1 Flashcards
What are the treatments for huntingtin’s
tetrabenazine
chlorpromazine
haloperidol, olanzapine, risperidone, quetiapine
What is tetrabenzaine
- HD treatment
- Inhibitor of vesicular monoamine uptake (VMAT)
- Decreases dopamine, less facilitation of movement-
What is chlorpromazine
- HD treatment
- DA antagonist, antipsychotic
What drugs can treat moderate Alzheimer’s
Tacrine
Donepezil
Rivastigmine
Galantamine
All have cholinergic side effects!
memantine
What is prescribed if acetylcholine esterase inhibitors can’t be tolerated in Alzheimer’s
What is used in conjunction with L-DOPA in PD
Carbidopa and benserazide
Don’t cross BBB
Entacapone and tolcapone
PNS drugs for PD treatment
COMT inhibitors
What are CNS drugs for PD treatment
- Tolcapone inhibits COMT, increases dopamine availability
- Selegiline and rasagiline - MAOb, increase DA availability
pramipexole and ropinirole
DA agonists used to treat PD
Benztropine and phencyclidine
mAChR antagonists can used to treat PD
difficult to manage side effects as non-selective
amantadine
mechanisms not understood
NMDA inhibitor that treats PD
What amfetamines are used medically
ADHD
modafinil - a2 adrenoreceptor activation, release of 5-HT. bad side effects
Convulsants
Pentylenetetrazol, penicilin, bicuculline, gabazine, strychnine
pentylenetetrazol
- induce seizures
- GABAa receptor antagonist
penicilin
- anti-GABA activity
- used widely as a seizure inducing agent to test anti-convulsives
- does not cross BBB, applied directly to cortical surface
strychnine
- induces seizures by acting as a glycine antagonist
- small doses given as ‘tonic’ give rise to ‘risus sardonicus’ - facial muscle tetany
- alkaloid from seed of tree nux vomica
- glycine acts as pentameric ligand-gated Cl- channel
action of NSAIDs
- inhibit both COX-1 and COX-2
- anti-inflammatory, anti-pyretic
- analgesic activity COX-2
- GI issues with COX-1
- COX-2 role in CNS unclear
neuropathic treatments
- capsaicin - licensed for symptomatic relief
- lidocaine - localised pain
opioids - agonist, antagonist, mixed
morphine, naloxone, buprenophine
buprenophine
- opioid
- partial agonist
- reduced abuse potential
- withdrawals not bad
nalorphine
- opioid
- delta, kappa partial agonist
- some analgesia, low abuse potnetial
- depression
pentazocine
- opioid
- combines mu antagonism and kappa agonist
tramadol
- opioid
- weak mu agonist
- weak inhibitor of monoamine reuptake
naloxone
- 1st opioid discovered
- competitive antagonist of all 3 opioid receptors
- little effect if given alone, can reverse all affects of full agonists
- used to treat respiratory depression in overdoses
how do you treat status epilepticus
Benzos: lorazepam, midazolam, diazepam
Na+ channel blockers and what for?
epilepsy
- phenytoin
- carbamazepine
- lamotrigine
Phenytoin
Na+ channel blocker
stabilises Na.v channels in inactivated state
effective in tonic clonic and partial
worsens absence and myoclonic
Side effects of phenytoin
teratogenic, risk of lupus, cerebellar atrophy, acne, gingival overgrowth
Carbamazepine
- blocks Na+
- first line for focal
- mood stabiliser, used for neuropathic pain
- also induces CYP3A4
Carbamazepine side effects
teratogenic
risk of lupus
worsens juvenile epilepsy
Lamotrigine
- anti-convulsant
- sedation
- sleep distrubances
- rash
Lamotrigine
- Na+ channel blocker
- 1st line treatment for tonic-clonic!
- 2nd line for absence
- can worsen myoclonic
- used to treat bipolar
Which benzodiazepines act on GABAA receptors in epilepsy
Clobazam - adjunct, treats anxiety
Clonazepam - refractory epilepsy, acts on Ca2+
Diazepam - status epilepticus
Tiagabine
- Anti-convulsant
- GAT1 inhibitor
- Side effects = sedation, dizziness
Vigabatrin
- Anti-convulsant
- irreversible GABAr inhibitor
- Sabril
- Adjuvant medication
- short plasma half life, once daily is okay
side effects = visual disturbances, teraogenic
Sodium valproate
- Anti-convulsant
- extremely useful, bad side effects
- 1st line treatment but don’t know its mechanism
- also used for bipolar
- bad teratogenic
Side effects of sodium valproate
- liver toxicity
- powerful teratogen
- autistic disorders, anencephaly, spina bifida, limb defects
- cognitive changes
- foetal valproate syndrome
Example of gabapentinoids
Gabapentin/pregabalin
What does gabapentin do
- anti-convulsants
- similar structure to GABA
- acts on a2d subunit of Ca channel
- increases GAD levels too
- street drugs now - gabbies
Ca2+ channel blockers
Ethosuximide, topiramate
Ethosuximide
- anti-convulsant
- Ca2+ blocker
- 1st choice for absence
- can worsen others
- side effects = sedation, nausea
Levetiracetam
- anti-convulsant
- adjunct for focal
- mechanism unknown
- reduces NT release
- focal, myoclonic and tonic-clonic
- stevens-johnson syndrome
Topiramate
- anti-convulsant
- adjunct for focal
- potentiation of GABAa
- blocks AMPA and kainate
- blocks Na and Ca channels
- inhibits carbonic anhydrase
Old monoamine oxidase inhibitor drugs
Phenelzine, tranylcypromine, isocarboxazid
Very effective in MDD and bipolar
cause cheese reaction
Newer monoamine oxidase inhibitors
molobemide
reversible, no dietary reactions
fewer adverse effects
SSRIs
fluoxetine
citalopram, paroxetinem sertraline
SNRIs
venlafaxine, duloxetine
NRIs
reboxetine, atomoxetine
Tricylic anti-depressants
amitryptiline, nortriptyline, imipramine
What does mirtazapine do
- noradrenergic and specific serotonergic antidepressant (NaSSA)- acts on receptors rather than reuptake system
- antagonist of a2 adrenoreceptors and 5HT2A receptors
- highly sedating (H2)
- faster onset than other anti-depressants
newer treatments of MDD
esketamine and ketamine
psychedelics
agomelatine
bipolar treatments
mood stabilisers
- lithium
- anticonvulsants (lamotrigine, valproate)
- olanzipine
1st line treatments for schizophreniza
Risperidone, olanzapine, quetiapine
What does chlorpromazine do
- old anti-psychotic
- also used for huntingtin’s
- first effective psychotic
- side-effects - sedative, galactorrhea
Aripiprazole
- anti-psychotic
- partial D2 agonist
- 3rd gen
- benign side effects
Risperidone
- 2nd gen anti-psychotic
- moderate risk of EPS and can cause sedation and weight gain
- galactorrhea
Haloperidol
- anti-psychotic
- antiemetic and tourette’s too
- lower sedative effects, higher risk of EPSP
Clozapine
- anti-psychotic
- useful for treatment-resistant patients
- agranulocytosis (WBC death)
Barbiturates
- many derivatives
- -barbital suffix
- historically widely used as anxiolytics, anticonvulsants, sedatives, anaesthetic
- fallen out of favour due to danger of OD
Barbiturate mechanism of action
- positive allosteric modulator of GABAA receptor
- at higher concentrations can directly activate the receptor
- inhibit AMPA
Current uses for barbiturates
medically - thiopental. induction agent in general anaesthesia
criminal justice - lethal injections. sodium thiopental
Name four benzodiazepine agonists
- Flunitrazepam
- Diazepam
- Tamazepam
- Nitrazepam
Highly addictive, increase GABAa receptor opening
What are examples of benzodiazepine inverse agonist
- proconvulsants
- anxiogenics
Clinical uses for benzodiazepines
used to be 1st line treatments for anxiety and sleep disorders, due to tolerance and dependence issue they are used less now
what drugs were identified in the 90s with the aim of treating anxiety without the sedative effects
Bretazenil, Alpidem and ocinaplon
