Lean Jonker 31668577 (SU 8)

Which two main groups of drugs are important in the treatment of Parkinsonism?

• Drugs that increase Dopamine’s Activity
• Drugs that decrease cholinergic activity

In what way does amantadine act as an anti-parkinsonism drug?

3 ways of action

• Metaffinoid potentiator of Dopamine (Increase Dopamine release and Syntheis & Blocks the reuptake of DA)
• NDA Antagonist
• Adenosine A2 Antagonist

Discuss the mechanisms of action of the anti-parkinsonism drugs that indirectly increase dopamine concentration.

L-DOPA (Increased L-DOPA causes an increase in dopamine synthesis causing a increase in dopamine that is available in the body) Needs to be used in combination with CARBIDOPA or BENSERAZIDE

AMABTADINE (See above question)

RASAGILINE & SELEGILINE  & SAFINAMIDE (MAO-B inhibiter, thus prevents the breakdown of breakdown of dopamine to DOPAC)

ISTRADEFYLIN (Adenosine A2 Antagonist)

ENTACAPONE (COMT-Inhibitor, thus prevent the breakdown of Dopamine to 3-MT)

Which of the dopamine agonists are ergot derivatives and which are not?

List the specific dopamine receptors that are stimulated by each agonist.

Bromocriptine – D2

Pramipexole -D3

Ropinirole-D2

Which of these drugs are classified as neuron protecting drugs?  What does this mean?

Pramipexole, it means that the drug counteracts the degenerative effect of Parkinson’s Syndrome. Thus, protecting the brain neurons from further damage.

What is the importance of monoamine oxidase B (MAO-B) selective drugs in the treatment of Parkinsonism?

The antagonist of inhibitory drugs for MAO-B would prevent the metabolism of Dopamine, thus increasing DA’s plasma levels and Bioavailability. This will also in effect reduce the side effect seen due to PD.

How do the COMT-inhibitors act in Parkinsonism?

In Much the same way is MOA-B initiators, the inhibit the action of COMT leading to a decrease in 3-OMD (a metabolite of dopamine that competes for active transport from the periphery to the brain via the BBB). This lead to an increase influx of L-DOPA into the brain thus a increase in Dopamine plasma levels in the brain.

How does istradephyline act?

It is an Adenosine A2-A Antagonist. A blockage of adenosine receptors causes an increase in Dopamine’s activity.

Discuss the MOA of safinamide

• MAO-B inhibition
• Dopamine reuptake inhibition presynaptic ally
• Decrease in Glutamate release.

Lean Jonker 31668577

Which drugs are used in chronic muscle spasm?

• Baclofen
• Diazepam
• Tizanidine
• Dantrolene
• Botulinum toxin
• Gabapentin
• Pregabalin

Which drugs are used in acute spasm?

• Methocarbamol
• Orphenadrine
• Mephenesin
• Cyclobenzaprine
• Metaxalone

Name and discuss the mechanisms of action of the drugs with an effect in the spinal cord.

3 drugs work in on the spinal cord. (BDT Brain Down To – Botton Part of Brain AKA the Spinal cord).

Baclofen

• Works in both Pre and Post Synoptically.
• Pre: Works in on the GABA-B receptor. Decreasing Glutamate release.
• Post: Facilitates the GABA-B inhibition effect.

Diazepam

• Post Synoptically Facilitates the GABA-A inhibition effect.

Tizanidine

• Pre-Synapse Alpha 2 antagonist effect.
• Leading to a decrease in glutamate release.

What is dantrolene, what is its mechanism of action and what is it used for?

                Dantrolene is a direct acting skeletal muscle relaxant.

It Work in the Skeletal Muscles’ sarcoplasmic reticulum (SR) causing a decrease in activator Ca+ release.

It is used in the treatment of Malignant Hyperthermia (a very

high temperature, tachycardia, tachypnoea, increased carbon dioxide

production, acidosis, rigid muscles, and rhabdomyolysis.)

In which of the drugs is sedation a side effect?

• Diazepam (Most)
• Baclofen (Less)
• Dantrolene (More Less)

What is the mechanism of action of methocarbamol and what is it indicated for?

Used to treat acute muscle spasm caused by spinal injury

It woks via inhibition of acetylcholinesterase at synapses in the autonomic nervous system

Use your SAMF, a MIMS or any other relevant source and list the preparations available in South Africa for the treatment of chronic and acute muscle spasm.

• Baclofen
• Orphenadrine
• Methocarbamol

-MIMS

Blog Summary

Which types of ion channels are found on the nerve cell membranes?

1. Voltage gated ion channels
2. Ligand gated ion channels
3. Metabotropic receptors

Name 3 differences between voltage-gated and ligand-gated ion channels.

Compare ionotropic and metabotropic receptors.

Ionotropic: The onset of the desired affects is very fast but only last for a short period of time. The ion tropic has an effect on ion channels. Specifically, the opening there of, this opening will lead to an Inhibiting or Activation of the post synaptic potential leading to an activation or deactivation effect.

Metabotropic: This has a much slower onset of time, but the effect is longer lasting. It involves the use of G-Proteins resulting in the creation of second messangers.2 Main system are present (Adenylyl cyclase & Phospholipase C)

Classify the CNS receptors into ionotropic and metabotropic and know the transduction mechanism of each receptor.

Explain the difference between an EPSP and an IPSP and give examples of each

EPSP: Excitatory Post synaptic Potential, This causes an increase in cation permeability

IPSP: Inhibitory post synaptic Potential Prevent the EPSP to great an action potential under resting conditions.

What is the role of calcium in the development of a synaptic potential?

Ca2+ triggers synaptic vesicle exocytosis, thereby releasing the neurotransmitters contained in the vesicles and initiating synaptic transmission.