Drugs for Anxiety and Insomnia - Benzodiazepines

anxiety

state of tension, apprehension, or uneasiness that. stems from the anticipation of danger - source of which is largely unknown or unrecognized

• someone sees a situation as threatening to their physical, emotional, social or economic well being

situational anxiety

a normal response to a stressful situation - can be beneficial when its motivational

anxiety disorder

when anxiety impairs a person’s ability to engage in normal day to day functions

separation anxiety

feelings of fear or anxiety about separation from attachment

selective mutism

consistant failure to speak in social situations where speaking is expected

specific phobia

fearful or anxious feelings about a particular situation or object

social anxiety disorder

fear, anxiety and avoidance of social interactions and situations

panic disorder

intense feelings of immediate apprehension, terror, or impending doom accompanied by increased autonomic NS activity

agoraphobia

a fear of open spaces or closed spaces

Generalized anxiety disorder

difficult to control, excessive anxiety that lasts 6 months or more

patho of anxiety

too much norepinephrine (excitatory neurotransmitter) and too little GABA (inhibitory neurotransmitter)

Norepinephrine is released from the locus cerelus due to a

actual or perceived threat

Norepinephrine travels to and stimulates the (pathway)

limbic system and cerebral cortex = feelings of panic and restlessness (in anxiety disorder, this is over active)

HPA axis

induces the release of CRF (CRH) in the hypothalamus

CRF (CRH) in the hypothalamus induces the releases of

Norepinephrine from the locus cerulues and then activates the limbic system and cerebral cortex

• can also include seratonin

locus ceruleus

a brain stem nucleus that contains many noradrengeric neurons and has extensive projections to the limbic system, cerebral cortex and cerebellum

GABA

main inhibitory nuerotransmitter in the brain and spinal cord

GABA receptors are located throughout the

brain and are accosted with Cl channels

when GABA binds to its receptor

Cl channels open allowing chloride ions to enter the neuron, leading to hyper polarization and decreased neuronal excitability (less responsive to norepi and neural firing slows down)

GABA is also associated with

sleep - therefore people with anxiety are more likely to experience sleep disturbances

Reticular activating system pathway

network of neurons that travel along the entire length of the brain stem ending in the thalamus - from thalamus neuronal signals are relayed to the cerebral cortex

Reticular activating system function

increased alertness and arousal - inhibition can cause drowsiness and can induce sleep

Hypothalamus is also connected to the

reticular activating system - during times of stress, HPA axis stimulates the RAS and this stimulates the cerebral cotext which promotes arousal (increased sleep disturbances)

insomnia

dissatisfaction with sleep quantity or quality associated with one or more of the following

• difficulty initiating sleep

• difficulty maining sleep (or returning to sleep)

• early morning wakings with an inability to go back to sleep

episodic / behavioural insomnia

normal stressors or specific activities that can interfere with sleep

• Symptoms last at least 1 month, but less than 3 months

Long term / persistant insomnia

associated with mood disorders such as depression, anxiety disorders, bipolar disorder or chronic pain due to illness

Selective central NS depressants

prescribed for the short term treatment of anxiety and insomnia

antidepressant drugs

are prescribed for the long term treatment of anxiety disorders

how to defrentiate Benzodiazepines

class of CNS depressors - mainly different from each other because of half life, clinical uses and active metabolites

Benzodiazepines with half life linger than 24 hours

produce active metabolites that have long half lives - tend to accumulate in plasma

Benzodiazepines with half life longer than 24 hours cant be used by

the elderly patients with impaired liver function because they accumulate in plasma

Benzodiazepines with half life longer than 24 hours cant be used for insomnia because

they accumulate in plasma and can result in day time drowsiness

Benzodiazepines with half life longer than 24 hours can be used for people with GAD since

it has a longer half life and stays in plasma = stablizes mood and reduces risk of withdrawls

Benzodiazepines used for anxiety are called

anti-anxiety drugs

Benzodiazepines used for insomnia are called

sedative hypnotic drugs

Short half-life benzodiazepines

do not produce active metabolites and are less likely to accumulate in plasma = better for insomnia

• cant be used to treat anxiety (not long acting)

Benzodiazepine drugs produce their anti-anxiety and sedative-hypnotic effects by

binding to benzodiazepine receptors located on the GABA receptor

• benzodiazepines bind to their receptor, the activity of GABA at its receptor is enhanced, increasing the entry of chloride ions into the neuron

• hyperpolorizes cell = releaves anxiety because not as much neurons firing

Benzodiazepine are highly

lipid soluble and distributed in body tissues and highly bound to plasma proteins = easily enters CNS and bind to Benzodiazepine receptors

• redistributed to tissues and slowly eliminated

long acting Benzodiazepine are metabolized by the

liver - CYP P450 oxidizes the drug to active metabolites and then go through again to get conjugated and then they are water soluble enough to be excreted

short acting Benzodiazepine are metabolized through

conjugation alone and don’t produce active metabolites, so thier elimination is faster

administration of Benzodiazepine

lowest possible dose to avoid adverse effects

When treating long-term anxiety disorders, benzodiazepines can be

prescribed in combination with antidepressant therapy to provide relief of symptoms during this period, after which benzodiazepine therapy can be slowly discontinued

benzos and insomnia

should be taken on an as needed bases and daily use can worsen it

• loses its effectiveness after 2-4 weeks of daily use

reconsider benzos for insomnia after

3 weeks of no improvement - may be something underlying that is causing the insomnia at that point

adverse effects of benzos

• over-sedation

• dizziness

• confusion

• impaired mobility

rare when meds are taken as prescribed (more common elderly)

• always gradually taper dose (insomnia can rebound if not)

  • can increase risk of dependance

flumazenil (IV admin)

benzo antagonist used to reverse the adverse effects associated with benzo OD

• once admin, pt. might wake up abruptly with dysphoria, agitation, anxiety, cardiac arythmeas and seizures

flumazenil does not reverse

respiratory depression

Physical Dependence of benzos

An altered physical condition caused by the nervous system adapting to repeated substance use (occur when it is discontinued)

• Over a prolonged period of time, the cells of the body

  function as though it is normal for the drug to be continually present

Symptoms of benzodiazepine withdrawal

Increased heart rate, loss of appetite, tremor, abdominal and muscle cramps, vomiting, sweating, insomnia, agitation, anxiety and panic

• can last 2-4 weeks

women are prescribed benzos

at twice the rate of men - benzo dependance is unrecognized in 75% of women who become addicted to the drug

benzos with short half life have more increased risk of dependance than

benzos with longer half life

Benzodiazepine Dependence

• Symptoms of physical dependence of often misdiagnosed as anxiety, depression or stress

• Diagnostic criteria for substance abuse many not adequately capture the profile of substance abuse or physical dependence in the elderly

• Elderly women do not fit the stereotype associated with an addicted individual

benzodiazepines use in older adults can lead to

impaired cognitive functioning, reduced mobility and driving skills, as well as an increased risk of falls