Exam 3 Drugs Flashcards
1
Q
MS Drugs that act in periphery (including BBB)
A
-IFN-B
-glatiramer acetate
-natalizumab
-mitoxantrone
-teriflunomide
-cadibrine
-rituximab
-ATL1102
2
Q
MS drugs that act in periphery and CNS
A
-gingolimod
-siponimod
-ozanimod
-ponesimod
-fumarates
3
Q
MS drugs that act in BBB
A
-IFN-B
-natalizumab
-ATL1102
4
Q
MS drugs with direct cytotoxic effect
A
-mitoxantrone
-teriflunomide
-cladribine
5
Q
Drugs that increase risk of PML
A
-fingolimod
-natalizumab
-fumarates
6
Q
MS drugs with neutralizing antibody-limiting effectiveness
A
-IFN-B
-natalizumab
-rifuximab (ocrelizumab)
7
Q
MS drugs that can treat PPMS
A
-rituximab (ocrelizumab
8
Q
First line MS drugs
A
-IFN-B1a/b
-glatiramer acetate
-fingolimod
9
Q
Second line MS drugs
A
-natalizumab (tysabri)
-Mitooxantrone (Novatrone)
10
Q
newer drugs for MS
A
-teriflunomide
-dimethyl fumarate
-clabridine
11
Q
Tx for acute MS attacks
A
-methylprednisone (IV or oral)
-prednisone (oral)
-ACTH ($$)
12
Q
methylprednisone dosing
A
-500-1000mg IV qd x 3-7 days
-with or without oral taper over 1-3 weeks
13
Q
prednisone dosing
A
-if outpatient MS acute attack
-oral 1250mg qOTHER day x 5 doses
-no need to taper
14
Q
corticosteroids
A
15
Q
IFN-B1a/b (Avonex, Rebif)/(Betaseron, Extavia) MOA
A
-first line MS
-periphery and BBB
-inhibit T cells and DCs
-block BBB penetration by dec matrix metalloproteinase (MMP)
-efficacy reduced by nerutralizing antibodies
16
Q
IFN-B1a/b (Avonex, Rebif)/(Betaseron, Extavia) clinical
A
-first line MS
-efficacy reduced by neutralizing antibodies
-SubQ or IM
-flu-like sx after injection (pretreat w analgesic)
-DEPRESSION/SUICIDAL
-LFTs and TSH monitoring
17
Q
Glatiramer acetate MOA
A
-synthetic polypeptide
-periphery
-mimics antigenic properties of myelin protein
-modulate APCs (DCs) = dec T cell activation
18
Q
glatiramer acetate clinical
A
-first line MS
-box warning for severe allergic rx/anaphylaxis
-flushing, weating, dyspnea, anxiety, itching
-lipoatrophy: rotate sites
-chest pain outside of injection but not clinically significant
-maybe preferred in pregnancy
19
Q
Fingolimod moa
A
-sphingosine-1-phosphate AGONIST
-periphery and CNS
-stimulate oligodendrocyte survival and remyelination
-interfere w T cell movement out of lymphoid organs
20
Q
Fingolimod clinical
A
-first line MS
-PML
21
Q
fingolimod structure
A
-aromatic ring w long single chain kinda like fat
22
Q
Natalizumab (tysabri) MOA
A
-periphery
-mAb for a4-integrin
-block VLA-4 binding to VCAM-1
=interferes w B and T cell movement into CNS
23
Q
Natalizumab (tysabri) clinical
A
-second line MS
-PML
-allergic reactions from inducing neutralizing antibodies
24
Q
Mitoxantrone (Novantrone) MOA
A
-CYTOTOXIC ACTIVITY
-DNA strand breaks by intercalation
-inhibit topoisomerase II (delay DNA repair)
=reduced lymphocyte numbers
-structure is flat to wedge between DNA base-pairs
25
Mitoxantrone clinical
-second line MS
-first licensed for SPMS
-cariotoxicity and malignncies
-induction therapy and then replaced w IFN-B or GLAT
-oc + preg test before each infusion
26
Teriflunomide MOA
-CYTOTOXIC
-inhibits dehydrogenase
=no proliferation of peripheral activated B and T cells
27
Teriflunomide clinical
-newer drug for MS
-AVOID in pregnancy
28
Dimetyl/Diroximel/Monomethyl fumarate MOA
-CNS and periphery
-metabolized by esterases in GI tract, blood, tissues
-activate Nrf2-mediated cellular antioxidant responses and anti-inflammatory pathways
-active form is monomethyl ester
-maybe remyelination
-suppress activated T cells in periphery
29
Dimetyl/Diroximel/Monomethyl fumarate clinical
-newer MS drug (oral, delayed release)
-PML
-do NOT CHEW OR CRUSH
-monitor LFTs and CBC
-can cause flushing, may take aspirin 30 min before
30
Dimetyl/Diroximel/Monomethyl fumarate STRUCTURE
-basically carboxylic acid
31
S1P agonist drugs
-siponimod
-ozanimod
-ponesimod
-also fingolimod
32
S1P agonist drugs MOA
-maybe oligodendrocyte survival, remyelination
-interfere lymphocyte movement out of lymph organs
33
S1P agonist drugs clinical
-RRMS and SPMS
-AVOID in past arrhythmia diagnosis or any of the following in past 6 months: MI, unstable angina, stroke/TIA, class III/IV HF
-d/c can = worsening of MS sx
-siponimod requires CYP2C9 genotype testing before Rx
-fing: oc 2 months
-ozan: oc+ 3 months
-pones: oc+7 days
-Sipon: oc +10 days
34
S1P contraindications
-arrhythmia diagnosis
-MI, unstable angina, stroke, HF in last 6 months
-test for CYP2C9 before starting siponimod
35
Clabridine MOA
-taken up into cells by purine neucleoside transporters
-phosphorylated to 2-chloro-dATP that damages DNA and intereferes w DNA metabolism = cell death = lymphocyte depletion
-
36
Clabridine clinical
-newer MS drug
-oc + 6months
-AVOID in breastfeeding
37
Clabridine STRUCTURE
-2-chlorodeoxyadenosine
-5 ring base, two N aromatic rings (one 5 bonds, one 6 bonds), Cl group
38
Rituximab (aka Ocrelizumab) MOA
-mAb targets CD20 (B-cell marker)
-avoids CD20 on plasma/stem cells tho which is good
-
39
Rituximab (aka Ocrelizumab) clinical
-new mAb for MS (off-label)
-approved non-hodgkin and rheumatoid arthritis
-STOPS RRMS (dec relapse)
-EFFECTIVE for some PPMS pt (slow progression)
-infusion q6months
-apporved for PPMS, CIS, RRMS, SPMS
-AVOID in Hep B
-inc malignancies
40
ATL 1102
-ASO targeting VLA-4
41
Alemtuzumab clinical
-increased risk of malignancies
-AVOID in HIV
42
MS drugs and contraception
-AVOID teriflunomide
-mitoxantrone: oc + preg test before each infusion
-fingolimod: 2months
-ozanimod: 3 months
-ponesimod: 7 days
-siponimod: 10 days
-Ocrelizumab: 6 months
-Cladribine: 6 months NO breastfeeding
43
Neudexta (dextromethorphan/quinidine)
-sigma 1 receptor agonist
-suppress release of excitatory NTs
-ANTAgoinst of NMDA
-P450 2D6 substrate
-metabolized in periphery (doesnt cross BBB)
-quinidine blocks metabolism so dext can cross CNS
-TX of pseudobulbar affect
44
Dalfampridine (ampyra)
-may improve walking speed in MS
45
PD drugs
-antimuscarinics
-L-DOPA
-carbidopa
-apomorphine (D1/D2 agonist)
-ropinirole (non-ergoline D2/D3)
-pramipexole (')
-rotigotine (')
-selegiline (MAO-B)
-rasagiline (')
-safinamide('*)
-entacapone (COMT)
-tolcapone (COMT)
-opicapone (COMT)
46
Antimuscarinics (benztropine and trihexyphenidyl)
-compensate for over activity of cholinergic pathways bc loss of DA
-adj tx for PD tremor
-avoid if >65
47
L-DOPA MOA
-DA precursor (can cross BBB unlike DA bc uncharged)
-replace lost dopamine
48
L-DOPA clinical
-PD
-Nausea, HTN, psychosis
-LD motor flux/dyskinesia
-take wf
-25/100mg PO BID-TID start and can inc upto 5-6x day!
-dose can be lowered by co-admin carbidopa
-on/off oscillations
49
L-DOPA and carbidopa structure
-aromatic ring w 2 OH and carboxyl group that gets removed to = DA
50
Carbidopa MOA
-peripheral (does NOT cross into CNS)
-DOPA decarboxylase (DDC) inhibitor
=more LDOPA can cross BBB where it can be converted in SN
-PD
51
Dopamine agonists MOA
-as PD progresses, brain cant keep converting L-DOPA, so use agonist
52
Dopamine Agonist drugs
-apomorphine (nonergoline)(d1/D2)
-ropinirole (nonergoline)
-pramipexole ("")
-rotigotine ("")
53
Apomorphine MOA
-D1/D2 agonist in late-stage PDs
-dopamine structure w cathchol and aminoethyl groups in rigid formation (looks like sterol to me tbh)
54
Apomorphine clinical
-SubQ
-late-stage PD for rapid relief of off state
-potent emetic effects tho
55
non-ergolines MOA (ropinirole, pramipexole, rotigotine)
-D2/D3
-fewer side effects than apomorphine
56
non-ergolines (ropinirole, pramipexole, rotigotine) clinical
-monotherapy for early-stage PD (2-4 year efficacy)
-inc dose q5-7 days to minimize side effects
-less side effects than ergolines
-rotigotine can be a patch
57
Dopamine agonists clinical
-first line PD
-minimize motor fluctuations
-fewer fluctuations
-long-acting formulas
-N/V
-sudden sleep
-hallucinations, impulse control disorder (ICD)
-orthostatic hypotension
-edema
-$$$
58
MAO-B inhibiting drugs
-selegiline (propargylamine)
-rasagline (")
-safanamide
59
MAO-B inhibitor MOA
-inhibit MAO
=block oxidation of dopamine to DOPAL
-propargylamines (selegiline and rasagiline) IRREVERSIBLE (triple bond)
-safanimide REVERSIBLE
-least effective for motor sx
60
MAO-B inhibitor clinical
-monotherapy to delay first LDOPA use or adj to L-DOPA (lower dose)
-safanamide adj L-DOPA/carbidopa (good for off episodes)
-1st line for mild sx
-2nd line for adj
-adj for PD depression
-N/V, HA
-insomnia (selegiline)
-hypo/hypertension
-dietary restrictions
-risk of serotonin syndrome (SSRIs/SNRIs, dextromethorphan, seroternigc opioids)
61
COMT inhibitor drugs
-entacapone
-tolcapone
-opicapone
62
COMT inhibitor MOA (entacapone, tolcapone, opicapone)
-inhibit methylation of 3-OH group of DA or LDOPA by COMT
-entacapone and opicapone in periphery
-tolcapone in CNS
-prolong Sinemet action (only duration not potency)
63
COMT inhibitor MOA (entacapone, tolcapone, opicapone) clinical
-combo to manage sx fluctuation (wearing off) in PD
-prolong Sinemet action
-inc duration of effect (not potency)
-N./V
-brown/orange urine (entacapone)
-hepatotoxicity (tolcapone use limiting se)
64
Stalevo
-LDOPA + Carbidopa + entacapone
65
PD tx
1. rule out drug-induced
1. Dopamine precursor
1. DA agonist
1. MAO-B inhibitor
2. COMT inhibitor
2. Amantadine
66
first line PD tx
-rule out drug-induced
-dopamine precursor
-dopamine agonists
-MAO-B inhibitor
67
second line PD tx
-COMT inhibitors
-Amantadine
68
Drug efficacy for PD motor sx
1. LD/CD
2. DA
3. MAOB
69
Amantadine clinical
-modest effect for tremor in PD but not monotherapy
-insomnia, confusion/hallucinations, livedo reticularis
-rare bc cognitive side effects
-usually for reserved CD/LD peak dose dyskinesias
70
Wearing off in PD tx
-inc CD/LD dose/freq
-add DA, MAO, COMT
-XR CD/LD
71
freezing in PD tx
-inc CD/LD dose/freq
-add DA (apomorphine)
-add ODT CD/LD
72
delayed onset in PD tx
-take CD/LD on empty stomach
-ODT CD/LD
-AVOID CR/XR CD/LD
73
Peak-dose dyskinesia in PD tx
-add amantadine
-dec dose of DA or CD/LD
74
Deep brain stimulation
-tx for PD motor fluctuations
75
Orthostatic hypotension tx in PD
-midodrine
-droxidopa
76
anxiety/depression in PD tx
-CBT
-SSRI/SNRI
-AVOID benzos
-caution tricyclic antidepressants
77
Dementia in PD tx
-cholinesterase inhibitor (donepezil, rivastigmine)
78
Psychosis/delirium tx in PD
-reduce PD med doses PRN
-PIMAVANSERIN (newish)
-atypical antipsychotics (clonazapine, quetiapine)
-AVOID haloperidol, olanzapine, paliperidone, risperidone
79
Cholinesterase inhibitor drugs
-Donepezil
-Rivastigmine
-Galantamine
80
Cholinesterase inhibitor MOA
-block slide 20 reaction
-blocks break down of ACh to acetic acid + choline
=compensates for loss of ACh that results from degeneration of cholinergic nerve terminals in AD
81
Cholinesterase inhibitor clinical
-1st line AD
-mild-mod dementia
-donepzil usually chosen first
82
Donepezil
-SPECIFIC, REVERSIBLE
-1st line AD
-mild-severe dementia
-qd and easy to titrate
83
Donepezil dosing
-5mg qd pm
-inc to 10mg after 4-6 weeks
84
Donepezil side effects
-Gi bleeding (watch NSAIDs)
-NVD
-bradycardia
-syncope, insomnia
-wt loss
-P450 2D6 and 3A3/4 substrate
85
Rivastigmine MOA
-inhibits ACETYL and BUTYRYL cholinesterase
-oral or patch
86
Rivastigmine dosing
-twice daily
-take w meals
87
Rivastigmine side effects
-GI bleeding, wt loss
-TOXICITY from not removing patch qd (NVD)
-esophageal rupture if therapy interuptted and restarted
-No P450 interactions tho!
88
Galantamine MOA
-selective, reversible
-enhances action of ACh on nicotinic receptor
89
Galantamine dosing
-twice daily 4 weeks w breakfast and binner
-doses > 16mg/day are NOT recommended for mod renal/hepatic impairment
90
Galantamine side effects
-GI, wt loss
-NVD, bradycardia, syncope, insomnia
-P450 2D6 and 3A4 substrate
91
NMDA antagonist drugs
-memantine
-can combo w donezepil
92
Memtantine MOA
-NMDA ANTAgonist
-blocks glutamergic NT via noncompetitive mech
-reduce excitotoxicity
-only IR generic
93
Memantine dosing
-adj in severe CrCl <30
= 5mg qd x 1 week
-target dose to 5mg BID
94
Memantine side effects
-caution in pt w seizures
-dizziness, HA
-hallucinations, insomnia, confusion!
-constipation
-caution w carbonic anhydrase inhibitors and sodim bicarbonate (Cl of memantine is reduced 80% if urine is alkalinized)
-No P450 interactions
95
Memantine clinical
-does not slow or prevent degeneration
-mod-severe only
-NOT useful in mild cognitive impairments
-marginal benefit in AD
96
Memantine/Donepezil (Namzaric) dosing
if on donepezil 10mg: start 7/10 and inc by 7 to 28/10
-if memantanine 10mg BID or ER 28mg qd: 28/10 w dinner
97
Memantine/Donepezil (Namzaric) side effects
-warning for vagotonic effects like bradycardia and heart block
-inc risk of GI ulcer
-NVD
-bladder obstruction
98
Anti-amyloid antibody drugs for AD
-lecanemab
-donanemab
-aducanumab?
99
anti-amyloid body MOA
-dec AB levels
-slows cognitive decline (esp in low/med tau)
100
anti-amyloid body side effects
-ARIA
-MRI monitoring is req esp in pt w 2ApoE4 alleles
101
ARIA
-amyloid-related imaging abnormalities
-brain swelling/microhemorrhage
102
Mechs of anticonvulsants
1. dec Na influx (promote Na channel inactivation)
2. dec Ca influx (crucial for absense seizures)
3. Enhance GABA-mediated neuronal inhibition
4. Antagonism of excitatory transmiters (like glutamate)
5. some others
103
anticonvulsants that dec sodium influx, prolong inactivation of Na channels
-ox + carbamazepine
-phenytoin
-lacosamide
-lamotrigine
-valproate
104
Anticonvulsants that reduce Ca influx
-ethosuximide
-lamotrigine
-valproate
105
Anticonvulsants that enhance GABA
-barbituates (activate GABA)
-benzos (")
-valproate (inc GABA levels)
-gapapentin (inc GABA release)
vigabatrin (inhibits GABA transaminase)
-tiagabine (inhibits GAT-1)
106
drugs that antagonize excitatory transmitters (like glutamate)
-felbamate (NMDA antagonist)
-topiramate (kainate/AMPA antagonist)
107
Phenytoin
