Neurology & Pain Pharmacotherapy Review (copy)

These question-and-answer flashcards cover key concepts, drug details, mechanisms, risk factors, clinical features, and treatment principles for Parkinson’s disease, Alzheimer’s disease, epilepsy, and pain management based on the provided lecture notes.

What neuronal pathway degenerates in Parkinson’s disease (PD)?

Dopaminergic neurons projecting from the substantia nigra pars compacta to the striatum (caudate nucleus + putamen).

List two broad etiologic categories for PD.

Environmental factors and genetic factors.

Name two major risk factors for developing PD.

Increasing age and male sex (men > women).

What four hallmark motor features characterize PD?

Bradykinesia, resting tremor, rigidity, and postural instability.

Give three non-motor symptoms often seen in PD.

Mental status changes, sleep disturbances, autonomic or sensory symptoms (e.g., constipation, orthostatic hypotension).

What lifestyle interventions are recommended for all PD patients?

Regular exercise, yoga/tai chi/dance, physiotherapy, and Lee-Silverman Voice Treatment/BIG therapy.

Describe the basic principle of deep-brain stimulation (DBS) for PD.

A battery-powered neurostimulator implanted subcutaneously below the clavicle delivers continuous electrical impulses to targeted brain structures to reduce motor symptoms.

Which PD surgical option is non-invasive and MRI-guided?

Focused ultrasound (unilateral).

Give two anticholinergic drugs used in PD.

Benztropine (Cogentin) and trihexyphenidyl (Artane).

Why do anticholinergics help tremor in PD?

Loss of dopamine increases striatal cholinergic activity, so blocking ACh can lessen tremor.

List two classic anticholinergic adverse effects.

Dry mouth and confusion (others: dry eyes, constipation, urinary retention, drowsiness).

State the suggested mechanisms of amantadine in PD.

Enhances presynaptic dopamine release and blocks glutamatergic NMDA receptors.

When is amantadine most commonly used in PD?

As adjunct to manage L-dopa-induced dyskinesia during “off” episodes.

Name one distinctive amantadine adverse effect visible on the skin.

Livedo reticularis (mottling).

Which controlled-release levodopa product may be split at the score mark?

Carbidopa/L-dopa CR (Sinemet CR).

What counseling point applies to Rytary capsules?

They may be opened and the beads sprinkled on food.

Give two common adverse effects of levodopa therapy.

Dyskinesias/motor fluctuations and orthostatic hypotension (others: nausea, impulse-control disorders, sleepiness, psychosis).

What is the only FDA-approved adenosine A2A receptor antagonist for PD?

Istradefylline.

Explain istradefylline’s pharmacologic action.

Blocks adenosine A2A receptors in the indirect movement pathway, reducing inhibitory output and improving movement.

Which cytochrome P450 enzymes metabolize istradefylline?

CYP1A1 and CYP3A4 (avoid strong inhibitors or adjust).

Name two irreversible MAO-B inhibitors used in PD.

Rasagiline (Azilect) and selegiline (Eldepryl, Zelapar).

Which MAO-B inhibitor is reversible and only approved as add-on to C/L?

Safinamide (Xadago).

Why must tolcapone use include liver monitoring?

Risk of fatal hepatotoxicity.

What color change can occur in urine with COMT inhibitors?

Brownish-orange discoloration.

Differentiate ergot- and non-ergot-derived dopamine agonists with one example each.

Ergot: bromocriptine; Non-ergot: pramipexole, ropinirole, rotigotine, apomorphine.

List two contraindications/cautions for dopamine agonists.

Avoid in dementia or significant cognitive impairment; use cautiously in older adults due to intolerance of side effects.

Which apolipoprotein allele is most strongly linked to Alzheimer’s disease (AD) risk?

APOE*4.

Name two genes other than APOE implicated in late-onset AD risk.

ABCA7 and TREM2 (also CLU, PICALM).

Which rare APP mutation is protective for AD?

A673T mutation in APP.

Give three environmental risk factors for AD.

Advanced age, low educational/brain reserve, vascular risks like hypertension, diabetes, hypercholesterolemia (others: head injury, depression, Down syndrome).

Summarize the amyloid cascade hypothesis.

Imbalance between production and clearance of β-amyloid leads to aggregation, plaque formation, and neuronal dysfunction driving AD.

What proteins form neurofibrillary tangles (NFTs) in AD?

Hyperphosphorylated tau proteins.

Which neurotransmitter deficit forms the basis for current AD symptomatic therapy?

Cholinergic deficiency (loss of acetylcholine activity).

State the primary treatment goal in AD.

Symptomatic treatment of cognitive deficits to preserve function as long as possible.

List the three cholinesterase inhibitors used for mild-to-moderate AD.

Donepezil, rivastigmine, and galantamine.

What NMDA receptor antagonist is used in moderate-to-severe AD?

Memantine (Namenda).

Give two key non-pharmacologic strategies in AD care.

Structured, consistent environment with orientation cues; avoid confrontation and validate patient feelings (others: adjust environment, monitor vascular health).

Define epilepsy according to ILAE.

At least two unprovoked seizures >24 h apart, OR one unprovoked seizure with ≥60 % 10-year recurrence risk, OR diagnosis of an epilepsy syndrome.

Name four common drugs that lower seizure threshold.

Imipenem (carbapenems), lithium, meperidine, bupropion (others: penicillin, quinolones, theophylline, clozapine, tramadol).

List three common seizure triggers.

Sleep deprivation, flashing lights (photostimulation), emotional or physical stress (others: hyperventilation, hormonal changes, drugs).

Describe the basic pathophysiology of a seizure.

Focal group of neurons becomes hyperexcitable and hypersynchronous, overwhelming normal inhibitory/excitatory balance.

Differentiate focal vs generalized seizure onset.

Focal: starts in one hemisphere; Generalized: starts simultaneously in bilaterally distributed networks.

Why is awareness assessment important in seizure classification?

Level of awareness affects patient safety and helps classify focal aware vs impaired-awareness seizures.

State the overarching treatment goals for epilepsy.

Achieve lifelong seizure freedom when possible with minimal adverse effects and optimal quality of life, preferably using monotherapy.

When should antiepileptic drug (AED) therapy be started?

Generally after ≥2 unprovoked seizures; after a single seizure based on clinical judgment of recurrence risk.

Give the five broad mechanisms of AED action.

1) Voltage-gated Na⁺ or Ca²⁺ channel inhibition, 2) enhancement of GABAergic inhibition, 3) suppression of glutamatergic excitation, 4) modulation of neurotransmitter release, 5) unique/unknown mechanisms.

List two shared adverse-effect categories of most AEDs.

CNS effects (dizziness, sedation) and risk of suicidal ideation.

Which HLA allele is linked to severe cutaneous reactions with aromatic anticonvulsants?

HLA-B*1502.

Provide two key counseling points for patients starting AEDs.

Do not abruptly discontinue medication; report any mood changes or suicidal thoughts promptly (others: avoid St. John’s Wort, caution with generics).

Name four inflammatory mediators involved in pain signal initiation.

Prostaglandins, bradykinin, histamine, and substance P (others: cytokines, serotonin).

Give two major consequences of inadequately treated pain.

Reduced quality of life/limited ADLs and increased healthcare utilization/costs (others: physiologic stress).

Identify three barriers patients face in pain management.

Reluctance to report pain, fear of addiction/adverse effects, financial constraints (others: communication issues).

Define nociceptive pain.

Pain from actual or potential tissue injury caused by activation of nociceptors; typically sharp, dull, or aching and localized.

What acronym helps systematically assess pain characteristics?

PQRST – Palliative/provocative, Quality, Radiation, Severity, Temporal factors.

Explain acetaminophen’s primary mechanism.

Central inhibition of prostaglandin synthesis (analgesic and antipyretic, minimal anti-inflammatory effect).

State the boxed warning for acetaminophen.

Severe liver injury leading to acute hepatic failure—dose-dependent hepatotoxicity.

How do NSAIDs produce analgesia?

Reversibly inhibit cyclo-oxygenase (COX-1 and COX-2), reducing prostaglandin synthesis → analgesic, antipyretic, and anti-inflammatory effects.

List two common NSAID adverse effects.

GI irritation/ulceration and renal impairment (others: inhibited platelet aggregation, bronchospasm).

Name three central nervous system effects of opioids.

Analgesia, sedation/mental clouding, and miosis (others: euphoria, nausea, respiratory depression).

What is the primary life-threatening adverse effect of opioids?

Respiratory depression.

Differentiate opioid tolerance from dependence in one sentence.

Tolerance is decreased drug effect requiring higher doses, whereas dependence is physiologic adaptation causing withdrawal symptoms upon cessation.

Define opioid addiction.

A chronic relapsing disease characterized by compulsive drug seeking and use despite harmful consequences.

Give an example of a pure opioid agonist and a mixed agonist-antagonist.

Pure agonist: morphine; Mixed agonist-antagonist: buprenorphine or nalbuphine.

List three non-pharmacologic modalities for acute musculoskeletal pain.

Ice, heat, rest/elevation/immobilization, and exercise/physical therapy (any three).

Identify two routes other than oral for delivering analgesics.

Intravenous (IV) and transdermal (others: rectal, subcutaneous, intrathecal).

What is naloxone and how is it supplied for layperson use?

A pure opioid antagonist that rapidly reverses opioid overdose; available as nasal spray or intramuscular autoinjector.

How soon may naloxone be re-administered if the patient does not respond?

Every 2-3 minutes until medical help arrives.

Describe ‘focused ultrasound’ in PD treatment in one phrase.

MRI-guided, non-invasive ultrasonic ablation of unilateral tremor target.

Which MAO-B inhibitor’s ODT formulation minimizes first-pass metabolism?

Selegiline ODT (Zelapar).

What serious psychiatric adverse effect can levodopa therapy provoke?

Impulse-control disorders (e.g., pathological gambling, shopping).

Why should ergot-derived dopamine agonists be used cautiously?

Risk of fibrotic complications (e.g., cardiac valvulopathy, pulmonary fibrosis).

Name two neurotransmitters implicated in AD besides acetylcholine.

Glutamate and serotonin.

What non-ergot dopamine agonist is available as a transdermal patch?

Rotigotine.

Which COMT inhibitor offers once-daily dosing?

Opicapone (Ongentys).

List the two primary goals when treating AD.

1) Preserve cognitive function and daily activities; 2) Manage behavioral and psychiatric symptoms.

State one benefit of combining donepezil with memantine.

Addresses both cholinergic deficit and glutamatergic excitotoxicity for moderate-to-severe AD.

Which diet can reduce seizure frequency in refractory epilepsy?

Ketogenic diet.

What device delivers periodic electrical impulses to reduce seizures?

Vagus nerve stimulator (VNS).

Give two common motor descriptors used in seizure classification.

Clonic (rhythmic jerking) and tonic (rigid/tense muscles) movements.

Name the screening allele for carbamazepine-induced Stevens-Johnson syndrome in Asian ancestry.

HLA-B*1502.

Which endogenous opioids act on mu receptors?

Endorphins (particularly β-endorphin).

Explain why mixed agonist-antagonist opioids can precipitate withdrawal.

They inactivate mu receptors in patients physically dependent on full agonists, abruptly lowering receptor activation.

What is the recommended approach to discontinuing long-term AED therapy?

Gradual taper over weeks to months to prevent withdrawal seizures.

Which inflammatory hypothesis factor involves free radicals in AD?

Oxidative stress.

Identify two patient factors increasing risk for opioid misuse.

Personal or family history of addiction and untreated mental health disorders (others: early substance use, poor coping skills).