BB PBLs Flashcards
Madopar®
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.
Rotigotine
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.
Selegiline
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.
Mirtazapine
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).
Cogwheel Rigidity
- 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).
Micrographia
Micrographia: Abnormally small and cramped handwriting, often seen in Parkinson’s disease.
Cause: Due to bradykinesia (slowness of movement) and impaired motor control.
Citalopram
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.
CBT (Cognitive Behavioral Therapy)
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).
Moderate Depression
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
What is Parkinson’s? - Symptoms and Risk Factors
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)
Pathophysiology of Parkinson’s (Normal Brain vs. Affected)
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
What is Depression? (Stages, How It Links to Parkinson’s)
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
what group of drugs prolong the effect of levodopa
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.
difference between madopar and levodopa?
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).
- 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. - 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.
Treatment of Depression in Parkinsons
- 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) - Second-line: Mirtazapine; Effective for insomnia and appetite loss (used in Mr Body)
- Cognitive Behavioral Therapy (CBT)
- Essential for managing mood symptoms
- Helps reframe negative thoughts - Other Options:
- Tricyclic Antidepressants (TCAs) (e.g., Amitriptyline) – Used in select cases
- Dopaminergic treatment optimization can improve mood
Give two examples of prodromal (first symptoms) non-motor symptoms in Parkinson’s.
- REM sleep behaviour disorder
- Constipation
Why do patients taking L-DOPA experience hallucinations?
Excess dopamine in the mesolimbic pathway leads to psychotic symptoms, including visual hallucinations.
What are anticholinergic e.g. procyclidine drugs used for
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).
- Dystonia & Muscle Spasms
Helps treat acute dystonic reactions (sudden involuntary muscle contractions), especially those caused by dopamine-blocking drugs (antipsychotics).
What is dyskenesia
Dyskinesias are involuntary, erratic, writhing movements of the face, arms, legs or trunk
what is degenerative lumbar spine disease (DLSD)
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.”
Mechanism of action of diclofenac
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.
Mechanism of action of tramadol
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.
Mechanism of action of Amitriptyline
- Amitriptyline: A tricyclic antidepressant (TCA) that inhibits serotonin & norepinephrine reuptake, enhancing descending pain inhibition and modulating neuropathic pain.
- Inhibits serotonin & norepinephrine reuptake – Enhances descending pain inhibition.
- Blocks sodium channels – Reduces neuronal excitability.
- Antagonizes NMDA receptors – Inhibits central sensitization.
Mechanism of action of Pregabalin
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.
what is Lumbar spinal stenosis; what surgical treatment is used for it
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).
what is Piriformis syndrome
Piriformis syndrome (compression of the sciatic nerve at the gluteal level)
what is Neuromodulation (Spinal Cord Stimulation - SCS) used for?
Neuromodulation (Spinal Cord Stimulation - SCS)= used for refractory neuropathic pain
How Do Paracetamol & Ibuprofen Work on Neuropathic vs MSK Pain?
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.
How Is Degenerative Lumbar Disease Diagnosed?
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.
what is radiculopathy
Radiculopathy is the pinching of the nerves at the root, which sometimes can also produce pain, weakness and numbness
Define what is meant by the term “central sensitization”, as it occurs following an injury
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
Define three consequences of central sensitization
- Allodynia – A normally non-painful stimulus is perceived as painful due to enhanced central pain processing.
- Hyperalgesia – A painful stimulus is felt as more intense pain due to amplified nociceptive signaling.
- Spontaneous Pain – Pain occurs without any external stimulus due to persistent neuronal hyperactivity
Allodynia is a prominent symptom in patients with neuropathic pain. What is the definition of this term?
An innocuous stimulus is felt as painful
explain how physiotherapy may improve the musculoskeletal pain in the patient’s back
- 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
Define each of the following types of pain
- MSK pain
- nociceptive pain
- arthritic pain
- neuropathic pain
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
