Unit 05: Pharmacology Flashcards
what does the CNS include? what does it do?
cerebrum, diencephalon, cerebellum, brainstem and spinal chord
- relays and processes signals received from the PNS; processing results in responses that are formualted and related back to periphery
- responsible for perception (sensory, auditory and visual), wakefulness, language and consciousness
how does communication occur in the CNS
- via neurons
- interneurons communicate within the same brain region and projection neurons have axons that project from one brain region to another
- neurons are organized into cirucits that allow for integration of information from interneurons and projection neurons
- nenurons relates neurotransmitters at synpase of target cells
anatomic organization of the CNS
- CNS has 7 major regions
- cerebral hemispheres, diencephalon (thalamus), cerebellim, midbrain, pons, medulla and spinal chord
- cerebal hemispheres include cerbral cortex, underlying white matter and basal ganglia
- midbrain, pons and medulla makeup the brainstem
- spinal chord is divided into cervical, thoracic, lumbar and sacral segments
what are the categoies of neurotransmitters used in the CNS
- amino acid neurotransmitters (glutemate and GABA)
- monomaine neurotramsitters (derived from decarboxylated aa: dopamine, norep/ep, serotonin)
Acetylcholine (nor aa or monoamine)
what are the primary excitatory and inhibitory neurotransmitters in the CNS
amino acid neutrotransmitters
- acidic amino acid glutamate is primarily excitatory
- GABA is primarily inhibitory
-
where is glutamate released from adn what does it act on?
- released from relay neurons throughout the CNS and acts on NMDA and non NMDA receptors
what are NMDA receptors
sub type of glutamate receptor that are ion channels
-when activted permit the influx of Ca2+, Na+ and efflux of K+
*hallucinogenic drugs like pencyclidine (PCP) inhibit NMDA receptors
where is GABA located and what does it act on
- located throughout the CNS and is associated with behaviour
- acts on postsynpatic GABA receptors such as GABAA - an ion channel that inc Cl- influx and GABAB - a G protein linked ion channel that inc efflux of K+
- GABAA receptor is the target for sedative hypnotics
where deos norepinephrine act adn what deos it do there
- located thoguhout the CNS and is very important in awarenes, arousal and autonomic control
- if NE bind to adrenergic receptors α1 and β1, then the effects are excitatory
- fi binds to the α2 and β2 receptors, the effects are inhibitory.
NE is synthesized from
dopamine
what does dopamine do
affect complex processes like mood, attentiveness and empotion
- this neurotransmitter system is the therapeutic target for a number of important CNS disorders: parkinsons and schizophrenia
what are dopamine receptors
- 5 subtypes - linked to G protein messanger system
- subtypes broken down into 2 families: D1 class which elads to increased cAMP and D2 class which leads to cAMP inhibition
describe serotonin
- also called 5hydroxytryptamine
- another monoamine neurotransmitter
- found in nerve terminals of neurons that have their cell bodies in the midbrain and brain stem and axons projecting throughout the brain
- plays role in behaviour, control of sleep, temperature, appetite and various neuroendocrine functions
how many different members are there in the 5-HT family, what types of receptors are they
- 7 members with diff subtypes
- all 5 HT receptors are linked to G-rptoein sceond messanger systems excpet for 5-HT3 which is ligand gated ion channel
- therea re more than 12 subtypes of 5-HT receptors that have both excitatory and inhibitory actions
ex: MOA of 5-HT1A is inhibitory, decreasing cellular levels of cAMP while 5-HT2A is excitatroy, inc levels of DAG and IP3
describe acetyl choline
In the CNS, acetylcholine acts as a diffuse system neurotransmitter.
Like the monoamines- its thought to regulate sleep and wakefulness. I
interneurons that release acetylcholine are associated with motor control
- projection neurons that release acetylcholine associated with learning, memory and cognition
- those are lost in Alzheimer disease which results in the symptoms observed.
Acetylcholine acts on many subtypes of muscarinic and nicotinic receptors.
what are drugs of the CNS limited by
blood brain barrier
- consists of endothelial cells and astrocytes
- astrocytes support cells in the CNS and endothelial cells form tight junctions in the CNS blood vessels and are different fromt he endothelial cells of other vessels in the body
- some drugs cant pass thorugh or between the BBB
- transport occurs primarily via passive diffusion - diffusion dependent on drug lipid solubility and pKa
what are neurodegenerative disorders
- progresive loss of a specific popualtion of neurons that lead to diff symptoms
- no cures available for these disorders but drugs can hep to alleviate symptoms
- with severe neuron loss, some drugs are no longer effective at treating symptoms
ex: alzheimers and parkinsons
what are the 2 types of alzheimers disease
familial easy onset - caused by genetic mutations and accounts for 5-10% of cases
- sporatic late osnet which has an unknown cause and accounts for 90-95%
what is memory loss and cognitive ipmairment from alzheimers caused by
- cholinergic neurons, specifically degeneration of cholinergic input to the hippocampus (memory) and cortex (cognitive)
- in AD progressive loss of sholinergic neurons in the basal forebrain projecting to the hippocampus and cortex results in symptoms previously mentioned
what anatomical cahnges occur in individuals with AD
- disease can be confirmed by neurofibrillary tangles and amyloid plaques present in hippocampus and cortex
- tangles represent intracellular accumulations of twisted fibers of phosphorylated tau protein
- plaques are extracellular deposits of beta-amyloid protein
what to approved treatments for AD aim to do?
restore neuron communication and imporve symptoms
what is Donepezil
acetylcholinesterase inhibtor used to treat AD
- easily enters the CNS and inhibts breakdown of acetylcholine
- effective tratment for mild to moderae AD when sufficient cholinergic neruons are still present
side effects: mainly autonomic and similar to AChE inhibitors
what is parkinsonsism
- daignosed based on medical histroy and neurological examination - symptoms are caused by degenerative depaminergic neurons at basal ganglic
- neuron loss is irreversible
what do therapeturic strategies aim to do for treatment of parkinsons
- aim to correct the imblanace of dopamine and acetylcholine activity in basal ganglia
- drugs that increase dopamine activity or decrease muscarinic receprot activation (or both) are desirable
treatment for parkinsonism
depamine agonists: levodopa and repinrole
monoamine oxidase inhibitors: selegiline and deprenyl
antimuscarinic drugs: benztropine
what are the two principal pathways in the basal ganglia that regualte movement and how does dopamine effect them
- two principle pathways = indirect pathway which inhibits morement and direct with enables movement
- dopamine inhibits indirect pathway and stimualtes direct pathway
*net bias allowing for purposeful movemnt
*excitatory pathway shown in blue and inhibitory in black
what does the direct and indirect dopaminergic pathways signal
- direct pathway signals from the putamen to HPi to thalamus to the cortex
- indirect pathway signals from putamen to GPe to STN to GPt to thalamus to cortex
*GPi = internal segment of the globus pallidus
GPe = external segnemnt of the globus pallidus
SNc = substantia nigra pars compacta
SNr = substantia nigra pars reticulate
STN = subthalmis nucleus
descibe onset of parkinsons
normally both direct and indirect pathways in putamen receive inputs from the nigrostriatal dopaminergic system (dotted blue arrow) and from cortical glutamatergic systems (solid blue arrow)
- inputs are processed in contect of local cholinergic influences and transmit GABAergic output
- Gegeneration of dopaminergic neurons in substantia bigra causes understimulation of the direct (movement enabling) pathway and underinhibtion of indirect (movement inhibiting pathway)
*net result = paucity of movement - dotted grey arrow indicated decreased activity caused by understimulation and thick black indicates increased activity caused by underinhibition
