BB PBLs

Question 1

Madopar®

Answer 1

Madopar®; A combination of Levodopa and Benserazide used to treat Parkinson’s disease.

Mechanism: Levodopa is a dopamine precursor that crosses the blood-brain barrier and is converted into dopamine, relieving motor symptoms. Benserazide inhibits peripheral levodopa breakdown, increasing its effectiveness in the brain.

Levodopa is in a class of medications called central nervous system agents. It works by being converted to dopamine in the brain.

Question 2

Rotigotine

Answer 2

Rotigotine; A dopamine agonist used in transdermal patch form for Parkinson’s disease and restless leg syndrome.

Mechanism: Stimulates dopamine receptors (D1, D2, D3) in the brain, helping to reduce motor symptoms without needing conversion like levodopa.

Question 3

Selegiline

Answer 3

Selegiline; A monoamine oxidase-B (MAO-B) inhibitor used to prolong dopamine activity in Parkinson’s disease.

Mechanism: Prevents the breakdown of dopamine by inhibiting MAO-B, thus enhancing levodopa effects and delaying disease progression.

Question 4

Mirtazapine

Answer 4

Mirtazapine; A noradrenergic and serotonergic antidepressant (NaSSA) used for depression, anxiety, and insomnia.

Mechanism: Increases noradrenaline and serotonin levels by antagonizing α2-adrenergic receptors and acting on serotonin receptors (5-HT2, 5-HT3).
Key Uses: Preferred in depressed patients with insomnia and poor appetite (such as Mr. Body).

Question 5

Cogwheel Rigidity

Answer 5

• Cogwheel Rigidity; A type of muscle stiffness seen in Parkinson’s disease, characterized by jerky resistance when moving a limb passively.

Cause: Increased muscle tone due to basal ganglia dysfunction (dopamine deficiency).

Question 6

Micrographia

Answer 6

Micrographia: Abnormally small and cramped handwriting, often seen in Parkinson’s disease.

Cause: Due to bradykinesia (slowness of movement) and impaired motor control.

Question 7

Citalopram

Answer 7

Citalopram; A selective serotonin reuptake inhibitor (SSRI) used to treat depression and anxiety.

Mechanism: Inhibits serotonin reuptake at the synapse, increasing serotonin availability in the brain, which improves mood.

Question 8

CBT (Cognitive Behavioral Therapy)

Answer 8

CBT (Cognitive Behavioral Therapy): A psychological therapy that helps patients identify and change negative thought patterns.

Mechanism: Focuses on behavioral changes and cognitive restructuring to treat depression, anxiety, and chronic illnesses (like Parkinson’s).

Question 9

Moderate Depression

Answer 9

Moderate Depression; A mental health condition characterized by persistent low mood, anhedonia (loss of pleasure), fatigue, and cognitive impairments that interfere with daily life but are not as severe as major depression.

Symptoms: Lack of motivation, sleep disturbances, appetite changes, and possible suicidal ideation

Question 10

What is Parkinson’s? - Symptoms and Risk Factors

Answer 10

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily affecting movement due to the loss of dopaminergic neurons in the substantia nigra.

It is characterized by both motor and non-motor symptoms.
Motor Symptoms:
- Resting tremor (e.g., in hands, usually asymmetrical)
- Bradykinesia (slowness of movement)
- Rigidity (cogwheel-type in limbs)
- Postural instability
- Micrographia (small handwriting)

Non-Motor Symptoms:
- Cognitive decline and memory issues
- Mood disturbances (depression, anxiety)
- Autonomic dysfunction (constipation, orthostatic hypotension)
- Sleep disturbances (insomnia, REM sleep behavior disorder)

Risk Factors:
- Age (most common in individuals >60 years)
- Genetics (LRRK2, PARK2, SNCA mutations)
- Environmental toxins (pesticides, heavy metals)
-Male gender (higher prevalence)

Question 11

Pathophysiology of Parkinson’s (Normal Brain vs. Affected)

Answer 11

In Parkinson’s disease, there is degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to:

• Reduced dopamine in the nigrostriatal pathway
• Disruption of basal ganglia circuits, impairing voluntary movements
• Loss of inhibitory control in the direct and indirect pathways, leading to rigidity, tremors, and bradykinesia

Question 12

What is Depression? (Stages, How It Links to Parkinson’s)

Answer 12

Depression is a mood disorder characterized by persistent low mood, anhedonia, and fatigue. It has multiple stages:
* Mild – Minor impairment, occasional mood disturbances
* Moderate – Functional limitations, significant mood changes
* Severe – Major functional disability, suicidal ideation
Link to Parkinson’s:
* Dopaminergic dysfunction contributes to both PD and depression
* Serotonergic system dysfunction is also implicated
* Cognitive impairment and psychosocial stressors further worsen mood disorders in PD patients

Question 13

what group of drugs prolong the effect of levodopa

Answer 13

COMT inhibitors ;Inhibits catechol-O-methyltransferase (COMT), preventing dopamine breakdown - prolongs levodopa effects.
(Entacapone, Opicapone)

Catechol-O-Methyltransferase (COMT) inhibitors work by blocking the COMT enzyme, which breaks down levodopa in the bloodstream. This prolongs levodopa’s action and helps with motor fluctuations.

Question 14

difference between madopar and levodopa?

Answer 14

What is Levodopa?
Levodopa (L-DOPA) is a dopamine precursor used in Parkinson’s disease.
It crosses the blood-brain barrier (BBB) and converts into dopamine.
Issue: When taken alone, most levodopa is converted into dopamine outside the brain, causing side effects (nausea, vomiting, hypotension).

2. What is Madopar?
   Madopar = Levodopa + Benserazide (a dopa-decarboxylase inhibitor, DDCI).
   Benserazide prevents premature dopamine conversion outside the brain, reducing side effects and improving effectiveness.
3. Why Are They Used Together?
   Levodopa alone: Requires higher doses, leading to more side effects.
   Madopar: Ensures more levodopa reaches the brain, improving symptom control with fewer side effects.

Question 15

Treatment of Depression in Parkinsons

Answer 15

1. First-line: SSRIs (e.g., Citalopram, Sertraline)
   - Chosen for mild to moderate depression
   - Caution: Some SSRIs interact with Levodopa (e.g. citalopram + sertraline; just they can cause a sedative effect in some patients when combined with Levodopa; u just need to monitor patients for this side effect)
2. Second-line: Mirtazapine; Effective for insomnia and appetite loss (used in Mr Body)
3. Cognitive Behavioral Therapy (CBT)
   - Essential for managing mood symptoms
   - Helps reframe negative thoughts
4. Other Options:
   - Tricyclic Antidepressants (TCAs) (e.g., Amitriptyline) – Used in select cases
   - Dopaminergic treatment optimization can improve mood

Question 16

Give two examples of prodromal (first symptoms) non-motor symptoms in Parkinson’s.

Answer 16

• REM sleep behaviour disorder
• Constipation

Question 17

Why do patients taking L-DOPA experience hallucinations?

Answer 17

Excess dopamine in the mesolimbic pathway leads to psychotic symptoms, including visual hallucinations.

Question 18

What are anticholinergic e.g. procyclidine drugs used for

Answer 18

Anticholinergic drugs are used in Parkinson’s Disease & Drug-Induced Parkinsonism

Procyclidine is used to reduce tremors and rigidity in early Parkinson’s disease.
It is mainly used for drug-induced parkinsonism, caused by antipsychotic medications (e.g., haloperidol).

2. Dystonia & Muscle Spasms
   Helps treat acute dystonic reactions (sudden involuntary muscle contractions), especially those caused by dopamine-blocking drugs (antipsychotics).

Question 19

What is dyskenesia

Answer 19

Dyskinesias are involuntary, erratic, writhing movements of the face, arms, legs or trunk

Question 20

what is degenerative lumbar spine disease (DLSD)

Answer 20

Pathophysiology: DLSD involves progressive degeneration of the intervertebral discs and facet joints, leading to disc herniation, nerve root compression, and inflammation. This compression causes neuropathic pain, described by the patient as “electric shocks” and “burning.”

Question 21

Mechanism of action of diclofenac

Answer 21

Diclofenac: A nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX-1 and COX-2 enzymes, reducing prostaglandin synthesis → decreases inflammation & nociceptive pain but is less effective for neuropathic pain.

Question 22

Mechanism of action of tramadol

Answer 22

Tramadol: A weak mu-opioid receptor agonist that also inhibits serotonin & norepinephrine reuptake, modulating pain signals. Works well for MSK pain but has limited efficacy for neuropathic pain.

Question 23

Mechanism of action of Amitriptyline

Answer 23

• Amitriptyline: A tricyclic antidepressant (TCA) that inhibits serotonin & norepinephrine reuptake, enhancing descending pain inhibition and modulating neuropathic pain.

1. Inhibits serotonin & norepinephrine reuptake – Enhances descending pain inhibition.
2. Blocks sodium channels – Reduces neuronal excitability.
3. Antagonizes NMDA receptors – Inhibits central sensitization.

Question 24

Mechanism of action of Pregabalin

Answer 24

Pregabalin: A GABA analogue that binds to voltage-gated calcium channels in the CNS, reducing excessive neuronal excitability seen in neuropathic pain → effective for radicular and neuropathic pain.

Question 25

what is Lumbar spinal stenosis; what surgical treatment is used for it

Answer 25

Lumbar spinal stenosis (narrowing of the spinal canal causing nerve impingement) Treated with; Laminectomy (for spinal stenosis, removing part of the vertebral arch to relieve pressure).

Question 26

what is Piriformis syndrome

Answer 26

Piriformis syndrome (compression of the sciatic nerve at the gluteal level)

Question 27

what is Neuromodulation (Spinal Cord Stimulation - SCS) used for?

Answer 27

Neuromodulation (Spinal Cord Stimulation - SCS)= used for refractory neuropathic pain

Question 28

How Do Paracetamol & Ibuprofen Work on Neuropathic vs MSK Pain?

Answer 28

Paracetamol: inhibits COX-2 Ibuprofen: inhibits COX-1 and COX-2 MSK/Nociceptive Pain: Both drugs reduce inflammation and nociceptive pain via COX inhibition → effective for muscle, joint, and soft tissue pain. Neuropathic Pain: Limited effect as neuropathic pain is not driven by inflammation but by aberrant nerve signaling. Neuropathic pain requires TCAs, gabapentinoids, or nerve blocks.

Question 29

How Is Degenerative Lumbar Disease Diagnosed?

Answer 29

Symptoms: Back pain, radiculopathy (AKA pinched nerve), reduced range of motion. Imaging: -MRI (gold standard) → Identifies disc degeneration, nerve root compression. - X-ray → Shows vertebral alignment, disc space narrowing, osteophytes. - CT scan → Better for bony changes but less effective for nerve visualization.

Question 30

what is radiculopathy

Answer 30

Radiculopathy is the pinching of the nerves at the root, which sometimes can also produce pain, weakness and numbness

Question 31

Define what is meant by the term “central sensitization”, as it occurs following an injury

Answer 31

Central sensitization is an increased excitability of neurons in the central nervous system (CNS) following an injury, leading to heightened pain perception due to enhanced synaptic transmission and reduced inhibition

Question 32

Define three consequences of central sensitization

Answer 32

1. Allodynia – A normally non-painful stimulus is perceived as painful due to enhanced central pain processing. 2. Hyperalgesia – A painful stimulus is felt as more intense pain due to amplified nociceptive signaling. 3. Spontaneous Pain – Pain occurs without any external stimulus due to persistent neuronal hyperactivity

Question 33

Allodynia is a prominent symptom in patients with neuropathic pain. What is the definition of this term?

Answer 33

An innocuous stimulus is felt as painful

Question 34

explain how physiotherapy may improve the musculoskeletal pain in the patient’s back

Answer 34

1. Reduces inflammation and stiffness – Through targeted exercises and mobilization, physiotherapy decreases muscle tension and improves flexibility, reducing musculoskeletal pain. Promotes neuroplasticity and pain modulation – Physiotherapy activates endogenous pain-inhibitory pathways, reducing maladaptive pain responses and preventing chronic pain development

Question 35

Define each of the following types of pain - MSK pain - nociceptive pain - arthritic pain - neuropathic pain

Answer 35

MSK pain= Pain affecting the muscles, ligaments, tendons, and bones. It can result from acute injuries, chronic conditions, or overuse. Nociceptive pain= Pain caused by the activation of nociceptors due to actual or potential tissue damage. It is typically a response to harmful stimuli affecting tissues. Arthritic pain= Pain associated with arthritis, characterized by inflammation of the joints leading to pain, swelling, and stiffness. Neuropathic pain (aka nerve pain/ neuralgia)= pain caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons

Question 36

what drug class are each of the following: A. Amitriptyline B. Donepezil C. Fentanyl D. Memantine E. Procyclidine

Answer 36

Amitriptyline is a tricylic antidepressant Donepezil an acetylcholinesterase inhibitor Fentanyl an opioid Memantine an NMDA receptor antagonist. Procyclidine is anticholinergic drug

Question 37

Schizophrenia is considered a neurodevelopmental disorder. What does this mean?

Answer 37

Schizophrenia may be due to abnormalities in the formation and maturation of brain circuits (e.g. synaptic maturation)

Question 38

Schizophrenia is likely caused by a combination of genetic and environmental factors. Give an example of a gene associated with schizophrenia that has a role in neurodevelopment ?

Answer 38

DISC1

Question 39

In schizophrenia, brain structural changes can be detected by MRI. Give an example of such structural changes

Answer 39

Increased ventricular volume and/or decreased medial temporal lobe structures (some students may also mention diffuse grey and white matter changes or losses, affecting multiple cortical regions)

Question 40

Give examples extrapyramidal adverse effects associated with treatment with antipsychotic drugs

Answer 40

Acute dystonia (painful muscle spasms) Parkinsonism (tremors, rigidity) Akathisia (restlessness) Tardive dyskinesia (involuntary facial movements, often irreversible)

Question 41

What is the “neuroleptic malignant syndrome” and how does it present?

Answer 41

It is a rare and potentially lethal complication of the use of antipsychotic drugs It is characterised by hyperthermia, autonomic instability, muscle rigidity, fluctuating levels of consciousness, and confusion

Question 42

What are “depot preparations” and what is their value in the management of schizophrenia? Give an example of a drug that can be used as such preparation

Answer 42

These preparations consist of intramuscular administration of a slow-release antipsychotic drug preparations/formulation; this is very useful to address the issue of non-compliance; examples: fluphenazine decanoate, haloperidol decanoate