PD, MS Flashcards
(60 cards)
1
Q
What is the role of non-ergots?
A
- non ergots such as Pramipexole or Ropinirole
- Direct Dopamine receptor agonist
- Treatment of patients <65 years with Parkinson symptoms without cognitive impairment
- Specifically presenting with bradykinesia
2
Q
Side effects of dopamine agonists?
A
- Non ergots e.g. pramipexole and ropinirole
- Drowsiness, nausea, orthostatic hypotension, hallucinations
- Long term use, male sex, high doses also increase chances of compulsive gambling
- Due to reduced neuronal activity in areas of brain response for impulse and inhibitory control
3
Q
What COMT inhibitors are used in PD?
A
- Centrally acting: Tolcapone
- Peripherally acting: Entacapone
*Tolcapone has risks of hepatotoxicity - Should always be used in combination of of L-DOPA and Carbidopa
4
Q
What are the main drugs used in PD treatment?
A
- Dopamine precursor; Levodopa
- Dopa Decarboxylase Inhibitors; Carbidopa
- COMT inhibitors
- MAO Inhibitors
- Anticholinergics
- Dopamine agonists (ergot or non-ergot)
- NMDA antagonist
5
Q
The risk of which adverse effects are reduced when carbidopa is prescribed alongside Levodopa?
A
- Orthostatic hypotension
- Nausea & Vomiting
6
Q
What is the MOA of amantadine?
A
- Increase Dopamine release and inhibits uptake
- NMDA antagonist
7
Q
What are the adverse effects of Amantadine?
A
-Livedo Reticularis (lower extremity purple rash)
- Ankle edema
- Orthostatic hypotension
- Ataxia
- Prolonged QT interval
- Anticholinergic effects: dry mouth and constipation
8
Q
What is the MOA of MAO-B inhibitors?
A
- Inhibit the breakdown of dopamine
- Increases availability of dopamine
-E.g. selegiline, Rasagiline
9
Q
What anticholinergic drugs are used for PD and what are their indications?
A
- Trihexyphenidol
- Benztropine
- Biperidine
- Patients < 65 years of age with main symptom of ONLY TREMOR
- Does not treat bradykinesia
10
Q
What drugs are ergots and non-ergots? What are their indications?
A
-Ergots: Bromocriptine
-Non- ergot: Pramipexole, Ropinirole, Apomorphine
- Ergots no longer recommended for PD therapy due to increased risk of Pulmonary, Cardiac and Peritoneal Fibrosis
- Indicated in early stages of PD, especially < 65 years
- Can be used at any age with used in adjunctive therapy
11
Q
What is parkinson’s disease
A
- Neurodegenerative Disorder
- Affecting dopaminergic neurons in substantia nigra
- Cardinal signs include: rigidity, bradykinesia or akinesia, postural instability and resting tremor
12
Q
What is Multiple Sclerosis?
A
- Chronic demyelinating degenerative disease of the CNS
- Demyelination and axonal degeneration in the brain and spinal cord
- Caused by an immune-mediated inflammatory process
13
Q
What drug is given as first line management (MS) ?
A
- Corticosteroids
- Methyprednisolone (PO or IV) or prednisone (PO)
- 3 to 7 days
14
Q
What are disease-modifying drugs?
A
- Medication for long term treatment of MS to prevent relapses
- These include: glatiramer Acetate, Interferon beta, monoclonal antibodies e.g. natalizumab, dimethyl fumarate
15
Q
What is the MOA of interferon beta in MS treatment?
A
- Decrease T cell activation to decrease cytokine secretion
- Limits T cell access into CNS whilst maintaining integrity of BBB
- Decreases inflammation (Th2 > Th1)
16
Q
What are the adverse effects of Interferon Beta Therapy?
A
- Flu like symptoms: fever, fatigue, myalgia, malaise etc
- Injection site reaction
17
Q
What is the MOA of Glatiramer Acetate (Copaxone)?
A
- Activates Th2 cells to reduce inflammatory processes
- Acts as a “decoy” for T cells instead of myelin- structurally similar to myelin
18
Q
What are the side effects of Glatiramer Acetate?
A
- Injection site reaction
- Chest pain or palpitations
- Flushing
- Anxiety
- SOB
19
Q
What is the MOA of Teriflunomide?
A
- Inhibits synthesis of pyrimidines
- Cytostatic effect on rapidly dividing B and T cells by inhibiting dihydro-orotate dehydrogenase
- Therefore causes anti-inflammatory reactions and proliferative processes
20
Q
What are the side effects of teriflunomide?
A
Side effects: Nausea, diarrhea, alopecia, teratogenicity, headache
21
Q
What is the MOA of Dimethyl Fumarate?
A
- An immunomodulator: protects nerve cells through its anti-inflammatory effect
- shift cytokine production from pro-inflammatory to anti-inflammatory
22
Q
What are the side effects of Dimethyl fumarate?
A
- GI disturbances: nausea, diarrhea
- Headache
- Liver dysfunction
- Immunosuppression
- flushing
23
Q
What is the MOA of Fingolimode?
A
- Agonists of the sphingosine 1-phosphate receptor
- Decrease lymphocyte invasion of the CNS through sequestration of lymphocytes in the lymph nodes
24
Q
What are the adverse effects of Fingolimode?
A
-Bradycardia
-Liver dysfunction
-Hypertension
-Macular edema
-Headache
-Infections
25
When is Fingolimode contraindicated?
- MI, HF, TIA, Prolongued QT Interval, AV block
- Anti-arrhythmic classes Ia and III
26
What is Natalizumab and its MOA?
- Monoclonal antibiotic
- An antibody against α4-integrin; inhibits lymphocyte invasion of the CNS
- Inhibits inflammation
27
What are the side effects of Natalizumab?
- Hypersensitivity: itchiness, fever, rash
- Hypotension
- Chest pain
- SOB
- headache
- dizziness
- nausea
- sweating
28
What is the MOA of mitoxantrone?
- Used for MS treatment
-strong non selective immunosuppressant
- inhibition of DNA and RNA synthesis- prevents synthesis of T cells, B cells and macrophages
- Apoptosis of T cells and APCs preventing T cell activation
29
What are the adverse effects of Mitoxantrone?
- cardiotoxicity
- Nausea
- Alopecia
- Bone marrow suppression
- Infection
30
What are the indications for Mitoxantrone?
- Secondary MS
- Progressive MS
- Progressive- relapsing MS
- Worsening relapsing-remitting MS
* reserved for patients with rapidly advancing disease- failed with other therapy
31
What is Alemtuzumab and it's MOA?
- monoclonal antibiotic
- Antagonist of superficial antigen CD52; found on the surface of lymphocytes and monocytes
- Depletes B and T lymphocyte
32
When is alemtuzumab indicated?
- 2nd or 3rd line patient without response to 1st line drugs
33
What are the adverse effects of alemtuzumab?
- Rash
- Headache, fatigue
- Infusion reactions
- Infections
- Autoimmune phenomena (e.g., ITP, glomerulonephritis, thyroid abnormalities)
- Malignancies
34
What is Ocrelizumab?
- Monoclonal antibiotics
- Antibodies against CD20; deplete B cells
- Humanized anti-CD20
- 1st drug registered for progressive MS
35
What are the side effects of Ocrelizumab?
- Injection site reactions
- Infections
- Hepatitis B virus reactivation
- URTI
- HPV infections
- Malignancies
36
What is the MOA of Cladibrine?
- Synthetic analogue of deoxyadenosine
- Analog of purine that interferes with DNA synthesis and repair, triggering apoptosis and subsequent lymphocyte depletion
37
What are the side effects of Cladibrine?
- URTI
- Headache
- Nausea
-Leukopenia
- Infections
38
What is a stroke and its types?
- acute neurological condition caused by abrupt disruption to cerebral perfusion
- Ischaemic (most common- 80%) and hemorrhagic
- Neurological deficit last > 24 hours
39
What are the symptoms of a stroke patient?
- weakness of one side of body- unable to raise arms
- inability to speak- slurred speech
- Loss of vision
- Vertigo
- Unsymmetrical face/smile
40
What is a TIA?
- Transient ischemic attack (TIA) is a temporary, focal cerebral ischemic event that results in reversible neurological symptoms but is not associated with a visible acute infarct on neuroimaging
- Neurological deficit lasting < 1 hour typically (24 hours by definition)
41
What are some risk factors of stroke?
Non-modifiable:
- Age > 55 years
- Male > Female
- Low birth weight
- Specific race
Modifiable:
- Hypertension
- AF
- Cardiac disease: mitral stenosis, Left atrial enlargment
- Diabetes
- Oral contraceptive
- Postmenopausal hormone therapy
- Lifestyle factors: obesity, smoking etc
42
What are primary prevention protocols for Stroke?
- Lifestyle changes
- Control risk factors:
maintain BP, glucose levels,
- Aspirin at low doses (100mg) has anti-platelet effect
- Aspirin in females > 45 years without increased risk of CNS bleeding
- Aspirin in females > 65 years with hyperlipidemia, DM
- Aspirin not effective in Males
- May increase risk of subarachnoid bleeding
43
What are the secondary prevention protocols for Stroke?
- Lifestyle changes
- Risk factor control
- Statins: Arvostatin 80mg
- Low HDL: niacine, gemfibrozil
- PCSK9 Inhibitors (e.g. Alirocumab) in combination with statins for high risk patients
- NO hormone replacement therapy
- dual antiplatelet therapy after CVI
44
What are the overall goals of stroke management?
- Correct Dx
- Revascularization via surgery
- Long term prevention of re-occlusion
- Decrease risk of TIA/ CVI
45
What are hyper-acute phase management of stroke?
- Oxygen supply
- Body temperature control
- Fluid electrolyte balance
- Glycemia control
- BP control
- Control of cerebral edema
46
What fibrinolytic therapy is used for Stroke?
- Alteplase (IV or intra-arterial)
- Within < 6 hours of symptoms onset
- Check inclusion & exclusion criteria
e.g. exclude in pregnancy or major trauma/surgery in last 14 days
Include if patient is < 18 age, Dx of ischemic stroke with symptom onset less than 4.5 hours before treatment would begin
47
What is the management plan for ischaemic stroke?
- Thrombolytic therapy (e.g. alteplase)
- NO anticoagulant or antiplatelets of 24 hrs of thrombolysis
- Aspirin after 24 hrs, within 48 hours (325mg/day)
- if BP> 185/105mmHg: antihypertensive
- paracetamol for pain management (every 4-6 hours)
- Statins within 48 hours
48
What is the management of intracerebral bleeding- CVI?
- Normalise BP: SBP < 140mmHg
- CAUSED BY ANTICOAGULATION?- FFP or prohrombin complex, Vit K
-CAUSED BY ANTIPLATELET?- supportive therapy
- Hydrocephalus and hematoma: surgical intervention
- reduce glycemia
- control body temp
- hydration
- anti-epileptics for any convulsions
- prophylaxis of DVT
49
What is epilepsy?
- a chronic neurologic disorder characterized by a predisposition to seizures as defined by one of the following:
- Two or more unprovoked or reflex seizures separated by more than 24 hours
- One unprovoked or reflex seizure in an individual with a high risk of subsequent seizures (e.g., after traumatic brain injury, stroke, CNS infections)
50
Epileptic seizures can be focal or generalised. Explain.
Focal: restricted to almost always 1 hemisphere w/o LOC with altered consciousness
Generalised: LOC, both hemispheres and can be tonic, clinic, tonic-clonic, myoclonic, atonic and absence
51
What are the treatment goals of epilepsy?
- the tolerable balance between reduced seizure severity and/frequency and medication adverse effects
- ease patient QOL
52
What are the antiepileptics used?
1st Generation:
Valproic acid, Carbamazepine, Ethosuximide, Phenytoin, Benzo's, Phenobarbitals
2nd Generation:
Lamotrigine, Topiramate, Gabapentin, Pregabalin, Tiagabine
(and many more 1st and 2nd generations)
53
When should you change the drug?
- inefficient therapy
- add 2nd drug, gradually decrease the 1st
- higher success rate if 2nd drug has different MOA to 1st drug
54
When can you use adjunct therapy for epilepsy?
- no success after 2nd drug
- add a drug with different or complimentary MOA
- one with max efficiency and one with max safety
- slow titration
55
When can therapy be ended and when not?
Pro:
- no seizures 2-4 yrs
- normal neurological findings and EEG
- full control of seizures in 1 year
Contra:
- Hx of frequent seizures
- repeated episodes of status epilepticus
- a combination of seizure types
- altered mental function
56
What are the common adverse effects of antiepileptics?
- Broad symptoms: sedation, dizziness, diplopia/blurred vision, impaired concentration and ataxia
Concentration specific: sedation, ataxia and diplopia
Idiosyncratic AE: rashes (progression into Steven Johnson Syndrome), hepatotoxicity, hepatotoxicity
*periodic lab testing, especially if emerging symptoms are related
Chronic AE: osteomalacia, osteoporosis, peripheral neuropathy, cerebral atrophy
*serious AE need discontinuation
57
What is status epilepticus (SE)?
- Neurological emergency which may lead to permanent brain damage or death
- continuous seizures lasting > 5mins or > 2 seizures w/o complete recovery of consciousness
- decompensation with brain hypoperfusion and brain damage
- mostly in patients w/o epilepsy
58
How is non-convulsive SE managed?
1st line: Benzo's and/or valproic acid
2nd line: general anaesthesia
- possible to try before anaesthesia with phenytoin or levetiracetam
59
How is convulsive SE managed according to its stages?
Developing (0-30 mins): Midazolam
Established (30-60 mins): Phenytoin, valproic acid etc
Refractory (> 2 hours): midazolam, pentobarbitone/thiopentone or propofol, sometimes ketamine
Super-refractory (> 24 hours): ketamine, hypothermia, lidocaine, general anaesthesia for over 24 hours
60
What are the MOA of antiepleptics?
Blocking VGNa Channels: reduce Na entry into neurons- Carbamazepine, Phenytoin etc
Block VGCC: lamotrigine and topiramate (can also block NMDA Rs)
Low voltage T-type CCBs: Valproic acid and Zonisamide
Inhibition of high voltage Ca Channel:
