Exam 1 Lecture 1 Neuro Pharm Flashcards
Astrocytes functions (8)
~Structural ~Metabolic support ~Blood-brain barrier ~Transmitter reuptake and release ~Regulation of ion concentration in the extracellular space (Na and K) ~Modulation of synaptic transmission ~Vasomodulation (neuron controlled) ~Repair of damaged neural tissue
Effects of drugs on neural activity (2 main categories)
~most active at synapse
~generalized increase or decrease in neural excitability (ionic pore blockers)
Effects of drugs on neural activity at the synapse (5)
~Agonist
~Antagonist
~Enhance excitatory or inhibitory transmitter binding to receptor by affinity of the receptor for the transmitter
~Block enzymatic degradation of transmitter
~Block reuptake of transmitters from the synaptic gap
Blood brain barrier is formed by (3)
~Tight junctions between brain capillary endothelial cells versus relatively porous elsewhere
~Astrocytic processes (feet) covering the outer surface of the capillaries
~Active removal of drugs and toxins within CNS
BBB function
designed to protect brain from infectious organisms and toxins
BBB has a ____ and ____ filter (details)
Size and Charge!
~that only molecules that have a molecular weight smaller than 500 Daltons can reliably get through the BBB
~(H2O = 18 Daltons, insulin = 5,000 Daltons)
~98% of all known potential CNS drugs have a molecular weight bigger than 500 daltons so they can’t cross the BBB
BBB: way to get across the BBB (and details)
~Pro-drug
~An inactive precursor of a drug, converted into its active form in the body by normal metabolic processes
~Used in cancer chemotherapy because of toxicity of active agent
~In neuropharmacology - best example is use of L-dopa a precursor of dopamine in Parkinson’s Disease (helps to aid in the rigidity)
Acetylcholine Transmitter System: Anticolinergic Drugs (what is it and the diseases associated with)
~blocks CNS (but also autonomic) cholinergic receptors
~Used to block excitatory action of cholinergic interneurons in the basal ganglia in Parkinson’s disease
Acetylcholine Transmitter System: anticholinesterase inhibitors (what are they and the disease it is associated with)
~Limits the enzymes ability to breakdown acetylcholine in synaptic cleft
~Helps to maintain memory, not regain
~The brain will atrophy in Alzheimer’s; the neuron will stay alive and not atrophy in a perfect world to decrease the effect of Alzheimers (decrease the break down of Ach synaptic cleft)
Norepinephrine transmitter system: what are they
Number of drugs used to block or stimulate adrenergic receptors- cardiac
Norepinephrine transmitter system: when to use them/ the type
~Group of selective serotonin/norepinephrine reuptake blockers- mental illness
~Depletion of NE following blockade of NE reuptake and re-release- Tegretol for seizures (Decreasing in multiple ways)
~Selective NE re-uptake blockers – amphetamines (uppers)
Norepinephrine transmitter system: when they are weak
Weak norepinephrine reuptake blocker activities are common in some tricyclic & atypical-antidepressants
Dopaminergic Transmitter system: principal drug tx
~L-dopa is the principle drug tx for Parkinson’s disease
Dopaminergic Transmitter system: 5 drugs in this system
~L-dopa ~dopamine agonist ~dopamine antagonists ~MAOIs ~catechol-O-methyltransferase inhibitor (COMTIs)
Dopaminergic Transmitter system: dopamine agonist
used in Parkinson’s
Dopaminergic Transmitter system: dopamine antagonist
antipsychotic medication and in bipolar disorder
Dopaminergic Transmitter system: MAOIs
~monoamine oxidase inhibitors
~used as antidressants, but interactions peripherally with tyramine from red wine and aged cheese cause hypertensive crisis when MAO-A was inhibited
Dopaminergic Transmitter system: Catechol-O metylthransferase inhibitors (COMTIs)
~in Parkinson’s disease as an adjunct therapy
~not going to allow the reuptake
Serotonergic Transmitter System: 3 types
~serotonin agonist
~SSRI
~SNRI
Serotonergic Transmitter System: serotonin agonists
for migraine headaches
Serotonergic Transmitter System: SSRI
~selective serotonin reuptake inhibitors
~most commonly used antidepressants
Serotonergic Transmitter System: SNRI
~selective serotonin/norepinephrine reuptake inhibitors
Histamine transmitter system (details)
~antihistamines- H1 receptor blocking agent
~anti-emetic (nausea reducing), anxiolytic (anxiety reducing)
GABA transmitter system: what does GABA stand for?
Gama amino butyric acid
GABA transmitter system: agonists
~treatment of spasticity, being more effective on spasticity of spinal cord injury than cortical injury
~acts to either inhibit the excitability of ventral horn motor neurons or cells that excite motor neurons
GABA transmitter system: increase the affinity of the GABA receptor by _____ (and what drugs)
:by binding to a specific receptor for the drug
~benzodiazepines- used as a minor tranquilizer and anti-anxiety med
~Topamax- actions may involve the blockade of Na channels; used as anti-seizure meds and for migraine headaches
GABA transmitter system: increase GABA levels
~Depakote (divalproex sodium)
~converts to valproic acid which is the active agent
~used as anti-seizure med and for migraine headaches
GABA transmitter system: enhances GABA inhibition
~Gabapentin (Neurotin)- also may act blockade of voltage- dependent Na channels; used as an anti-seizure med and to control the pain of diabetic polyneuropathies
~Phenobarbital- also may act by decreased release of glutamate by blocking Ca++ entry into synaptic terminals; major tranquilizers, sedative, anti-seizure meds
Glutamate transmitter system: 3 meds
~Namenda
~Topamax
~Phenobarbital
Glutamate transmitter system: Namenda
(memantine hydrochloride)
~low to moderate affinity uncompetitive (open channel) NMDA receptor antagonist which binds preferentially to the NMSA receptor-operated cation channels
~used in the treatment of Alzheimer’s disease
Glutamate transmitter system: Topamax
(topiramate)
~may involve the attenuation of kainite-induced response
Glutamate transmitter system: Phenobarbital
~decreased release of glutamate (block Ca++ entry into synaptic terminals)
Drugs that act by mechanisms other than at synapse
~blocks resetting of Na+ channels from inactive to active thus increasing absolute refractory period btw action potential to sleep action potential frequency
~blocking voltage-dependent Na+ channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of the propagation of synaptic impulses
~increases in K+ and Ca++ permeability (conductance)
