Clinical pharmacology of the CNS drugs Flashcards
What is a neurotransmitter
Endogenous chemicals that enables neurotransmittion
*They transmit chemical signals from one neuron to another , glad or muscle
Types of neurotransmitters ?
6 classes
*Class> Example >Deficiency
Amino acids > Gaba> Huntingtons / epilepsy
Monoamines > Dopamine, seritonin, NE > DA; Parkinson s disease ,NE : Depression , Serotonin : Depression
peptides > Somatostatin , substance P > metabolic syndrome
Purines > ATP > Myopathies
Gaso-transmiters > NO> Cardiovascular disease
Others >ACh > Alzeimers disease
Function of BBB
To prevent delivery of large molecules and drugs into the CNS
Discuss the pharmacotherapy of the CNS
How are drugs used in the CNS
*Most drugs affect the CNS by altering some step in the neurotransmission process
Drugs act by
1. Act presynaptically ( by influencing the production, storage, release, reuptake, or termination of action of neurotransmitters )
- Activate (agonistic) or block (antagonistic ) postsynaptic receptors
Acetyl Choline synthesis ,storage ,release and effect
- Synthesis of ACh: Choline acetyltransferase catalyzes the synthesis of ACh from choline and acetyl-CoaA
- Uptake into vesicle : ACh is then protected from degradation in the vesicle
- Release of ACh : Release is blocked by botulinum toxins
Spider Venum causes the release of ACh
- Binding to receptor: Postsynaptic receptor (nicotinic/muscarinic) is activated by ACh binding
- Degradation of ACh: ACh is rapidly degraded by ACh-esterase in the synaptic cleft
- Recycling of choline: Choline is transported back to neuron this transport can be blocked by hemicholinium
Deficiency of ACh = Alzheimer’s disease
*The progressive loss of cholinergic neurons has been linked to loss of memory
Hallmark of Alzheimer’s disease: Loss of memory loss
*Inhibition of ACh-esterase within the CNS will improve the cholinergic transmission for the neurons that are still functioning
*Reversible ACh-esterase inhibitors for treatment are: Rivastigmine, galantamine
NE lifecycle
1.Synthesis: Hydroxylation of tyrosine is the rate-limiting step
- Uptake and storage: Dopamine enters a vesicle and it is transformed into NE
* NE is protected from degradation in the vesicle
* Transport of NE into transport is inhibited by reserpine + guanethidine - Release of NE: Influx of Ca2+ causes fusion of the vesicle with the membrane in the process known as exocytosis
- Binding to the receptors: Postsynaptic receptor is activated by NE
- Removal of NE: ReleasedNE is removed from the synaptic cleft
- Metabolism: NE is methylated by COMT and oxidized MAO
Moods and depression disorders
Sushi Rice = flour ,sushi and egg plant
Nost antidepressants drugs potentiate either directly or indirectly the actions of NE or ST in the brain
Monoamine hypothesis: Depression is due to a deficiency of monoamines such as ST NE at key sites in the CNS
Drugs :
SSRI,s : Fluoxetine ,Sertraline , Escitalopram
SNRI : Venlafaxine
Tricyclic antidepressant: Amitriptyline, Imipramine
Dopamine deficiency
Parkinsons disease: A progressive disorder of the CNS marked by tremor, muscular rigidity, and imprecise movement
- It is associated with degeneration of the basal ganglia of the brain and deficiency of DE and ACh
- There are agents that relieve the symptoms but do not arrest the neural degeneration
Treatment of dopamine
The precursor of dopamine : levodopa ( DA precursor ) and Carbidopa( DA decarboxylase inhibitor )
DA agonist : ERGOT DERIVATIVES ( Bromocriptine ) nad a non ergot derivative : Ropinirole
MOA inhibitor: Selegiline, rasagiline
COMT inhibitors: Entacapone
Antiviral: Amantadine
Anticholinergic: Benzhexol
Epilepsy :
A neurological disorder characterized by the spontaneous recurrence of 2 / more seizures which are a result of synchronous discharge of neural activity and result in a range of behavioral symptoms
Antiepileptics
Drugs reduce seizures through different mechanisms
- Blocking voltage-gated channels ( Ca2+, Na 2+)
- Enhancing GABA impulses
- Interfering with the excitatory glutamate transmission
antiepileptics stop the seizures but do not cure or prevent epilepsy
Class> MOA> Adverse effects
Benzodiazepine > Potentiate GABA receptors > double vision
Carbamazepine > blocks sodium chaneels > renal impairement
