CNS Disorders 2: Sedatives, Hypnotics, Anti-anxiety, and Alzheimer's Disease

Question 1

List out Sedative- hypnotic Benzodiazepines and the overall goal of these drugs

Answer 1

Temazepam
Triazolam
Estazolam
Quazepam
*Goal- promote normal
sleep without feeling
& awake feeling
refreshed

Question 2

List out anti-anxiety benzodiazepines and the overall goal of these drugs

Answer 2

Diazepam
Lorazepam
Alprazolam
Goal-Relaxation without excessive sedation

Question 3

How do Benzodiazepines work?

Answer 3

BZs potentiate GABA which increases
frequency of Cl- ion channel opening and causes hyperpolarization. This raises firing
threshold which inhibits the formation of action potentials. Inhibitory effect on different sites of the brain especially motor cortex,
and limbic system

Question 4

Describe the mechanism of action of benzodiazepines and discuss how these drugs modulate GABA-A receptors

Answer 4

Benzodiazepines work by increasing the inhibitory effects at CNS synapses that use GABA.
There are 6 intrinsic effects: anxiolysis, anterograde amnesia, sedation, hypnosis, anticonvulsive, antimesis, and muscle relaxation.

Question 5

List out the pharmacological effects of benzodiazepines.

Answer 5

Reduction of anxiety and aggression, Induction of sleep, Anterograde amnesia, Anticonvulsant effect, Reduction of muscle tone and coordination, Effects of respiration, Effects on CVS

Question 6

What are the side effects of benzos

Answer 6

Excessive sedation: hangover
Motor impairment
Confusion in the elderly
Discontinuation syndrome
Rebound insomnia
Potentiates the CNS: depressant effect of ethanol
Tolerance
Dependence

Question 7

What drug is used as antidote for benzos

Answer 7

Flumazenil

Question 8

Describe the importance of onset and duration action of benzodiazepines with relevance to side effects and therapeutic benefits

Answer 8

Anxiolytic benzodiazepines typically reach peak blood levels 2 to 4 hours after oral administration, so scheduling the rehabilitation session during that time may improve the patient’s participation in treatment.
Benzodiazepines and other drugs used to treat sleep disorders and anxiety are often associated with falls and subsequent trauma, including hip fractures, especially in older adults

Question 9

Describe and name Z drugs, MOA and SE

Answer 9

*MOA: Z drugs bind to GABA receptors in brain; possibly more selective, Fewer problems when discontinued (less rebound insomnia)
*Drugs: Zolpidem, Zaleplon, EsZopiclone
*SE: GI upset, headache, dizziness

Question 10

What are melatonin receptor agonists MOA and SE

Answer 10

*Drugs: Ramelteon and Tasimelteon
*MOA: Melatonin receptor agonists (MT1 and MT2)
*Indication: Tasimelteon is indicated for non-24 sleep-wake disorder (non-24)
*SE:
Ramelteon: Headache, dizziness, somnolence
Tasimelteon: Headaches, nightmares, Hepatotoxicity

Question 11

What are Orexin Receptor antagonists MOA and SE

Answer 11

*MOA: Orexins activate orexin receptors 1 and 2 in the lateral hypothalamic region of the brain. Orexin receptor stimulation releases a variety of neurotransmitters responsible for the maintenance of arousal, wakefulness,
and appetite.
* Suvorexant is a dual orexin receptor antagonist that is used to treat insomnia
* This agent has an onset of action of 30 minutes and a half-life of 12 hours.
* SE: Somnolence
* Other drugs: Lemborexant, Daridorexant

Question 12

Describe atypical anxiolytic agents MOA and cons

Answer 12

Buspirone
*MOA: Acts as a partial agonist for serotonin 5-HT1A receptors in the
brain; May decrease anxiety with less sedation with no abuse potential due to lack of interaction with ethanol
*Cons: slow onset, moderate efficacy (not as effective in severe anxiety)

Question 13

What are anti-anxiety agents that can be used as anti-anxiety agents

Answer 13

*SSRIs (Selective serotonin reuptake inhibitors)
*SNRIs (Selective norepinephrine reuptake inhibitors
* TCAs (Tricyclic antidepressants)

Question 14

What are pathological hallmarks of AZ?

Answer 14

Hallmarks: increased Tau tangles, AB plaques, glutamate, cholesterol in neurons, decreased acetylcholine

Question 15

What drug therapy is used for mild to moderate Alz?

Answer 15

Start with a cholinesterase inhibitor (donepezil,
rivastigmine, galantamine) in mild-to-moderate disease.

Question 16

What drug therapy is used for moderate-to-severe Alz

Answer 16

In moderate-to-severe disease, consider adding memantine (anti-glutamatergic therapy)

Question 17

What is the role of combination therapy in Alz?

Answer 17

*Memantine added to cholinesterase inhibitor therapy is generally prescribed for patients with moderate to
severe AD. Has been shown to slow cognitive and functional
decline compared to cholinesterase inhibitor
monotherapy or no treatment.

Question 18

What are cholinesterase inhibitors?

Answer 18

Cholinesterase inhibitors are a class of drugs that prevent the
breakdown of acetylcholine by inhibiting the enzyme
acetylcholinesterase. This results in increased levels of acetylcholine in the brain, which can help alleviate some of the symptoms of AD particularly those related to memory and cognition.

Question 19

What is the MOA, AE, and clinical uses of Donepezil, Rivastigmine, Galantamine

Answer 19

*MOA: Reversible acetylcholinesterase
inhibitor; increase the concentration of Ach in
CNS synapses
*clinical use: mild to moderate Alz
*Donepezil AE: nausea, vomiting, diarrhea, dizziness, blurred vision
*Rivastigmine AE: bradycardia, AV block, bronchoconstriction
*Galantamine AE: Serious skin reaction

Question 20

What is the MOA, clinical uses, and AE of Memantine?

Answer 20

*MOA: *NMDA receptor antagonist; Helps prevent Ca 2+mediated
excitotoxicity
*clinical uses: Mod to severe Alz
*AE: headache, confusion, dizziness, hallucination, constipation

Question 21

What is Aducanumab?

Answer 21

-An amyloid beta directed antibody for mild cognitive impairments