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123 Cards in this Set
- Front
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management acute MS relapse?
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IV methylprednisolone
Plasma exchange IVIg |
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3 types of MS therapy
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1. acute therapy for relapse
2. immunomodulatory 3. symptomatic/adjunctive therapy |
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immunomodulatory therapy available for RR multiple sclerosis?
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Interferon-b1b* (Betaferon) –sc alternate days
Interferon-b1a (Avonex) – im once weekly Interferon-b1a (Rebif) – sc three times weekly Glatiramer acetate (Copaxone) – sc daily |
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side effects of IFN treatment in MS
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flu-like Sx / Injection site reactions / leukopenia /
hepatotoxicity / depression / ”Copaxone reaction” |
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treatment for spasticity in MS?
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physio/baclofen/tizanidine/botox/cannabinoids
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treatment for sphincter dysfn in MS?
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continence advice/anticholinergices/botox/ISC/surgical approaches/SPC
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treatment for pain in MS?
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medication vs holistic approach / exercise/cannabinoids
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treatment for fatigue in MS ?
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conservative vs. medication (amantadine / modafinil – promote wakefulness)
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what type of immunomodulatory drug/s do you use in relapsing remitting MS?
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IFNs
Glatiramer acetate |
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Mitoxantrone
= ? |
anthracycline
chemotherapy drug with immunosuppressive actions, administered every three months IV. It was previously used in the treatment of MS but has been superseded in practice. |
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Natalizumab=?
give brand name and MOA |
Brand = Tysabri.
MOA = Humanised monoclonal antibody to alpha4-integrin. the first in class of Selective Adhesion Molecule (SAM) inhibitors. binds specifically to the alpha4beta1-integrin blocking its interaction with VCAM-1 and additional ligands such as the extra-cellular matrix molecules osteopontin and fibronectin. It also blocks the interaction of alpha4beta7-integrin with its ligand MadCAM-1 (mucosal addressin cell adhesion molecule-1). BASICALLY: r binds to and blocks the binding molecules by which leukocytes pass through blood vessels. This particularly applies to the blood–brain barrier. Therefore it acts as a regional immunosuppressant, largely stopping immunological surveillance and attack of the CNS while in practice not significantly affecting immunological function elsewhere. |
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Would you expect to see PML when using natalizumab?
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PML typically occurs in severely immunocompromised patients and natalizumab does not cause immunosuppression. If natalizumab did produce immunosuppression, then one would expect to have observed an increase in other atypical infections. However, there was no significant increase in atypical infections associated with natalizumab. It is likely that the development of PML is a stochastic process dependent upon multiple steps in the life-cycle of the JC virus and its interactions with the immune system. It is possible that natalizumab intersects the process at multiple points, favouring the development of PML over other types of infections.
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Fingolimod=?
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complex actions but
the primary mechanism is the partial blocking of the egress of lymphocytes from lymph nodes; it therefore has a systemic immunosuppressive effect ==>Catches the lymphoctes – doesn’t allow them to leave the LNs Compared to IFN Shown to have better effects Side effects: Can cause macula oedema Bradycardia , complete heart block -->NEED TO MONITOR Pts |
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treatment for Secondary progressive MS and progressive relapsing MS ?
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1. Natalizumab
2. Fingolimod 3. IFN-beta-1b |
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Acetazolamide =?
indications? |
carbonic anhydrase inhibitor and this enzyme is essential for the production of CSF from the choroid.
indications =Glaucoma, seizures, pseudotumor cerbri |
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Pharmacological treatment AD
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sublingual nifedipine/glyceryl trinitrate or occasionally injected agents.
Rarely, regional epidural or spinal anaesthesia may be required where control of the noxious stimulus is difficult. |
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Baclofen = ?
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Spasticity in multiple sclerosis patients may be improved by Baclofen (Lioresal - a GABA analogue).
However, the dose needs careful titration since too much causes weakness. |
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Interferon reduces the relapse rate in relapsing and remitting multiple sclerosis by.........?
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one third
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T/F: Immunosuppression with Cyclosporin A is beneficial to multiple sclerosis patients.
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F
Although a mild affect on disease progression has been demonstrated, this is far outweighed by toxic effects of the drug. |
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t/f
Antidepressant drugs are contra-indicated in multiple sclerosis patients. |
false
Depression is a common problem and both drug therapy and psychological support may be helpful. |
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t/f:
Corticosteroids given in high dosage for short periods reduce attack duration but not long term disability. |
true
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biculculline = ?
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competitive antagonist of GABA-A
i.e. convulsant |
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how does ethanol modulate GABA receptors?
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incr. open time
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how do general anaesthetics eg propofol modulate GABA receptors?
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enhance GABA-A action
may directly stimulate at high concns |
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allopregnanolone = ?
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neurosteroid .. promotes GABA-A channel opening (esp. delta subunit)
intercalates into membrane |
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drug of choice for partial or focal seizures
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carbamazepine
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drug of choice for absence seziures
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ethosuximide
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drug of choice for generalised seizures
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sodium valproate
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phenytoin = ?
MOA = ? |
ANTI-EPILEPTIC
use-dependent Na+ channel blocker --> specifically acts on rapidly firing neurons SE: |
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Carbamazepine = ?
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ANTI-EPILEPTIC
use-dependent Na+ channel blocker --> specifically acts on rapidly firing neurons also shown to potentiate GABA-Rs SE: skin rash, drowsiness, fatigue |
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Lamotrigine = ?
when is it indicated? SE? |
ANTI-EPILEPTIC
use-dependent Na+ channel blocker --> specifically acts on rapidly firing neurons treat FOCAL seizures, TONIC-CLONIC seziures SE: skin rash, fever, hepatic dysfn |
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ethosuximide = ?
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AED - treat absence seizures
T-type Ca2+ channel blocker - decr. glutamate MAY EXACERBATE OTHER SEIZURE TYPES!! |
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sodium valproate = ?
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AED. also treats bipolar.
drug of choice for generalised seizures. MOA: Ca2+-channel blocker (weaker) Causes significant increase in GABA in brain because it is a weak inhibitor of 2 enzyme systems that inactivate GABA = GABA transaminase and succinic semialdehyde dehydrogenase |
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side effects sodium valproate
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weight gain, hair loss, hyponatraemia, hepatic toxicity, birth defects
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phenobarbital = ?
when is it indicated? side effects? |
AED. acts alone or enhances GABA @ GABA-A receptors
indicated in all seizures EXCEPT ABSENCE SE: sedation, megaloblastic anaemia, hypotension, bradycardia, dependence |
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drug of choice for status epilepticus?
MOA? why not for maintenance therapy? |
benzodiazepines
MOA = incr. open freq of some GABA-A receptors. pts can develop tolerance and don't use for maintenance cos they get too drowsy |
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vigabatrin = ?
indicated when ? |
Synthetic structural analogue GABA
specific inhibitor of GABA transaminase so decr. breakdown of GABA tend to use as adjunctive treatment in treatment-resistant epilepsy, complex partial seizures and secondary generalised seizures |
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Tiagabine = ?
indications? |
GABA analogue
Binds and inhibits GAT1 (=GABA transporter). Competes w GABA. Adjunct for partial seizures. Also adjuvant in anxiety and neuropathic pain |
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GABAPENTIN = ?
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GABA analogue.
incr. csf concentration of GABA - MOA unknown |
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PREGABALIN = ?
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more potent GABA analogue cf. gabapentin.
MOA unknown incr. csf concnetration of GABA |
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Dizolcilpine, dextrorphan
? |
Stroke (neuroprotective to penumbra of)
glut Rc antagonist |
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Lubeluzole, Riluzole ?
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Stroke (neuroprotective to penumbra of)
voltage gated Na+ channel blockers |
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nimodipine, lifarizine
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Stroke (neuroprotective to penumbra of)
voltage gated Ca2+ channel blockers |
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Tirilazad
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Stroke (neuroprotective to penumbra of)
free radical scavenger |
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Dipyridamole (slow release)
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Pts with hx of stroke
usually used in combination with aspirin, thromboxane (A2) synthetase inhibitor |
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Acyclovir
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HSV and VZV infection
Anti-viral |
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Naproxen
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inhibiting both the COX-1 and COX-2 enzymes
pain, inflammation |
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Amitriptyline
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tricyclic anti-dep
Antidepressant, Headache (Tension) |
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L-DOPA
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PD and dystonias
crosses BBB readily and is converted by dopa decarboxylase to dopamine |
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Carbidopa
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Dopa-decarboxylase inhibitor
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Benserazide
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Dopa-decarboxylase inhibitor
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Bromocriptine
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non-selective dopamine PD/hyperprolactinaemia
agonist which activates both D1-like and D2-like receptors |
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Apomorphine
SE? |
Dopamine Rc agonist (preferred in clinical practice)
SE:potent emetic, makes you vomit |
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Pergolide
SE? |
PD
Dopamine Rc agonist SE:fibrosis, eg valvular heart fibrosis, pulmonary fibrosis |
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cabergoline
SE? |
parkinsons and prolactinomas
SE:fibrosis, eg valvular heart fibrosis, pulmonary fibrosis Dopamine Rc agonist |
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Clozapine
se? |
schizophrenia, bipolar
Dopamine Rc Antagonist se= agranulocytosis |
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Domperidone
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PD, antiemetic
Dopamine Rc Antagonist (D2) |
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Doxepin
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depression, insomnia, anxiety
Antidepressant (tricyclic), anxiolytic |
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Selegiline
SE? |
PD, depression, dementia
MAOB inhibitor, used in combination with levadopa SE: postural hypotension, weight gain, severe hypertensive response to tyramine containing foods |
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Rasagiline
SE? |
PARKINSONS
MAOB inhibitor SE:postural hypotension, weight gain, severe hypertensive response to tyramine containing foods |
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Entacapone
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Parkinson disease
COMT inhibitor only one available in Aus |
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Stalevo ?
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Combination preparation of L-Dopa, carbidopa and Entacapone
use in PD |
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Pramipexole
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PD, restless leg syndrome
Dopamine Rc agonist (preferred in clinical practice) |
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Amantidine
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Parkinson Disease, dyskinesias
usually anti-viral, likely mechanism is release of dopamine from nerve terminals, non selective NMDA antagonist |
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Lithium indications and side effects
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mood disorders.
Future possibility in AD (inhibits GSK-3 which is activated by A-beta and hyperphosphorylates tau) SE: tremor acute toxic: cerebellar effects, nephrogenic diabetes insipidous |
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Olanzapine
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schizo, bipolar
5HT2 and D2 Rcs antaongist |
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Donepezil
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anticholinesterase used in mild-mod AD
selective and reversile AChEI. widely bioavailable long half life (given once daily) NB not disease modifying |
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Galantamine
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anticholinesterase used in mild-mod AD
selective and reversile AChEI that also acts as an allosteric modulator on nAChRs to increase the strength of residual acetylcholinergic synapses NB not disease modifying |
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Clioquinol
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Neurodegenerative disease
Chelator of Cu and Zn once A-beta is released, it becomes dimerised via copper bonds (metal chelation may break this bond to prevent dimerisation) not successful in human studies |
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Gingko biloba
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Dementia
increase blood supply, decrease viscosity, decrease free radicals |
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Rivastigmine
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anticholinesterase used in mild-mod AD
pseudoirreversibly inhibits AChE and also butyrylcholinesterase (clinical signif of dual activity remains unclear though) NB not disease modifying |
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metronidazole
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Antibacterial and antiprotozoa
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Quetiapine
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schizophrenia, bipolar and depression (in some cases)
DA, 5HT and Adr antagonist |
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imipramine
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mood disorders - tricyclic antidep
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MOA and SE of Tricyclic antidepressants
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inhibition of 5HT and NAd reuptake
SE; autonomic, postural hypotension, sexual dysfn, sedation, weight gain, cardiac dysrhythmias |
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Moclobemide
what's good about it? |
depression anxiety
MAOI (no increase in blood pressure with tyramine containing food ingestion) |
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SSRIs
SE and MOA |
inhibiton of 5HT reuptake
insomnia sexual dysfn, nausea |
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Oxazepam
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benzo
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Alprazolam
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benzo
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Buspirone
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Non-benzo anxiolytic, high affinity for 5HT1A Rcs
use in anxiety |
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Flumazenil
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benzo OD
antagonises action of positive and negative modulators |
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Chlopromazinem
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typical antipsychotic
phenothiazine gorup, D2 Rc blocker, |
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thioridazine
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typical antipsychotic phenothiazine gorup, D2 Rc blocker,
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Haloperidol
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typical antipsychotic Butyropherone group, D2 Rc blocker.
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Rispiridone
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atypical antipsychotic antagonise D2 Rcs, high affinity for 5HT rcs, effect on both +ve and -ve symptoms
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aripiprazole
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atypical antipsychotic antagonise D2 Rcs, high affinity for 5HT rcs, effect on both +ve and -ve symptoms
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problems with levo-dopa
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hypotension esp orthostatic
dyskinesia- appears after yrs, usually dynamic psychiatric disturbance loss of efficacy (decr. duration, on/off phenomenon) |
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commonest problem ass'd with PD pharmacotherapy
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nausea
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when we try to agonise/antagonise dopamine receptors - which ones do we normally target?
pre or post synaptic ? |
normally target D2 receptors - these are not linked to adenylate cyclase.
both pre and post synaptic |
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what do we give with L_DOPA?
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a dopa decarboxylase inhibitor that can't cross the BBB. so that all the L-dopa gets into the brain before its converted to dopamine
don't want dopamine in the periphery (causes nausea) |
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what breaks down dopamine ?
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monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)
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where does dopamine act in the CNS?
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post-synaptic Rs
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on what receptor do direct dopamine agonists act? why is this good? when do we use them?
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in parkinson disease.
act on D2 post synaptic receptor. this is good because it 'bypasses' the sick or dead neurons because it goes straight to the post-synaptic membrane |
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direct dopamine agonists (DDA) vs. L-dopa
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DDA much more expensive
behave in similar way (nausea, hypoT, psychiatric disturbance) DDA cause more trouble w mental disturbance DDA longer t1/2 |
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indications for dopamine agonists
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dyskinesia (usually in combination with L-dopa/DDI to reduce dosage)
longer t1/2 may smooth fluctuations |
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side effects anti-cholinergics
can you take ppl off straight away? |
ACh = widely used so affects lots of things
paralyse ciliary m urinary retention constipation impaired sweating delirium and hallucinations must withdrawal SLOWLY to avoid cholinergic storm |
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what drugs can cause DIMD (drug-induced movement disorders)?
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antipsychotics
antidepressants stimulants alcohol mood stabilising drugs dopamine agonists neuroleptics anticonvulsants |
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what movement disorder can tricyclic anti-deps cause?
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hand tremor
myoclonic jerks |
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which anti-depressant more commonly causes DIMD?
what sx do you see? |
SSRIs
mild parkinsonian symptoms dystonia dyskinesia akathisia |
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what drug is most commonly ass'd with peripheral tremor?
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lithium
usually mild action tremor, but becomes course when toxic levels are reached |
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what movement disorder can lithium cause?
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mild action tremor (which becomes course when toxic levels are reached)
myoclonus (less often) exacerbates parkinsonian side effects of neuroleptics |
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what movements are ass'd with stimulants?
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stereotypies
dyskinesia tremor dystonia myoclonus |
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what movements are ass'd with anticonvulsants?
and in toxic doses? |
dyskinesia
tremor and tics toxic doses --> nystagmus ataxia dysarthria |
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T/F: anticholinergics can exacerbate dyskinesias
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TRUE
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dopamine agonists - what movement disorders can they cause?
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commonly ass'd with dyskinesia, dystonia, myoclonus, esp in late stage PD
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what movement disorder has oral contraception been ass'd with ?
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chorea
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how are movement disorders caused by neuroleptic drugs classified?
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acute
delayed onset (tardive) |
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acute symptoms of neuroleptic-induced movement disorder
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dystonia
drug-induced parkinsonism akathisia neuroleptic malignant syndrome (NMS; rare) |
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define akathisia
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an inability to sit still due to unpleasant sensations of "inner" restlessness
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what is neuroleptic malignant syndrome?
what would you see in a blood test? common or rare? can it be fatal ? |
fever
muscle rigidity altered sensorium autonomic instability ass'd with raised creatine kinase and leucocytosis rare! can be fatal if not detected early |
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T/F: the delayed onset movement disorder induced by neuroleptics is reversible
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false
chronic treatment with neuroleptics causes movements that are potentially irreversible |
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what is the most common movement disorder ass'd with LT use neuroleptics?
what other symptoms have been described? |
tardive dyskinesia (choreo-athetoid movements)
other = tardive dystonic, akathisic, myoclonic and tic-like movements |
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are atypical antipsychotics better or worse in terms of DIMD?
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newer, atypical antipsychotics have much lower propensity to produce movement disorders incl. parkinsonism
BUT clozapine may induce agranulocytosis! |
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what actions of drugs are ass'd with DIMD ?
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DIMD usually attributed to the actions of these drugs on DOPAMINE and SEROTONIN systems
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rationale behind and therapeutic effects of cholinesterase inhibitors in AD?
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we use them because:
significant neuronal loss in basal forebrain where there's lots of cholinergic activity reduced choline acetyltransferase in brain anti-cholinergics induce memory deficits anti-cholinesterases induce memory gains by inhibiting hydrolysis of ACh in the synapse therapeutic effects: the three ChEIs show similar efficacy maintenance of higher level of cognitive fn cf. placebo over 6-36mo small but statistically signif effect on cognition NNT=12 |
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what is the NNT and NNH of anticholinesterases in AD ?
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NNT=12
NNH=12 |
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MEMANTINE.
Brand name? when is it indicated? Rationale behind use? Cf conventional drugs of same class? |
Brand = Ebixa
NMDA antagonist Indicated in mod-severe AD rationale = glutaminergic excitotoxicity. A wide range of neurodegenerative diseases are characterised by sustained overactivity of NMDA-Rs --> impairs synaptic plasticity --> neuronal degeneration probs due to incr. Ca2+ conventional NMDA-antagonists are limited by side effects caused by interfering w/ physiological role of glutamate signalling. Memantine has voltage-dep action so seems to reduce low-level activation without interfering with physiologic functioning of NMDA-Rs |
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T/F: there are no significant clinical benefits by combining memantine with an AChEI in AD cf. an AChEI alone
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true
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alternative medicine in AD
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gingko bilboa = natural product incr. blood supply by
dilating BVs reducing blood viscosity modifying NT systems reducing density O free rads No consistent clinical benefits has anti-platelet effects :S |
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T/F:
clinicians often prescribe benzodiazepines to try and control behavioural sx ass'd with AD |
FALSE!!!!!!!!
avoid benzos because they make confusion and cognition WORSE and increase the risk of falls |
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what pharmacological treatment can help control behavioural sx in AD?
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no specific meds available.
can prescirbe small doses of anticonvulsants, antipyschotics and antidepressants .. short amount of time and small dose though b/c they have SEs! |
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treatment aspiration pneumonia
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ANTIBIOTICS:
penicillin +/- metronidazole PHYSICAL THERAPY: clearance of secretions and small particulate matter clearance of larger matter may require bronchoscopy |
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what suggests the need for further clearance of secretions/solid matter in aspiration pneumonia ?
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presence of collapse or loss of lung/lobar volume
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