Physiology and Application
Fill in the blank:
Activated opioid receptors _(activate/inhibit)_ neurotransmitter release.
Fill in the blank:
Activated opioid receptors inhibit neurotransmitter release.
Presynaptically, activation of opioid receptors inhibits the release of neurotransmitters involved in pain, including substance P and glutamate. Postsynaptically, activation of opioid receptors inhibits neurons by opening potassium channels that hyperpolarize and inhibit the neurons.
A 26-year-old man is brought to the emergency department after being found unresponsive in his apartment. He has no known medical conditions and does not take any medications. On examination, his temperature is 37.1°C (98.7°F), pulse is 55/min, respirations are 8/min, and blood pressure is 110/89 mm Hg. The patient’s pupils are 2 mm in size and are nonreactive to light. Skin examination reveals evidence of injectable drug use on the patient’s forearms.
The patient’s respiratory depression is most likely caused by which of the following mechanisms?
a) Activation of κ opioid receptors
b) Activation of μ opioid receptors
c) Blockade of norepinephrine reuptake
d) Inhibition of γ-aminobutyric acid type A receptors
e) Inhibition of muscarinic receptor
f) Potentiation of γ-aminobutyric acid type A receptors
Activation of μ opioid receptors
High-Yield Summary
Step 1: Disease Diagnosis
This unresponsive 26-year-old man with cardiorespiratory depression, pinpoint pupils nonreactive to light, and evidence of injectable drug use on his forearms presents a clinical picture that is most consistent with opioid intoxication. Opioid overdose can lead to respiratory depression (respiratory acidosis), miosis, coma, and death.
Step 2: Drug Mechanism
Opioids act as agonists at μ opioid receptors, which stimulate pain relief along with euphoria and decreased anxiety. Naloxone, which is primarily used in an emergency setting, acts as an antagonist at the μ opioid receptor and is used either alone to reverse acute opioid intoxication or in combination with buprenorphine to manage opioid use disorder. Opioids also act as agonists at κ and δ opioid receptors, which elicit different symptoms and adverse effects.
The other choices are incorrect:
This federal act by the DEA (US Drug Enforcement Administration) places all substances which were in some manner regulated under existing federal law into one of five schedules. This placement is based upon the substance’s medical use, the potential for abuse, and safety or dependence liability. What is it?
BONUS: (500 points) Which drug has a higher potential for abuse, Schedule II or Schedule V?
The Controlled Substances Act
The CSA also provides a mechanism for substances to be controlled (added to or transferred between schedules) or decontrolled (removed from control). The procedure for these actions is found in Section 201 of the Act (21U.S.C. §811).
In determining into which schedule a drug or other substance should be placed, or whether a substance should be decontrolled or rescheduled, certain factors are required to be considered. These factors are listed in Section 201 (c), [21 U.S.C. § 811 (c)] of the CSA as follows:
(1) Its actual or relative potential for abuse.
(2) Scientific evidence of its pharmacological effect, if known.
(3) The state of current scientific knowledge regarding the drug or other substance.
(4) Its history and current pattern of abuse.
(5) The scope, duration, and significance of abuse.
(6) What, if any, risk there is to the public health.
(7) Its psychic or physiological dependence liability.
(8) Whether the substance is an immediate precursor of a substance already controlled under this subchapter.
Schedule II. Substances in this schedule have a high potential for abuse which may lead to severe psychological or physical dependence.
Interesting to note: Schedule I - Substances in this schedule have no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse.
What does activation of mu-opioid receptors do to the body? Be descriptive.
Activated mu-opioid receptors lead to inhibition of nociceptive pain reflexes and induce profound analgesia without affecting other sensory modalities such as touch.
What is the FDA recommendation for drinking alcohol when taking Vicodin? Give a general why.
BONUS POINT: Why should you avoid grape fruit juice when taking hydrocodone?
GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.
Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.
Is Xanax a controlled substance in Texas?
How about federally?
Penalty groups are drug classifications based on the drug's potential for addiction and medical use.
Penalty group 3 includes opioids and opiates not listed in Penalty Group 1, benzodiazepines, and sedatives like Valium and others, anabolic steroids, methylphenidate (commonly known as Ritalin), and other prescription drugs that have either a stimulant or depressant effect and potential for abuse.
Federal
Benzodiazepines are a Schedule IV drug under the Controlled Substances Act, and have the potential to cause dangerous addictions.
Schedule IV drugs, substances, or chemicals are defined as drugs with a low potential for abuse and low risk of dependence. Some examples of Schedule IV drugs are: Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, Ambien, Tramadol.
What is the main way that Alprazolam is distributed in the body?
Alprazolam is 80% bound to serum protein, mainly albumin.
Alprazolam is rapidly absorbed after oral administration with a peak plasma concentration at 1 to 2 hours. The bioavailability of oral alprazolam averages 80 to 100%.
A 47-year-old man is brought to the emergency department after being struck with a beer bottle during a bar fight. He reports many unsuccessful prior attempts to “get sober” and has recently lost his job due to being intoxicated at work. He presents with tremors and agitation. Temperature is 38.7°C (101.7°F), pulse is 112/min, and blood pressure is 185/105 mm Hg.
What is the mechanism of action of the first-line medication that is most appropriate for the patient’s current condition?
a) Activate N-methyl-D-aspartate receptors
b) Competitive inhibition of alcohol dehydrogenase
c) Competitive inhibition of γ-aminobutyric acid receptors
d) Decreased affinity of ligands to γ-aminobutyric acid receptors
e) Increase affinity of γ-aminobutyric acid receptors
Increase affinity of γ-aminobutyric acid receptors
High-Yield Summary
Step 1: Disease Diagnosis
This patient meets the criteria for alcohol use disorder, which is a problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by behaviors like craving, unsuccessful attempts to quit, impact on work or family, tolerance, or withdrawal. He is demonstrating signs and symptoms of acute alcohol withdrawal, which is marked by fever, agitation, hypertension, tachycardia, and tremulousness.
Step 2: Pharmacotherapy
This patient would benefit from benzodiazepine therapy. Benzodiazepines are used to treat the psychomotor agitation associated with alcohol withdrawal and prevent progression to seizures, delirium tremens, or death.
Step 3: Drug Mechanism
Benzodiazepines work by binding to γ-aminobutyric acid (GABA) type A receptors, leading to a conformational change that increases the binding of GABA to the receptor and increases the frequency of channel opening and influx of chloride ions. This enhancement of neuronal hyperpolarization (increased chloride conductance) by benzodiazepines results in a decrease in neuronal activity and relative sedation.
The other choices are incorrect:
Hydrocodone is classified under what schedule in the CSA?
What does this mean?
Schedule II/IIN Controlled Substances (2/2N)
Substances in this schedule have a high potential for abuse which may lead to severe psychological or physical dependence.
Examples of Schedule II narcotics include: hydromorphone (Dilaudid®), methadone (Dolophine®), meperidine (Demerol®), oxycodone (OxyContin®, Percocet®), and fentanyl (Sublimaze®, Duragesic®). Other Schedule II narcotics include: morphine, opium, codeine, and hydrocodone.
Examples of Schedule IIN stimulants include: amphetamine (Dexedrine®, Adderall®), methamphetamine (Desoxyn®), and methylphenidate (Ritalin®).
Other Schedule II substances include: amobarbital, glutethimide, and pentobarbital.
What does Alprazolam do to the activity of GABA on its target receptors?
(Enhances or diminishes and why?)
Studies in mice suggest that the alpha-1 subunit mediates sedation, amnesia, and ataxic effects of benzodiazepines, and alpha-2 and alpha-3 subunits mediate anxiolytic and muscle-relaxing effects of benzodiazepines. Also, research suggests that BNZ-1 receptors affect sedation and anti-anxiety, while the BNZ-2 affects muscle relaxation, anticonvulsant activity, memory, and motor coordination. Benzodiazepine binding site appear to exhibit coupling with GABA-A receptors, and this enhances the effects of gamma-aminobutyric acid (GABA) by increasing GABA affinity at the GABA-A receptor. The major inhibitory neurotransmitter GABA, when bound to the GABA-A receptor, mediates the calming or inhibitory effects of alprazolam on the human nervous system.
What is the mechanism behind alcohol and benzodiazepine causing additive interactions?
Benzodiazepine is a depressant.
Alcohol affects the GABA-benzodiazepine-chloride ionophore complex and has an agonist-like action. Thus, additive interactions should be expected from combining alcohol with benzodiazepines.
In drug-combination studies, subeffective doses of alcohol, in combination with subeffective doses of other GABAmimetics, potentiate each other's effect in several seizure models. In functional studies, alcohol has been reported to potentiate GABA receptor-mediated 36Cl-flux in microsacs, neurosynaptosomes, and cultured spinal cord neurons at pharmacologically relevant concentrations.
Benzodiazepines + alcohol or opiates (such as heroin): breathing difficulties, an increased risk of overdose and death.
What is the time limit on issuing an electronic prescription of Opioids for the treatment of acute pain?
According to section (f) in the Texas Administrative Code covering Schedule II Prescriptions:
(1) For the treatment of acute pain, as defined in §481.07636 of the TCSA, a practitioner may not:
(A) issue a prescription for an opioid in an amount that exceeds a 10-day supply; or
(B) provide for a refill of the opioid prescription.
Describe the mechanism of how GABA binding to its GABA-A receptor changes neuron excitability.
Receptors for GABA are embedded in the post-synaptic membrane. When two molecules of GABA bind to its receptor, the receptor channel opens, and chloride ions rush into the neuron.
A 42-year-old woman comes to the clinic for a follow-up examination. She was prescribed a medication 1 month ago to treat insomnia and “nervousness” due to worry over her financial situation. Though she was initially prescribed a 2-month supply of medication, she has already run out. She reports that she now needs twice her original dose to achieve the same effect and does not feel well when she does not take the medication. She continues to sleep irregularly. The patient appears more anxious. She is sweating profusely and tapping her feet restlessly.
Which of the following medications was most likely prescribed?
a) Buspirone
b) Diazepam
c) Hydroxyzine
d) Oxazepam
e) Thiopental
Oxazepam
High-Yield Summary
Step 1: Drug Adverse Effects
This patient was most likely prescribed oxazepam, a short-acting benzodiazepine that is commonly used to treat anxiety. Her sweating, changes in sleep pattern, and increasing anxiety are signs of benzodiazepine dependence. Physiologic dependence is more likely to occur with short-acting agents (ie, those with a shorter half-life). Note that benzodiazepines are not commonly used as solo agents for treating anxiety disorders. Instead, they are often used as a bridge during the first few weeks of treatment while selective serotonin reuptake inhibitors (the first-line agents for anxiety disorder treatment) take effect. Although very effective for the symptoms of anxiety, the potential for dependence and tolerance mean that benzodiazepines should be used with great caution and very rarely as solo therapy for generalized anxiety disorder (GAD).
The other choices are incorrect:
Who may prescribe controlled substances in Texas? (list all the degrees that allow you to do this). Need to get all of them and NO extra to get the points.
Interesting to note: