Module 3: Drugs that Influence the CNS

Question 1

What is the main excitatory neurotransmitter in the brain?

Answer 1

Glutamate

Question 2

What is the main inhibitory neurotransmitter in the brain?

Answer 2

Gamma-aminobutyric acid (GABA)

Question 2

How do drugs increase the GABA inhibitory signalling in the brain?

Answer 2

The drugs mimic the inhibitory effects of GABA by binding onto the chloride channel, slowing excitatory CNS transmission

Question 3

What is the definition of Drug Classes?

Answer 3

A class of drugs is a group of drugs that have the same mechanism of action and similar pharmacological properties

Question 4

T/F Each class of sedative-hypnotic agents bind to a different site on the chloride channel

Answer 4

True!

Question 5

What are the three main classes of sedative-hypnotic drugs that bind to the chloride ion channel?

Answer 5

Benzodiazepines, barbiturates, the “Z” drugs

Question 6

What are the three classes of barbiturates?

Answer 6

Long acting (1-2 days)
Short acting (3-8 hours)
Ultrashort acting (20 minutes)

Question 6

What receptor do benzodiazepines bind of the chloride ion channel? What happens when it binds?

Answer 6

The benzodiazepine receptor. Upon binding, benzodiazepines increase the frequency of the opening of the chloride channel, enhancing GABA’s effect

Question 6

What are some of the pharmacological properties of Benzodiazepines?

Answer 6

High therapeutic index, relieve anxiety, produce sedation, decrease aggression, minimal suppression of REM sleep, skeletal muscle relaxation

Question 6

How do benzodiazepines negatively effect pregnant/breastfeeding individuals?

Answer 6

Benzodiazepine freely crosses the placenta and distributes to the fetus. In the first trimester, can cause fetal abnormalities. Also transfers through the milk, which can expose infants to doses, leading to sedation or death

Question 6

Which of the GABA modifying drugs are used to treat insomnia? Why?

Answer 6

The “Z” drugs and short-acting benzodiazepines; The depressive nature makes users feel drowsy

Question 6

Describe the pharmacology of barbiturates

Answer 6

• Low therapeutic index
• Suppress REM type sleep
• Lethality is common when combined with alcohol
• No antidote
• Death can occur from withdrawl

Question 6

Why do benzodiazepines have a high misuse potential?

Answer 6

They are wildly prescribed and are often used with other CNS depressants (alcohol) or stimulants

Question 6

Describe the clinical use of barbiturates

Answer 6

Ultrashort and short acting can be used to induce anesthesia.
Long acting have been used as anti-seizure medications
Limited clinical use

Question 6

How do benzodiazepines work?

Answer 6

They bind to the chloride channel at the barbiturate receptor, and act as an allosteric activator, increasing the duration of the opening of the chloride channel, increasing GABA effects

Question 6

How do benzodiazepines negatively effect the elderly?

Answer 6

Can produce cognitive dysfunction. Due to slower metabolism, are more likely to experience over-sedation and falls

Question 7

Why do barbiturates have a high misuse potential?

Answer 7

They have quite a bit of pleasurable effects, tolerance is rapidly made

Question 7

T/F Benzodiazepines are first line of treatment for anxiety? Explain.

Answer 7

False. They are second-line due to their potential for over-sedation, cognitive impairment, and psychomotor incoordination

Question 8

Which of the GABA modifying drugs are used to treat anxiety?

Answer 8

Benzodiazepines

Question 9

Which of the GABA modifying drugs are used to treat seizures?

Answer 9

Long acting barbiturates for partial seizures, benzodiazepines for status epilepticus

Question 9

Which of the GABA modifying drugs are used to treat skeletal muscle spasm (e.g., cerebral palsy). Why?

Answer 9

Benzodiazepines; relax the muscles

Question 9

Which of the GABA modifying drugs are used to treat alcohol withdrawl syndrome? Why?

Answer 9

Benzodiazepines; have cross tolerance with alcohol

Question 9

What are generalized seizures?

Answer 9

Involve the entire CNS, accompanied by loss of consciousness. Subdivided based on the type of movement and duration of loss of consciousness that occurs during the seizure

Question 10

What are the three ways anti-seizure drugs decrease glutamate-induced excitation?

Answer 10

Increasing the inhibitory input (GABA)
Blocking electrical activity of the nerve to slow nerve impulses (blocking sodium channel activity)
Decreasing excitatory transmission (decreasing the release of glutamate at the synapse)

Question 10

What are partial (focal) seizures?

Answer 10

Involve focal areas of the brain and have more restricted symptoms. May involve motor disturbances, as well as alterations of perceptions or behaviour

Question 11

What are some of the adverse effects of anticonvulsants?

Answer 11

Sedation, tremor, cognitive impairment, nausea, vomiting, diarrhea, elevated hepatic enzymes, skin rashes

Question 12

How are adverse effects of anticonvulsants minimzied?

Answer 12

By starting with a low dose and slowly increasing; administering with meals

Question 13

T/F Most anticonvulsants reduce biotransformation enzymes

Answer 13

False! They induce biotransformation enzymes - so the metabolism of concurrently administered drugs is also increased

Question 14

What are the three types of depression?

Answer 14

Reactive (secondary) depression Major depression Depression associated with dipolar disorder

Question 15

What are the three theories surrounding the cause of major depression? Give a brief description

Answer 15

The amine hypothesis Neurotrophic hypothesis Neuroendocrine hypothesis

Question 16

Give a brief description of the amine hypotheisis

Answer 16

Suggests that depression is the result of a deficiency of the excitatory neurotransmitters in the CNS (norepinephrine, serotonin, and dopamine)

Question 16

Give a brief description of the neurotrophic hypothesis

Answer 16

Depression is associated with reduced neurotrophic support characterized by a decrease in neurogenesis and synaptic connectivity

Question 16

Give a brief description of the neuroendocrine hypothesis

Answer 16

Depression may be due to an abnormality in hormones affecting mood

Question 16

What are the three ways antidepressants work?

Answer 16

Via blocking neurotransmitter reuptake systems Blocking neurotransmitter metabolism - increasing the amount released Directly increasing the amount of neurotransmitter released

Question 17

What is the overall end goal of antidepressants?

Answer 17

To increase the amount of neurotransmitter within the synaptic cleft

Question 17

What are the three kinds of antidepressants that function by blocking the neurotransmitter reuptake systems?

Answer 17

Tricyclic antidepressants (TCAs) Serotonin reuptake inhibitors (SSRIs) Serotonin norepinephrine reuptake inhibitors (SNRIs)

Question 17

How do SNRIs work?

Answer 17

They block the transporters for both serotonin and norepinephrine

Question 17

How do tricyclic antidepressants (TCAs) work?

Answer 17

Inhibit the reuptake of transporters of both serotonin and norepinephrine into the presynaptic axon, causing an increased concentration of the neurotransmitters left in the synaptic cleft

Question 17

What are some adverse effects of SSRIs?

Answer 17

Nausea, headache, nervousness, insomnia, sexual dysfunction, decreased metabolism Key: Serotonin syndrome, sexual dysfunction

Question 17

What are some of the common adverse effects of TCAs

Answer 17

Anticholinergic effects (dry mouth, constipation) Hypotension when standing uo Sedation block sodium channels; arrhythmias, seizures Weight gain Key: Anticholinergic, antiadrenergic and antihistaminic effects; weight gain

Question 17

How do SSRIs work?

Answer 17

Block the serotonin transporter protein in the presynaptic terminal

Question 17

When are TCAs used over other drugs of this class?

Answer 17

Only used when other drugs fail to control the symptoms of depression, due to their intense adverse effects

Question 17

When are SSRIs used over other drugs?

Answer 17

First line of treatment for depression due to their high safety profile

Question 17

What is serotonin syndrome?

Answer 17

Something that occurs due to concurrent use of multiple drugs that increase serotonin. Characterized by muscle rigidity, elevated body temp, confusion, agitation

Question 17

What are the adverse effects of SNRIs?

Answer 17

Key: Same as SSRIs and Increased BP and heart rate

Question 18

When are SNRIs used over other drugs?

Answer 18

When they don't respond to SSRIs

Question 19

What is the common example of antidepressants that function by blocking the neurotransmitter metabolism?

Answer 19

Monoamine oxidase (MAO) inhibitors

Question 20

How do MAO inhibitors work?

Answer 20

MAO inhibitors block the enzyme that metabolizes norepinephrine, serotonin, and tyramine (MAO-A) and dopamine (MAO-B). This allows for more amines to accumulate in the presynaptic stores, so more can be released when the nerve impulse reaches the presynaptic neuron

Question 21

What are some key adverse effects of MAOis?

Answer 21

Hypertensive crisis (severe increase in BP) Serotonin syndrome

Question 22

When are MAOIs used over other drugs?

Answer 22

Are second line therapy; used when other drugs have failed

Question 23

What is the common antidepressant that functions by directly increasing the amount of neurotransmitter released from the presynaptic nerve?

Answer 23

Autoreceptor antagonists

Question 24

How do autoreceptor antagonists work?

Answer 24

Inhibits the activation of a2 receptors, which removes a negative feedback loop in the neuronal membrane, allowing the presynaptic neuron to release more neurotransmitter

Question 25

What is a key adverse effect of Autoreceptor antagonists?

Answer 25

Are also an antagonist at some serotonin and histamine receptors

Question 26

When are autoreceptor antagonists used over other drugs?

Answer 26

Prescribed if they don't response to SSRI therapy

Question 27

What is electroconvulsive therapy? When is it used?

Answer 27

ECT are electrodes that are put on the head and spark a brief seizure. Has minimal adverse effects, and is valuable in those who have psychotic depression

Question 28

What are the two phases of treatment in bipolar disorder?

Answer 28

Reduction of patient's mood to a "normal" range with antipsychotics Stabilization of a patient's mood within "normal" range with a mood stabilizers

Question 29

T/F Antidepressants can make the depressive phase of bipolar disorder worse

Answer 29

True