DRUGS ACTING ON THE NERVOUS SYSTEM

nervous system

is responsible for controlling the functions of the human body, analyzing incoming stimuli, and integrating internal and external responses.

central nervous system

peripheral nervous system

The nervous system is composed of the

Peripheral nervous system

is composed of sensory receptors that bring information into the CNS and motor nerves that carry information away from the CNS to facilitate response to stimuli.

Autonomic nervous system

uses components of both systems to control involuntary activities such as heartbeat, respiration, and digestion.

Neurons

What is the structural unit of the nervous system?

DENDRITE

CELL BODY

AXON

What are the parts of a neuron?

Action Potential

Sudden change in electrical charge of a nerve cell membrane; the electrical signal by which neurons send information

−70 mV

An axon at rest maintains a small electrical tension across its membrane: the inside is relatively negative, and the outside is positive, creating the resting membrane potential of about _____.

Sodium–potassium pump

Selective ion permeability

This resting potential is maintained by the ______ and ______ (K⁺ can move out, Na⁺ mostly stays out).

1 millisecond

This rapid rise and fall in voltage, lasting approximately ______, is the action potential.

Sodium–potassium pump

After the peak, the______ restores the membrane to the resting potential (repolarization).

Afferent Fibers

Nerve axons that run from peripheral receptors into the central nervous system

Axon

Long projection from a neuron that carries iinformation to another nerve or effector.

Depolarization

- opening of the sodium channels in a nerve membrane to allow the influx of positive sodium ions, reversing the membrane charge so it is no longer polarized. - And stimulation of a neuron causes depolarization, and it means that sodium channels open.

Repolarization

- return of a membrane to a resting state, with more sodium ions outside the membrane and a relatively negative charge inside the membrane.

Schwann Cell

- insulating cell found on nerve axons; allows “leaping” electrical conduction to speed the transmission of information and prevent tiring of the neuron.

- Between the Schwann cells are areas of uncovered nerve membrane called the nodes of Ranvier.

Soma

cell body of a neuron; contains the nucleus, cytoplasm, and various granules

Synapse

- junction between a nerve and an effector; consists of the presynaptic nerve ending, space called the synaptic cleft, and the postsynaptic cell.

Effector Cell

cell stimulated by a nerve; may be a muscle, a gland, or another nerve cell

Efferent Fiber

nerve axons that carry nerve impulses from the central nervous system to the periphery to stimulate muscles or glands.

Engram

Short-term memory made up of a reverberating electrical circuit of action potentials.

Forebrain

The upper level of the brain; consists of the two cerebral hemispheres, where thinking and coordination of sensory and motor activity occur, containing the hypothalamus and thalamus and the area of the limbic system.

Ganglia

Groups of nerve bodies

Hindbrain

- The most primitive area of the brain, the brainstem; consists of the pons and medulla, which control basic vital functions, and the cerebellum, which controls motor functions that regulate balance.

Limbic System

- area in the forebrain that is rich in epinephrine, norepinephrine, and serotonin and seems to control emotions.

- Stimulation of this area appears to be responsible for the expression of emotions, and may lead to anger, pleasure, motivation, stress, and so on.

- seems to be largely responsible for the “human” aspect of brain function.

Midbrain

- middle area of the brain; it consists of most of the cranial nerves and areas related to arousal and awareness; sits just below the hypothalamus

Neuron

- structural unit of the nervous system.

- The human body contains about 14 billion neurons.

- About 10 billion of these are located in the brain, and the remainder make up the spinal cord and PNS

Neurotransmitter

- chemical produced by a nerve and released when the nerve is stimulated;reacts with a specific receptor site to cause a reaction.

Acetylcholine

• Communicates between nerves and muscles

• Preganglionic NT throughout the ANS

• Postganglionic NT in several pathways in the brain

Norepinephrine and epinephrine

• Released by nerves in the sympathetic branch of the ANS

• Classified as hormones when released in the adrenal medulla

• Occur in high levels in the limbic system

Dopamine

• High levels in certain parts of the brain

• Involved in the coordination of impulses and responses both motor and intellectual

Gamma-aminobutyric acid or GABA

• Found in the brain

• Inhibits nerve activity and is important in preventing overexcitability or stimulation such as seizure activity.

Gamma-aminobutyric acid or GABA

is one known for inhibition. So if you have a question about inhibition, if you don't know the answer, try ______. 80% of the time, that's the answer.

Serotonin

• Also found in the limbic system

• Important in arousal and sleep and in preventing depression and promoting motivation.

Acetylcholine

Norepinephrine and epinephrine

Dopamine

Gamma-aminobutyric acid or GABA

Serotonin

NEUROTRANSMITTERS :

Nervous system

controls the body, analyzes external stimuli, and integrates internal, external responses.

Regenerate

Nerves cannot reproduce but can ________ if soma and axon hillock are intact

Efferent nerves

carry info out of CNS; afferent nerves carry info into CNS.

Action potentials

trigger neurotransmitter release at axon terminals.

Neurotransmitters

cross synapse, stimulate effectors (nerve, muscle, gland).

Anxiety

- unpleasant feeling of tension, fear, or nervousness in response to an environmental stimulus, whether real or imaginary.

Anxiolytic

- drug used to depress the central nervous system (CNS); prevents or reduces the signs and symptoms of anxiety.

- it just means that you are dampening or lowering the actions of your central nervous system.

Barbiturate

- former mainstay drug used for the treatment of anxiety and for sedation and sleep induction; associated with potentially severe adverse effects and many drug–drug interactions, making it less desirable than some of the newer agents.

- We also have barbiturates, barbitals. Phenobarbital is the model drug for these subgroups. So these drugs are used to alter an individual's response to environmental stimuli.

Benzodiazepine

drug that acts in the limbic system and the reticular activating system to make gamma-aminobutyric acid (GABA) more effective, causing interference with neuron firing; depresses CNS to relieve anxiety; may cause sedation and hypnosis in higher doses.

- So for benzodiazepines, you have a lot of names, like Zepam, Zolam, and Zepoxide. The most common or the model drug that is used for this is diazepam.

Hypnosis

- Extreme sedation resulting in further depression of the central nervous system; this stage of CNS depression causes sleep.

Hypnotic

- drug used to depress the CNS; causes sleep

Hypnotic

are also used to treat insomnia, but for short-term use only.

Hypnotic

And you need to avoid driving and making legal decisions when taking these drugs because one of the common side effects of anxiolytics and hypnotic agents is the most common side effect of these drugs. Drowsiness.

Sedation

Loss of awareness of and reaction to environmental stimuli.

Sedative

drug that depresses the CNS; a loss of awareness of and reaction to the environment.

zepams

zolams

zepoxide

Sedative Agents:

Drug Usage

Used to alter an individual’s responses to environmental stimuli.

Anxiolytics

reduce or prevent feelings of tension or fear.

Sedative

they can calm patients and make them unaware of their environment.

Hypnotics

they can cause sleep

Minor Tranquilizer

they can produce a state of tranquility in anxious patients.

ANXIOLYTIC AND HYPNOTIC AGENTS IN -CHILDREN

- Response of the child to the drug may be unpredictable - inappropriate

- aggressiveness, crying, irritability, and tearfulness are common.

BENZODIAZEPINES

- only chlordiazepoxide, clonazepam, clorazepate, midazolam, and diazepam have established pediatric dosages.

BARBITURATES

- must be used with caution because of the unexpected responses

- children must be monitored very closely for CNS depression and excitability.

Diphenhydramine

Promethazine

used in helping to calm children and to induce rest and sleep.

ANTIHISTAMINES

Assess for possible dried secretion and effects on breathing.

ANXIOLYTIC AND HYPNOTIC AGENTS IN - ADULTS

- used for treatment of insomnia - short term use only

- reason for the insomnia should be sought (e.g., medical, hormonal, or anxiety problems)

- avoid driving and making legal decisions when taking these - contraindicated during pregnancy and

Lactation: 1. Potential for adverse effects on the fetus. 2. possible sedation of the baby.

Antihistamines

may be the safest to use,with caution, if an anxiolytic or hypnotic drug must be used

ANXIOLYTIC AND HYPNOTIC AGENTS IN - OLDER ADULTS

● Major safety concern - more susceptible with the adverse effects of these drugs.

● Unanticipated CNS effects increased sedation, dizziness, and hallucinations.

● Dosage should be reduced, and the patient should be monitored very closely for toxic effects and provide safety measures if CNS effects do occur

● Baseline liver and renal function tests should be performed and should be monitored periodically.

● Non Drug measures to reduce anxiety and to help induce sleep are important with older patients.

● Patients should be screened for physical problems, neurological deterioration, or depression, which could contribute to insomnia or anxiety.

BENZODIAZEPINES

● Most frequently used anxiolytics drugs.

● Prevents anxiety without causing much sedation.

Anxiety disorders

Alcohol withdrawal

Hyperexcitability and agitation

Preoperative anxiety and tension

Adjunct in seizure disorders

Benzodiazepines are indicated for the treatment of:

30 minutes to 2 hours

Absorption of Benzodiazepins

○ Gastrointestinal tract

○ Peak levels achieved in _______.

BENZODIAZEPINES

They are lipid soluble and well distributed throughout the body, cross the placenta, and enter breast milk. These drugs are metabolized extensively in the liver, and their metabolites are excreted in the urine.

● allergy to benzodiazepines

● psychosis

● acute narrow-angle glaucoma

• pregnancy

● shock

● coma

● acute alcoholic intoxication

Benzodiazepines are contraindicated in:

Fetal movement

kayano na dre kita nga sedated it baby? Kay? Bangin namatay? Pede naman pero morbid, sakit Muna. What do we monitor or ask the pregnant mother to monitor?

Antihistamines

So, among the anxiolytics and hypnotic agents, the _____ are the safest to use.

BARBITURATES

● Were once the sedative–hypnotic drugs of choice.

● Likelihood of sedation and other adverse effects greater and risk of addiction and dependence is also greater.

BARBITURATES

used as anxiolytic–hypnotics include butabarbital (Butisol), pentobarbital (Nembutal Sodium), phenobarbital (generic), and secobarbital (Seconal).

BARBITURATES

are general CNS depressants that inhibit neuronal impulse conduction in the ascending reticular activating system (RAS), depress the cerebral cortex, alter cerebellar function, and depress motor output. As a result, they can cause sedation, hypnosis, anesthesia, and, in extreme cases, coma.

BARBITURATES

are still used as anxiolytics and hypnotics, but they are less desirable than some of the newer agents because of their likelihood of physical dependence and addiction, as well as their greater adverse effects and drug–drug interactions.

20 to 60 minutes

Pharmacokinetics of Barbiturates

● Absorption

○ Absorbed well - peak levels achieved in _________

Barbiturates

are well absorbed and metabolized in the liver and excreted in the urine. They reach peak levels in 20 to 60 minutes. They cross the placenta and enter breast milk.

Anxiolytic and hypnotic drugs

are used to depress the central nervous system, promoting sedation, relaxation, and sleep.

Benzodiazepines

are the most commonly used drugs for treating anxiety and sleep disorders; they act on the limbic system and reticular activating system to make GABA more effective, interfering with nerve firing and depressing the CNS.

Barbiturates

once the mainstay of therapy for anxiety and insomnia, are now less commonly used due to high risk of dependence, severe adverse effects, and dangerous interactions.

Benzodiazepines

Barbiturates

can cause CNS depression, drowsiness, lethargy, confusion, and other side effects.

ANTIDEPRESSANTS

feeling that a person experiences when he or she responds emotionally to the environment.

BIOGENIC AMINE

one of the neurotransmitters norepinephrine, serotonin, or dopamine; it is thought that a deficiency of these substances in key areas of the brain results in depression.

Depression

affective disorder in which a person experiences sadness that is much more severe and longer lasting than is warranted by the event that seems to have precipitated it, with a more intense mood; the condition may not even be traceable to a specific event or stressor

Monoamine Oxidase Inhibitor (MAOI)

drug that prevents the enzyme monoamine oxidase from breaking down norepinephrine (NE), serotonin (SHT), and dopamine (DA), leading to increased neurotransmitter levels in the synaptic cleft; relieves depression and also causes sympathomimetic effects.

Selective Serotonin Reuptake Inhibitor (SSRI)

drug that specifically blocks the reuptake of serotonin and increases its concentration in the synaptic cleft; relieves depression and is not associated with anticholinergic or sympathomimetic adverse effects.

Serotonin Norepinephrine Inhibitors (SNRIs)

drug that increases both serotonin and norepinephrine concentrations in synaptic cleft; relieves depression with varying serotonergic or noradrenergic activity.

Tricyclic Antidepressants (TCAs)

drug that blocks the reuptake of norepinephrine and serotonin; relieves depression and has anticholinergic and sedative effects

Tyramine

an amine found in food that causes vasoconstriction and raises blood pressure; ingesting foods high in tyramine while taking an MAOI poses the risk of a severe hypertensive crisis.

triptyline

● amitriptyline

● amoxapine

● clomipramine

● desipramine

● Doxepin

● pramine

● imipramine

● maprotiline

● nortriptyline

● protriptyline

● trimipramine

TRICYCLIC ANTIDEPRESSANT

isocarboxazid

● phenelzine

● Tranylcypromine

MONOAMINE OXIDASE INHIBITORS:

talopram

xetine

Selective Serotonin Reuptake Inhibitor(SSRIS)

fluoxetine

fluvoxamine paroxetine sertraline

vilazodone

vortioxetine

xetine:

○ citalopram

○ escitalopram

Talopram

desvenlafaxine

duloxetine levomilnacipran

venlafaxine

SEROTONIN NOREPINEPHRINE INHIBITORS

● Bupropion

● milnacipran

● mirtazapine

● nefazodone

● selegiline

OTHER ANTIDEPRESSANTS:

Biogenic Amine Theory of Depression

● Scientists have theorized that depression results from a deficiency of biogenic amines in key areas of the brain.

● Biogenic amines include - norepinephrine (NE), dopamine, and serotonin (SHT).

Tricyclic antidepressants (TCAs)

Monoamine oxidase inhibitors (MAOIs)

Selective serotonin reuptake inhibitors (SSRIs)

Serotonin norepinephrine inhibitors (SNRI)

4 main groups:

MAOIs

should be avoided in children; because of drug food-interactions and serious side effects.

TCA

Clomipramine, imipramine, nortriptyline, and trimipramine have established pediatric doses in children older than 6 years.