powdered cocaine.
28
Pharmacokinetics (How Cocaine Moves in the Body)
Lipophilic — easily crosses the blood-brain barrier.
Metabolism:
Broken down by blood and liver enzymes (not CYP450).
Short half-life: ~0.5 to 1.5 hours → short-lasting high (~30 minutes).
Metabolites:
Benzoylecgonine: major metabolite, detectable in urine for days.
Cocaethylene: forms if cocaine and alcohol are used together; more toxic, longer half-life.
29
How Cocaine Works & evidence
Blocks reuptake of three major monoamines:
Dopamine (DA)
Norepinephrine (NE)
Serotonin (5-HT)
SSRIs (like Prozac, block 5-HT reuptake) do NOT produce euphoria → serotonin isn't enough.
DAT knockout (KO) mice:
No increase in activity after cocaine → shows that dopamine transporter (DAT) is critical.
NET KO and SERT KO mice:
Still show cocaine-induced increases → norepinephrine and serotonin matter less for the high.
30
Other Actions at High Doses of cocaine
Cocaine also blocks voltage-gated sodium (Na⁺) channels:
Acts as a local anesthetic (like Novocain or lidocaine).
Prevents nerve signal transmission.
Also causes vasoconstriction — tightens blood vessels.
31
Behavioral effects of cocaine
Psychological Effects:
Euphoria
Increased energy
Heightened self-confidence
Reduced fatigue
Decreased appetite
Decreased need for sleep
Higher doses can cause:
Anxiety
Paranoia
Irritability
Restlessness
In severe cases: panic attacks or even psychotic symptoms.
32
Mesolimbic DA pathway with cocaine
rats/other animals will self-adminster, will not eat/drink
knock in mouse - has a DAT molecule tranportign the DA across the membrane without blocking cocaine, therefore they will not experience the rewardign effects of cocaine
33
Saccharin vs. Cocaine Study
A study compared rats choosing between saccharin (artificial sweetener) and cocaine.
Findings:
When offered saccharin alone → rats choose saccharin.
When offered saccharin and cocaine together → preference varies depending on conditions.
Takeaway: While cocaine is powerful, natural rewards can compete under some circumstances.
34
Sympathomimetic Effects
Increased heart rate (tachycardia)
Increased blood pressure (hypertension)
Vasoconstriction (tightening of blood vessels)
Pupil dilation (mydriasis)
Hyperthermia (increased body temperature)
35
Chronic cocaine exposure
- most start by snorting, some receive a strong anxiety response and stop, other receive euphoria and stimulation
- become more tolerant=increased drug intake, trying to seek initial high
comorbidity w/ other psychiatric disorders
incubation of craving leads to relaspe
dysfunction in prefrontal cortext, "driving without brakes"
36
systemic effects of cocaine
organ systems with blood: heart, kidneys, damage to nasal passage, restriction of blood flow = cell death, "coke nose"
37
Amphetamines
derivative of phenylethylamine, a molecule naturally found in the body.
Related natural compounds:
Cathinone (from khat plants)
Ephedrine (from ephedra plants)
38
Basic Pharmacology
Amphetamines are indirect agonists of catecholamines (dopamine and norepinephrine).
Their actions:
Stimulate release of dopamine (DA) and norepinephrine (NE) from neurons.
Reverse transporters (DAT and NET), pushing DA and NE into the synapse.
Inhibit reuptake by keeping DAT and NET busy.
At high doses, they can inhibit MAO (monoamine oxidase) — the enzyme that normally breaks down dopamine and NE.
39
methamphetamine
40
Medical Use of Amphetamines
ADHD:
Medications like Adderall® (mixed amphetamine salts) improve attention by enhancing PFC function.
Low doses increase dopamine and norepinephrine in the prefrontal cortex (PFC) → better cognitive control.
Narcolepsy:
Amphetamines help maintain wakefulness.
41
stimulant psychosis
At very high doses, amphetamines can trigger:
Paranoia
Delusions (especially persecutory beliefs)
Auditory hallucinations
formication
42
neurotoxicity
Chronic high-dose methamphetamine use causes damage to brain neurons:
Particularly dopamine (DA) and serotonin (5-HT) neurons.
Damage seen in:
Striatum (motor and reward systems).
Prefrontal cortex (executive function, decision-making).
✅ Long-term meth users show:
Decreased dopamine transporter (DAT) availability.
Decreased serotonin transporter (SERT) levels.
43
Physical Health Effects of meth
"Meth mouth":
Severe tooth decay and gum disease.
Caused by dry mouth (xerostomia), poor hygiene, teeth grinding (bruxism).
Skin sores:
From compulsive skin-picking (formication = feeling of bugs crawling on skin).
Weight loss:
Due to suppressed appetite and neglect of nutrition.
44
withdrawal from psychostimulants
Withdrawal from psychostimulants (like cocaine, methamphetamine, cathinones) does not involve intense physical symptoms (like opioid withdrawal).
Main withdrawal symptoms are psychological:
Fatigue
Depression
Increased appetite
Anhedonia (inability to feel pleasure)
Craving
45
Vaping
Key difference between vaping and smoking = how nicotine is delivered:
Cigarette combustion → reaches up to 900°C → produces harmful carcinogenic chemicals (from burning tobacco).
Vaping = no combustion.
Heats ingredients into an aerosol (vapor).
Thought to release fewer harmful chemicals — although health risks still exist.
46
what is nicotine?
Nicotine = primary psychoactive ingredient in tobacco.
Naturally found in the leaves of the Nicotiana tabacum plant.
Step Description
Absorption Rapid through lungs (smoking), slower through mouth (chewing tobacco, nicotine gum)
Distribution Quickly enters bloodstream → crosses blood-brain barrier in ~10 seconds after inhalation
47
basic pharmacology of nictoine
CYP2A6 enzyme activity varies:
Some people metabolize nicotine faster → smoke more to maintain nicotine levels.
Slower metabolizers may smoke less or find quitting easier.
faster metabolism in women
Nicotine binds to nicotinic acetylcholine receptors (nAChRs):
These are ionotropic receptors — they are ligand-gated ion channels.
Found in the brain, autonomic nervous system, and muscles.
Normal function:
nAChRs respond to acetylcholine (ACh) — an important neurotransmitter for movement, attention, learning, and memory.
48
nicotine administration
high doses - persistent activation of nicotonic receptors
depolarization = cell cant fire until nicotine is removed
biphasic effect = nicotine acts as agonists, as nicotine remains, it will remain bound, and receptors will remain open, neurotoxicity
49
behavioral and physiological effects
smokers = calming/relaxed state, nicotine withdrawal is psychological in nature
non smokers = heightened tension, nausea, tolerance with repeated use
50
animal studies with nicotine
5-CSRTT
- improved performace with acute/chronic nicotine administration
-poor performance during withdrawal from chronic nicotine
- non smokers showed enhanced performance on cognitive/motor tasks
51
how nicotine reinforces behavior
Nicotine causes dopamine release from the ventral tegmental area (VTA) to the nucleus accumbens (NAc).
This dopamine surge leads to:
Feelings of pleasure.
Positive reinforcement to repeat smoking behavior.
52
parasympathetic and sympathetic nictotine
parasympathetic "rest and digest" = increased hcl secretion, more bowel activty
sympathetic = fight or flight, heart, blood pressure
53
averse effects of nicotine
mediated by subunit a5-nAChR
