Module 2- Introduction to nervous system Flashcards
Introduction to nervous system
The Nervous System is the body’s…
control and communication system
The NS consists of…
brain, spinal cord, sensory organs, nerves
How does the NS function?
- Recognize: changes in internal or external environment
- Process and Integrate: perceives the changes in environment
- React: reacts to changes in the environment by producing a response or an action to counteract the change
Neurons
Functional unit of the brain and are nerve cells capable of generating and transmitting electrical signals
Neurotransmission
Process by which neurons communicate with each other
- electrical impulse travels down axon of a neuron
- when electrical impulse reaches the end of the presynaptic neuron, it causes the vesicles (containing neurotransmitters), to fuse w the presynaptic membrane –> releasing the neurotransmitters into synaptic cleft
- neurotransmitters then diffuse across synaptic cleft and bind w receptors on the post synaptic membrane
- activation of these receptors will cause a change in permeability of the membrane, allowing ions such as calcium to move into post synaptic neuron
- this changes electrical activity of the membrane, thereby generating an action potential or electrical impulse, which will then travel down the neuron’s axon
2 main systems of the nervous system
- CNS- brain and spinal cord
- PNS- contains all nerve fibers outside the CNS
Organization of PNS
- Sensory (afferent)- transmits sensory info from periphery to CNS
- Motor (efferent)- transmits motor controls from CNS to periphery
a. somatic NS - voluntary control
of skeletal muscle
b. Autonomic NS- involuntary
control of cardiac/smooth muscle
i) Parasympathetic- rest/digest
ii) Sympathetic- fight/flight
Autonomic nervous system
controls involuntary responses by influencing organs, glands, and smooth muscle and is often involved in maintaining a stable internal environment
Helps to control processes without conscious effort (i.e. blood pressure, heart rate, bowel movements, urinary output, sweating)
Neurons of ANS
- The first neuron’s cell body is in the CNS
- The second neuron’s cell body is in the ganglia
Preganglionic nerve
The neuron before the ganglia
Postganglionic nerve
The neuron after the ganglia
Parasympathetic NS
“Rest and Digest”- Activated under non-stressful conditions
i.e. pupil constriction, decreased heart rate, increased digestive intestinal activity
Sympathetic NS
“Fight or flight”- activated under conditions of stress
i.e. pupil dilation, increased sweating, increased heart rate, increased blood pressure
Parasympathetic neurons originate from what 2 places on the spinal cord?
- cranial, or brainstem region
- sacral, or bottom, region
All PNS nerve release what neurotransmitter?
Acetylcholine
Within PNS, acetylcholine binds to what 2 receptors
- Nicotinic receptors (Nn)
- Muscarinic receptors (M)
Termination of response
to terminate acetylcholine-mediated response within the PNS, acetylcholinesterase (AchE) breaks down acetylcholine in the synaptic cleft into acetate and choline
How can the PNS be activated
- Drugs can bind to and activate nicotinic receptors
- drugs can bind to and activate muscarinic receptors
- drugs can block the metabolism of acetylcholine (by inhibiting AchE) thereby increasing the concentration of acetylcholine in synaptic cleft
PNS activators
Drugs that stimulate the parasympathetic nervous system produce characteristics of rest and digest
Cholinomimetics
direct and indirect agents that mimic the actions of acetylcholine (at Nn or M receptors)
Clinical use of activators
- Glaucoma- condition where the patient experiences in intraocular pressure due to poor drainage of the fluid in the eye
- muscarinic receptor agonists increases PNS activation, leading to contraction of the ciliary body of the eye - Poor muscle tone in bladder
- admin of muscarinic agonists will cause bladder to contract, allowing patient to urinate
- Asthma- methacholine is a muscarinic agonist, and when inhaled it causes the bronchioles to constrict which inhibits breathing
PNS Inhibitors
Drugs that inhibit the activity of the PNS, and cause the effects of “fight or flight”
Anticholinergic drugs
Most common PNS inhibitors, drugs that antagonize or block M or Nn receptors
Ganglion blocking drugs
Drugs that specifically antagonize or inhibit the Nn receptors found in all autonomic ganglia
Limited clinical use due to broad range of adverse effects
Muscarinic receptor blockers
used much more commonly
Sympathetic neurons originate from which 2 places on the spinal cord
- Thoracic region
- Lumbar region
Organization of SNS
- short preganglionic neurons that release Ach at ganglia
- Ach binds/activates Nn receptors at sympathetic ganglia, conducting the signal to the long postganglionic neurons
- sympathetic postganglionic neurons predominately release norepinephrine at the target organ, which binds to alpha or beta receptors
- exception: the sympathetic postganglionic neurons that innervate sweat glands and renal vascular smooth muscle –> these neurons release ach which binds to M receptors, and dopamine which binds to D receptors
- Axons of SNS are highly branched and therefore influence many organs
The adrenal medulla
specialized organ that functions as a sympathetic autonomic ganglia, located in the centre portion of adrenal gland
What is the adrenal medulla innervated by
short sympathetic preganglionic fibres, when these fibres are activated they release Ach, which binds to Nn receptors on adrenal medulla
- activation of the Nn receptors results in the release of predominately epinephrine and norepinephrine from adrenal medulla
Sympathetic neurotransmitters and receptors
- alpha receptors
a. A1 receptors
b. A2 receptors - beta receptors
a. B1 receptors
b. B2 receptors
Alpha 1 receptors
- Located post-synoptically, predominately on smooth muscle
- Activation leads to contraction of muscle
Alpha 2 receptors
- located post synoptically on smooth muscle and presynoptically on neuronal membrane
- receptors
presynoptically are
autoreceptors - Activation leads to contraction
- activation of a2 autoreceptors leads to a decrease in the release of norepinephrine from presynaptic nerve, decreasing sympathetic activation
Beta 1 receptors
- found predominately in heart and GI muscle
- activation leads to increased force and rate of contraction of the heart, and relaxation of GI smooth muscle
Norepinephrine in SNS
Postganglionic neurons release norepinephrine at the target organ and it binds to alpha or beta-1 receptors in the postsynaptic membrane to exert action
Beta 2 receptors
- found in lungs, blood vessels, GI muscle, and uterus
- activation leads to muscle relaxation
Cholinergic drugs
drugs that stimulate parasympathetic nervous system
- mimics the action of Ach binding to nicotinic or muscarinic receptors
Adrenergic drugs
drugs that stimulate the sympathetic nervous system
- produce organ-specific effects due to receptor subtypes they bind to
Activation of SNS
Drugs acting directly or indirectly on the SNS can mimic the actions of norepinephrine, increasing SNS activity
- direct stimulation- drugs bind directly to receptors and produce an effect
- indirect stimulation- drug increases the release of norepinephrine from presynaptic neuron
- combo of both- drug binds directly to receptor AND increases release of norepinephrine
Clinical indications of Adrenergic drugs
- anaphylaxis
- cardiac applications
- nasal congestion
- ophthalmic
- pulmonary
Clinical indications of antiadrenergic drugs
- pheochromocytoma
- benign prostatic hyperplasia (BPH)
- angina and congestive heart failure
- glaucoma
- neurological diseases
Somatic nervous system
Innervates skeletal muscle, under voluntary control and consists primarily of the muscles of posture and movement
Organization of Somatic Nervous System
voluntary motor nerves extend from the CNS all the way to the skeletal muscle
- at skeletal muscle, the neuron release Ach, which binds to nicotinic receptors on skeletal muscle (Nm)
- receptor activation causes contraction of muscle
Neuromuscular junction
The synapse between a motor neuron and skeletal muscle
- when Nm receptors are activated, they cause muscle to contract
- for them to contract, multiple Nm receptors on the muscle fibre have to be activated at once, causing depolarization of skeletal membrane followed by muscle fibre contraction
Neuromuscular blocking drugs
drugs that target skeletal muscle act by interfering with neurotransmission at the neuromuscular junction
- Non-depolarizing neuromuscular blockers
- depolarizing neuromuscular blockers
Non-depolarizing neuromuscular blockers
- act like competitive antagonists, blocking the Nm receptors, thereby inhibiting the binding of Ach to the receptors
- since less Nm receptors are available for acetylcholine to bind to, the muscle is unable to depolarize and muscle contraction is inhibited
Depolarizing Neuromuscular blockers
Function like agonists, activating the Nm receptor, thereby initially causing muscle contraction
- resistant to AchE breakdown and cause continual activation of the Nm receptors without allowing time for the muscle to repolarize, leading to muscle paralysis
Example of Non-depolarizing neuromuscular blocker
Tubocurarine
- onset of action is about 4 mins, and pharmacological effects lasts 45-60 mins
Example of depolarizing neuromuscular blockers
Succinylcholine
- rapid onset (30-60secs), short duration of action (5-10 mins)
Why does succinylcholine have a short duration of action
It is metabolized by cholinesterase in the plasma of the blood, which is why the duration of action is short compared to non-depolarizing blocking agents
Phases of depolarizing blockers action
- depolarizing phase
- muscular fibres depolarize in a disorganized manner, resulting in muscular fasciculation (i.e. twitching)
- once muscle fibres depolarize, they are unable to repolarize due to the continual presence of the drug activating the receptors, resulting in paralysis
- Desensitizing phase
- once Nm receptors become desensitized to the depolarizing blocker, the Nm acts as if an antagonist is binding instead of an agonist
- binding Ach no longer activates them
- this desensitization, the effects of depolarizing blocks afents is prolonged by the use of AchE
Adverse effects of depolarizing blockade
- Hyperkalemia- during sustained depolarization, potassium can rush out of the cell and into the blood (elevated potassium can lead to cardiac arrest)
- Muscle pain- use of depolarizing blockers are associated with postoperative pain
- Malignant hyperthermia- genetically linked condition that can occur after exposure to succinylcholine and manifests as a rise in body temp, tachychardia, and muscle rigidity
Clinical indications of neuromuscular blockers
- surgery- to produce muscle paralysis as adjuncts to anesthetics OR to reduce spasticity- muscle relaxants for chronic back pain
- Endotracheal intubation- relaxation of tracheal and pharyngeal muscles, facilitating the insertion of an endotracheal tube
What does parasympathetic nervous system release
acetylcholine from presynaptic neurons and postsynaptic neurons
What does sympathetic nervous system release
acetylcholine from presynaptic neurons and norepinephrine from postsynaptic neurons
Anesthesia
state of loss of sensation; purpose to protect patients from pain in surgery
General Anesthesia
- hypnosis - loss of consciousness
- amnesia- loss of memory
- analgesia- loss of response to pain
- areflexia- loss of autonomic response
- relaxation- skeletal muscle
Ideal anesthetic
induce anesthesia quickly, while allowing for prompt recovery after its administration has stopped
high therapeutic index and have no adverse effects
Anesthesia Mechanisms of Action
- facilitation of GABA-mediated inhibition at GABA receptor chloride channel
- antagonism of glutamic acid excitation of NMDA channel receptor
Inhaled anesthesia route of admin
- inhaled
- reaches alveoli of lungs, transferred into blood, and travels to brain
- increased pulmonary ventilation will increase the speed of anesthetic uptake
Two types of inhaled anesthetics
- nitrous oxide- low potency and produces incomplete anesthesia
- volatile anesthetics (i.e. isoflurane, halothane)- potent drugs that produce unconsciousness
intravenous anesthetics
administered directly into the blood, and travels to brain to exert effects
- patient awakes after given a bolus of a drug often because of redistribution of the drug
Types of intravenous anesthetics
- Propofol - most frequent
- Ketamine- provides analgesia and is the choice for compromised blood flow
Local anesthesia
Loss of sensation that is confined to a discrete area of the body (blocking sensory nerve conduction)
The unionized local anesthetic enters the cell, where it becomes ionized and blocks the voltage-gated sodium channels, which inhibits nerve transmission
Local anesthetics and the ANS
not only blocks pain, but also blocks autonomic function, temp sensation, light touch sensation, proprioception, and motor function
Clinical application of local anesthetics
- topical
- local infiltration (injection in area of terminal nerve endings)
- spinal
- epidural
Allergies
most “allergies” are not allergies to anesthetic itself, but are due to added preservatives in the solution
System toxicity
occurs to excessively high blood vessels of the local anesthetic and is associated with drug overdose or accidental intravascular injection
what is SUD stand for?
Substance use disorder
SUD criteria
Min of 2…
- social impairments
- risky use
- impaired control
- withdrawal
- tolerance
Factors influencing SUD
- genetic factors
- pre-existing disorders
- environmental factors
- developmental factors
Potential for misuse of a drug
- nature of drug
- route of administration
- amount/frequency of use
- availability
- inherent harmfulness
Drug tolerance
- a state in which repeated administration of a given dose has progressively less pharmacological effect
- a state in which the dose of a drug must be increased to obtain the same magnitude of pharmacological effect as was produced by the original dose
Extent of drug tolerance
expressed as shortened duration of action and a decreased magnitude of effect
Cross tolerance
resistance or tolerance to one drug because of the resistance or tolerance to a pharmacologically similar drug
Withdrawal
abnormal physiological state produced by repeated administration of a drug that leads to the appearance of a withdrawal syndrome when drug administration is discontinued or the dose is decreased
Withdrawal symptoms
Usually the opposite to the effects of the drug (i.e. withdrawal from amphetamine (CNS stimulant) would manifest sleepiness (CNS depressant)
Severity of symptoms increases with the speed of withdrawal
Drug addiction
A state in which stopping or abruptly reducing the dose of a given drug produces non-physical symptoms
The dopamine hypothesis
commonly misused drugs increase dopamine in the reward systems of the brain
the dopaminergic systems are also responsible for natural rewards such as food and sex, as well as stimulus-related rewards (i.e. video games + gambling)
Characteristics of addictive drugs
- Increase dopamine (in brain reward systems)
- CNS stimulants
- opioids
- other drugs (alcohol +
cannabis)
- Produce novelty
- reduce anxiety
- CNS depressants
