psychopharm 3

What type of alcohol is safe to drink?

Ethanol is the only type of alcohol safe for human consumption.

How is alcohol content listed as proof converted to percent alcohol by volume?

Divide the proof number by 2.
(Example: 80 proof = 40% ABV)

What feature of the alcohol molecule allows it to pass through biological barriers (e.g., blood

brain barrier)?

Alcohol is small, non-ionized, and lipid-soluble, allowing it to cross membranes like the blood-brain barrier easily.

How is the amount you drink related to the rate of absorption of alcohol

Larger amounts can saturate enzymes and slow down absorption, but drinking quickly (e.g., chugging) increases the rate of absorption.

How does food in the stomach affect alcohol absorption?

• Food slows alcohol absorption by delaying gastric emptying and reducing alcohol's contact with the stomach lining.

]On average, why does the same amount of alcohol result in a higher blood alcohol

On average, why does the same amount of alcohol result in a higher blood alcohol concentration (BAC) in women compared to in men? Why is this still the case even after adjusting for body size?

Women generally have less alcohol dehydrogenase, higher body fat, and less total body water → higher BACs even when adjusting for size.

Be familiar with the enzymes responsible for breaking down alcohol

Alcohol dehydrogenase (ADH) converts ethanol to acetaldehyde.
→ Aldehyde dehydrogenase (ALDH) converts acetaldehyde to acetate.

An accumulation of what metabolite of alcohol might be responsible for the symptoms of a hangover?

• Acetaldehyde buildup is toxic and linked to hangover symptoms.

Why might taking a drug that competes over the same enzymes as alcohol result in a potentially dangerous interaction when combined with alcohol?

Competition can slow metabolism of one or both substances → increased toxicity or prolonged effects.

Be familiar with the genetic differences in aldehyde dehydrogenase discussed in class, and how they influence risk for alcohol use disorder.

Some people (e.g., East Asian populations) have a deficient ALDH gene, causing unpleasant effects when drinking → this may protect against alcohol use disorder.

Does alcohol follow first-order or zero-order elimination? What does that mean?

• Alcohol is eliminated via zero-order kinetics: a constant amount is metabolized per hour regardless of concentration (~1 drink/hour).

What are the main pharmacodynamic effects of alcohol?

Enhances GABA-A (inhibition), inhibits NMDA (excitatory). Results in sedation, poor coordination, impaired memory.

How can alcohol increase the release of dopamine in the mesolimbic dopamine system?

Alcohol inhibits GABA interneurons in the VTA → disinhibits dopamine neurons → increased dopamine release in the nucleus accumbens.

What else, besides the pharmacological effect of the drug, can influence someone’s response to alcohol? Does this depend on dose?

Expectations, context, mood, and experience play roles.
→ Yes, effects can depend on dose (e.g., placebo effect stronger at low doses).

What is alcohol priming? How can it contribute to binge drinking?

Initial alcohol use increases craving or desire to continue → may lead to loss of control and binge drinking.

What is the difference between metabolic tolerance and pharmacodynamic tolerance?

Metabolic: body increases enzymes to break down alcohol faster.
→ Pharmacodynamic: neurons adapt (e.g., receptor downregulation) to reduce alcohol’s effect.

What compensatory changes occur with chronic alcohol use? How can they contribute to a dangerous alcohol withdrawal syndrome?

Brain becomes hyper-excitable due to upregulation of NMDA and downregulation of GABA receptors → withdrawal causes anxiety, seizures, delirium tremens.

What is Korsakoff’s syndrome? What is it caused by?

• A memory disorder due to thiamine (vitamin B1) deficiency in chronic alcoholics → leads to confabulation and irreversible memory damage.

Be familiar with the treatments for alcohol use disorder discussed in class (especially acamprosate and disulfiram).

Acamprosate: balances GABA/glutamate to reduce cravings.
→ Disulfiram: blocks ALDH → causes unpleasant reaction if alcohol is consumed.
→ Also: naltrexone (reduces reward), therapy.

How can the benzodiazepines interact with alcohol? Why can they help alleviate alcohol withdrawal symptoms?

Both act on GABA-A receptors → combined use is dangerous (additive CNS depression).
→ Benzos are used to ease withdrawal and prevent seizures.

What is opium?

A natural extract from the poppy plant containing active opioids like morphine and codeine.

Know the main differences between schedules 1, 2 and 3 under the controlled substances act.

• Schedule I: no accepted medical use, high abuse risk (e.g., heroin).

• Schedule II: medical use, high abuse risk (e.g., oxycodone, morphine).

• Schedule III: medical use, moderate abuse risk (e.g., Tylenol with codeine).

What is an opioid? How do the opioids help relieve pain?

Drugs that bind to opioid receptors and inhibit pain signaling in the CNS.

What is a narcotic? Why is this term no longer useful as a drug classification?

Originally meant sleep-inducing drugs; now overly broad and outdated as a scientific term.

Be familiar with the three major types of opioid receptors. Which receptor is responsible for most of the analgesia and addiction liability associated with opioids?

Mu (μ): primary site of pain relief and addiction.
→ Also: Delta (δ) and Kappa (κ).

How can you locate and measure the levels of a particular protein in the brain? Why is this technique useful?

Techniques like immunohistochemistry or PET scans with labeled ligands help visualize and measure receptor density, useful for studying drug effects.

What opioid effects are the medulla, periventricular gray area, and ventral tegmental area most associated with?

• Medulla: controls respiration → opioids depress breathing.

• Periventricular gray: involved in pain modulation.

• VTA: part of reward pathway, increases dopamine.

Does tolerance to opioid analgesia and respiratory depression develop at the same rate, or at different rates? Why is this important?

Different rates — tolerance to pain relief develops faster than tolerance to respiratory depression → higher overdose risk in long-term users.

How can the opioids increase the release of dopamine in the mesolimbic dopamine system?

Opioids inhibit GABA interneurons in the VTA → dopamine neurons fire more → more dopamine in nucleus accumbens.

What are the differences between the opioids discussed in class (heroin, morphine, fentanyl, carfentanyl)?

• Heroin: fast-acting, highly addictive.

• Morphine: gold standard for pain relief.

• Fentanyl: ~100x potency of morphine.

• Carfentanyl: ~10,000x potency, not safe for humans.

Be able to draw a dose response curve showing how the potency and efficacy of morphine compare to that of fentanyl.

Fentanyl curve is shifted left (more potent).
→ Both may have similar efficacy (same height), but fentanyl reaches effect at lower doses.

How does the story of the frozen addicts illustrate the danger of street drugs?

Contaminated synthetic drug (MPTP) caused irreversible brain damage like Parkinson’s. Highlights risks of unregulated drug synthesis.

What was wrong with the frozen addicts, and how could it be treated?

MPTP destroyed dopaminergic neurons in the substantia nigra.
→ Treated with L-DOPA, a dopamine precursor.

Be familiar with the pharmacological treatments for opioid use disorder discussed in class (especially methadone, buprenorphine, naloxone, naltrexone, and suboxone).

• Methadone: long-acting full agonist.

• Buprenorphine: partial agonist.

• Naloxone: fast-acting antagonist (reversal).

• Naltrexone: long-acting antagonist.

• Suboxone: buprenorphine + naloxone combo.

What is the difference between nociceptive pain and neuropathic pain? Which type are the opioids more effective for?

• Nociceptive: due to tissue injury (e.g., cuts).

• Neuropathic: nerve damage (e.g., diabetic neuropathy).
  → Opioids work better on nociceptive pain.

As discussed by Van Zee (2009), describe two ways in which drug companies like Purdue market their products.

• Downplayed addiction risk of OxyContin.

• Used aggressive marketing with incentives and misleading information to promote overprescribing.