lecture 9 Flashcards
(57 cards)
Excitatory Ion Channel Synapses
More likely to cause a signal to happen
The neurotransmitter at excitatory synapses depolarizes the postsynaptic membrane of a neuron.
These synapses have neuroreceptors that are SODIUM CHANNELS
When the channels open, positive ions flow in, causing a local DEPOLARIZATION and making an action potential more likely.
Typical neurotransmitters are ACETYLCHOLINE, GLUTAMATE, ASPARATE, or CATECHOLAMINES (dopamine, etc) .
*SODIUM IS POSITIVE
(SEE IMAGE)
Inhibitory Ion Channel Synapses
More likely to stop a signal from happening
The neurotransmitter at inhibitory synapses HYPERPOLARIZES the postsynaptic membrane.
These synapses have neuroreceptors that are CHLORIDE CHANNELS.
When the channels open, negative ions flow in causing a local hyperpolarisation and MAKING ACTION POTENTIAL LESS LIKELY
Example: GAMMA AMINOBUTYRIC ACID (GABA) and GLYCINE
*Ex. increase GABA for epilepsy
**CHLORIDE IS NEGATIVE
Non Channel Synapses
These synapses have neuroreceptors that are not channels but MEMBRANE-BOUND ENZYMES. When activated by the neurotransmitter, they catalyse the production of a “messenger chemical” inside the cell.
Neuromuscular Junctions (synapse)
These are the synapses formed between MOTOR NEURONS AND MUSCLE CELLS.
They always use the neurotransmitter ACETYLCHOLINE and are always EXCITATORY.
Electrical Synapses
In these synapses the membranes of the two cells actually TOUCH, and they share proteins.
This allows the action potential to pass directly from one membrane to the next.
They are very FAST, but are quite RARE, found only in the HEART and the EYE.
How drugs work on the nervous system (IMPORTANT TO KNOW THIS)
(MUST SEE IMAGE AND UNDERSTAND… SUPER IMPORTANT!!!)
Types of neurotransmitter receptors
- Adrenergic
- Dopaminergic
- GABAergic
- Glutaminergic
- Histaminergic
- Cholinergic
- Opioid
- Serotonergic
- Glycinergic
Attention-deficit disorder and Attention-deficit/hyperactivity disorder (ADHD)
inattentiveness and impulsive actions often causing problems at work, at home and with relationships.
Hard to get organized, control their behavior, remember details or listen to instructions.
ADHD causes/mechanisms
NEUROTRANSMITTER DYSREGULATION
- Excess dopamine reuptake, decreased dopamine availability
- Reduced norepinephrine levels
- STIMULANTS will increase these 2 neurotransmitters
Lower serotonin levels may contribute as well.
PREFROTNAL CORTEX DYSFUNCTION
- The prefrontal cortex which controls executive functions like attention, planning and impulse control is less active in the ADHD brain.
DEFICIENT REWARD SYSTEM (Motivation deficit)
- The mesolimbic dopamine pathway is underactive, leading to lower sensitivity to rewards
INCREASED CORTISOL AND STRESS SENSITIVITY Increased cortisol and stress sensitivity
- Many ADHD brains show higher cortisol responses to stress, making emotional regulation more difficult
- May contribute to higher anxiety and emotional reactivitY
CNS Stimulants
medicines that speed up physical and mental processes. They are used to treat attention-deficit hyperactivity disorder (ADHD), narcolepsy, and other disorders of the central nervous system.
While the effects caused by CNS stimulants are dramatic, the therapeutic usefulness of these medications is limited due to their side effects.
They increase energy, improve attention and alertness, and elevate blood pressure, heart rate and respiratory rate. They decrease the need for sleep, reduce appetite, improve confidence and concentration, and lessen inhibitions.
The exact mechanism of action is not clear, but it may involve stimulating the cerebral cortex and INCREASING THE ACTIVITY OF NOREPINEPHRINE, DOPAMINE, and other catecholamines in the prefrontal cortex, which control attention and impulse regulation.
ADHD: mechanism of action
Stimulants are commonly used to treat ADHD
Methylphenidate
Acts by blocking the dopamine transporter and norepinephrine reuptake transporter, leading to increased concentrations of dopamine and norepinephrine
More norepinephrine based effect, better for inattention
Amphetamine
Blocks dopamine and norepinephrine reuptake
Promotes dopamine release
Caffeine
Blocks ADENOSINE receptors in the brain, promoting alertness and wakefulness;
ANTAGONIZING the naturally occurring “sleep-promoting” effects of adenosine, leading to a STIMULATING effect.
Stimulants –mechanism of action
AT HIGH DOSES, AMPHETAMINE increases the concentration of dopamine in the synaptic cleft in 4 ways:
- BINDING TO THE PRE-SYNAPTIC MEMBRANE OF DOPAMINERGIC NEURONES and inducing the release of dopamine from the nerve terminal;
- INTERACTION WITH DOPAMINE CONTAINING SYNAPTIC VESICLES, releasing free dopamine into the nerve terminal;
- BINDING TO MONOAMINE OXIDASE IN DOPAMINERGIC NEURONES and preventing the degradation of dopamine, leaving free dopamine in the nerve terminal; and
- BINDING TO THE DOPAMINE RE-UPTAKE TRANSPORTER, causing it to act in reverse and transport free dopamine out of the nerve terminal.
(SEE DIAGRAM!!)
CNS Stimulants: Adverse Effects
Common: headache, palpitations, cardiac dysrhythmias, hypertension, nervousness, nausea
Highly addictive and widely abused outside therapeutic therapy (especially methamphetamine)
(It’s a stimulant.)
Non-stimulant medications for ADHD
They use different active ingredients that have similar effects on the symptoms of ADHD, though they’re not as effective as stimulants.
Non-stimulant medications don’t have potential for abuse
There are several reasons why a doctor might recommend a nonstimulant medication for ADHD.
Stimulant medications didn’t work.
Stimulant medications had intolerable side effects.
A child with ADHD might have another disorder as well.
Stimulants could be risky for a teenager with substance-use problems or a history of drug use.
Nonstimulant medications fit into two different categories based on how they affect the brain:
NOREPINEPHRINE MODULATORS
(Ex. Atomoxetine (Strattera), and Viloxazine (Qelbree).
ALPHA AGONISTS
(Ex, Clonidine (Catapres, Kapvay) and Guanfacine (Tenex, Intuniv)
!!2 mechanisms
Stops reabsorbed (so they stay)
Promotes release (so more is secreted)
Atomoxetine (Strattera)
works by boosting the amount of norepinephrine which facilitates better signaling between nerves and areas of the brain.
It does that by blocking the removal of norepinephrine (SNRIs, SELECTIVE NOREPINEPHRINE REUPTAKE INHIBITORS)
(SEE THE MECHANISM IMAGE!!!)
Clonidine (Catapres, Kapvay) and Guanfacine (Tenex, Intuniv)
ALPHA AGONISTS!!
Originally developed to lower high blood pressure, but reclassified as ALPHA 2 ADRENERGIC AGONISTS because they stimulate specific receptors in the brain to trigger the release of norepinephrine.
Reduce hyperactivity and impulsivity
MEDICATIONS TO KNOW FOR ADHD
amphetamine/ dextroamphetamine
atomoxetine
lisdexamfetamine
methylphenidate
Vyvanse – stronger dopamine effect – better for motivation and impulse control
Anxiety
A common disorder defined as a persistent and irrational fear of specific objects, activities or situations.
Most common psychiatric disorder.
May be accompanied with stress or depression.
Has both psychological and physical components.
- PSYCHOLOGICAL: fear, apprehension, dread, uneasiness.
PHYSICAL- tachycardia, palpitations, trembling, dry mouth, sweating, weakness, fatigue, shortness of breath.
Respond well to behavior therapy, psychotherapy or medications.
*INCREASED brain activity
Generalized anxiety disorder
To control excessive anxiety that lasts for 6 MONTHS OR MORE
Restlessness, fatigue, muscle tension, nervousness, inability to focus or concentrate, an overwhelming sense of dread and sleep disturbances.
