Alzheimer's Disease Medications Quiz

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Questions and Answers

Which characteristic differentiates donepezil from tacrine regarding administration frequency?

Donepezil is administered multiple times a day.

Donepezil is more hepatotoxic than tacrine.

Donepezil has a longer half-life allowing for once-daily administration. (correct)

Donepezil requires a higher dose for cognitive improvement.

What is the mechanism of action for rivastigmine in treating dementia?

It is solely a peripheral cholinergic agonist.

It primarily acts on nicotinic receptors only.

It increases acetylcholine levels by inhibiting acetylcholinesterase. (correct)

It is a non-reversible acetylcholinesterase inhibitor.

Which drug is specifically approved for managing dementia associated with Parkinson's disease?

Donepezil

Rivastigmine (correct)

Tacrine

Galantamine

What significant side effect is associated with tacrine that is not seen with donepezil?

Hepatotoxicity Signup and view all the answers

Which of the following best describes the formulation of rivastigmine?

Available as both oral and transdermal formulations. Signup and view all the answers

Galantamine was discovered from which source?

Bulbs of the daffodil, Narcissus pseudo-narcissus Signup and view all the answers

What is a common adverse effect of donepezil?

Muscle cramps Signup and view all the answers

How does galantamine enhance cholinergic neurotransmission?

By serving as an allosteric modulator of the nicotinic receptor. Signup and view all the answers

What mechanism does memantine primarily affect in relation to Alzheimer Disease?

Acts as a noncompetitive antagonist at NMDA receptors Signup and view all the answers

Which of the following is NOT a common adverse effect of drugs: donepezil and rivastigmine?

Dehydration Signup and view all the answers

What is the purpose of caprylidene (Axona®) in treating Alzheimer Disease?

It provides ketone bodies as an energy source for the brain Signup and view all the answers

How does excessive intracellular Ca2+ contribute to neuronal damage in Alzheimer's Disease?

It activates apoptotic pathways leading to cell death Signup and view all the answers

Which drug is a combination of memantine extended-release and donepezil?

Namzaric® Signup and view all the answers

What is the primary characteristic of multiple sclerosis (MS)?

It involves autoimmune inflammatory demyelination. Signup and view all the answers

Which symptom is least likely to be associated with the adverse effects of AD medications?

Insomnia Signup and view all the answers

What is the role of NMDA-glutamate receptor antagonists in neuroprotection?

They prevent excitotoxic effects on neurons. Signup and view all the answers

What is the mechanism of action of Dalfampridine in patients with MS?

It blocks potassium channels to improve nerve conduction. Signup and view all the answers

Which of the following adverse effects is most commonly associated with Dalfampridine?

Flushing and abdominal pain Signup and view all the answers

Which statement is true regarding the action of Mitoxantrone in multiple sclerosis?

It suppresses the activity of lymphocytes and macrophages. Signup and view all the answers

What differentiates Ocrelizumab from the other monoclonal antibodies used for MS?

It is the first approved treatment for primary progressive forms of MS. Signup and view all the answers

What is the primary risk associated with Natalizumab treatment?

Progressive multifocal leukoencephalopathy Signup and view all the answers

What is the mechanism of action of Daclizumab in treating MS?

It blocks the IL-2 receptor, preventing lymphocyte activation. Signup and view all the answers

Which adverse effect is specifically associated with Alemtuzumab?

Infusion reactions Signup and view all the answers

Which disease is primarily characterized by the degeneration of motor neurons, impacting muscle movement control?

Amyotrophic lateral sclerosis Signup and view all the answers

What is one potential mechanism by which Interferon β-1b may halt the progression of MS?

Reducing the amount of interferon-γ secreted by activated lymphocytes Signup and view all the answers

Which symptom is NOT typically associated with Multiple Sclerosis?

Hypertension Signup and view all the answers

What distinguishing feature characterizes the relapsing-remitting form of MS?

Intermittent exacerbations followed by partial or complete recovery Signup and view all the answers

Which of the following medications is NOT indicated for MS?

Acetaminophen Signup and view all the answers

What is a common treatment approach during acute exacerbations of MS?

Administration of prednisone Signup and view all the answers

What is one of the primary roles of Riluzole in the treatment of ALS?

To inhibit glutamate release Signup and view all the answers

Which of the following accurately describes the role of disease-modifying therapies in MS?

To prevent disability and reduce relapse rates Signup and view all the answers

In which scenario is parenteral administration of Interferon β-1b most likely indicated?

In cases of severe exacerbation Signup and view all the answers

Which of the following statements about Edaravone is correct?

It acts as a free radical scavenger and antioxidant. Signup and view all the answers

What is a significant characteristic of ALS as mentioned?

Muscle wasting and respiratory failure are common. Signup and view all the answers

What primary effect do all approved drugs for MS aim to achieve?

Modify white blood cell activity Signup and view all the answers

How does Baclofen relieve spasticity in patients with ALS?

By reducing motor neuron excitability Signup and view all the answers

What is the main challenge with the treatment of ALS?

Current treatments are largely symptomatic. Signup and view all the answers

Which drug is cited as having the first specific approval for ALS treatment?

Riluzole Signup and view all the answers

What effect does Riluzole have on survival time for ALS patients?

It prolongs the time before a tracheotomy is needed. Signup and view all the answers

What mechanism is thought to contribute to the neuroprotective effects of Edaravone?

Counteracting oxidative stress Signup and view all the answers

What is the primary mechanism of action attributed to methocarbamol?

Causes general CNS depression. Signup and view all the answers

What is a significant concern regarding the use of carisoprodol?

Its main metabolite, meprobamate, has largely been replaced by benzodiazepines. Signup and view all the answers

What important role does dantrolene play in medical treatments?

It directly blocks calcium ion release from muscle fibers. Signup and view all the answers

Which condition is botulinum toxin A specifically NOT indicated to treat?

Acute muscle spasms due to trauma Signup and view all the answers

What is the main indication for baclofen use?

Management of spasticity due to multiple sclerosis. Signup and view all the answers

Which of the following statements about tizanidine is accurate?

It acts as a muscle relaxant without reducing muscle strength. Signup and view all the answers

Which statement best describes the relationship between carisoprodol and meprobamate?

Meprobamate is a direct metabolite of carisoprodol, indicating it may not have effects itself. Signup and view all the answers

What common condition is associated with the use of dantrolene?

Malignant hyperthermia caused by halogenated anesthetics. Signup and view all the answers

Study Notes

Pharmacology-Stage (4)

Lecture 2: Drugs for Neurodegenerative Diseases (Part 2)
Date: 2/10/2024

Drugs Used in Alzheimer's Disease

Alzheimer's disease (AD): A progressive dementia with no known cause or cure.
Distinct from vascular dementia, which is associated with brain infarction, stroke, trauma, or alcohol.
Characterized by brain shrinkage and loss of neurons, primarily in the hippocampus and basal forebrain.
Has a devastating impact on cognitive, emotional, and physical function of patients and their families.

Alzheimer's Symptoms

Confusion with time and location
Withdrawal from social activities
Difficulty completing familiar tasks
Difficulty solving problems
Poor judgment
Trouble with images and spaces
Misplacing items
Memory loss
Unfounded emotions
Difficulty with words

Dementia of the Alzheimer Type Distinguishing Features

Accumulation of senile plaques (β-amyloid accumulations)
Formation of numerous neurofibrillary tangles
Loss of cortical neurons, especially cholinergic neurons
Deficit in cholinergic neurotransmission due to neuron destruction, causing acetylcholine production deficiency.

Pharmacologic Intervention

Palliative
Modest short-term benefit
Current therapies aim to improve cholinergic transmission within the CNS or prevent excito-toxic actions resulting from overstimulation of N-methyl-D-aspartic acid (NMDA)-glutamate receptors.

1) Acetylcholinesterase Inhibitors

Donepezil, Galantamine, Rivastigmine, and Tacrine
Linked to progressive loss of cholinergic neurons and memory loss.
Treatment aims to improve cholinergic neurotransmission.
Does not affect the underlying neurodegenerative process; disease is fatal.

Tacrine (Cognex®)

First centrally-acting cholinesterase inhibitor approved.
Lower bioavailability and shorter half-life than donepezil, requiring multiple daily administrations.
Significant hepatotoxicity and peripheral cholinergic side effects (diarrhea, nausea, urinary incontinence).
Withdrawn from the market due to adverse effects.

Donepezil (Aricept®)

Reversible cholinesterase inhibitor selectively inhibiting cholinesterase in the CNS and increasing acetylcholine levels in the cerebral cortex.
Well absorbed after oral administration and crosses the blood-brain barrier (BBB).
Long half-life (approximately 70 hours), allowing once-daily administration.
Common adverse effects include nausea, diarrhea, vomiting, anorexia, tremors, bradycardia, and muscle cramps.
Unlike tacrine, it is not associated with hepatotoxicity.

Rivastigmine (Exelon®)

Newer, centrally acting, reversible cholinesterase inhibitor available as a transdermal formulation.
Significantly delays global cognitive impairment in AD.
Transdermal formulation provides 24-hour administration and increases patient compliance.
No interactions with drugs that alter P450-dependent enzyme activity.

Galantamine (Razadyen®)

Newer, centrally acting, competitive reversible cholinesterase inhibitor.
May also act as an allosteric modulator of nicotinic receptors, increasing cholinergic neurotransmission.
Discovered from daffodil extracts.
Shown to slow the progression of AD(like rivastigmine).
Common side effects include nausea, diarrhea, vomiting, anorexia, tremors, bradycardia and muscle cramps.

1) Memantine (Namenda®)

N-methyl-D-aspartic acid (NMDA) - glutamate receptor antagonist.
A new mechanism of action for dementia of AD treatment.
Normal glutamate stimulation is critical for memory formation; however, overstimulation leads to excito-toxic effects.
Memantine assists in preventing neuronal damage through reduced glutamate receptor overstimulation.
Helps prevent programmed cell death.
NMDA-glutamate receptor antagonists are neuroprotective. They help prevent neuronal loss following injuries.

2) Caprylidene (Axona®)

New approach to treat AD developed as medical food.
Metabolism into ketone bodies that the brain uses for energy when glucose processing is impaired.
MRI scans reveal a significant decrease in glucose uptake by the brain.
Replaces depleted glucose levels to treat age-associated memory impairment and AD.

Drugs Used in Multiple Sclerosis (MS)

Autoimmune inflammatory demyelinating disease of the CNS.
Variable course; may be acute or chronic (relapsing or progressive).
Course of disease spans 10 to 20 years.
Affected areas' neurologic symptoms are varied and depend on affected brain areas, including pain, spasticity, weakness, ataxia, fatigue, speech and vision problems, gait issues, and bladder dysfunction.
Many experience relapses and remissions.

Disease-Modifying Therapies

Drugs aim to reduce relapse rates and prevent disability accumulation.
Primary target: Modify the immune response and limit white blood cell-mediated inflammation that damages myelin sheaths and reduces axonal communication.

1) Interferon β-1b and Interferon β-1a (Betaseron®)

Interferon β-1b is the first drug to demonstrate an ability to stop or reverse MS progression in some cases. Immunomodulatory effects help diminish the inflammatory responses leading to axon sheath demyelination.
Clinical trials showed decreased relapse frequency and reduced new MRI lesions in ambulatory, relapsing-remitting MS patients, who had at least two exacerbations over the past two years.

2) Interferon β-1a

Approved for relapsing forms of MS, acting as an immunomodulator.

3) Peginterferon β-1a

PEGylated derivative of interferon β-1a (for longer duration).

2) Glatiramer (Copaxone®)

Synthetic polypeptide mimicking myelin basic protein.
Acts as a decoy to T-cell attack.
Reduced relapse episodes in clinical trials.

3) Fingolimod (Gilenya®)

Oral drug altering lymphocyte migration for lower levels in the CNS of MS patients.
Sphingosine-1-phosphate receptor modulator.
Reduces the number of lymphocytes in peripheral blood and lymph node egress.
May cause first-dose bradycardia, infections, macular edema.

4) Teriflunomide (Aubagio®)

Oral pyrimidine synthesis inhibitor.
Reduces active immune cell proliferation, especially T and B-cells that attack nerves in the CNS.
Potential hepatic toxicity (elevated liver enzymes).

5) Dimethyl fumarate (Tecfidera®)

Oral agent altering cellular response to oxidative stress to reduce disease progression.
Unknown mechanism of action but involves the mono-methyl fumarate (MMF) metabolite and the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which regulates the cellular response to oxidative stress
Flushing and abdominal pain are common adverse effects.

6) Dalfampridine (Ampyra®)

New drug for MS to improve walking speed by blocking potassium channels. Enhances conduction in damaged nerves to improve walking speed.

7) Mitoxantrone (Novantrone®)

An anti-neoplastic agent for treating MS.
Reduces the activity of T cells, B cells, and macrophages that attack the myelin sheaths

8) Monoclonal Antibodies

Reserved for patients who haven't responded to other therapies.

1) Ocrelizumab

First agent approved for primary progressive forms of MS.

2) Natalizumab (Tysabr®)

Monoclonal antibody blocking lymphocyte adhesion pathways into the CNS.
The presence of lymphocytes is linked to immune processes contributing to MS pathology.
Significant toxicity as progressive multifocal leukoencephalopathy (PML).

Daclizumab

Monoclonal preparation targeting Interleukin-2 (IL-2) receptor.
Blocking Interleukin-2 receptor blocks lymphocyte activation.

Alemtuzumab

CD52-directed cytolytic monoclonal antibody for relapsing MS.
Reserved for patients who did not respond to other treatments due to potential life-threatening adverse effects.

Drugs Used in Amyotrophic Lateral Sclerosis (ALS)

Progressive degeneration of motor neurons, causing muscle wasting, weakness, and respiratory failure, ultimately leading to death within 2-5 years.
Unknown cause but evidence suggests a defect in superoxide dismutase (an enzyme that removes superoxide radicals).

1) Riluzole (Rilutek®)

First drug specifically approved for ALS.
Oral NMDA receptor antagonist.
Mechanism unclear, but believed to limit glutamate release, reduce sodium channel activity (protects motor neurons from neurotoxins like glutamate),and limit oxidative stress.
May improve survival time, prolonging time before tracheotomy and life by approximately 3 months.

2) Edaravone (Radicava®)

Intravenous free radical scavenger and antioxidant reducing neuronal damage from oxidative stress.
Effective in slowing ALS progression.
Officially FDA-approved for ALS treatment.

Anti-spastic Agents for MS & ALS

Used for skeletal muscle spasms resulting from injury or neurologic diseases.

1) Baclofen (Lioresal®)

GABAB receptor agonist to lessen motor excitability.
Reduces spasticity, pain, clonus, muscle rigidity.
Available in oral, injectable, intrathecal infusion formulations.

2) Methocarbamol

CNS depressant with sedative and musculoskeletal relaxant properties.
Mechanism of action is not precisely understood.

3) Carisoprodol (Soma®)

Short-term muscle spasm treatment.
Major metabolite is meprobamate (an older, barbiturate-like tranquilizer).

4) Tizanidine (Zanaflex®)

Centrally acting alpha2-adrenoceptor agonist.
Reduces spasticity by inhibiting motor neuron impulses via presynaptic inhibition without affecting muscle strength.

5) Dantrolene (Dantrium®)

Blocks calcium release in muscle fibers, decoupling excitation-contraction and relaxing skeletal muscle directly.
Used for malignant hyperthermia triggered by halogenated anesthetics, neuroleptic malignant syndrome (associated with high-potency antipsychotics), and spasticity from various neurological disorders.

6) Botulinum toxin A (Botox®)

Used for cosmetic purposes, also approved for treating upper-limb spasticity in stroke patients, cervical dystonia, and related PD symptoms, strabismus, and blepharospasm.
Blocks acetylcholine release at the neuromuscular junction.
Treating urinary incontinence resulting from detrusor overactivity (patients with spinal cord injury or MS).

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Description

Test your knowledge on various medications used to treat Alzheimer's disease and related dementias. This quiz covers drug mechanisms, side effects, and forms of administration. Assess your understanding of donepezil, tacrine, rivastigmine, and more.