Pharmacology Flashcards
Which of the following best describes bromocriptine’s mechanism of action?
A. Partial antagonist for the D1 dopamine receptor and selective agonist for the D2 dopamine receptor.
B. Selective agonist for the D1 dopamine receptor and selective agonist for the D2 dopamine receptor.
C. Partial agonist for the D1 dopamine receptor and selective antagonist for the D2 dopamine receptor.
D. Selective antagonist for the D1 dopamine receptor and partial agonist for the D2 dopamine receptor.
E. Partial antagonist for the D1 dopamine receptor and selective antagonist for the D2 dopamine receptor.
**Partial antagonist for the D1 dopamine receptor and selective agonist for the D2 dopamine receptor.
**
The correct answer choice is partial antagonist for the D1 receptor and selective agonist for the D2 receptor. In treating prolactinomas, bromocriptine’s D2 agonistic effect on the pituitary lactotrophs blocks prolactin exocytosis and gene expression while also suppressing cell growth. In acromegaly, the dopaminergic effect causes blocking of growth hormone release through the tuberoinfundibular pathways.
Bromocriptine’s antagonistic effect via the D1 receptor is less significant as it is only a partial antagonist.
The mechanism of action of lidocaine is which of the following?
A. Altering depolarization by blocking voltage-gated sodium channels.
B. Binding to 5-HT receptor
C. Enzymatic inhibition
D. Inhibition of pre-synaptic gated calcium channels
E. Blocking dopamine reuptake
Altering depolarization by blocking voltage-gated sodium channels.
Lidocaine alters depolarization by blocking voltage-gated sodium channels.
Cocaine acts on the CNS at the presynaptic terminal through blocking reuptake of dopamine in the neuronal synapse. Dopamine then accumulates in the synapse to produce an amplified signal to the receiving neurons. This contributes to the euphoria commonly experienced when taking cocaine.
Binding to the 5-HT receptor is the mechanism of action of serotonin.
Enzymatic inhibition is the mechanism by which non-steroidal anti-inflammatory drugs induce pain modification.
Inhibition of pre-synaptic gated calcium channels is the mechanism of action of opioids.
Which of the following mechanisms is most likely to explain the antinociceptive effects of cannabinoids?
A. Modulation of inhibitory interneurons
B. Inhibition of pre-synaptic gated calcium channels
C. Descending inhibition on nociceptor neurons
D. Binding to pre-synaptic membrane receptors to decrease excitability
E. Enzymatic inhibition
Binding to pre-synaptic membrane receptors to decrease excitability
Cannabinoids likely create their antinociceptive effects by binding to pre-synaptic membrane receptors to decrease excitability.
Enzymatic inhibition is the mechanism by which non-steroidal anti-inflammatory drugs induce pain modification.
Descending inhibition on nociceptor neurons is the mechanism of action of the intrinsic serotonin system.
Inhibition of pre-synaptic gated calcium channels is the mechanism of action of opioids.
Modulation of inhibitory interneurons is the mechanism of action of tactile stimuli in gate-control of pain fibers. This is the rationale and idea behind tactile electrical stimulation or TENS units.
Cocaine acts on the CNS at the presynaptic terminal through which of the following mechanisms?
A. Binding to 5-HT receptor
B. Enzymatic inhibition
C. Binding to pre-synaptic membrane receptors to decrease excitability
D. Inhibition of pre-synaptic gated calcium channels
E. Blocking reuptake of dopamine in the neuronal synapse
Blocking reuptake of dopamine in the neuronal synapse
Cocaine acts on the CNS at the presynaptic terminal through blocking reuptake of dopamine in the neuronal synapse. Dopamine then accumulates in the synapse to produce an amplified signal to the receiving neurons. This contributes to the euphoria commonly experienced when taking cocaine.
Enzymatic inhibition is the mechanism by which non-steroidal anti-inflammatory drugs induce pain modification.
Binding to the 5-HT receptor is the mechanism of action of serotonin.
Inhibition of pre-synaptic gated calcium channels is the mechanism of action of opioids.
Binding to pre-synaptic membrane receptors to decrease excitability is the mechanism of action of cannabinoids.
Succinylcholine produces blockade of neuromuscular transmission by which of the following means?
A. Cleaving presynaptic snare proteins
B. Blocking the release of acetylcholine from the presynaptic motor neurons
C. Activating the acetylcholine receptor and depolarizing myocytes
D. Blocking the acetylcholine receptor and preventing myocyte depolarization
E. Blocking the breakdown of acetylcholine by acetylcholinesterase in the motor endplate
Activating the acetylcholine receptor and depolarizing myocytes
Succinylcholine works by binding to the post synaptic acetylcholine receptor with a greater affinity than acetylcholine. This results in depolarization of the myocyte. Because succinylcholine has a greater affinity for the acetylcholine receptor than acetylcholine and because succinylcholine
cannot be cleaved by acetylcholinesterase (which normally breaks down acetylcholine), the myocytes remain polarized and are unable to be depolarize again when exposed to acetylcholine, and thus muscle contractions are blocked. It is for this reason that succinylcholine is considered a “depolarizing blocking agent.”
Botulinum toxin produced by Clostridium botulinum blocks neuromuscular transmission by cleaving snare proteins and preventing the fusion of acetylcholine-containing vesicles with the presynaptic cellular membrane. This results in a block of acetylcholine release from the presynaptic motor neurons.
Non-depolarizing blocking agents such as the drug rocuronium work by blocking the post synaptic acetyl choline receptor on myocytes.
Which of the following is a motor end-plate competitive blocking agent?
A. Succinylcholine
B. Botulinum toxin
C. Sugammadex
D. Neostigmine
E. Rocuronium
Rocuronium
Rocuronium and other non-depolarizing neuromuscular blocking agents work by competing with acetylcholine to block the post synaptic acetyl choline receptor in myocytes. Blocking acetylcholine prevents myocytes from depolarizing and thus inhibits muscle contractions.
Succinylcholine is another neuromuscular blocking agent, however, succinylcholine is a depolarizing agent that works by activating the acetylcholine receptor and depolarizing myocytes. This prevents the myocytes from responding to acetylcholine, thus preventing contraction.
Botulinum toxin produced by Clostridium botulinum blocks neuromuscular transmission by cleaving snare proteins and the preventing the fusion of acetylcholine containing vesicles with the presynaptic cellular membrane. This results in a block of acetylcholine release from the presynaptic motor neurons.
Neostigmine, a drug use to treat myasthenia gravis, functions by blocking the protein that is responsible for breaking down acetylcholine, acetylcholinesterase. In doing so, neostigmine increases the amout of acetylcholine available to active the post synaptic acetylcholine receptor and thus increasing motor end plate potentials.
Sugammadex is used to reverse non-depolarizing neuromuscular blocking agents by binding them and thus preventing them from binding to the acetylcholine receptor.
Which of the following actions mediates the majority of behavioral effects of diazepam (Valium)?
A. Prevents the delivery of calcium cannels to the cell membrane to decrease release of neurotransmitters
B. Potentiation of the inhibitor effect of GABA on GABAA receptors
C. Acts to inhibit calcium channels to increase the expression of L-glutamic acid decarboxylase
D. Binds to opioid receptors in the nervous system to modulate GABAergic neurotransmission
E. Activates GABAB receptors to inhibit the release of excitatory transmitters
Potentiation of the inhibitor effect of GABA on GABAA receptors
Benzodiazepines (ie, diazepam) work as positive allosteric modulators of GABAA receptors. When benzodiazepines bind to these receptors, they promote further binding of GABA, which increases the transport of chloride ions across the neuronal cell membrane. This hyperpolarizes the neuron’s membrane potential and decreases the chance of neuronal firing, leading to a reduction of central nervous system arousal. These drugs have specific affinity to GABAA receptors in the limbic system and hypothalamus, which leads to overall anxiolytic effects. Baclofen activates GABAB receptors to inhibit the release of excitatory transmitters. Pregabalin acts as a gabapentinoid to
inhibit calcium channels to increase the expression of L-glutamic acid decarboxylase to synthesize GABA. Gabapentin prevents the delivery of calcium cannels to the cell membrane to decrease release of neurotransmitters. Opioids bind to opioid receptors in the nervous system to modulate GABAergic neurotransmission.
Which of the following is the mechanism of action of most antipsychotic drugs (neuroleptics)?
A. Inhibiting serotonin reuptake
B. Blocking H2 receptors
C. Inhibiting dopaminergic neurotransmission
D. Inhibiting alpha-2 receptors
E. Binding to cannabinoid receptors
Inhibiting dopaminergic neurotransmission
Inhibiting dopaminergic neurotransmission is the mechanism of action of most antipsychotic drugs (neuroleptics). Prior studies have demonstrated increased dopamine production and release in the striatum of the brain in schizophrenic patients. Amphetamine administration in schizophrenic patients was found to create greater dopamine release when compared to controls. Typical antipsychotics primarily bind and inhibit dopaminergic D2 receptors and treat positive symptoms. Atypical antipsychotics bind to D2 receptors as well as serotonergic 5-HT2a receptors. Atypical agents treat positive symptoms of schizophrenia, but may also have an effect in improving negative symptoms because of 5-HT2a receptor antagonism.
Inhibiting the reuptake of serotonin is the mechanism of action of selective serotonin reuptake inhibitors.
Inhibiting alpha-2 receptors is the mechanism of action of drugs such as mirtazapine. Binding to cannabinoid receptors is the mechanism of action of cannabinoids. Blocking H2 receptors is the mechanism of action of anti-histamine drugs.
Diphenhydramine has been observed to improve extrapyramidal symptoms in patients taking antipsychotic medications. This effect is most likely caused by blocking receptor binding of which of the following neurotransmitters?
A. Dopamine
B. Acetylcholine
C. Gamma-aminobutyric acid
D. Serotonin
E. Histamine
Acetylcholine
The nigrostriatum of the basal ganglia is a central neuronal pathway in the production of motor responses. Within the nigrostriatum dopamine and acetylcholine have opposing roles in which dopamine signaling promotes movement and acetylcholine signaling inhibits movement, and as such, the balance of dopamine and acetylcholine in this circuit is critical to normal tone and movement. Extrapyramidal symptoms are potential side effects of antipsychotic medications that are related to antagonism of the dopamine receptor in the basal ganglia. This dopamine blockade leads to the extrapyramidal symptom of dystonia through imbalance of nigrostriatal dopamine and acetylcholine, with excess acetylcholine signaling through muscarinic receptors. Diphenhydramine acts as a muscarinic receptor antagonist, thereby blocking the effect of excess acetylcholine and reversing dystonia by restoring dopamine and acetylcholine balance in the nigrostriatum. Diphenhydramine acts as an inverse agonist of the H1 histamine receptor and has effects on serotonin signaling, but these actions are not directly related to its effect on extrapyramidal symptoms. Gamma-aminobutyric acid (GABA) receptor agonists can be utilized in the treatment of extrapyramidal symptoms. However, diphenhydramine’s effect on extrapyramidal symptoms is not mediated through GABA signaling.
Potentiation of postsynaptic inhibition mediated by GABA is part of the mechanism of action of which of the following agents?
A. Naloxone
B. Propanolol
C. Baclofen
D. Flumazenil
E. Clonidine
**Baclofen
**
Drugs that act to potentiate the inhibitory effects of GABA include alcohol, barbiturates, benzodiazepines, and baclofen. Pharmacodynamic effects depend primarily on the type of GABA receptor that is activated. For example, alcohol, barbiturates, and benzodiazepines are positive allosteric modulators of GABAA receptors, while baclofen is an agonist at GABAB receptors.
Flumazenil is works as a selective GABAA receptor antagonist, often used as an antidote to benzodiazepines. Propanolol is a non-selective beta receptor antagonist that works to inhibit sympathetic stimulation. Naloxone is a non-selective competitive opioid receptor antagonist. Clonidine has different roles at multiple receptors, one of them being as an agonist at alpha-2 receptors to decrease peripheral vascular resistance and lower blood pressure.
Acetylcholine antagonists block transmission at the neuromuscular junction through which of the following actions?
A. Competitive inhibition of the nicotinic acetylcholine receptors
B. Irreversibly inhibiting nicotinic acetylcholine receptors
C. Binding and inhibiting acetylcholinesterase
D. Acetylcholine inhibitors do not function at the neuromuscular junction
E. Preventing the release of acetylcholine in the neuromuscular junction by inhibiting vesicle binding to the neuronal membrane
**Competitive inhibition of the nicotinic acetylcholine receptors
**
Neuromuscular transmission at the skeletal muscle occurs when a quantum of acetylcholine from the nerve ending is released and binds to the nicotinic acetylcholine receptors on the postjunctional muscle membrane. The nicotinic acetylcholine receptors on the endplate respond by opening channels for the influx of sodium ions and subsequent endplate depolarization leads to muscle contraction. The acetylcholine immediately detaches from the receptor and is hydrolyzed by acetylcholinesterase enzyme. At the neuromuscular junction, acetylcholine antagonists act as competitive inhibitors of the nicotinic acetylcholine receptors. Thus, they impair normal acetylcholine signaling as there are less sites for acetylcholine to bind. They do not bind acetylcholinesterase, as this would increase acetylcholine signaling. They do not impair vesicle binding in the neuron at the neuromuscular junction.
The amplitude of the muscle endplate potential produced by stimulation of the motor nerve is most likely to be increased by application of
A. Succinylcholine
B. Atropine
C. Rocuronium
D. Physostigmine
E. Botulinum toxin
Physostigmine
The motor endplate potential is produced when acetylcholine released by the presynaptic activate post synaptic receptors, who then allow sodium into the post synaptic cell, resulting in depolarization. Acetylcholine is then removed from the synaptic cleft by acetylcholinesterase. By
blocking acetylcholineesterase, physostigmine increases the amount of acetylcholine available to activate the post synaptic cell. Thus, phystigmine can be used to treat myasthenia gravis (MG), which usually caused by antibodies against the acetylcholine receptor. Edrophonium, a shorter acting acetylcholinesterase inhibitor that can temporarily improve MG symptoms, has been previously used to diagnose MG.
Rocuronium and Atropine are acetylcholine receptor antagonists. Physostigmine can be used to reverse their effects.
Succinylcholine also blocks the motor endplate potential, but it does so by activating the acetylcholine receptor and maintaining it in an open depolarized position. Thus, when endogenous acetylcholine is unable to interact with the acetylcholine receptor, the muscle end plate potential is not produced.
Botulinum toxin blocks the release of acetylcholine from the presynaptic neuron, thus reducing the endplate potential.
Ketamine acts by blocking which of the following receptors?
A. Delta receptor
B. GABA-B receptor
C. Mu receptor
D. NMDA receptor
E. GABA-A receptor
NMDA receptor
Ketamine antagonizes NMDA receptors on GABAergic interneurons and on post-synaptic neurons; the former disinhibits cortical glutamatergic neurons and the latter increases synthesis of intracellular growth factors, such as brain-derived neurotrophic factor (BDNF). Additionally, via the kainate receptor, ketamine increases activity of mammalian target of rapamycin (mTOR) and other molecules responsible for neuroplasticity and synaptogenesis. A recent study examining both signaling pathways found that ketamine increased BDNF by generating nitric oxide, leading to the stabilization of Nitrergic Rheb, a small G-protein that enhances mTOR signaling. Changes in these signaling pathways due to ketamine have been implicated in the transmission of pain as well as antidepressant activity.
Benzodiazepines and Baclofen are common medications that act through interaction of GABA receptors.
Barbiturates and Ethanol are non-selective modulators of AMPA receptors.
Opiods act on mu and delta receptors.
Which of the following is the mechanism of action of alendronate (Fosamax) on bone physiology?
A. Gets converted into synthetic osteoprotegerin to inhibit activation of osteoclasts
B. Acts as a pyrophosphate analog that is taken up by osteoclasts leading to apoptosis
C. Binds to RANK to stimulate osteoclastic bone formation
D. Binds to prostaglandin E2 to activate adenyl cyclase to stimulate bone formation
E. Inhibits osteoblast differentiation and activation
Acts as a pyrophosphate analog that is taken up by osteoclasts leading to apoptosis
The process of bone remodeling primarily involves two types of cells: osteoclasts and osteoclasts. In simple terms, osteoclasts resorb bone while osteoblasts form new bone. Osteoclasts resorb bone using an enzyme called carbonic anhydrase, which requires a molecule called pyrophosphate. Bisphosphonates (i.e., alendronate) are essentially defective pyrophosphate analogs that bind to the hydroxyapatite crystals of previously formed bone that are then taken up by osteoclasts and cause apoptosis with the end effect of reducing bone resorption. Bisphosphonates do not bind to RANK to stimulate osteoclastic bone formation; rather, it is RANK- ligand (RANKL) that binds to RANK receptors to stimulate osteoclastic bone resorption. Bisphosphonates similarly do not inhibit osteoblast differentiation, are not converted into osteoprotegerin, and do not bind to prostaglandin E2.
Levodopa is formed in the body from
A. Melanin
B. Norepinephrine
C. Tyrosine
D. Tryptophan
E. Dopamine
Tyrosine
Levodopa is produced from the amino acid tyrosine by hydroxylation of the phenyl group. L-Dopa can then be converted to dopamine, epinephrine, norepinephrine, and melanin by further modifications.
Similarly, serotonin is produced from the amino acid tryptophan by hydroxylation of the terminal group.
