CNS drugs Flashcards
You want to design a new drug that you will administer peripherally, for example intravenously, but that will have its effects in the central nervous system. What are the obstacles you need to consider and what properties of your drug can you modify to better circumvent this?
1: Paracellular diffusion, water soluble, can pass through tight junctions
2: Passive diffusion, high lipophilicity and low molecular weight
3: Protein transporters
etc
You are looking into a novel treatment for a CNS disorder that seems to be dependent on neurotransmitter concentration in the synaptic cleft.
Which process(es) or type of molecular target in the synapse, or the pre- and/or post- synaptic cell (neuron) may you want to target to possibly treat the disease? (6p)
Block the reuptake of dopamine and noradrenaline into the terminal by blocking dopamine transporter (DAT) and noradrenaline transporter (NAT), increasing levels of dopamine and noradrenaline in the synaptic cleft.
Inhibit CNS neuronal reuptake of serotonin.
They are a positive allosteric modulator of GABA which means they increase the affinity of GABA and decrease dectivation of the channel. GABA is the primary inhibitory neurotransmitter in the brain. Benzodiazepins modulates the synapses in the limbic system. They induce tolernce and dependance but have a safe profile.
Parkinson: 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.
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.
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.
Mark is a 40-year-old man who goes to see his physician because he has been having
strange thoughts and even having hallucinations that felt very real. His wife has also
detected that he has reduced speech, lack of initiative and flattened affect. The physician
determines that Mark symptoms and signs are most likely due to schizophrenia, and she
prescribes a trial of haloperidol (typical antipsychotic).
Could you give an alternative pharmacological approach to haloperidol to treat
Mark symptoms? (
A second generation medication like risperidone inhibit D2 receptor with low affnity which decreases side effects and also treats negative symptoms by binding to other receptors such as serotonergic and adrenergic.
Mark is a 40-year-old man who goes to see his physician because he has been having
strange thoughts and even having hallucinations that felt very real. His wife has also
detected that he has reduced speech, lack of initiative and flattened affect. The physician
determines that Mark symptoms and signs are most likely due to schizophrenia, and she
prescribes a trial of haloperidol (typical antipsychotic).
Is haloperidol (typical antipsychotic) the best choice for Mark symptoms?
No first generation treats positive symptoms but aren’t very effective against negative symptoms. They can inhibit receptor D2 with high affninity but isn’t well at treating positive symptoms.
Mark is a 40-year-old man who goes to see his physician because he has been having
strange thoughts and even having hallucinations that felt very real. His wife has also
detected that he has reduced speech, lack of initiative and flattened affect. The physician
determines that Mark symptoms and signs are most likely due to schizophrenia, and she
prescribes a trial of haloperidol (typical antipsychotic).
How is the dopaminergic dysfunction related to the symptoms that Mark is
experiencing?
The dopamenergic dysfunciton is an overactivity in the mesolimbic pathway and deficit in the mesocortical pathway. The overactivity in the mesolimbic pathway creates positive symptoms such as delusions, hallucinations etc. The deficit in the mesocortical pathway creates reduces speech and lack of initiative etc.
You are looking into a novel treatment for a CNS disorder that seems to be dependent on neurotransmitter concentration in the synaptic cleft. Which process(es) or type of molecular target in the synapse, or the pre- and/or post- synaptic cell (neuron) may you want to target to possibly treat the disease?
Antidepressants for example that block seratonin and norephinierhine transporters so the substances are longer in the brain, adhd medication that blocks dopamine and nordadrenaline transporter etc.
In relation to psychotic illness the term ”positive symptoms” is used. What does this term mean in relation to symptoms? (2p)
Also, schizophrenia can be treated using two groups of antipsychotics, typical and atypical, give a generic drug from each group. (1p)
Positive symptoms for psycotic illnesses include hallucinations which can be visual, audio halusionaitons or tactic hallunicaitons. It can also mean paranoia etc. It means symptoms that add something to the patients life it didn’t hvae before while negative symptoms mean a loss such as flattened mood, unable to take initiative, apathy etc the patient loses abilties it had prior.
Typical (first-generation): haloperidol
Atypical (second-generation): risperidone
A 25-year-old woman presented to the psychiatric hospital describing a one year history of
anxiety. She has been feeling tense most of the time, was often irritable and found hard to
focus. She was prescribed an anxiolytic drug (Diazepam) and a cycle of psychotherapy. Which of
the following neurotransmitters are most likely involved in the therapeutic action of the
prescribed drug? Choose the single best option motivate your answer and explain how the drug
is modulating the selected neurotransmitter. (2p)
GABA
Mark is a 40-year-old man who goes to see his physician because he has been having strange thoughts and even having hallucinations that felt very real. His wife has also detected that he has reduced speech, lack of initiative and flattened affect. The physician determines that Mark symptoms and signs are most likely due to schizophrenia, and she prescribes a trial of haloperidol (typical antipsychotic).
c. Could you give an alternative pharmacological approach to haloperidol to treat Mark symptoms?
Atypical antipsychotics: Some atypical antipsychotics, such as risperidone, have been found to be more effective in treating negative symptoms than typical antipsychotics.
Mark is a 40-year-old man who goes to see his physician because he has been having strange thoughts and even having hallucinations that felt very real. His wife has also detected that he has reduced speech, lack of initiative and flattened affect. The physician determines that Mark symptoms and signs are most likely due to schizophrenia, and she prescribes a trial of haloperidol (typical antipsychotic).
b. Is haloperidol (typical antipsychotic) the best choice for Mark symptoms? (2p
Haloperidol, a typical antipsychotic medication, is often used to treat the positive symptoms of schizophrenia, such as hallucinations and delusions. However, it is not as effective in treating the negative symptoms of schizophrenia, such as flattened affect, reduced speech, and lack of initiative.
The negative symptoms of schizophrenia are thought to be related to a deficiency in the dopamine and/or the glutamatergic system, and antipsychotic medications, including haloperidol, have limited efficacy in treating these symptoms. Other medications, such as antidepressants and stimulants, as well as psychosocial interventions, may be needed to effectively treat the negative symptoms of schizophrenia.
Mark is a 40-year-old man who goes to see his physician because he has been having strange thoughts and even having hallucinations that felt very real. His wife has also detected that he has reduced speech, lack of initiative and flattened affect. The physician determines that Mark symptoms and signs are most likely due to schizophrenia, and she prescribes a trial of haloperidol (typical antipsychotic).
a..How is the dopaminergic dysfunction related to the symptoms that Mark is experiencing?
The dopamine hypothesis suggests that excessive dopamine activity in certain brain regions, particularly the mesolimbic pathway, leads to positive symptoms of schizophrenia, such as hallucinations and delusions. Antipsychotic medications, including both typical and atypical antipsychotics, work by blocking the dopamine receptors in the brain, reducing the dopamine transmission and thereby reducing the positive symptoms of schizophrenia.
Question 10
Mark the true sentence (1,5p)
a) Parkinson is characterized by a degeneration of the mesolimbic dopaminergic pathway.
b) Levodopa should be administered together with carbidopa to increase the bioavailability in the brain.
c) Methylphenidate is a stimulant drug that acts by inhibiting the dopamine receptors in the postsynaptic neuron.
d) Propofol (barbiturate) is extensively prescribed for sleep problems.
e) All the above are correct
Dopamine precursor, give L-dopa (give dopamine directly) but it’s very fast metabolized in our intestine so we give it with carbidopa because it inhibits AADC, carbidopa doesn’t cross the blood brain barrier so when the L-dopa reaches the brain the carbidopa does not cross and we have more L-dopa reaching the brain.
The rest is false.
Therefore B is the correct sentence.
