🖋️ Interactive Notes: Overview of Neuropharm | NSB

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Parkinson's Disease

Parkinson’s Disease is a hypokinetic neurological disorder that leads to the degeneration of the substantia nigra pars compacta

so less dopamine is produced for the basal ganglia

💊L-DOPA- synthetic dopamine

💊Ropinirole– D2 receptor agonist

💊Apomorphine– D1 and D2 receptor agonist

💊Amantadine– blocks dopamine reuptake channel

💊Domperidone– D2 antagonist (stops nausea and vomiting by preventing dopamine activating the chemoreceptor trigger zone.

💊 Selegiline + Entacopone– drugs that allow dopamine to remain
in high quantities in the CNS, without being further
converted to other products

💊Carbidopa– dopa-decarboxylase inhibitor (prevents
dopamine leaving the CNS to the PNS)

Anxiety & Sleep Disorders

OCD, PTSD, phobias, panic, social anxiety, generalised anxiety disorders
(due to increased glutaminergic activity (treat by increasing GABA activity)

💊 Benzodiazepines (“-lam/-pam”)

  • GABAa agonists. open Cl- channels more frequently for more hyperpolarisation.
    (bind at the alpha-gamma junction on the GABA channel)
  • Good for sedative, muscle relaxant, amnesia (surgeries)

    4 Hours: Midazolam
    15 Hours: lorazepam, oxazepam, temazepam
    24 Hours: alprazolam, nitrazepam
    48 Hours: chlordiazepoxide (lithium) diazepam (valium)
    60 Hours: clonazepam, flurazepam

  • Side Effects: confusion, drowsiness, tolerance, dependence (tremor), respiratory depression 🫁 with alcohol

(Flumazenil- used in BDZ overdose)

💊 Buspirone- for general anxiety. (5HT agonist)

💊 Barbiturates:
cause respiratory depression

  • thiopental- anaesthetic
  • phenobarbitone- epilepsy

 

💊Sleep:
antihistamines (H1), nytol, valerenic acid (valarion extract)
chlormethiazole- for elderly as no hang-over effect
Insomnia: transient -> intermediate -> chronic

😴 Z-drugs: (zzzz for sleep)
Zolpidem, zopiclone (REM deficiency)

Anaesthetics 😴

General Anaesthetics enhance GABA (inhibitory = sleepy) receptors, apart from NOx which acts on NMDA (glutamate-R)

💊Local anaesthetics (“-caine”) work by blocking Na+ channels to stop pain action potentials

Amide Types:

  • (‘i’ before the “-caine”)
  • Lidocaine, Prilocaine
  • metabolised in liver

Ester Types:

  • (no ‘i’ before the “-caine”)
  • procaine, tetracaine
  • metabolised in blood

💊General Anaesthetics (“-caine”) (drug induced reversible loss of consciousness)

 Inhaled- (maintain anaesthetic):

  • isoflurane, desflurane – GABA
  • nitrous oxide, xenon, ketamine
    • block NMDA (non-competitive), so Ca2+ cannot carry the pain signals to the post-synaptic neurone
 Intravenous (induce anaesthesia) 
  • thiopentone, propofol, etomidate
    • keep GABAa open for hyperpolarisation of post-synaptic neuron

Huntington's Disease

Huntington’s Disease occurs due to degeneration of the indirect pathway & overstimulation of dopamine receptors which cause hyperkinetic movement

💊Tetrabenazine- dopamine depletion (inhibit nigrostriatal pathway)

💊Restless leg – ropinirole (D2 agonist – desensitise to movement)

💊Tourettes – haloperidol (D2 antagonist)

Parasympathetic Nervous System

Parasympathetic nervous system works on muscarinic (Ach) receptors

Muscarinic Agonist

💊 Pilocarpine (used in glaucoma – increases trabecular outflow)

Muscarinic Antagonist

💊 atropine
💊 tropicamide

Epilepsy

  • Epileptic Seizure- a seizure resulting from epilepsy (excess activity of
    neurones in the brain)
  • Epileptic Disorder- chronic neurological condition characterised by
    recurrent epileptic seizures
  • Seizure- sudden, short event involving a change in a person’s awareness of
    where they are or what they are doing, their behaviour or feelings.
  • Status Epilepticus = seizure longer than 5 minutes (treat with lorazepam)

 

To treat epilepsy, need to dampen neuronal hyperexcitability (reduce
excitation/ increase inhibitory influences)

  • a ketogenic diet may help children who have epilepsy

💊  Na+ channel blockers: carbamazepine, phenytoin, valproate, lamotrigine
💊  Ca2+ channel blockers: ethosuximide, gapapentine
💊  GABA breakdown inhibitors: valproate, vigabatrin (keeps GABA working to hyperpolarise cells)
💊 GABAa modulator: benzodiazepines
💊 NMDA antagonist: felbamate
💊 AMPA antagonist: perampanel
💊 Vesicle depletion: levetiracetam (reduce glutamate release)
💊 GABA reuptake blocks: tiagabine (also used for anxiety)

unipolar depression & bipolar

 

Characterised by:

  • Dysphoria (low mood)
  • Anhedonia (lack of positive feelings)

Can be treated with:

  • Electroconvulsion Therapy- non-responsive depression (controversial therapy due to misuse histroically)
  • Lithium and ketamine 

💊 Tricyclic Antidepressants (TCAs):

  • imipramine, amitriptyline, clomipramine
  • block 5HT and noradrenaline (NA) reuptake transporters
  • 2-3 weeks to take effect
  • not a very selective drug
  • Cardiotoxic

 

 💊 Selective Serotonin Reuptake Inhibitors (SSRIs):

  • sertraline, fluoxetine, citalopram
  • blocks 5HT reuptake transprters (SERT) (safe in overdose)

 

💊 Selective Noradrenaline Reuptake Inhibitors (SNRIs):

  • venlafaxine, maprotiline
  • blocks NA reuptake transporters (NET)

 

💊 Monoamine Oxidase Inhibitors (MAOIs):

  • phenelzine
  • inhibit MAO, so monoamines can remain in high quantities in the synapse
  • Side effect: Cheese Reaction- consuming foods with high tyramine

neuromuscular junction (NMJ)

Pain

Pain can either be

  • Inflammatory – as a result of tissue damage 🙁
  • Neuropathic – pain neurones being overactive (this pain tends to be chronic)

🔥 Inflammatory pain

NSAIDS

  • Aspirin (COX-1 inhibitor)
  • ibuprofen (COX-1 inhibitor)
  • diclofenac (COX-2 inhibitor)

Steroids (SAIDS)

  • hydrocortisol, cortisone
    • (block conversion of phospholipids to arachidonic acid)

Triptans

  • sumatriptan (‘-triptan” used for headaches and migraine
    • inhibit 5HT receptors vasodilation

 

⚡ Neuropathic Pain

  • Na+ channel blockers- carbamazepine
  • Ca2+ channel blockers- gabapentin, pregabalin
  • NMDA blockers-
  • ketamine (extreme pain)
  • antidepressants

 

Opiates

  • Mu, delta, kappa receptors.
    • Mu- opiates
      • Mu receptors- morphine, codeine, fentanyl (mimics endorphin,
        opens K+ channels, hyperpolarising the post-synaptic neurone,
        so pain signal cannot continue)
    • delta- enkephalins
    • kappa- dynorphin

 

💊 naloxone- opiate antagonist (give for overdose)

Others:

Paracetamol. (in overdose, treat with activated charcoal in first
hour, then use acetylcysteine) (can lead to hepatotoxicity)

Anti-pyschotics

Schizophrenia- excess dopamine (so give dopamine antagonists). Leads to positive (auditory/visual hallucinations)  and negative symptoms (withdrawal, lack of pleasure)

 Typical Antipsychotics:

  • chlorpromazine (aplastic anaemia)
  • flupenthixol
  • haloperidol
  • D2 antagonists, targets positive symptoms
  • Side effects: movement disorders (extrapyramidal symptoms), hyperprolactinaemia

Atypical Antipsychotics: (first-line)

  • clozapine (agranulocytosis)
  • risperidone
  • olanzapine
  • D2 and 5HT antagonists, targets positive and negative symptoms
  • same side effects as typical antipsychotics, but less severe, + weight gain

Aripiprazole: (third generation)

  • D2 agonist,
  • 5HT1a agonist, 5HT2a antagonist
  • targets positive and negative symptoms and hallucinations
  • side effects: weight gain, hyperprolactinaemia. Much less EPS side effects 🙂

Neuropharm, NMJ, P450