3m-CNS Pharma

✓ Brain

✓ Spinal Cord

✓ Nerves

✓ Ganglia

NERVOUS SYSTEM:

composed of all nerve tissues

NERVOUS SYSTEM

Receives stimuli and transmits information to nerve centers for an appropriate response.

CENTRAL NERVOUS SYSTEM (CNS)

1. Composed of brain and spinal cord.

2. Regulates body functions.

3. Stimulation of the _______ may either increase the neuron activity or block nerve cell activity.

True

The CNS interprets information sent by impulses from the PNS and returns the instruction through the PNS for appropriate cellular actions

Somatic nervous system (SNS)

Autonomic nervous system (ANS)

PERIPHERAL NERVOUS SYSTEM (PNS) Two division

Somatic Nervous System (SNS)

- voluntary

- for locomotion and respiration

Autonomic Nervous System (ANS)

- Also called the Visceral System

- involuntary

- for functioning of the heart, respiratory system,

gastrointestinal system and glands

a) Sympathetic Nervous System (SNS)

b) Parasympathetic Nervous System (PNS)

Autonomic nervous system (ANS) two division

SYMPATHETIC NERVOUS SYSTEM

✓ Also called the Adrenergic System, because its neurotransmitter is norepinephrine.

✓ Response: Excitability

PARASYMPATHETIC NERVOUS SYSTEM

✓ Called the Cholinergic System because

its neurotransmitter is acetylcholine.

✓ Because organs are innervated by both the

sympathetic and the parasympathetic

systems, they can produce opposite

responses.

✓ Response: Inhibition

STIMULANTS-PATHOPHYSIOLOGY

Indications:

• Attention-Deficit/Hyperactivity Disorder in children (ADHD)

• Narcolepsy

ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD)

✓ Dysregulation of the transmitter's serotonin, norepinephrine, and dopamine.

✓ May occur before 7 years of age and may continue through teenage years.

Characteristics: Inattentiveness, inability to concentrate, restlessness, hyperactivity, inability to complete tasks, and impulsivity.

NARCOLEPSY

✓ Characterized by falling asleep during normal waking activities.

✓ Sleep paralysis usually accompanies narcolepsy and affects the voluntary muscles.

1. Amphetamines and Caffeine

2. Anorexiants

3. Analeptics and Caffeine

STIMULANTS

Major groups of CNS stimulants:

Amphetamines

Causes euphoria and increased alertness as well as insomnia, restlessness, tremors, irritability, xerostomia (dry mouth) and weight loss.

AMPHETAMINE-LIKE DRUGS

✓ Used for ADHD and narcolepsy.

✓ More effective in treating ADHD than amphetamines.

✓ Classified as Controlled Substance Schedule (CSS) II drug.

✓ Food affects absorption rate → given 30-45 minutes before meals.

✓ Should be given at least 6 hours before sleep.

✓ Transdermal patch may be worn for 9 hours

1. Methylphenidate hydrochloride 2. Modafinil

3. Dexmethylphenidate hydrochloride

4. Armodafinil

AMPHETAMINE-LIKE DRUGS examples

METHYLPHENIDATE HCI

is the most frequently prescribed drug used to treat ADHD.

-HYPERTENSIVE CRISIS

MODAFINIL

Increases wakefulness in patients with sleep disorders such as narcolepsy.

ANOREXIANTS

-cause a stimulant effect on the hypothalamic and limbic regions of the brain to suppress appetite

1. Benzphetamine

2. Diethylpropion HCI

3. Phentermine HCI 4. Phentermine topiramate

5. Phendimetrazine 6. Liraglutide

7. Naltrexone HCI

8. Bupropion HCI

ANALEPTICS

- Used to stimulate respiration.

- One subgroup is the xanthines (methylxanthines) of which CAFFEINE and THEOPHYLLINE are the main drugs.

-Excess caffeine → CONVULSION or DYSRHYTHMIA

DEPRESSANTS

- Sedative-hypnotics

-General Anesthetics

- Analgesics (opioid and nonopioid)

- Anticonvulsants

-Antidepressant

- Antipsychotic

SEDATIVE-HYPNOTICS

- Hypnotic drug therapy should be short term.

- Abrupt discontinuation of a high dose of hypnotic medication → WITHDRAWAL SYMPTOMS.

-GENERAL RULE: The lowest dose should be taken to achieve sleep.

Sedative-hypnotics

a. Barbiturates

b. Benzodiazepines

c.Nonbenzodiazepines

d. Melatonin Agonist

Ramelteon

is the only major sedative-hypnotic approved for long term use. This drug may be used to treat chronic insomnia.

BARBITURATES

-Useful as sleep sustainers for maintaining long periods of sleep.

- Classifications:

1. Long-acting: Phenobarbital and Mephobarbital

2. Intermediate-acting: Butabarbital 3. Short-acting: Secobarbital

-Must be short term use only.

BENZODIAZEPINES

-Used to induce sleeping

Examples: Alprazolam, Estazolam, Lorazepam, Temazepam, Triazolam, Quazepam, Diazepam

-Antagonist: Flumazenil

-Must not be used for longer than 3-4 weeks.

-Adverse Reaction: Anterograde amnesia

-Alprazolam Side Effects: lethargy, drowsiness, dizziness, headache, constipation, anterograde amnesia

NONBENZODIAZEPINES

-For short term use; not associated with rebound insomnia when discontinued (ZOLPIDEM (Ambien), Zaleplon (Sonata))

-It is used for short-term treatment (

MELATONIN AGONIST

Ramelteon is the newest category of sedative hypnotics.

ANESTHETICS

Classified as:

▪ General

▪ Local

-Monitor vital signs following general and local anesthesia

Balanced Anesthesia

Is a combination of drugs frequently used in general anesthesia.

Stage 1 - Analgesia

Stage 2 - Excitement of Delirium

Stage 3 - Surgical

Stage 4 - Medullary Paralysis

STAGES OF ANESTHESIA

Stage 1 - Analgesia

Begins with consciousness and ends with loss of consciousness; speech is difficult, sensations of smell and pain are lost, dreams and auditory and visual hallucinations may occur; this stage may be called the induction stage.

Stage 2 - Excitement of Delirium

Produces a loss of consciousness caused by depression of the cerebral cortex; confusion, excitement, or delirium occur, and induction time is short.

Stage 3 - Surgical

Procedure is performed during this stage. There are four phases: surgery is usually performed in phase 2 and upper phase 3. As anesthesia deepens, respirations become shallower, and the respiratory rate is increased.

Stage 4 - Medullary Paralysis

Toxic stage of anesthesia in which respirations are lost, and circulatory collapse occurs; ventilatory assistance is necessary.

INHALATION ANESTHETICS

-Example of Volatile Liquids: Halothane, Methoxyflurane, Enflurane, Isoflurane, Desflurane, Sevoflurane.

-Example of Gas: Nitrous Oxide

-Adverse Reaction: Respiratory depression, hypotension, dysrhythmia, and hepatic dysfunction.

INTRAVENOUS ANESTHETICS

-Examples: Propofol, droperidol, etomidate and ketamine hydrochloride.

-TIVA: Total Intravenous Anesthesia

TOPICAL ANESTHETICS

Use of this is limited to mucous membranes, broken or unbroken skin surfaces, and burns.

it comes in different forms.

It decrease the sensitivity of nerve endings in the affected area.

Local anesthetics

block pain at the site where the drug is administered by preventing conduction of nerve impulses.

Examples:

o Chloroprocaine HCI

o Procaine HCI

o Lidocaine HCI

o Mepivacaine HCI o Prilocaine HCI

o Bupivacaine HCI

o Dibucaine HCI

o Etidocaine HCI

o Tetracaine HCI

SPINAL ANESTHESIA

-Requires that a local anesthetic be injected into the subarachnoid space:

o Below the first lumbar space (L1) in adults and;

o The 3rd lumbar space in children (L3).

- Postdural-puncture headache

-MONITOR BLOOD PRESSURE

-Spinal Block

- Epidural Block

-Caudal Block

-Saddle Block

- Into the subarachnoid space.

- In the epidural space.

- Through the sacral hiatus.

- Lower end of spinal column

-Generalized Seizure

-Tonic-clonic Seizure

-Tonic Seizure

-Clonic Seizure

-Absence Seizure

-Myoclonic Seizure

-Atonic Seizure

-Infantile Spasms

-Partial Seizure

-Simple Seizure

- Motor

-Sensory

-Autonomic Response

-Psychological

- Complex Seizure

- Psychomotor

- Cognitive

- Affective

- Compound

-Seizures involve both cerebral hemispheres of the brain.

- Also called grand mal seizure, the most common form; in the tonic phase, skeletal muscles contract or tighten in a spasm that lasts 3-5 seconds; in the clonic phase, a dysrhythmic muscular contraction occurs with a jerkiness of legs and arms that lasts 2-4 minutes.

- Sustained muscle contraction.

- Dysrhythmic muscle contraction.

- Also called petit mal seizure; brief loss of consciousness lasts less than 10 seconds with fewer than three spike waves on the electroencephalogram (EEG) printout. This type usually occurs in children.

- Isolated clonic contraction of jerks that lasts 3-10 seconds may be limited to one limb (focal myoclonic) or may involve the entire body (massive myoclonic); may be secondary to a neurologic disorder such as encephalitis or TaySachs disease.

- Head drop, loss of posture, and sudden loss of muscle tone occurs. If lower limbs are involved, the patient could collapse.

- Muscle Spasm.

- Involves one hemisphere of the brain; no loss of consciousness occurs in simple partial seizures, but there is a loss of consciousness in complex partial seizures.

- Occurs in motor, sensory, autonomic, and psychic forms; no loss of consciousness occurs.

- Formerly called the Jacksonian seizure, this type involves spontaneous movement that spreads; it can develop into a generalized seizure.

- Visual, auditory, or taste hallucinations.

- Paleness, flushing, sweating, or vomiting.

- Personality changes.

- Loss of consciousness occurs, and the patient does not recall behavior immediately before, during, and immediately after the seizure.

- Complex symptoms include automatisms (repetitive behavior such as chewing or swallowing motions), behavioral changes, and motor seizures.

- Confusion or memory impairment.

- Bizarre behavior.

- May lead to generalized seizures such as tonic or tonic-clonic.

ANTISEIZURE DRUGS

(ANTICONVULSANTS)

1. Hydantoins

2. Barbiturates

3. Succinimides

4. Benzodiazepines

5. Iminostilbenes

6. Valproate

✓ By suppressing sodium influx.

✓ Suppressing the calcium influx.

✓ Increasing the action of Gamma Aminobutyric Acid (GABA).

HYDANTOINS

-Phenytoins

-Should not be used during pregnancy.

HYDANTOIN: PHENYTOIN

-Must not be administered through IM route.

- Cimetidine, Sulfonamides → the ACTION OF HYDANTOINS

-Antacid, Calcium preparations, Sucralfate, Antineoplastic → the ABSORPTION OF HYDANTOINS

BARBITURATES

- Phenobarbital is prescribed to treat tonic-clonic, partial and myoclonic seizures as well as status epilepticus.

-Therapeutic range is 20-40-mcg/mL.

SUCCINIMIDE

-Example: Ethosuximide

-Used to treat absence seizure.

- Therapeutic range is 40-100mcg/mL.

BENZODIAZEPINES

-Have antiseizure effects: clonazepam, clorazepate, dipotassium, lorazepam and diazepam.

-Clonazepam is effective for absence and myoclonic seizures but tolerance may occur 6 months after drug therapy starts.

-Clorazepate dipotassium is for partial seizures.

-Diazepam is administered through IV to treat status epilepticus.

IMINOSTILBENES

-Example: Carbamazepine

-Therapeutic range is 4-12mcg/mL.

-A potentially toxic interaction can occur when grapefruit juice is taken with carbamazepine.

VALPORATE

-For tonic-clonic absence and mixed type of seizure.

-Hepatotoxicity is one of the adverse reactions. Liver enzymes should be monitored. Therapeutic serum range is 50- 100mcg/mL.

✓ Neurologic

✓ Extrapyramidal Motor Tract

✓ Posture

✓ Balance

✓ Locomotion

Parkinson's Disease:

o Rigidity (abnormal increased muscle tone)

o Bradykinesia (slow movement)

o Gait Disturbances

o Tremors

Major features of parkinson's disease

DOPAMINE (DA)

o An inhibitory neurotransmitter.

o Released from dopaminergic neurons.

o Maintains control of Ach and inhibits its excitatory response.

ACETYLCHOLINE (ACh)

o An excitatory neurotransmitter.

o Released from cholinergic neurons.

Degeneration of Dopaminergic Neurons → LESS DA PRODUCED.

-Excitatory response exceeds the inhibitory response of the DA.

-Excess amount of Ach stimulates neurons that produce GABA (inhibits the activity of neuron).

HOW PARKINSON'S DISEASE DEVELOPS?

✓ Exercise

✓ Nutrition

✓ Group Support

NONPHARMACOLOGIC MEASURES FOR PARKINSON'S DISEASE

-Anticholinergics

-Dopaminergic Replacement Theory

-Dopamine Agonists

-Monoamine oxidase B (MAO-B) inhibitors

-Catechol-O-methyltransferase (COMT) inhibitors

-Dopamine Antagonists

DRUGS FOR PARKINSON'S DISEASE

Anticholinergics

which increase the effects of DA in the brain by reducing the effects of ACh

Dopaminergic Replacement Theory

- Stimulates the production of DA in the brain.

Dopamine Agonists

Which mimic the effects of DA in the brain by directly stimulating DA receptors.

Monoamine oxidase B (MAO-B) inhibitors

Which inhibit the inactivation of DA in the brain

Catechol-O-methyltransferase (COMT) inhibitors

which inhibit COMT enzyme that inactivates DA.

Dopamine Antagonists

Which disrupt the activity of DA by blocking DA receptor sites without activating them.

Anticholinergics

-Inhibit the release of acetylcholine.

- Examples: term-61Benztropine mesylate, Trihexyphenidyl hydrochloride

- GLAUCOMA is contraindicated.

Side Effects:

Dry mouth, dry secretions, urinary retention, constipation, blurred vision, increase in heart rate.

DOPAMINERGICS

Levodopa/Carbidopa (Sinemet)

Levodopa

- effective in diminishing Parkinson's disease and increasing mobility. This is because the blood brain barrier admits ____________, but not Dopamine.

Large doses are needed to achieve a pharmacologic response, which results to many side effects.

Carbidopa

-To inhibit the enzyme, dopa

decarboxylase.

-By inhibiting the enzyme in the PNS,

more Levodopa reaches the brain.

-Carbidopa is combined with Levodopa

-Ratio of:

o 1 part Carbidopa:10 parts

Levodopa

DOPAMINE AGONIST

-Also called Dopaminergics.

-Stimulate dopamine receptors.

-Examples:

1. Amantadine

2. BROMOCRIPTINE

3. Pramipexole

4. Ropinirole HCI

(DOPAMINE AGONIST):

Amantadine

-Can be taken alone or in combination with Carbidopa

-Levodopa or anticholinergic.

-Produces improvement in symptoms but drug tolerance develops.

-Can also be used for drug-induced parkinsonism.

-SYMMETREL

(DOPAMINE AGONIST):

Bromocriptine mesylate

-More effective than amantadine and anticholinergics.

- Not as effective as Carbidopa

-Levodopa in alleviating the symptoms.

-Patient who cannot tolerate Carbidopa

-Levodopa are given with this medication.

-PARLODEL

(DOPAMINE AGONIST):

MONOAMINE OXIDASE B INHIBITOR

MAO-B INHIBITOR

-Examples: Selegiline HCI and

Rasagline

-Inhibits MAO-B → PROLONGS THE ACTION OF LEVODOPA

Selegiline HCI

-Can delay the use of Carbidopa-Levodopa by 1 year.

(DOPAMINE AGONIST):

CATECHOL-O-METHYLTRANSFERASE (COMT) INHIBITORS

Entacapone, Tolcapone

TOLCAPONE

-1st COMT inhibitor given with levodopa.

-Can affect liver function - NURSING ACTION?

-May cause liver damage.

-Side Effects: Dark discoloration of urine, perspiration may also be dark.

ENTACAPONE

-Does not affect liver function.

-Combination of Carbidopa, Levodopa, and Entacapone.

o Provides greater dosing flexibility and individualization to the patient.

-Urine can have brownish orange discoloration.

TOLCAPONE AND ENTACAPONE

-Can intensify the actions of Levodopa.

-May lead to intense, uncontrollable urges (sex, gambling, spending money) in addition to suddenly falling asleep.

-Warn patient to avoid driving and other potentially dangerous activities.

Levodopa Inhalation

Carbidopa-Levodopa

DOPAMINERGICS drugs

Levodopa Inhalation

is administered via an inhalation pump directly into the lungs. It is used "as needed" for Parkinson Disease (PD) patients who are affected by an off period. These periods may come on slowly between regularly scheduled carbidopa/levodopa doses or abruptly at unpredictable times.

Carbidopa-Levodopa

To decrease symptoms of PD and parkinsonism; carbidopa, a decarboxylase inhibitor, permits more levodopa to reach the striatum nerve terminals, where levodopa is converted to dopamine. With the use of carbidopa, less levodopa is needed

-Apomorphine

-Bromocriptine mesylate

-Cabergoline

-Pramipexole dihydrochloride,

-Ropinirole hydrochloride

Dopamine agonists drugs

Apomorphine

It contains dopamine receptor agonist properties and is used for acute, intermittent treatment of "off" episodes ("end-of-dose weaning off") and unpredictable "on/off" episodes associated with advanced Parkinson disease

Bromocriptine mesylate

A D2- dopamine receptor agonist, an ergot derivative, bromocriptine can be used for early treatment of Parkinson disease.

Cabergoline

A synthetic ergoline-derived dopamine agonist beneficial for motor fluctuations associated with PD.

Pramipexole dihydrochloride, Ropinirole hydrochloride

D2- and D3-dopamine, a non-ergot alkaloid receptor agonist, can be used in combination with carbidopa-levodopa and has fewer side effects than many of the older dopamine agonists.

Rotigotine hydrochloride

- A transdermal nonergoline dopamine agonist used for the treatment of idiopathic PD and restless leg syndrome (RLS).

Safinamide

Selegiline hydrochloride

Rasagiline mesylate

MONOAMINE OXIDASE B INIBITORS Drugs

Safinamide

selective and reversible inhibitor of monoamine oxidase (MAO) Type B.

Selegiline hydrochloride

is a MAO-B inhibitor. It works by inhibiting the catabolic enzymes of dopamine and extends its action. It can be used for early treatment of PD and parkinsonism.

Rasagiline mesylate (Azilect)

is a potent, irreversible MAO-B that inhibits the breakdown of dopamine at synapses in the brain and allows neurons to reabsorb more dopamine for use later.

Amantadine

Istradefylline

Pimavanserin

DOPAMINE ANTAGONIST drugs

Amantadine(Symmetrel)

-decreases the symptoms of PD and drug-induced extrapyramidal reactions.

It is a synthetic antiviral agent that was found to cause symptomatic improvement in PD

Istradefylline (Nourianz)

It is a xanthine derivative and an oral adenosine A2A receptor antagonist.

It is used as an adjuvant with levodopa-carbidopa therapy in adult PD patients who experience "off" episodes.

Pimavanserin (Nuplazid)

It is a DA antagonist, also classified as an atypical antipsychotic, indicated for the treatment of hallucinations and delusions associated with PD psychosis.

ALZHEIMER'S DISEASE

→ Is an incurable dementia illness.

→ Characterized by chronic, progressive neurodegenerative conditions with marked cognitive dysfunction.

Onset usually occurs between 45 and 65 years of age.

ACETYLCHOLINESTERASE / CHOLINESTERASE INHIBITOR

The cure for Alzheimer disease is unknown.

FDA-approved medications to treat Alzheimer

disease symptoms include

________________________.

AChE is an enzyme responsible for breaking

down ACh and is also known as

____________________.

RIVASTIGMINE

✓ Increases the amount of ACh at the cholinergic synapses.

✓ Given twice a day.

✓ Contraindicated to patients with liver disease because hepatotoxicity may occur.

MYASTHENIA GRAVIS (MG)

Is an acquired autoimmune disease that impairs the transmission of messages at the neuromuscular junction, resulting in varying degrees of skeletal muscle weakness that increases with muscle use

Caused by ACETYCHOLINE (ACh) sites

Neostigmine, Pyridostigmine

Myasthenia Gravis drugs

✓ Ptosis

✓ Diplopia

✓ Dysphagia

✓ Dysarthria

✓ Respiratory Muscle Weakness

Manifestations of Myasthenia Gravis

- Drooping of eyelid.

-Double vision

-Difficulty of swallowing

-Difficulty speaking