NEW - FINAL EXAM - STUDY GUIDE Flashcards
(160 cards)
1
Q
Acute and Chronic Pain
A
Acute
* Tissue damage
– Injury
– Surgery
* Serves a useful purpose
– Helps to avoid further injury
by limiting activity in a
productive way
– Helps to avoid future injuries
by enhancing
perception/learning/memory
Chronic (3+ months)
* Not immediately associated
with tissue damage
– Fibromyalgia
– Chronic fatigue syndrome
– Back pain
– Depression
– Anxiety
* Does not serve a useful
purpose
– Limits activity in a non-
productive manner
– Does not heighten perception
or learning
6
2
Q
Nociceptive versus Neuropathic pain
A
Nociceptive
* Tissue damage
Your pain nerves (called nociceptors) are warning you: “Something is wrong—protect this area!”
Neuropathic -> Pain caused by damage to the nerves themselves
* NS dysfunction/damage (trauma, injury, infection)
* Hyperalgesia
* Increased sensitivity to painful and/or innocuous stimuli
The nerves are “misfiring” and sending pain signals even when there’s no injury.
3
Q
Non-myelinated C fibers
A
Two fiber types
C - unmyelinated, slow
Ao - myelinated, fast
Non-myelinated C fibers (small diameter, slow conduction rate); dull, diffuse pain; palaeo spinothalamic tract
4
Q
Myelinated A fibers
A
Two fiber types
C - unmyelinated, slow
Ao - myelinated, fast
Myelinated A (delta) (medium diameter); sharp, localized pain; neopinothalamic tract
5
Q
What is the difference between Non-myelinated C fibers and myelinated A fibers
A
Both C fibers and A fibers are types of nerve fibers that carry pain and other sensory signals to your brain. But they’re built differently, and that changes how fast and what kind of pain they carry.
C fibers are non-myelinated, meaning they don’t have a protective insulation (called myelin) around them. Because of this, they carry signals slowly. These fibers are responsible for the sensation of dull, aching, or throbbing pain, which usually comes after the initial injury. C fibers are also small in diameter, and they carry pain signals related to inflammation, heat, or deep tissue damage.
In contrast, A-delta fibers are myelinated, which means they are wrapped in a layer of myelin that helps signals travel faster. These fibers carry the feeling of sharp, stabbing pain, and you feel this pain immediately after an injury—like when you touch something hot or get a paper cut. A-delta fibers are larger in diameter than C fibers and transmit pain from quick, mechanical, or thermal stimuli.
6
Q
Biological and behavioral reward
A
Behavioral: A “reward” is something that makes a behavior more likely to occur again in the future.
Biological: Activation of the mesolimbic DA pathway, a projection from the VTA to amygdala, nucleus accumbens, hippocampus, striatum, OFC, PFC (When you experience something rewarding, your brain releases dopamine through a pathway that helps you feel good, remember it, and want to do it again)
The mesolimbic dopamine pathway starts in the VTA, spreads dopamine to key brain areas like the nucleus accumbens, amygdala, hippocampus, striatum, Orbitofrontal Cortex, and Prefrontal Cortex
7
Q
COX-1
A
Analgesic drug
Cox = cyclooxygenase
Synthesized from arachidonic
acid
COX-1
– Always active (constitutive)
– Produces prostaglandins
– GI and blood platelets
– Allows for aggregation and
clot formation
COX-1 stands for Cyclooxygenase-1. It’s an enzyme—basically, a special type of protein in your body that helps certain chemical reactions happen faster.
Think of COX-1 like a tiny machine inside your cells. Its job is to help make prostaglandins, which are chemicals that do a lot of important things, like:
🛡️ Protect the stomach lining from being damaged by stomach acid
💧 Help your kidneys function properly
🩸 Help your blood clot when you get a cut
In pharmacology (the study of how drugs work), COX-1 becomes important when we talk about NSAIDs—nonsteroidal anti-inflammatory drugs. Examples include:
Aspirin
Ibuprofen (Advil)
Naproxen (Aleve)
These drugs block COX-1 (and sometimes COX-2, its “cousin”) to reduce pain, swelling, and fever.
Since COX-1 also helps protect the stomach and keep the kidneys healthy, blocking it can lead to side effects like:
Stomach ulcers
Bleeding
Kidney problems
So while NSAIDs help with pain, they can also cause problems if taken too often or without food.
8
Q
What is the inhibition of COX-1?
A
– GI upset, ulcers, kidney
disease
– Anticoagulant
* Can reduce risk of
heart attack and stroke
* 80-160mg/day*
– Durlaza
Inhibition of COX-1 = stopping an enzyme that does helpful stuff, but also causes pain. Blocking it helps pain, but can also cause side effects.
Example:
Aspirin inhibits COX-1 and is used to reduce pain and prevent blood clots. But if taken too much, it can cause stomach bleeding or ulcers.
9
Q
COX-2
A
Analgesic drug
Cox = cyclooxygenase
– Synthesized in response to
inflammation (inducible)
– Peripheral tissues
– Spinal cord
COX-2 is mostly made when there’s injury, inflammation, or infection.
Think of COX-2 as the “emergency responder.” 🚨 It shows up when something’s wrong—like a cut, a swollen ankle, or a fever.
-DIFFERENCE FROM COX 1 AND COX 2-
Non-selective NSAIDs (like ibuprofen, aspirin) – block both COX-1 and COX-2
Selective COX-2 inhibitors (like Celecoxib/Celebrex) – block only COX-2
10
Q
What is the difference between Cox-1 and Cox-2?
A
COX-1 is always active and protects the stomach, kidneys, and helps with blood clotting, while COX-2 is made during injury or inflammation and causes pain, swelling, and fever; blocking COX-1 can cause stomach issues, while blocking COX-2 mainly reduces inflammation with fewer stomach side effects.
Feature | COX-1 | COX-2 |
11
Q
What is the inhibition of COX-2?
A
– Reduction of inflammation
– Pain relief
– Fever relief (antipyretic)
12
Q
What are non-specific COX inhibitors?
A
Non-specific COX inhibitors, also known as non-selective NSAIDs, are a class of drugs that inhibit both COX-1 and COX-2 enzymes
Examples with:
Aspirin
Acetaminophen (Tylenol)
Ibuprofen (Advil)
Indomethin (Indocin)
Sulindac (Clinoril)
Ketorolac (Toradol)
Diclofenac (Voltaren)
Nabumetone (Relafen)
Naproxen (Aleve)
Meloxicam (Mobic)
Oxaprozin (Daypro)
Piroxican (Feldene)
Tolmetin (Tolectin)
13
Q
What is acetaminophen?
A
Tylenol
– Estimated >600 prescription and OTC products contain acetaminophen
– Fun fact: Highly toxic to cats
– Non-specific COX inhibitor, but NOT an NSAID (only works in CNS)
– ROA: Oral, IV, Rectal
– Recommended dose of 1000mg per 6 hours, LD ~7500mg.
– TI ~7.5
– FDA recommends 4000mg/daily MAX
– When taken at correct dosage arguably the safest analgesic
14
Q
What is the pharmacokinetics of acetaminophen?
A
Pharmacokinetics
– A: Rapid; peak plasma levels 0.4-1 hour
– D: VD ~0.9L/kg; protein binding ~10-20%.
– M: Primarily metabolized in liver; primarily CYP2E1
* #1 cause of acute liver failure
– E: Kidneys; T1/2 2-3 hours
15
Q
What are the three possible pharmacodynamic mechanisms for acetaminophen?
A
– 3 possible mechanisms:
* Possible COX-1 antagonist, minor COX-2 antagonist.
– Similar to the way NSAIDs work, but only in the CNS
* Mediation in serotonin system of pain
– 5-HT3 agonist analgesic activity
* Cannabinoid system
– CB1 agonist analgesic activity
ESSENTIALLY RAISES THRESHOLD REQUIRED FOR NERVE STIMULATION
16
Q
Acetaminophen’s main concerns
A
Estimated >600 prescription and OTC products contain acetaminophen
Non-specific COX inhibitor, but NOT an NSAID
#1 cause of acute liver failure
Liver damage, particularly if combined with alcohol
17
Q
What is the safety/toxicity of acetaminophen?
A
Safety/Toxicity
– Probably the most dangerous OTC med
– TI is pretty low ~10
– Liver damage, particularly if combined with alcohol
* NAPQI (toxic metabolite) oxidative stress in liver necrosis
* NAPQI antidote only effective within 8 hours of overdose
* Onset of serious symptoms can appear 3-4 days after overdose, requiring liver
transplant
* Fasting/anorexia greatly increases risk for toxicity
* Don’t take Tylenol for a hangover!
– You still have alcohol in your system
18
Q
What are the contraindications for acetaminophen?
A
Contraindications
– Regular alcohol use
– Blood thinners
– Other drugs that contain acetaminophen (Nyquil, Vicodin, etc)
19
Q
What are some concerns among special populations taking acetaminophen?
A
Special Populations
– Liver damage
– Wasting diseases
– Alcoholics
– Pregnancy category = B (yay!)
20
Q
What is Ibuprofen?
A
Non-specific COX Inhibitors
* Ibuprofen (Advil)
– 400-1600mg/day
– Analgesic, antipyretic, anti-inflammatory
– Not recommended for pxts with history of ulcer or GI
upset
*****– Not found in breast milk
21
Q
What is Ketorolac?
A
Non-specific COX Inhibitors
Ketorolac (Toradol)
– Pain, inflammation
* surgery
– i.v. and oral
– As potent as low dose morphine
****– Concurrent administration can decrease morphine
requirement
– Renal failure
– Not recommended for extended use
22
Q
What is Indomethin?
A
Non-specific COX Inhibitors
Indomethin (Indocin)
– Pain, fever, inflammation
* Rheumatoid arthritis
**– Increased side-effect liability
* GI upset, headache (?)
23
Q
What is Sulindac?
A
Non-specific COX Inhibitors
Sulindac (Clinoril)
– Similar to indomethin
– Active metabolite = sulindac sulfide
– Less GI upset than indomethin
24
Q
What is Diclofenac?
A
Non-specific COX Inhibitors
* Diclofenac (Voltaren)
– Pain, inflammation
* Arthritis, menstrual pain
– Half-life = 2 hrs
*****– Several preparations: delayed release,
topical, skin patch
25
What is Nabumetone?
Non-specific COX Inhibitors
Nabumetone (Relafen)
– Pain, inflammation
* Arthritis
– Less GI upset vs. aspirin
******– Recommended for long-term txt
26
What is Celecoxib?
COX-2 Inhibitors
* Celecoxib (Celebrex)
– Pain, inflammation
– Rheumatoid arthritis,
osteoarthritis
– Low liability for GI upset
*******– No cardioprotective
effects
****** May actually increase
risk
– May reduce risk for
certain cancers (colon,
breast)
27
What are opiates?
Opiates
– Derived from opium
poppy
– Opium, heroin, codeine,
morphine
28
What are opioids?
Opioids
– Anything exogenous that
binds to opiate receptors
and stimulates
– Synthetic, semisynthetic,
natural
Opiates are the natural stuff that comes straight from the poppy plant.
Think: "plant-made"
Opioids is the bigger category that includes:
Natural opiates (like morphine)
Semi-synthetic drugs (like heroin, oxycodone)
Fully synthetic drugs (like fentanyl, methadone)
29
What are the effects of opioids?
Analgesia
Euphoria
Respiratory Depression
Cough Suppression
Sedation/Anxiolysis
Nausea/Vomiting
Anti-diarrheal
Pupil Constriction
Endocrine Dysfunction
30
Opioids and Addiction
* 8-12% of pxts prescribed opioids develop an
addiction (2015)
* ~23% of people who use heroin become
addicted
– ~80% of heroin users started with
prescription painkillers (2013)
* 63% of lethal drug overdose deaths are from
opioids
– ~50,000 people in 2019
* In 2012 259 million prescriptions
* Females more likely to
– have chronic pain
– be prescribed pain meds
– given higher doses
– become addicted
31
What are some examples of Opioids?
Morphine, Codeine, Fentanyl, Oxycodone
32
What are the mechanisms of action of opioids?
Opioids exert their psychopharmacological effects by binding to opioid receptors, primarily in the central nervous system, and modulating neurotransmitter release and neuronal activity. This leads to a variety of effects, including pain relief, euphoria, sedation, and respiratory depression.
33
Difference between agonists and antagonists -> EASY
agonists "turn on" a process, while antagonists "turn off" or prevent it
34
What is the Mu Opioid Receptor?
Mu (MOP)
B-endorphin, endomorphin-1 endomorphin-2
Periphery, spine, medulla, area postrema, thalamus, PAG, nucleus accumbens, basal ganglia
Analgesia, anti-inflamatory, euphoria, addiction
Presynaptic inhibition of NT release
35
What is the Kappa Opioid Receptor?
Kappa (KOP)
Dynorphin-A, Dynorphin-B
Periphery, spine, medulla, PAG, hypothalamus, VTA, cortex
Antagonize mu activity (?)
Alterations in perception
36
What is the Delta Opioid Receptor?
Delta (DOP)
Met-enkephalin, leu-enkephalin
Periphery, spine, VTA, PAG, hypothalamus, thalamus, cortex
Antidepressants, anxiolytic
Increases BDNF
37
Define each for -> Opioid drugs
1. Pure Agonists
2. Partial Agonists
3. Pure Antagonists
4. Mixed Agonists-Antagonists
Opioid Drugs
* Pure Agonists
– Binds to opiate receptors and
stimulates
– Affinity determines potency
* Partial Agonists
– Binds to receptors and
stimulates submaximally
* Pure Antagonists
– Competitive
– Binds to receptor, but does not
activate
* Mixed Agonist-Antagonists
– Agonist at one receptor type,
antagonist at another
– Kappa agonists/mu antagonists
Pure Agonists – 🔓 Full Effect
Fully turn on opioid receptors → strong pain relief & high
Examples: Morphine, Heroin
Partial Agonists – 🔓 Half Effect
Partially turn on receptors → mild pain relief, safer
Example: Buprenorphine
Pure Antagonists – 🚫 Blocker
Block receptors → no high, stops overdose
Examples: Naloxone, Naltrexone
Mixed Agonist-Antagonists – ⚖️ Some On, Some Off
Turn on some receptors, block others → moderate relief, fewer risks
Examples: Pentazocine, Nalbuphine
38
What are some examples of pure agonists for opioid drugs?
Morphine
Codeine
Heroin (3x)
Hydromorphone (6x; Dilauded, Palladone, Exalgo)
Oxymorphone (10x)
Meperidine (.1x)
Methadone
Levo-alpha acetylmethadol (LAAM)
Oxycodone (Percodan, OxyContin)
Propoxyphene (Darvon)
Fentanyl (80x; Sublimaze)
39
What is Morphine?
Effects: Analgesia, euphoria,
sedation, anxiolysis, cough
suppression, anti-diarrheal
* ROA: injection, oral, rectal
* Metabolized by liver; active
metabolite is morphine-6-
glucorinide
* ½ life: 3-5 hrs
******* Side Effects: respiratory
depression, pupillary
constriction, constipation,
decreased sex drive/fertility
problems, itching
40
What is the tolerance/dependence and the withdrawal for Morphine?
Tolerance/Dependence
– Develops rapidly with repeated use
– Glutaminergic mechanisms
– Cross-tolerance to other opioids
*
Withdrawal
– Pain, irritability, dysphoria, hyperventilation, diarrhea, pupil
dilation, general leakage
– Clonidine reduces sympathetic activation; makes withdrawal
more tolerable
– Maintenance with other opioids (methadone)
41
What is Codeine?
* Commonly prescribed to manage mild-
moderate pain and coughs
– Often combined with aspirin or
acetaminophen (Empirin, Tylenol with
codeine)
* Analgesia, euphoria, addiction
* Usually taken in tablet or liquid form
– Also available i.v.
* Half-life = 3-4 hrs
******** Metabolized to morphine (CYP 2D6)
– SSRIs can block this transformation
42
What is Hydrocodone?
A type of pain medication/analgesic opioid
Hysingla ER, Zohydro ER
***** Often mixed with
acetaminophen: Vicodin,
Norco
**** Mild-Moderate pain, cough
suppression
* ROA: oral
43
What are the pharmakinetics of hydrocodone?
Pharmacokinetics
– Absorption
* Well absorbed in the GI tract, bioavailability 70%
* IR peak concentrations after 1.3-1.7 hrs, ER capsules peak concentration at 5 hrs
* Antitussive action maintained for 4-6 hrs
– Distribution
* Skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen, and brain
* Plasma protein binding = 36%
* Metabolism
– Hepatic and intestinal mucosa
– CYP2D6, CYP2B6, CYP2C19
– Half life:
* ER = 7-9 hrs
* IR = 3.8-4.5 hrs
* Elimination
– Kidneys
– About 99% of administered dose eliminated within 72 hrs
44
What is the efficacy/potency, safety/toxicity, and the side effects of hydrocodone?
- this isn't on the study guide, and it's not red
Efficacy/Potency
– Antitussive activity slightly great than codeine
– Compared to acetaminophen alone, hydrocodone had faster
onset of pain relief
* 2 acetaminophen tablets provided analgesia comparable to
hydrocodone, but with better tolerability
– No difference in pain b/w oxycodone & hydrocodone at 30mins
– Reduction in musculoskeletal pain by 50%
Safety/Toxicity
– Toxicity may be increased in renal-impaired pxts (geriatric pxts)
– Overdose symptoms: Respiratory depression, extreme
somnolence, confusion, cold/clammy skin, nausea, vomiting,
apnea, circulatory collapse, cardiac arrest, and death
* Side Effects
– Common: Dizziness, light-headedness, nausea, sedation,
vomiting, constipation
– Less common: Blood disorders, mood changes, mental cloudiness,
anxiety, lethargy, urine retention, irregular breathing, respiratory
depression, skin rash
45
What is the tolerance/dependence of hydrocodone?
* Tolerance/Dependence
– Hydrocodone is one of
the most frequently
abused prescription
drugs in the US
(Covvery, 2015)
– Should gradually taper
dosage to avoid
withdrawal symptoms
– Abuse seen more with
ER capsules/tablets
46
What is heroin?
A highly addictive drug made from morphine.
* Semi-synthetic
* Increased lipid solubility
* Metabolized into morphine and monoacetylmorphine
and excreted by kidneys
* 3X potency of morphine
* Intense euphoria
* Highly addictive
FOCUS ON:
Semi-synthetic
Increased lipid solubility
3X potency of morphine
Intense euphoria
47
Which opioid receptor (MOP, KOP, DOP) do opioids bind to the most?
Most opioid drugs (like morphine and heroin) mainly work by binding to the mu-opioid receptor, because that's the one responsible for strong pain relief and the “high” feeling.
48
What is Hydromorphone/Oxymorphone?
* Dilauded/Numorphan
* Semi-synthetic
– Increased lipid solubility
– *******6-10X potency of morphine
– Half-life = 2-3 hrs
– Oral, i.v.
– Palladone, Exalgo = extended
release (once daily)
* Analgesic efficacy = morphine
* Less sedation, equal respiratory
effects, lower risk of dependence
* Mod-severe pain, cough, chronic pain
****** Antihistamines, MAOIs may inhibit
effects
49
What is meperidine?
to relieve pain severe enough to require opioid treatment and when other pain medicines did not work well enough or cannot be tolerated
* Demerol
* Synthetic
– 1/10th potency of morphine
– Half-life = 3-5 hrs
– Oral, i.v., i.m., s.c.
– Active metabolite =
normeperidine; activating
effects (tremor, delirium,
seizures)
****** Greater euphoric effects than
morphine
* Risk of dependence
* Mod-severe pain, fast acting
* Interactions with MAOIs, SSRI
(serotonin syndrome)
50
What is methadone?
a synthetic analgesic drug that is similar to morphine in its effects but longer acting, used as a substitute drug in the treatment of morphine and heroin addiction
Dolophine
* Synthetic
– 80-125mg/day for
methadone maintenance
*******– Half-life = 24-36 hrs
– Oral
– Metabolism depends on
several CYP enzymes, so
many drug interactions
* Less sedation, equal respiratory
effects, lower risk of
dependence (?)
* Opioid dependency (suppresses
craving, decreased euphoria),
analgesia (less costly)
***** Agonist substitution for opioid dependency
51
What is levo-alpha acetylmaethadol ?
is a synthetic opioid medication used in the treatment of opiate addiction
* LAAM
* Similar to methadone
****** Half-life = 2.5 days
* Long duration of action allows for less frequent dosing
****** Increased risk of cardiac effects
52
What is propoxyphene?
Propoxyphene is in a group of drugs called narcotic pain relievers.
* Darvon, Darvocet (when
combined with
acetaminophen)
* Synthetic
– Weak agonist
– Half-life = 3-7 hrs
– Oral
******– Effects do not depend on
metabolism; good choice
for “poor metabolizers”
– Less GI upset
****** Lower risk of dependence
* Chronic pain
53
What are some examples of partial agonists that are pain medications?
Buprenorphine
(Subutex)
Tramadol (Ultram)
Tapentadol
(Nucynta)
54
What is Buprenophine?
* Subutex
* Semi-synthetic
– 80-125mg/day for methadone
maintenance
– Half-life = 20-70 hrs
– Oral
***** Opioid dependency (suppresses craving,
decreased euphoria)
***** Suboxone; combination of buprenorphine and
naloxone
****** Txts opioid dependency without risk of
abuse
55
What is tapentadol?
Tapentadol is an opioid medicine your doctor can prescribe to treat severe pain, only available with a prescription from your doctor.
* Nucynta
* Synthetic
– Half-life = 4 hrs
– Oral
***** Mu agonist + blocks
NET
* Moderate-severe
acute pain, chronic
pain, diabetic
neuropathy,
fibromyalgia
* Should not be taken
with SSRIs
(serotonin
syndrome)
* May induce seizures
in pxts with a history
56
What are mixed agonist antagonists opioids?
Weak mu agonists or antagonists; strong kappa
agonists
Moderate analgesia at low doses, but not as
much liability for abuse
Less respiratory depression; safer
Pentazocine (Talwin)
Butorphanol (Stadol)
Nalbuphine (Nubain)
Dezocine (Dalgan)
57
What is pentazocine?
Pentazocine is used to relieve severe pain in people who are expected to need an opioid pain medication and who cannot be treated with other pain medications. Pentazocine is in a class of medications called opiate (narcotic) analgesics
* Talwin
* Synthetic
– Half-life = 2-3 hrs
– IV, IM
* Weak mu antagonist, kappa agonist
* Analgesia at low doses
* Adverse effects include hallucinations
****** Low risk of dependence or
respiratory depression
* Mod – severe pain, rheumatoid
arthritis, fibromyalgia
* Should not be taken with SSRIs
(serotonin syndrome)
58
What are some pure antagonists that are pain relievers?
Naloxone (Narcan)
Naltrexone (Trexan)
Nalmefene (Revex)
Methylnaltrexone (Relistor)
Alvimopan (Entereg)
59
What is naloxone?
Naloxone is a medicine that rapidly reverses an opioid overdose. It is an opioid antagonist. This means that it attaches to opioid receptors and reverses and blocks the effects of other opioids.
* Narcan
* Synthetic
– Half-life = 1-1.5 hrs
– IV, IM, intranasal
* No effect on non-addicts, but blocks
effects of opioids
* Quickly induces withdrawal
symptoms
****** Reverses respiratory depression
caused by opiate OD
* Can also be used in newborns
60
what is Nalmefene
A medication used to help lower alcohol use in adults with alcohol dependence and reverse an opioid drug overdose.
Nalmefene (Revex)
*****– Similar to naloxone, but lasts
longer
– Used primarily for opioid OD
61
What is Naltrexone?
Naltrexone binds and blocks opioid receptors and is reported to reduce opioid cravings. There is no abuse and diversion potential with naltrexone.
* Trexan
* Synthetic
– Half-life = 4 hrs
– Oral
* No effect on non-addicts, but
blocks effects of alcohol and
opioids
* Must be taken daily; a s.c. ROA
has been developed
***** Used to txt opioid and alcohol
dependence
62
What is Methylnaltrexone/Alvimopan
Methylnaltrexone/Alvimopan
Methylnaltrexone and Alvimopan are both peripherally acting μ-opioid receptor antagonists. They are designed to counteract the constipation-inducing effects of opioid pain relievers without interfering with the pain-relieving effects of these medications.
* Relistor/Enterg
* Synthetic
– Oral, IV, SC
***** Do not cross BBB, so only peripheral
effects
* Primarily used to reduce constipation,
especially in pxts on opioid txt
* May also be useful as an antiemetic
63
What is Fentanyl?
entanyl is a powerful synthetic opioid that is up to 50 times stronger than heroin and 100 times stronger than morphine
64
Tramadol (Ultram)
Mechanism of action:
Tramadol, also known as Ultram, works through a dual mechanism involving both opioid receptor binding and inhibition of serotonin and norepinephrine reuptake. It binds to μ-opioid receptors in the brain, which slows down the transmission of pain signals. Additionally, it inhibits the reuptake of serotonin and norepinephrine, increasing their levels in the brain and enhancing pain relief.
65
Most abused substances act on ______.
POSITIVE REINFORCERS
66
Types of drug abuse therapy
Abuse
Maladaptive pattern of use leading to clinically significant impairment or distress characterized by one or more of the following (12 months)
Pharmacological Methods of Drug TReatment
* Agonist Substitution
* Partial Agonist Substitution
* Antagonists
* Withdrawal Maintenance
* Mesolimbic DA regulation
* Other NT system regulation
67
NSAIDS vs opioids for pain management
NSAIDs are great for everyday pain and inflammation (like a sore knee or headache).
Opioids are stronger and used for serious pain, but carry higher risks, especially for addiction.
68
What are the primary indications for caffeine?
People most commonly use caffeine for mental alertness, headache, migraine, athletic performance, memory, and obesity
Primary Indication
Stimulant
Cafcit, Stay Awake, Vivarin, Revive, Lucidex
Premature apnea
10-20 mg/kg up to 34 weeks
4
69
What are the pharmacodynamics of caffeine
*****Adenosine antagonist
(non-specific)
High affinity for A1
and A2a
A2a in tuberculum
olfactorium important
for wakefulness
Phosphodiesterase
inhibitor
cAMP, cGMP
70
What is the tolerance developed after a few weeks of caffeine ?
Tolerance seen after a few weeks of
continuous use
decrease in adenosine receptors
DSM-V:
Caffeine Addiction:
Withdrawal symptoms can occur 12-24 hours
after last dose
Withdrawal symptoms
difficulty sleeping (insomnia)
nervousness or anxiety
irritability
nausea
headache
7
71
What is the ceiling effect for caffeine?
Ceiling effect
Less effective and potent than
cocaine, amphetamine,
modafinil
Greater effectiveness than
theobromine, theophylline
1 cup of coffee: You feel more alert ✅
2–3 cups: A bit more alert ✅
5 cups: No extra benefit ❌, just feeling jittery or anxious ⚠️
72
What is the toxicity for nicotine?
A lethal dose for an adult is generally considered to be between 40-60mg,
73
What is varenicline?
Chantix
FDA approved 2006
Tyrvaya approved in 2021 (nasal spray)
Pharmacokinetics:
A: oral, peaks in 3-4 hours
D: <20% plasma protein binding, Vd = 415 liters
M: 90% unchanged
E: urine, 24 hr half life
*** Pharmacodynamics:
Blocks nicotine-induced DA release in NAc at α4β2 and α6β2
45% of nicotine's maximal efficacy at the α4β2 receptors
*** Side Effects: gas, constipation, nausea, vomiting, sleep issues
Special Populations
Children: not approved
Pregnant/Nursing: not recommended (vomiting, seizures)
Elderly: special dosing
Contraindications: seizures, cardiovascular disease, renal impairment
Efficacy: better than bupropion
74
What are the pharmacodynamics of stimulants?
* PNS
********– Sympathomimetic
– Mimic effect of
adrenaline/epinephrine
– Activate sympathetic NS
– HR, BP
* CNS
– Increase monoaminergic tone
* DA, NE, 5-HT
* Block reuptake, increase release,
stimulate receptors
* hyperthermia
– Nucleus accumbens
– Limbic
– Prefrontal cortex
A sympathomimetic is a drug or substance that mimics the effects of the sympathetic nervous system. This means it stimulates the "fight or flight" response, increasing alertness, boosting energy, and potentially causing effects like increased heart rate and blood pressure
75
What are the behavioral effects of stimulants for LOW-MODERATE doses?
Low-Moderate Dose
* Increased alertness, arousal
* Increased mood
* Increased motor performance
* Increased cognitive
performance
– Simple tasks only
– Increased errors
* Anxiety
* Irritability
* Insomnia
76
What are the behavioral effects of stimulants for HIGH doses?
High Dose
* Psychosis
* Compulsive, stereotyped
behavior (stereotypy)
* Hallucinations
* Formication (the feeling of
insects crawling on one’s
body or under one’s skin)
77
What is the tolerance and dependence of stimulants?
Pleasurable effects show
acute tolerance rapidly
Sympathomimetic effects are
slower
Do not induce a severe
physical withdrawal syndrome
Severe cognitive withdrawal
syndrome
78
What is amphetamine?
Amphetamines
* Amphetamine (Adderall; racemic)
* Dextroamphetamine (Dexedrine)
* Clinical uses: ADHD, narcolepsy, weight loss
* Off-label use: memory enhancer,
attention/focus
* Illicit use: anti-fatigue, anorectic effects,
euphoria
79
What are the pharmacokinetics for amphetamines?
Pharmacokinetics
* ROA: oral, i.v., inhalation
* Bioavailability: 75% oral, low protein
binding (~20%)
* Half-life: 10-13 hrs
* Dose range:
* Low: 2.5-20 mg (oral)
* Medium: 5-50mg (oral)
* High: 100mg (i.v.)
* Dextroamphetamine 3-4x more
potent
* Metabolism: hepatic, CYP2D6
* Excretion: renal, majority unchanged
80
What are examples of non-amphetamine stimulants?
Ephedrine Methylphenidate
(Ritalin) Pemoline (Cylert)
Sibutramine
(Meridia)
Modafinil
(Provigil) Kava
Khat Ma Huang
81
What is meridia?
Meridia
* sibutramine
* Pharmacokinetic:
– ROA: oral
– Metabolism: Liver
* ½ life = 1 hour
* Active metabolites *1/2 life = 15
hours
– Excretion: Renal
* Pharmacodynamic: 5-HT, NE reuptake
inhibitor
– Also DA, but not as much
******** Primary Indication: Obesity
* Contraindications: cardiovascular disease,
concurrent txt with SSRIs or MAOIs, migraine
txts
82
What is provigil?
Provigil
* Modafinil
* Pharmacokinetic:
– ROA: oral
– Metabolism: Liver
* ½ life = 10 hours
– Excretion: Renal
* Pharmacodynamic: DA reuptake
inhibitor, histamine agonist (?)
******* Primary Indication: Narcolepsy, shift-
work sleep disorder, sleep apnea
– Off-label: cocaine dependence
* Contraindications: cardiovascular
disease, liver disease, children
"Provigil helps you win the battle against sleep.
With MODafinil, you're MODivated, not napping!"
83
What are the clinical uses and pharmacodynamics of adderall?
Adderall is a stimulant medication made up of mixed amphetamine salts (mainly dextroamphetamine and levoamphetamine).
Clinical use: ADHD and narcolepsy
Pharmacodynamics: Increases dopamine & norepinephrine to boost focus, alertness, and control impulses.
84
What are the medical uses for cocaine?
Blocks DA reuptake transporter
Cocaine in medicine is a powerful topical anesthetic and vasoconstrictor, mainly used during nasal and throat surgeries—but only under strict medical supervision.
85
What is methylphenidate ?
methylphenidate (Ritalin)?
Methylphenidate is a stimulant that treats attention-deficit/hyperactivity disorder (ADHD). It works by improving your focus and reducing impulsive behaviors. It can also treat narcolepsy by promoting wakefulness. The brand names of this medication are Methylin® and Ritalin®.
86
What is methamphetamine? (mainly, what's the mechanism of action?)
Methamphetamine affects the central nervous system (CNS) by enhancing the release of monoamine neurotransmitters such as serotonin, dopamine, and norepinephrine. [4] The use of methamphetamine can lead to many pharmacological effects because of its ability to use various molecular processes.
It's similar to amphetamine (used in ADHD meds like Adderall), but stronger and longer-lasting.
It increases levels of dopamine, a brain chemical linked to pleasure, motivation, and movement.
Sold under the brand name Desoxyn
Used very rarely for:
ADHD
Obesity (as a last resort, short-term)
illegally -> street meth
87
What are the first and second most used psychoactive substances in the world?
The most widely consumed psychoactive substances globally are caffeine and alcohol, followed by nicotine. Caffeine is found in coffee, tea, and other beverages, while alcohol is found in alcoholic beverages. Nicotine is a key component of tobacco and tobacco-based products
88
Why to women metabolize alcohol slower than men?
Women generally metabolize alcohol slower than men primarily due to differences in body composition and enzyme activity. Women have a higher percentage of body fat and less water, which affects how alcohol is diluted and distributed in the body. Additionally, women produce less of the enzyme alcohol dehydrogenase, which is responsible for breaking down alcohol in the stomach, further contributing to slower metabolism.
89
Alcohol accounts for ___% of all fatal car accidents?
50%
90
Alcohol metabolism is _______ over time.
Pharmacokientics - Alcohol
* ROAs: oral
* Absorption: water and lipid soluble (but does not tend to stay in fat), GI tract, rapid
* Bioavailability: Excellent
* Peak times: 30-90 minutes, depending on stomach contents
* Distribution: concentration dependent on water content
* Half-life: varies, dependent on several factors:
– size and weight
– individual metabolism rate
– related food intake
– the specific beverage consumed
Metabolism
– 95% by alcohol dehydrogenase and aldehyde dehydrogenase into acetate
– Liver (85%), stomach (15%; first pass)
– Women metabolize less ethanol than men
* Less gastric metabolism
* Less blood (less muscle)
* More fat (alcohol concentrates in plasma)
* Metabolism cont.
– Constant over time
* NOT dependent on dose!
– 0.010-0.015 grams/hour
* If more alcohol than this is consumed per hour, blood alcohol levels will build (i.e. you will become progressively more drunk)
– BAC of .08 is considered legally intoxicated
* .04-.08 car accidents x4!
* Excretion
– Urine
– Lungs (unchanged)
CONSTANT OVER TIME CONSTANTTTT
91
What are the pharmacodynamics of alcohol?
GABAA receptors
– Agonist
– Increases inhibition
– Affects other NT systems
indirectly
* Increases DA release
in NAc and frontal
lobes
– Decreased
anxiety,
alertness
– Decreased
problem
solving, risk
assessment
92
What is the pharmacokinetics of alcohol?
* ROAs: oral
******** Absorption: water and lipid soluble (but does not
tend to stay in fat), GI tract, rapid
* Bioavailability: Excellent
* Peak times: 30-90 minutes, depending on
stomach contents
* Distribution: concentration dependent on water
content
****** Half-life: varies, dependent on several factors:
**– size and weight
**– individual metabolism rate
**– related food intake
**– the specific beverage consumed
Metabolism
– 95% by alcohol
dehydrogenase and
aldehyde
dehydrogenase into
acetate
– Liver (85%),
stomach (15%; first
pass)
*****– Women metabolize
less ethanol than
men
* Less gastric
metabolism
* Less blood
(less muscle)
* More fat
(alcohol
concentrates
in plasma)
9
93
What are the physiological effects of alcohol?
Physiological
– Respiratory depression
– Anticonvulsant
– Decreased BP
– Decreased body temp
(hypothermia)
– Cardiac atrophy
* Low daily doses
might be cardio-
protective
– Increase
HDL, lowers
LDL
– Decreases
platelet
aggregation
(anti-
clotting)
94
What are the behavioral effects of alcohol?
* Behavioral
– Depression of cognition,
mental function
* Slower time
perception
* Memory
impairments
* Concentration
impairments
– Depressed motor function,
coordination
– Behavioral disinhibition at
low doses, behavioral
depression at higher doses
* Decreased impulse
control
* Decreased
estimation of
consequences
95
What are the tolerance of alcohol?
Occurs with chronic, heavy use
******* Does not tend to occur in sporadic or light
drinkers
Metabolic
* Up regulation of liver enzymes
* Accounts for ~25% of tolerance in chronic
users
Tissue
* Neural changes
* Not equal in all neurons/systems
Associative
* Environmental stimuli becomes conditioned
to both metabolic and neural changes
96
What is the dependence and withdrawal symptoms of alcohol?
* Neural “hyperexcitability”
– Seizures
– BZDs, anticonvulsants
– “kindling” model
* Previous
withdrawals
increase severity of
future withdrawals
* Delerium Tremens
– Tremors
– Hallucinations
– Psychomotor agitation
– Confusion/disorientation
– Sleep disturbances
97
What are the side effects of alcohol?
* Cognitive impairment
* Amnesia/memory deficits
* Respiratory depression
******* Liver damage
–** Hepatitis/cirrhosis
**– 75% of alcoholism
deaths
**– 12th cause of death in
US (CDC, 2015 data)
* Neural damage
– Korsakoff’s
syndrome/alcohol
dementia
– B1 deficiency
* Pancreatitis
* Gastritis
* Cancer
– Acetaldehyde is a
tumor promoter
– Particularly of GI tract
98
What is the toxicity of alcohol?
* LD50 = 7,060 mg/kg (rat, oral); 0.40-0.50% BAC
humans
– 3 bottles of wine
– 20 shots
– 12 pints of beer
****** Respiratory depression
* Organ failure
– Acetaldehyde and acetic acid
* Thiamine deficiency can prevent
metabolism
99
What are the teratogenic effects of alcohol?
teratogenic means birth defects and developmental problems when consumed during pregnancy.
Crosses placenta easily;
BAC of mother is BAC of
fetus
* Alcohol competes in
synthesis of retinoic
acid, necessary for brain
development
* Fetal Alcohol Syndrome
– CNS dysfunction
* Cognitive
deficiencies,
hyperactivity,
motor slowing
– Decreased/slowed
body growth rate
– Facial abnormalities
* Alcohol-related
neurodevelopmental
disorder (ARND)
20
100
What are some abuse/dependence treatments for alcohol use?
**Abuse/Dependence Treatments **
Reverse the acute pharmacological effects of alcohol
- None available
Txt and prevention of withdrawal symptoms
Limit neuronal injury during withdrawal
Decrease cravings and reduce relapse
Txt co-existing psychiatric disorders
**Withdrawal Treatments **
Goal: to prevent hyperexcitability due to decreased GABA and increased glutamate function
Barbiturates
Paraldehyde; induces sedation
* BZDs
– Increase GABAergic tone
– Long acting (Librium, Valium), low dose
– Short acting (Ativan); seizure control
* Anticonvulsants
– Older: Tegretol, Depakote
– Effective, but have harmful side effects
– Newer: Neurontin, Lyrica, Trileptal, Lamictal, Topamax
– Effective and fewer toxic effects
101
What are some withdrawal treatments for alcohol?
Goal: to prevent hyperexcitability due to decreased
GABA and increased glutamate function
* Barbiturates
– Paraldehyde; induces sedation
* BZDs
– Increase GABAergic tone
– Long acting (Librium, Valium), low dose
– Short acting (Ativan); seizure control
* Anticonvulsants
– Older: Tegretol, Depakote
– Effective, but have harmful side effects
– Newer: Neurontin, Lyrica, Trileptal, Lamictal,
Topamax
– Effective and fewer toxic effect
102
How should you maintain abstinence for alcohol?
*
**** this whole slide was basically red
**Maintaining Abstinence **
* Antabuse (disulfram), Temposil – blocks metabolism, allowing acetaldehyde build-up.
* Vivitrol/Revia (naltrexone) – blocks opioid receptors, decreases reinforcing value of alcohol
* Campral (acamprosate) – GABA agonist/glutamate NMDA antagonist
– 2mg/day, 18 hr half-life, best when combined with naltrexone and/or psychotherapy
* Wellbutrin (buproprion) – DA agonist, especially good when pxts are also depressed
* Serotonin agonists – SSRIs, 5-HT1A, 5-HT3; best for pxts who started drinking later and less psychopathology
* Chantix (varenicline) – nicotinic partial agonist
* Accomplia (rimonabant) – cannabinoid antagonist
**Dealing with Other Problems **
* Alcoholics with comorbid diagnoses more likely to relapse
* Alcohol often used as a coping mechanism during stress
* Most pharmacological therapies are only marginally effective alone
* Addition of psychotherapy significantly increases success rate
103
What are barbiturates?
* Amytal, Alurate, Butisol, Nembutal,
Luminal, Seconal, Latusate
* Half-lives 10-50 hours
* Water-soluble, peak times are
several hours following oral
ingestion
***** Low safety index
* High potential for dependence and
abuse
* Leave pxts feeling groggy the next
day
Barbiturates are old-school sedatives that calm the brain but are rarely used now due to high overdose and addiction risks.
Replaced by safer drugs like benzodiazepines (e.g., Valium, Ativan)
104
What are some non-barbiturate sedatives?
* Doriden, Placidyl,
Noludar, Noctec
* Most have half-lives
longer than 10 hours
– Noctec is
exception (8-10
hrs)
* Same
safety/dependence
issues as with
barbiturates
105
What are BZDs?
Benzodiazepines are a class of medications that slow down activity in your brain and nervous system. They’re most often used for treating anxiety and related mental health conditions, as well as brain-related conditions like seizures.
106
What are some BZDs?
Dalmane, Dormalin, ProSom, Restoril
– Fairly rapid onset
– 12-80 hr half-life
*****– Active metabolites
* Halcion, Versed, Rohypnol
– Rapid onset
– 2-3 hr half-life
– No active metabolites
*****– Amnestic ED50 lower than somnolent ED50
* Low toxicity
– Unless combined with other GABA agonists (I’m looking at
YOU alcohol)
– Overdose may be intentional , but often due to accumulation
of doses (memory issues)
– Symptoms: somnolence, impaired coordination, slurred
speech, diminished reflexes, confusion, respiratory
depression, hypotension
* Amnestic effects
* Suppress REM sleep
* High liability for dependence
107
What are some benzodiazepines - sedative/hypnotics?
Benzodiazepines-Sedative Hypnotics
Flurazepam (Dalmane)
Onset of action 15-45 minutes
Dose: 15-30mg
***More effective the longer you take it due to accumulation of active metabolites with long half-life
Triazolam (Halcoin)
Short half-life
Short term treatment (7-10 days)
Dose 0.125mg-0.5mg
***Best for sleep-onset insomnia
Flunitrazepam (Rohypnol)
18-26 hour half-life (activty metabolite half-life = 36-200 hours)
Dose 1mg
Developed for use in hospital where heavy sedation was required; generally not used for insomnia
**Amnestic
108
What are non-benzodiazepine BZRAs?
Non-benzodiazepine benzodiazepine receptor agonists (NBBRAs), often called "Z-drugs," are a class of medications used to treat insomnia and anxiety
* Ambien, Sonata, Lunesta
* GABA1A
– Primarily hypnotic
* Absorbed slowly
* 1-7 hour half-lives
* Amnestic
* Lower risk for dependence
* Best for sleep-onset insomnia
**** Ambien, Sonata, Lunesta
GABA1a
Lower risk for dependence
Best for sleep onset insomnia
109
What is cannabis?
Cannabis sativa (C. sativa)
– ∆-9 THC (intoxicating)
– Cannabidiol (non-
intoxicating)
– THCA (turns into THC
upon heating)
* Product Type
– Flower; 0-30% THC
– Extract/concentrate/
vape; 40-80%
– Edibles; 5-30%
– Tinctures; less than
5%
110
What are the pharmacokinetics of cannabis?
* ROAs: smoked, oral, transdermal
* Absorption: smoked = rapid, oral = slow
* Lipid-soluble, cross cell and placenta
membranes easily
* Bioavailability: smoked = excellent, oral = poor
* Average joint contains ~75mg THC
* Therapeutic concentrations: 3-6ng/ml plasma
* Experience a “high” at 5-10ng/ml plasma
* Peak times: smoked = ~1-5 minutes, oral = 30-90
minutes
* Peak levels 50-100ng/ml plasma
******* Distribution: lipid-soluble, concentrated in fat
* Half-life: 30 min-1 hr; traces in urine up to 30 days
(frequent users; 50ng/mL sensitivity)
– Heavy, frequent users can have marijuana
detected in urine tests 3 months after last
use
111
What are the pharmacodynamics of cannabis?
* Cannabinoid Receptors
– CB1; central
****** Possibly most populous receptor
in the brain
* Highest densities in limbic
system, cerebellum, basal
ganglia, cortex
– CB2; periphery
* Heart, spleen, tonsils, immune
cells, pain receptors in dorsal
horn of spinal cord
* Often colocalized on glutamate terminals
112
What type of agonist (pharmacodynamics) is cannabis?
* Partial agonist
– Inhibits AC (decreases cAMP)
– Stimulates intracellular ERK cascade
– proliferation, differentiation, survival,
vasodilation
– Decreases Ca2+ influx into synaptic
terminals
– Effects other NT systems indirectly
* Increases mesolimbic DA
pathway and DA release in NAc
* Endogenous ligands
– Anandamide – agonist
– 2AG – agonist
– NADA – agonist
– Virodhamine - antagonist
– May be other endogenous ligands
(~150)
– “Entourage Effect”
10
113
What are the effects of cannabis?
* CNS
– Behavioral Euphoria
– Not as intense as opioids
– Also depends on variety
of marijuana (sativa vs
indica)
* Relaxation
* Decreased aggression
– Cognitive
* Perceptual changes (temporal,
sensory enhancement)
* Dissociation of ideas
* Decreased memory function
(attention, encoding,
consolidation, recall)
* Decreased spatial abilities
CNS
– Motor
* Impaired coordination
– Some evidence it can improve coordination in pxts with movement
disorders
****** Reaction time
– 2-5ng/ml plasma associated with increased auto accidents (i.e. you
might not feel effects!)
– Analgesia
* Independent effects
* “Cross-talk” with opioid systems (may improve response to opioids, thus
allowing for lower doses of opioids to control pain)
* Pain relief
* Hypothermia
* Sedation
* Hypotension
114
What are the effects of cannabis on the body? cardiovascular, pulmonary, immune, and reproductive?
Cardiovascular
– Increase h.r.
– Decrease b.p.
– Dilation of corneal vessels
* Pulmonary
– More tar in joints than cigarettes
– Bronchial irritation/inflammation
– Lung cancer
* Immune System
– Immunosuppression
– Anti-tumor
* Reproduction
– Males
* Decreased testosterone
* Decreased sperm production
– Females
* Decreased FSH and LH
* Increased anovulatory cycles
115
What is the withdrawal like for cannabis?
* 1 in 10 users
* Common Symptoms
***** Irritability
* Anxiety
* Craving
* Sleep disturbances
* Anger/aggression
* Depressed mood
* Decreased appetite/weight loss
* Less common
* Headache, tension, sweating,
stomach pain, chills
* Syndrome lasts 2-30 days, depending
upon prior usage
* No known lasting effects
116
What is the toxicity for cannabis?
* LD50
*****– None known for humans
* Estimated to be 20,000-40,000
average dose
* ~1500 lb (consumed within 15 min)
– Rats: 42 mg/kg (pure THC, inhaled)
* In a 150 lb individual that would
mean smoking ~57 joints (assuming
50mg THC per joint)
* Use of other sedatives (alcohol, BZDs) will
increase effects of cannabis
117
What is Rimonabant?
Rimonabant
* Accomplia
* First in class of therapeutic agents
called cannabinoid 1-receptor
blockers.
* Not FDA approved
******* Primary Indication
****– Adjunct to diet and exercise in
the treatment of obese patients
with associated risk factors, i.e.
type 2 diabetes, dyslipidaemia
****– Marijuana dependence
19
118
What is Epidiolex (cannabidiol)
Primary indications: Treatment of pediatric epilepsy, MS
No psychoactive effects, not addictive
119
What is Dronabinol?
Smoking cannabis vs oral (pure THC)
synthetic form of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. It is available as a prescription medication under the brand names Marinol and Syndros
Smoked THC: Quick relief, more control, but short-acting and harder to dose consistently.
Oral dronabinol: Slower onset, longer-lasting, more stable dosing—but takes patience.
Dronabinol is used to treat nausea and vomiting caused by chemotherapy in people who have already taken other medications to treat this type of nausea and vomiting without good results.
120
What are the general effects of psychodelics?
* Perceptual distortion
– synesthesia
* Hallucinations
* Euphoria
* Paranoia, anxiety
* Analgesia
* Pupil dilation
* Drying of secretions (tears, mucus,
etc)
* Nausea, Vomiting
* Hyperthermia
121
What are the adverse effects of psychodelics?
* Adverse effects
– “Bad trip”
* Paranoia, anxiety
* Damage to oneself or others
***** “Set and Setting”
– The context of the
experience has a
tremendous impact on
the quality of the
experience
– Flashbacks
***** Hallucinogen Persisting
Perception Disorder
– Exacerbation of existing psychosis or
emotional disturbance
122
What are anticholingerics?
Anticholinergics are a class of drugs that block the action of a chemical messenger called acetylcholine
*** Scopolamine; ACh antagonist
* Natural sources: belladonna,
datura, mandrake, moonflower
* PNS: dry mouth, hyperthermia,
dilated pupils, blurred vision,
tachycardia, hypertension
* CNS: drowsiness, euphoria
(mild), amnesia, confusion,
delirium, hallucinations,
disorientation
*** Sometimes found in motion-
sickness preparations
123
What are catecholaminelike?
Catecholamines are a group of neurohormones, including dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), that act as both neurotransmitters and hormones in the body.
Catecholaminelike
* Enactogens
* Combined stimulant- and psychedelic-
effects
– Increased energy, sociability,
hyperthermia, increased blood
pressure, tachycardia
– hallucinations
* DA, NE and 5-HT agonists
* -OCH3 (methoxy) addition to phenyl ring
124
What are some examples of catecholaminelike ?
* Mescaline
* Myristicin
* Elemicin
* Synthetics
– Derived from amphetamine
* DOM
* MDA
* MDE
* TMA
* AMT
* 50MeO-DIPT
* MDMA
125
What is Myristicine and Elemicin?
*****Found in nutmeg and mace,
respectively
* Oral (tea)
* Euphoria, hallucinations,
disorientation
* Nausea, vomiting, tremors
126
What is Methylated Amphetamines?
Methylated amphetamines are a class of stimulant drugs where a methyl group (a single carbon atom with three hydrogen atoms) has been added to the amphetamine molecule
* Synthetic
****** Very potent, highly toxic
* Less visual hallucinations
* Stimulate DA, NE and 5-HT release/receptors
* Intense euphoria, feelings of empathy, “oneness”
* DOM
– Oral, 1-6mg
– 100x mescaline, but less than LSD
– Toxic reactions: tremor, convulsions, death
* MDA/MDE/DMA/TMA
– “designer psychedlics”
* AMT
– Slow onset (2-3hrs), long duration (12-24hrs)
* 5-MeO-DIPT
– Rapid onset (20-30mins), short duration (3-
6hrs)
127
What are some examples of Serotonike?
* LSD
* Psilocybin / Psilocin
* DMT
* Bufotenine
* 5-HT2A (cerebral cortex)
128
What are some NMDA Receptor Antagonists?
* Phencyclidine (PCP)
* Ketamine
* Dissociative anesthetics
* Psychedelic anesthetics
* Developed for anesthetics purposes
* Analgesic
* Amnestic
* NMDA, sigma
* Do not directly affect DA, NE, 5-HT
129
What is ketamine?
Ketamine is a dissociative anesthetic that has some
hallucinogenic effects.
* Ketalar, Special K, Vitamin K
* Dissociative anesthetic
* 1960
* Medical Uses:
– Pediatric anesthesia
– Asthma/COPD
– Topical application for nerve pain
– Emergency surgery in field condition
– To supplement spinal/epidural
anesthesia/analgesia using low doses
***** No bp or respiratory effects
* Less psychiatric side effects
* Schedule 3
130
Ketamine ROA and Pharmacokinetics
* ROI: intramuscular (IM), insufflated
(IN)
* Average dose: 50-150mg
* Peak time: 5-10 min
* Half-life: 2.5-3 hours
* Metabolism: hepatic, CYP3A4
* Excretion: renal
* Toxicity: 4.5-5.5g
131
From study guide: Catecholamine-like
Entactogens (stimulating)
Combined stimulant and psychedelic effects
DA, NE, 5-HT agonists
132
From study guide: Mescaline
Derived from peyote cactus
Schedule 1 narcotic
Mescaline is a classic, natural psychedelic found in cacti. It causes strong visual and emotional effects, lasts a long time, and has a long history of traditional spiritual use.
oldest hallucinogens
5-HT2A agonist, major activity in prefrontal cortex
banned in 1970s
133
From study guide: Derived from amphetamine
MDA, AMT, MDMA, DMT (shortest trip)
DMT has the shortest trip — often called the "businessman’s trip" because it's so fast.
MDMA is often called “ecstasy” and is more about emotional warmth than visuals.
MDA is similar to MDMA but with more visuals and stimulation.
AMT lasts the longest and combines psychedelic and stimulant effects.
134
From study guide: MDMA (Ecstasy)
General and adverse effects:
Increase release of DA, NE, 5-HT:
*Possible* treatment for:
MDMA makes people feel emotionally connected and euphoric, but can lead to serious problems like dehydration, overheating, or long-term brain changes with heavy use.
If misused, treatment focuses on supportive care, cooling, hydration, and therapy
135
From study guide: Serotonin-like
Serotonin-like
LSD, Psilocybin (act on 5-HT2a)
136
From the study guide: Ketamine
Dissociative anesthetic
Pediatric anesthesia
No bp/ respiratory effects
Analgesic effects:
Psychological effects:
137
NMDA (glutaminergic) receptor antagonists – Mechanism of Action
Block NMDA subtype of glutamate receptors, preventing calcium influx and reducing excitatory neurotransmission; linked to dissociation, analgesia, and neuroprotection in some contexts.
138
PCP (Phencyclidine)
A non-competitive NMDA receptor antagonist; induces psychotomimetic effects via glutamate disruption; also affects dopamine and opioid systems, contributing to hallucinations and agitation.
139
Ketamine – Mechanism and Uses
NMDA receptor antagonist with additional activity at opioid, monoaminergic, and nicotinic receptors; used for anesthesia, treatment-resistant depression, and analgesia.
140
Pediatric anesthesia – Ketamine's Role
Preferred in pediatric populations due to minimal respiratory depression and preservation of airway reflexes; acts mainly through NMDA antagonism and secondary opioid receptor modulation.
141
What is dextromethorphan?
Dextromethorphan
* Dex, DXM
* Approved for use 1958
* Synthesized in the search for a
cough suppressant that was less
addictive than codeine
* Opiate derivative
* Antagonist of NMDA
* Antagonist at certain nicotinic
receptors
– Txts nicotine addiction
* Increases 5-HT release
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What is the ROI and pharmacokinetics of dextrothorphan?
Dextromethorphan
* ROI: oral
* Average dose: 200-1,000+mg
* Duration: 4-8 hours (depending on
dose)
* Peak time: 40-60 minutes (oral)
* Half-life: 3-5 hours
* Metabolism: hepatic, CYP2D6
* Excretion: Renal
* Toxicity: ~3000mg
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Pain medication: Tramadol
Atypical opioid; weak μ-opioid receptor agonist and serotonin/norepinephrine reuptake inhibitor (SNRI); risk of seizures and serotonin syndrome.
schedule IV controlled substance, potential for abuse/dependence
binds to mu opioid receptors, inhibits norepinephrine and serotonin reuptake
take exactly as prescribed, not more or less (talk to doctor)
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Pain medication: Duloxetine
SNRI used for neuropathic pain and depression; increases serotonin and norepinephrine in descending pain pathways.
antidepressant and nerve pain medication
prescription needed, taken orally
overdose at 1000mg
symptoms: somnolence, coma, serotonin syndrome, seizure, syncope, hypo/hypertension, tachycardia, vomiting
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Pain medication: Fentanyl
Potent synthetic μ-opioid receptor agonist; rapid onset; high risk for respiratory depression and overdose.
contraindicated with MAOIs, SSRIs, opioids, CNS depressants
schedule II drug, high abuse potential
leading cause of overdose death (70,000+ in 2023)
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Caffeine and Nicotine: Vaping
Nicotinic acetylcholine receptor agonist; increases dopamine in mesolimbic pathway; addictive and linked to cardiovascular risks.
FDA regulated but not approved
underage vaping deemed “epidemic”
long term effects research inconclusive
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Caffeine and Nicotine: Bupropion
NDRI (norepinephrine-dopamine reuptake inhibitor); used for depression and smoking cessation; reduces nicotine craving.
FDA approved for smoking cessation, significant chance of quitting compared to NRT
reduces cravings/withdrawal symptoms by effecting dopamine and norepinephrine
caution for those with history of seizures, eating disorders, or uncontrolled hypertension
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Stimulants: Amphetamine
Increases synaptic dopamine and norepinephrine via reuptake inhibition and reverse transport; used for ADHD and narcolepsy.
used for disorders
schedule II controlled substance
treatment: avoidance, CBT, taking care of body/mind
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Stimulants: MDMA
Increases serotonin, dopamine, and norepinephrine; causes empathogenic effects; risk of serotonin syndrome and neurotoxicity.
reverses monoamine transports (SERT, NET, DAT) causing flood of monoamines into synapses
not likely to cause addiction, extremely undesirable “comedown”/hangover
fatalities rare, fatality increased in polydrug interactions
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Stimulants: Azstarys
Mixed d-methylphenidate formulation (serdexmethylphenidate + d-MPH); extended-release stimulant for ADHD.
CNS stimulant, combination of fast acting drug and extended release prodrug
approved to treat ADHD symptoms in children 6+ and adults
acts as DAT and NET inhibitor and 5-HT1A agonist
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Stimulants: Desoxyn
Front: Desoxyn (Methamphetamine HCl)
Back: Prescription methamphetamine; powerful CNS stimulant for ADHD; high abuse potential.
sympathetic agent used to treat ADHD and obesity
schedule II/federally controlled substance with high abuse potential
rehabilitation from methamphetamine abuse disorder is difficult
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Alcohol and Sedatives: Temazepram
Benzodiazepine; enhances GABA-A activity; used for short-term insomnia; tolerance and dependence risk.
short term treatment for insomnia
high risk of addiction and dependence (7-10 day treatment must be adhered to)
avoid using with alcohol, opioids, and other meds that cause sleepiness (increased risk of respiratory depression and overdose)
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Alcohol and Sedatives: Eszopiclone
Z-drug; binds GABA-A receptor at benzodiazepine site; used for insomnia; fewer cognitive side effects.
insomnia treatment, long term use with significant efficacy and low tolerance development
higher affinity for GABAα and longer half-life compared to other non-BDZ sedatives
caution for coexisting anxiety, substance abuse history, or complex sleeping behaviors
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Alcohol and Sedatives: Daridorexant
Dual orexin receptor antagonist (DORA); promotes sleep without GABA modulation; lower risk of dependence.
blocks orexin receptors (OX1R + OX2R) to reduce wakefulness without GABA, lower next day sedation
effective for sleep onset and maintenance, no tolerence/withdrawal/dose increase
less accessible ($509-$648/month) insurance needed
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Marijuana: Dronabinol
Synthetic THC; CB1 receptor agonist; used for appetite stimulation and nausea.
synthetic delta-9-THC, appetite stimulant and anti-nauseant (cannabinoid receptors)
interacts with drugs that impact CNS, inhibit/induce CPY2C9/CPY3A4, or highly bound by proteins (affects systemic exposure, worsens side effects)
not recommended for pregnant, nursing, or children, elderly monitored
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Marijuana: Cannabidiol (CBD)
Non-intoxicating cannabinoid; modulates multiple receptor systems (including serotonin and TRPV1); used for epilepsy and anxiety.
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Marijuana: Nabilone
Synthetic cannabinoid similar to THC; used for chemotherapy-induced nausea and vomiting.
pediatric epilepsy
neonatal hypoxic-ischemic encephalopathy, glioma, schizophrenia
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Psychedelics: LSD
Potent 5-HT2A receptor agonist; causes altered perception and cognition; long duration of action.
alters perception and cognition via serotonin receptor modulation
can be used to treat certain mental health conditions (anxiety, depression, PTSD)
teratogenic effects and neurodevelopmental risks in pregnant individuals and adolescence
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Psychedelics: Mescaline
Naturally occurring phenethylamine; 5-HT2A agonist; hallucinogenic effects from peyote cactus.
oldest hallucinogens
5-HT2A agonist, major activity in prefrontal cortex
banned in 1970s
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Psychedelics: DMT
Short-acting tryptamine psychedelic; 5-HT2A agonist; intense visual/auditory hallucinations; found in ayahuasca.
potent serotonin agonist (5-HT2A receptor)
potential risks: history of mental health disorders, serotonergic medications (serotonin syndrome)
antidepressant effects
