FINAL EXAM - RED STUFF Flashcards
What is the difference between Dependence and Abuse.
Dependence
Tolerance
Withdrawal
Taken in larger amounts (over time) than initially
Desire or effort to cut down or control use
Great deal of time spent
Other activities are given up
Use is continued despite knowledge of problems created by usage
Abuse
Maladaptive pattern of use leading to clinically significant impairment or distress characterized by one or more of the following (12 months)
A failure to fulfill major role obligations (work, school, home)
Use in physically hazardous situations
Legal problems
Continued use despite recurrent social/interpersonal problems
What does Agonist Substitution mean?
Does not necessarily cure the addiction, but often improves outcomes for patient and communities
Tend to have longer half-lives
Opiates – Methadone (dolophine)
Nicotine – patches, gum, lozenges, bupropion (Zyban)
Stimulants – modafinil (Provigil)
What does partial agonist substitution mean?
Provide a level of receptor stimulation that prevents cravings, but does not induce abuse
Opiates – buprenorphine (Butrans)
Longer half life than Methadone
Often combined with an opiate antagonist such as naloxone (Narcan)
Nicotine – varenicline (Chantix)
Stimulants – aripiprazole (Abilify) ?
What does Agonists mean?
Block receptors stimulated by the abused drug so that taking the drug no longer has an effect.
Pxt non-compliance is the biggest problem
Opiates – naloxone (Narcan), naltrexone (Revia), nalmefene (Revex)
Alcohol – naltrexone
Cannabis – rimonabant (Accomplia)
What does withdrawal maintenance mean?
Easing withdrawal symptoms can make a pxt less likely to relapse
Opiates/Alcohol – clonidine (Catapres), lofexidine (Britlofex; not currently available in US)
Alpha-2-adrenergic agonists
Ease sympathomimetic withdrawal symptoms
Stimulants – propanolol (Inderal)
Beta-adrenergic antagonists (beta blockers)
What does Mesolimbic DA regulation mean?
Blocking DA receptors does not seem to work.
Increasing DA does seem to be beneficial
bupropion (Zyban/Welbutrin)
Antabuse (blocks β-hydroxylase)
What are some NT system regulations?
Just as certain drugs stimulate the mesolimbic DA system through other NT systems, those systems can be targeted in an attempt to modulate the DA system.
Glutamate
NMDA agonists; D-cycloserine (DCS), N-acetyl cysteine
GABA
GABAB agonists; baclofen (Lioresal)
Anticonvulsants; vigabatrin (Sabril), tiagabine (Gabitril)
Norepinephrine
Beta receptor antagonists; propranolol (Inderal)
Opioid
Mu receptor antagonists; naltrexone (Revia)
Cannabinoid
Endocannabinoid system interacts with endorphin system
rimonabant (Accomplia)
What’s the difference between Acute versus Chronic pain?
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
What are NSAIDS?
Nonsteroidal anti-inflammatory drugs (NSAIDS)
Diverse molecules
Peripheral site of Action
Inhibit release of Prostaglandins
Inhibit Cyclooxygenase (COX)
COX inhibitors
“Ceiling” where increased doses do not increase pain relief
Aspirin, Ibuprofen (Advil, Motrin), Phenylbutazone (Butazolidine), Diclofenac (Voltaren), Indomethacin (Indocin), Ketorolac (Toradol), Naproxen (Aleve, Naprosyn), Celecoxib (Celebrex), Refecoxib (Vioxx), Valdecoxib (Bextra)
What are COX Inhibitors?
Inhibition of COX-1
GI upset, ulcers, kidney disease
Anticoagulant
Can reduce risk of heart attack and stroke
80-160mg/day*
Durlaza
Inhibition of COX-2
Reduction of inflammation
Pain relief
Fever relief (antipyretic)
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)
Name three NSAIDS
Aspirin, Ibuprofen (Advil and Motrin), Naproxen (Aleve, Naprosyn).
“Ceiling” where
increased doses do
not increase pain
relief
What are the CNS mechanisms for Opioid analgescis?
CNS mechanisms
Endorphins
Natural ligands
Opiates
Derived from opium poppy
Opium, heroin, codeine, morphine
Opioids
Anything exogenous that binds to opiate receptors and stimulates
Synthetic, semisynthetic, natural
What are some pure agonists opioids?
Binds to opiate receptors and stimulates
Affinity determines potency
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)
What are the alcohol pharmacokinetics? *****
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
Women metabolize less ethanol than men
Less gastric metabolism
Less blood (less muscle)
More fat (alcohol concentrates in plasma)
What are Sedative Hypnotics?
Hypnotics: Agents that induce sleep
Pharmacologic effects are dose related
small doses: sedation
medium doses: hypnosis (sleep)
larger doses: loss of sensation (anesthesia)
Hypnotics are usually anxiolytic
But not all
Most common cause of insomnia!
What are sedative hypnotics that are GABA agonists?
Barbiturates
Amytal, Alurate, Butisol, Nembutal, Luminal, Seconal, Latusate
Low safety index
Non-barbiturate sedatives
Doriden, Placidyl, Noludar, Noctec
Same safety index problems as barbiturates but with shorter half-lives
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 effects ED50 lower than somnolent ED50
Low toxicity
Unless combined with other GABA agonists (ALCOHOL)
What are psychedelics?
-Hallucinogens
-Alterations in perception, mood, cognition
-Used in many cultures
Religious rituals, spirituality
-Types
Anticholinergic
**Scopolamine; ACh antagonist
Natural sources: belladonna, datura, mandrake, moonflower
**Sometimes found in motion-sickness preparations
What are 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
Mescaline
Myristicin, Elemicin
Found in nutmeg and mace, respectively
Synthetics
Derived from amphetamine
DOM, MDA, MDE, TMA, AMT, 50MeO-DIPT,
**MDMA (hyperthermia; increases release of DA, NE, 5-HT via reuptake mechanism)
What are adverse effects for psychedelics?
“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
What is the #1 cause of acute liver failure?
Acetamineophen -> metablized in the liver.
Don’t take ___ after a hangover
Tylenol
What are non-specific COX inhibitors?
Indomethin (Indocin)
– Pain, fever, inflammation
* Rheumatoid arthritis
**– Increased side-effect liability
* GI upset, headache (?)
* Sulindac (Clinoril)
– Similar to indomethin
– Active metabolite = sulindac sulfide
**– Less GI upset than indomethin
Diclofenac (Voltaren)
– Pain, inflammation
* Arthritis, menstrual pain
– Half-life = 2 hrs
**– Several preparations: delayed release,
topical, skin patch
* Nabumetone (Relafen)
– Pain, inflammation
* Arthritis
– Less GI upset vs. aspirin
**– Recommended for long-term txt
What are 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)
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What are the side effects of Morphine?
Side Effects: respiratory
depression, pupillary
constriction, constipation,
decreased sex drive/fertility
problems, itching
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
What is Hydrocodone?
Hysingla ER, Zohydro ER
** Often mixed with
acetaminophen: Vicodin,
Norco
** Mild-Moderate pain, cough
suppression
* ROA: oral
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What is the tolerance for 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
What is Heroin?
Heroin
* Semi-synthetic
** Increased lipid solubility
* Metabolized into morphine and monoacetylmorphine
and excreted by kidneys
** 3X potency of morphine
* Intense euphoria
* Highly addictive
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
What is Meperidine?
- 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)
