Pharmacology Chapter 12 (Unit 1)

Question 1

• A drug that has a calming effect or that depresses the central nervous system(CNS)
• Drugs that have an inhibitory effect on the CNS to the degree that they reduce:

-Nervousness
-Excitability
-Irritability without causing sleep

• Can become a hypnotic if given in a large enough dose

Answer 1

Sedative

Question 2

• This drug causes sleep

-Much more potent effect on CNS than sedatives

• A sedative can become this if it is given in large doses
• These drugs are regularly prescribed for insomnia and other sleep disorders and are habit forming

-Ex: Diphenhydramine, trazodone, and amitriptyline

Answer 2

Hypnotics

Question 3

-Can act as either a sedative or a hypnotic depending on the dose

-At low doses, calm the CNS without inducing sleep

• At high doses, calm the CNS to the point of causing sleep

Classified into three main groups: Barbiturates, Benzodiazepines, and miscellaneous drugs

Answer 3

Sedative- Hypnotics

Question 4

• Transient, reversible, and periodic state of rest in which there is a decrease in physical activity and consciousness

-Cyclic and repetitive

• A persons response to sensory stimuli are markedly reduced during this

Answer 4

Sleep

Question 5

Sleep research involves study of the patterns of sleep

• Consist of two basic elements that occur cyclically: rapid eye movement(REM) and non rapid eye movement(non-REM)

Answer 5

Sleep Architecture

Question 6

The prolonged sedative hypnotic use may reduce the cumulative amount of REM sleep

• Can result in daytime fatigue because REM sleep provides a certain component of the “restfulness” of sleep

Answer 6

REM interference

Question 7

This happens when a patient has an abnormally large amount of REM sleep, and often leading to frequent and vivid dreams

• The discontinuance of a sedative hypnotic drug

Answer 7

REM rebound

Question 8

• These kinds of drugs were the most commonly prescribed sedative hypnotic drugs Favorable adverse effect profiles, efficacy, and safety when used appropriately

-Classified as either sedative-hypnotics or anxiolytics (depending on their primary use)

-Are prescription drugs only and are a schedule 4 controlled substances

Mechanism of Action
- Depresses CNS activity
- Affects the hypothalamic, thalamic, and limbic systems of the brain
- Thought to have gamma-aminobutyric acid receptors (GABA)
- Does not suppress rapid eye movement (REM)
- Does not increase metabolism of other drugs

Indications
- Used for: Sedation, Sleep induction, skeletal muscle relaxation, anxiety relief, anxiety related depression, treatment of acute seizure disorders, treatment of alcohol withdrawal, agitation relief, balanced anesthesia, moderate or conscious sedation
- Combined with anesthetics, analgesics, and neuromuscular blocking drugs in balanced anesthesia and also moderate sedation for their amnestic properties to reduce memory of painful procedures
-recommended for short term use

Contraindications
include: Drug allergy, narrow angle glaucoma, and pregnancy

Adverse Effects include mild and infrequent
-Headache
-Drowsiness
-Dizziness
Cognitive impairment
-Vertigo
-Lethargy
-Fall hazard for older adults
- “Hangover” effect or daytime sleepiness

Toxicity and Overdose includes the following:
- Somnolence
-Confusion
-Coma
-Diminished reflexes
- Does not cause hypertension and respiratory depression unless taken with other CNS depressants
-rarely results in death

Treatment is symptomatic and supportive
- Flumazenil Can be used to acutely reverse the sedative effects of this
- It antagonizes the action of this on the CNS by directly competing with the (blank) for binding at the receptors
- Flumazenil Is used in the cases of oral overdose or excessive intravenous sedation

Interactions
-Azole antifungals, verapamil, diltiazem, protease inhibitors, macrolide antibiotics, and grapefruit juice
- CNS depressants (Alcohol, opioids)
-Olanzapine
-Rifampin
-Herbal interactions
-Food- drug interactions
- Opioids

effects include: Reduced blood pressure, reduced respiratory rate, sedation, confusion, and diminished reflexes, and the supplements cava and Valerian
- black box warning

Answer 8

CNS depressants: Benzodiazepines

Answer 9

Nonbenzodiazepine drugs

Question 10

• These drugs are used to reduce the intensity of feelings of anxiety
• These drugs can function along a continuum as a sedative and or hypnotic and or this depending on the dosage and patient sensitivity

-There are 5 benzodiazepines used as sedative-hypnotic drugs

Answer 10

Anxiolytic Drugs

Question 11

• These drugs functions like benzodiazepines but are chemically distinct

these drugs include: Ramelteon, Suvorexant (belsomra), and Tasimelteon (Hetlioz)

Answer 11

Miscellaneous Hypnotic drugs

Question 12

• A hypnotic drug not related to any other hypnotics

-Non- Benzodiazepine

• Structurally similar to the hormone melatonin works as an agonist at melatonin receptors in the CNS

-Technically, it is not a CNS depressant; used as a hypnotic

• Not classified as a controlled substance
• Indicated for patients who have difficulty with sleep onset rather than sleep maintenance

-Has a shorter duration of action

-Contraindicated in cases of severe liver dysfunction

• Avoid in patients receiving fluconazole or ketoconazole, both of which can impede its metabolism

Answer 12

Ramelteon

Question 13

• This drug is in a new class of drugs called selective orexin receptor antagonists
• Neuropeptides involved in the regulation of the sleep-wake cycle

Answer 13

Suvorexant (Belsomra)

Question 14

• This drug is used only for disturbance of sleep wake cycle and patients who are totally blind

-Limited Use

Answer 14

Tasimelteon (Hetlioz)

Question 15

• These receptors are the primary inhibitor neurotransmitter of the brain and it serves to modulate CNS activity by inhibiting overstimulation

Answer 15

GABA receptors

Question 16

• This drug is used to treat benzodiazepine intoxication

Answer 16

Flumazenil

Question 17

• An herbal product that is used to relieve anxiety, stress, and restlessness, and promote sleep
• May cause temporary yellow skin discoloration with extended intake, visual disturbance, and the hepatotoxicity
• Potential interactions with alcohol, barbiturates, and psychoactive drugs
• Contra indicated in liver disease, alcoholism, and other conditions
• Patients should not operate heavy machinery during use

Answer 17

Kava

Question 18

• A herbal product that is used to relieve anxiety, restlessness, and insomnia

-May cause CNS depression, hepatotoxicity, nausea, vomiting, anorexia, restlessness, insomnia

-Many interactions, including with CNS depressants, MAOIs, phenytoin, warfarin, and alcohol

-Contraindicated in cardiac, renal, and liver disease

-Patients should not operate heavy machinery during use

Answer 18

Valerian

Question 19

• This drug is the first clinically available benzodiazepine drug. It has varied uses
  -Treatment of anxiety
  -Procedural sedation and anesthesia adjunct
• Anticonvulsant therapy
  -Skeletal muscle relaxation
• This drug is available orally, rectally, and injectable

Answer 19

Diazepam (Valium)

Question 20

• This drug is most commonly used preoperatively and for moderate sedation
• Can cause amnesia and anxiolysis (reduce anxiety) as well as sedation
• Normally administered by injection in adults
• Liquid oral dosage form is also available for children
• High alert medication

Answer 20

Midazolam

Question 21

• This drug is an intermediate acting benzodiazepine (Most commonly used as a hypnotic)
• One of the metabolites of diazepam
• Normally induces sleep within 20 to 40 minutes
• Has a long onset of action, so it is recommended that patients take it approximately 1 hour before going to bed
• Still an effective hypnotic, it has been replaced by the newer drugs

Answer 21

Temazepam (Restoril)

Question 22

• This drug is a Non-Benzodiazepine
• The first hypnotic to be FDA approved for long term use
• Designed to provide a full 8 hours of sleep
• Considered a short- to intermediate acting agent
• Patients should allot 8 hours of sleep time and should avoid taking hypnotics when they must awaken in less than 6 to 8 hours

Answer 22

Eszopiclone (Lunesta)

Question 23

This is thought to regulate circadian rhythms (day-night sleep cycles) in the body

Answer 23

Melatonin

Question 24

• This drug is a short acting non benzodiazepine hypnotic

-Short half-life, lack of active metabolites, And has lower incidence of daytime sleepiness compared with benzodiazepine hypnotics

• FDA recommends a max dose of 5 mg for women and 5 to 10 mg for men

Ambien CR- Is a longer acting form with two separate drug reservoirs

-Concerns about somnambulation (sleep-walking)

Only one of the two hypnotics to be FDA approved for long term use; the other is eszopiclone (Lunesta)

Answer 24

Zolpidem (Ambien)

Question 25

- This drug class is hypothalamic neuropeptides that play a key role in promoting wakefulness and regulating the sleep wake cycle

Answer 25

Orexin A and B

Question 26

- This drug is the first drug in a new class called orexin receptor antagonist -Oral dual orexin receptor antagonist with a 12-hour half-life -safety concerns: daytime somnolence and unconscious nighttime behaviors -Adverse effects: Drowsiness, headache, dizziness, diarrhea, dry mouth, cough, and increased serum cholesterol -Adverse side effects are commonly found in women

Answer 26

Suvorexant (Belsomra)

Question 27

- These types of drugs were first introduced in 1903; were the standard drugs for insomnia and sedation - Chemically they are derivatives of barbituric acid - Only if you are commonly used today partially because of the safety and efficacy of benzodiazepines - Can produce many unwanted adverse effects - Physiologically habit forming and have a low therapeutic index Mechanism of Action - CNS depressants that act primarily on the brainstem (reticular formation) -Sedative and hypnotic effects are dose related, and they act by reducing the nerve impulses traveling to the cerebral cortex - By potentiating the action of GABA, nerve impulses traveling in the cereal cortex are inhibited - Raise the seizure threshold and can be used to treat seizures Indications -No longer recommended for sleep induction -Ultrashort acting: Anesthesia for short surgical procedures, anesthesia induction, control of convulsions, reduction of intracranial pressure in neurologic patients -Short acting: Sedation and control of convulsive conditions -Intermediate acting: Sedation and control of convulsive conditions -Long acting: Epileptic seizure prophylaxis Contraindications -Must not be taken if: Drug allergy, pregnancy, significant respiratory difficulties, severe kidney or liver disease -Caution in older adults: Their sedative properties and increased fall risk Adverse Effects - effects include: Drowsiness, lethargy, dizziness, hangover, and paradoxical restlessness or excitement -Deprive people of REM sleep, which can result in agitation - Rebound phenomenon may occur which can cause sleep increase and nightmares often ensue - If this is recommended for older adults the usual dosage is reduced by half whenever possible Toxicity and Overdose - Overdose frequently leads to respiratory depression and subsequent respiratory arrest - Overdose produces CNS depression (sleep to coma and death) -Can be therapeutic: Anesthesia induction, Uncontrollable seizures "phenobarbital coma" Drug Interactions - Enzyme inducers which means that they increase metabolism of other drugs - Additive effects: Alcohol, Antihistamines, benzodiazepines, opioids, and tranquilizers - Drugs most likely to have marked interactions with these kinds of drugs include monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, anticoagulants, glucocorticoids, and oral contraceptives -Inhibited metabolism: MAOIs prolong the effects of these drugs -Increased metabolism: Reduces Anticoagulant response, leading to possible clot formation - Co administration of these drugs with oral contraceptives can result in accelerated metabolism of the contraceptive drug and possible unintended pregnancy

Answer 27

Barbiturates

Question 28

- This drug is a short acting barbiturate - Used preoperatively to relieve anxiety and provide sedation - Also used occasionally to control status epilepticus - May be used to treat withdrawal symptoms in patients who are physically dependent on barbiturates or barbiturate hypnotics -Available in oral, injectable, and rectal dosage forms - No longer used as a sedative hypnotic drug for insomnia

Answer 28

Pentobarbital (Nembutal)

Question 29

- This drug is considered the Pro typical barbecue and is classified as a long-acting drug - Available in oral and injectable forms - Used for the following: - Prevention of generalized tonic- colonic seizures and febrile convulsions -Hyperbilirubinemia in neonates - Raely used as a sedative No longer recommended as a hypnotic

Answer 29

Phenobarbital

Question 30

- Non-prescription sleeping aids often contain antihistamines, which have CNS depressant effect -Ex: Doxylamine (Unisom) and Diphenhydramine (Sominex) and acetaminophen/ diphenhydramine (Extra strength Tylenol PM); melatonin - As with other CNS depressants, concurrent use of alcohol can cause respiratory depression or arrest

Answer 30

Over the Counter Hypnotics

Question 31

- A group of compounds that act predominantly with the CNS to relieve pain associated with skeletal muscle spasms -Known as Centrally acting -CNS is the site of action -Similar in structure and action to other CNS depressants -Direct acting -Act directly on skeletal muscle - Closely resemble GABA Indications - relief of painful musculoskeletal conditions -Muscle spasms -Management of spasticity of severe chronic disorders (multiple sclerosis, cerebral palsy) -IV dantrolene used for malignant hyperthermia - Works best when used along with physical therapy Adverse Effects - An extension of their effects on the CNS and skeletal muscles - effects include: Euphoria, lightheadedness, dizziness, drowsiness, fatigue, confusion, and muscle weakness - These adverse effects are generally short lived because patients grow tolerant to them overtime Toxicity and Management of Overdose - Primarily involve the CNS - No specific antidote or medication or reversal - Best treated with conservative supportive measures - If taken along with other CNS depressants - Adequate airway must be maintained - EKG monitoring -Administer fluids to avoid crystalluria Interactions -Caution with other CNS depressants such as Benzodiazepines, and alcohol Mental confusion, anxiety, tremors, an additive hypoglycemic activity also have been reported with this combination. A dosage reduction and/or discontinuance of one or both drugs is recommended

Answer 31

Muscle Relaxants

Question 32

-Baclofen (Lioresal) -Cyclobenzaprine (Flexeril) - Dantrolene (Dantrium) -Metaxalone (Skelaxin) -Tizanidine (Zanaflex) - Carisoprodol (Soma) - Chlorzoxazone (Paraflex) -Methocarbamol (Robaxin) The two most commonly used drugs in this classification are Baclofen and Cyclobenzaprine

Answer 32

Common Muscle Relaxants

Question 33

When combining Carisoprodol, an opioid, and a benzodiazepine It is known as this. Combination produces a heroin like effect

Answer 33

The Holy Trinity

Question 34

- This drug is available in both oral and injectable dosage forms. Injectable form is for use with an implantable this pump device - Used to treat chronic spastic muscular conditions - A test dose is administered to confirm a positive response - The injection is diluted before infusion. Oral and injectable doses are titrated to a desired response

Answer 34

Baclofen (Lioresal)

Question 35

-This drug is available in a five milligram and 10 milligram dose and an extended-release formulation (Amrix) - Centrally acting muscle relaxant that is structurally and pharmacologically related to the tricyclic depressants - Most commonly used muscle relaxer to reduce spasms after musculoskeletal injuries - Can cause marked sedation

Answer 35

Cyclobenzaprine (Flexeril)