Exam 3 Flashcards
How do you estimate the affinity for the different drugs based on a table or a graph of Emax and E50
The affinity of a drug can then be inferred from the EC50 value. A drug with high affinity for its target molecule will produce a response at a lower concentration (i.e., lower EC50 value) compared to a drug with lower affinity. Therefore, a drug with a lower EC50 value indicates higher affinity for its target molecule, while a drug with a higher EC50 value indicates lower affinity.
How can you determine from a table or a dose response curve which drug has highest efficacy?
In a dose-response curve, the drug with the highest efficacy will produce the highest maximum response (i.e., highest Emax).
From a dose response curve how can you determine if the antagonist is competitive or non competitive?
If the antagonist is competitive, it will produce a rightward shift of the dose-response curve without decreasing the maximum response. The concentration of the agonist required to produce a certain response will be increased in the presence of the antagonist, but the maximum response will remain the same. This is because the antagonist can be displaced by higher concentrations of the agonist.
If the antagonist is noncompetitive, it will produce a rightward shift of the dose-response curve with a reduction in the maximum response. The concentration of the agonist required to produce a certain response will be increased in the presence of the antagonist, and the maximum response will be reduced. This is because the antagonist cannot be displaced by higher concentrations of the agonist.
Overuse of an agonist could result in receptor desensitization. How is the pharmacological response affected? Discuss and motivate different scenarios.
It depends on the potency and if there are spare receptors avaible. If the drug has high potency and there are spare receptors the drug will still give an effect but someitmes you need to increase the doseage. If there are no spare receptors the drugs effect will decrease and increasing the dose won’t help.
Describe in detail the mechanism of action for the most commonly used bronchodilating drug used in the treatment of asthma.
the mechanism of action of salbutamol involves binding to beta2-adrenergic receptors on airway smooth muscle cells, leading to activation of the cAMP-PKA pathway and inhibition of smooth muscle contraction. These effects contribute to the bronchodilatory and anti-inflammatory effects of salbutamol.
Activation of PKA by cAMP leads to a decrease in intracellular calcium levels, which is the main trigger for smooth muscle contraction. This occurs via two mechanisms:
Inhibition of myosin light chain kinase (MLCK): PKA phosphorylates and inhibits MLCK, which is the enzyme responsible for phosphorylating myosin light chains and initiating smooth muscle contraction. By inhibiting MLCK, salbutamol reduces the ability of smooth muscle cells to contract.
Activation of myosin light chain phosphatase (MLCP): PKA also activates MLCP, which is the enzyme responsible for dephosphorylating myosin light chains and promoting smooth muscle relaxation. By activating MLCP, salbutamol promotes smooth muscle relaxation.
Most drugs used in asthma are delivered by inhalation.
Describe one advantage and one disadvantage when administering the drug by inhalation.
It gives less adverse effects since it’s administrated locally and will act more local. One disadvantage is that sometimes it’s not sufficient for severe cases of airway distributive diseases.
What side effects can come from COX-1 and COX-2 inhibitors?
Gastric issues such as bleeding, ulcers et since it disturbs the stomach lining because it inhibits prostaglandins and one prostaglandin is protective of the gastric lining. It also inhibits TAX2 which reduces platelets ability to be activated and clot.
COX-2 inhibitors have more serious side effects which include cardiac arrest.
Define the monoamine theory of depression and exemplify by giving the generic names of two pharmacological treatments, stating which treatment group they belong to, and briefly describe their main mechanism of action.
The monoamine theory of depression suggests that a deficiency in the neurotransmitters serotonin, norepinephrine, and/or dopamine is the primary cause of depression.
More specifically, citalopram selectively inhibits the serotonin transporter (SERT), which is responsible for removing serotonin from the synaptic cleft after its release. By inhibiting SERT, citalopram prolongs the action of serotonin at the synaptic cleft, leading to increased activation of postsynaptic serotonin receptors.
More specifically, duloxetine inhibits both the serotonin transporter (SERT) and the norepinephrine transporter (NET). By inhibiting these transporters, duloxetine prolongs the action of both serotonin and norepinephrine at the synaptic cleft, leading to increased activation of postsynaptic receptors for these neurotransmitters.
Treatment strategies for Parkinson’s disease currently is often a combination of two different types of compounds. Which are they and what are their pharmacological targets?
L-DOPA (levodopa), is in a class of medications called central nervous system agents. It works by being converted to dopamine in the brain. Carbidopa is in a class of medications called decarboxylase inhibitors. It works by preventing levodopa from being broken down before it reaches the brain.
You are a cardiomyocyte who wants to spontaneously generate action potentials. Describe how you can make this possible. Your description should include information about what ion channel(s) to use and what ions to utilize.
Nodal cells do not have a stable resting membrane potential but instead exhibit a slow depolarization due to the influx of sodium (Na+) and calcium (Ca2+) ions through specialized ion channels called funny channels (If). This phase gives the nodal cells their automaticity, meaning they can generate an action potential spontaneously without external stimulation.
Once the membrane potential reaches a threshold level, voltage-gated calcium channels (Ca2+) open, leading to a rapid depolarization of the cell membrane. This phase is responsible for the initiation of the action potential.
After reaching its peak, the membrane potential repolarizes slowly due to the opening of voltage-gated potassium (K+) channels and closing of the voltage-gated calcium channels. This phase prepares the cell for the next action potential.
Mechanistically, the unique ability of nodal cells to fire spontaneously and act as pacemakers is due to the presence of specialized ion channels and transporters. The main contributors to the spontaneous depolarization are the funny channels (If) that allow a slow influx of sodium (Na+) and calcium (Ca2+) ions during phase 4. The Na+/K+ ATPase pump maintains the ion concentration gradient necessary for the function of the cardiac cells. The rate of funny channel activation determines the rate of depolarization, which determines the heart rate.
In addition to the funny channels, nodal cells also have a variety of other ion channels that contribute to the action potential, such as voltage-gated calcium channels (Ca2+) and potassium channels (K+). The interplay between these channels determines the shape and duration of the action potential.
You are developing an experimental model of a cardiomyocyte with decreased action potential duration. Describe two types of ion channels you could target to achieve this and explain how channel activity would need to be altered. Motivate your choice by explaining the role of these ion channels in the cardiac action potential.
One type of ion channel that could be targeted to decrease the action potential duration of a cardiomyocyte is the potassium ion channel. Specifically, the rapid delayed rectifier potassium current (Ikr) is a crucial player in repolarizing the cardiac action potential. Therefore, targeting Ikr channels could result in a shorter action potential duration. In order to achieve this, the activity of Ikr channels would need to be reduced. This can be done using drugs such as dofetilide, which specifically blocks the activity of Ikr channels.
Another type of ion channel that could be targeted is the L-type calcium ion channel. During the plateau phase of the cardiac action potential, the influx of calcium ions through L-type calcium channels helps to maintain depolarization. Therefore, inhibiting the activity of these channels can lead to a shorter action potential duration. This can be achieved using drugs such as verapamil, which specifically block L-type calcium channels.
Both of these ion channels play crucial roles in the cardiac action potential. Ikr channels are responsible for the repolarization phase of the action potential, while L-type calcium channels are responsible for the depolarization phase.
