ic17 parkinson's disease Flashcards

Question

what are the ddi for levodopa

Answer 1

1. pyridoxine (vitB): cofactor for DOPA decarboxylase, generally not an issue if levodopa administered with DCI but just need be aware of possible interactions if (a) high dose B6 for hematological problems or (b) high potency vitB complex tabs 2. Fe: affects absorption from levodopa, space out 3. protein: from food, protein powder; affects absorption of levodopa, space out 4. dopamine antagonists: metaclopramide, prochlorperazine, risperidone, FGA (antiemetic of choice for PD is domperidone)

Answer 2

1. ergot derivatives (older ver, not really used alr) i) bromocriptine ii) cabergoline** iii) pergolide* 2. non ergot derivatives i) pramipexole ii) ropinirole iii) rotigotine (TD patch)* iv) apomorphine (SQ inj)* *note that these are not in SG; rotigotine became an exemption item **only dostinex brand avail in SG

Answer 3

ergot derivatives: bromocriptine, pergolide, cabergoline non ergot derivatives: pramipexole, ropinirole, rotigotine, apomorphine moa: act on dopamine D2 receptor and mimics dopamine PK: i) longer halflife and duration of action than levodopa ii) ergot derived have lower F than non ergot derived due to first pass effect iii) ropinirole is metabolised in the liver into inactive metabolites iv) pramipexole is large excreted unchanged in the urine

Answer 4

peripheral: i) N/V ii) postural hypotension iii) leg edema central: i) hallucinations (visual>auditory) ii) somnolence, day time sleepiness iii) compulsive behaviours eg. gambling, shopping, eating, hypersexuality *pt edu ergot derived have these additional s/e: i) fibrosis (peritoneal, pulmonary, pericardiac) - may be partially reversible upon withdrawal *lower risk with non ergot derived ii) valvular heart disease

Answer 5

i) lesser motor complications than levodopa ii) but more hallucinations, sleep disturbances, leg edema, postural hypotension iii) no clinically significant differences in efficacy iv) dopamine agonists more preferred in younger pts to maximise tx options and delay onset of levodopa induced motor complications

Answer 6

IR and SR forms

Answer 7

1. monotherapy in young onset PD 2. adjunct in moderate to severe PD with levodopa 3. management of motor complications caused by levodopa

Answer 8

MAO-A for 5HT, NE (peripheral) MAO-B for DA (central)

Answer 9

selegiline and rasagiline are MAO-BIs moa: irreversible selective MAO-B inhibitors (but not totally selective for MAO-B) PK: i) short half life of 1.5-4hr but long duration of action ii) selegiline is hepatically metabolised into amphetamines which are stimulating (thus give last dose latest 4pm if not will have sleep issues) and have no effect on MAO-B ii) rasagiline is not metabolised into amphetemines (thus not as concerned with sleep issues)

Answer 10

i) monotherapy for early stages (more commonly for young onset PD) ii) adjunct for later stages

Answer 11

selegiline: 5mg OM to BD (second dose in afternoon) rasagiline: 0.5-2mg QD

Answer 12

i) SSRIs, SNRIs, TCAs (wash out period req) ii) pethidine, tramadol iii) linezolid iv) dextrametorphan v) dopamine vi) sympatomimetics: nasal decongestants like pseudoephedrine vii) another MAOI

Answer 13

key chemical of concern is tyramine (cheese rxn) bc it is metabolised by both MAO-A and MAO-B thus try to avoid aged cheeses and meat, draft beer, fermented food like sauerkraut and kimbhi, marmite, banana peel, soy sauce bc these foods contain high levels of tyramine

Answer 14

for levodopa: [motor sx] more improvements [ADL] more improvements [motor complications] more complications [s/e] fewer non motor s/e (sleepiness, hallucinations, impulsive control disorders) for dopamine agonists: [motor sx] less improvement [ADL] less improvement [motor complications] less complications [s/e] more non motor s/e for MAO-BIs: [motor sx] less improvement [ADL] less improvement [motor complications] less complitcations [s/e] less non motor s/e

Answer 15

with DCI like carbidopa and benserazide, the major metaboliser of levodopa is catechol-o-methyl transferase (COMT) entacapone and tolcapone are COMTis reduces OFF time of levodopa

Answer 16

moa: selective reversible COMTi administration: must be taken at the same time as levodopa s/e: urinary discolouration (orange), D, note may cause dyskinesia upon initiation, note may potentiate other dopaminergic effects of postural hypotension, N/V ddi: Fe, Ca, avoid concom non selective MAOIs (but ok with MAO-Bi; caution for selective MAO-Ai), any cathecolamine drug (cathecolamines are epinephrine, norepinephrine and dopamine), enhance anticoagulant effect of warfarin caution: i) hepatic impairment (but monitoring of LFTs not required) ii) to note that may cause dyskinesia upon initiation thus should decr dose of levodopa (which is also good bc can reduce risk of motor complications) formulations: i) comtan: entacapone ii) stalevo: levodopa, carbidopa, entacapone (to decr pill burden)

Answer 17

epinephrine has more effect on heart while norepinephrine has more effect on blood vessels

Answer 18

trihexyphenidyl and benztropine are anticholinergics use: limited use in PD, primarily used to control tremor (indicated either as monotx or adjunct to levodopa to control tremors and stiffness) s/e: anticholinergic s/e (dry mouth, urinary retention, constipation, sedation, confusion, hallucination, delirium

Answer 19

glutamate is the most abundant excitatory NT and is assoc with neurotoxicity and glutamate activates N-methyl-D-aspartate (NMDA) receptor activity which activates the processes that causes cell death incr glutamatergic activity is also linked to the development and maintenance of levodopa induced dyskinesia

Answer 20

moa: 1. NMDA receptor antagonist 2. dopamine D2 receptor agonist 3. enhances release of stored dopamine 4. inhibit presynaptic uptake of catecholamine s/e: N, lightheadedness, insomnia, confusion, livedo reticularis PK features: excreted renally thus reduce dose in renal impairment caution: second dose in afternoon and not at night bc can be stimulating, avoid concom use with memantine (also a NMDA receptor antagonist) indications: monotx ok but more for adjunctive for managing levodopa induced dyskinesia

Answer 21

1. levodopa + DCI: i) + ii) - iii) + iv) - 2. pramipexole/ ropinirole: i) + ii) + iii) + iv) - 3. selegiline/ rasagiline: i) + ii) + iii) + iv) - 4. entacapone/ tolcapone: i) - ii) + iii) + iv) - 5. trihexyphenidyl: i) + ii) + iii) - iv) - 6. amantadine: i) + ii) + iii) - iv) +

Answer 22

note that currently no supplements are proven to have additional clinical benefits but safe to take if pt wishes to but also as PD progresses, pt will probably find it incr harder to swallow so apart from additional pill burden from these supplements, it is also probably harder for them to swallow anyway i) co-enzyme Q10 ii) creatine iii) vitE iv) glutathione v) riboflavin vi) lipoic acid vii) acetyl carnitine viii) curcumin

Answer 23

DIP: i) typically in elderly ii) symmetrical iii) acute/ subacute (approx 3m within exposure to offending drug) iv) reversible (not always) v) variable vi) poor vii) orofacial dyskinesia, akathisia viii) uncommon ix) more often in females x) uncommon xi) normal xii) normal uptake of presynaptic markers, decr uptake of dopamine receptor ligands iPD: i) sixth decade (80-90yo) ii) asymmetrical iii) chronic iv) progressive v) poor vi) marked vii) - viii) common ix) more often in males x) common xi) abnormal xii) decr uptake of presynaptic markers, normal uptake of dopamine receptor ligands

Answer 24

assessing either presynaptic (e.g. dopamine synthesis and storage, transporter density) or postsynaptic terminals (i.e. D2 receptors availability) in PD, it typically involved degeneration of the dopaminergic nerve terminals thus it is likely that the presynaptic markers would be affected compared to the postsynaptic terminal

Answer 25

refers to ON OFF response based on the response to levodopa

Answer 26

no withdrawal of causative drug is effective in improving sx in 80% of pts and takes approx 8w

Answer 27

high risk: i) D2 receptor antagonist: FGA (haloperidol, amisulpride, prochlorperazine), high dose SGA (risperidone, olanzapine, aripirprazole) ii) DA depleters: tetrabenazine, reserpine iii) DA synthesis blockers: alpha-methyldopa iv) Ca channel antagonist (P-channel): flunarizine, cinnarizine intermediate risk: i) Ca channel antagonist (L-channel): diltiazem, verapamil ii) ASM: PHT, VPA, LVT iii) antiemetics/ gastric motility agents: metoclopramide, prochlorperazine iv) SGA: ziprasidone v) mood stabilisers: lithium low risk: i) immunosuppressants: ciclosporin, tacrolimus ii) antiarrhythmics: amiodarone iii) antidepressants: SSRIs (fluoxetine, sertraline), TCAs (phenalzine), MAOIs (meclobemide) iv) statins: lovastatin v) abx: cotrimoxazole vi) antifungal: amphotericin B vii) antiviral: acyclovir viii) hormones: norepinephrine, levothyroxin, medroxyprogesterone

Answer 28

prevention is the best treatment, if not use anticholinergics (trihexyphenidyl, benztropine) or NMDA receptor antagonist (amantadine)

Answer 29

medication review: i) correct levodopa preparation (check 1:4 or 1:10 and check IR or CR) ii) can pt swallow pills whole iii) ddi (dopamine antagonists, antiemetics, SSRIs) iv) comorbidities and their meds ddi v) timing (specific administration timings)