Anxiety Flashcards
What is a drug that has a calming effect, relieving anxiety and tension.?
Sedative
What is A drug that produces sleep by depressing brain function?
Often cause hangover effects in the morning
Hypnotic
What is a drug that reduces anxiety?
Anxiolytic
What is a normal emotional state in response to a stressful situation that;s usually transient and commonly caused by the perception of real or potential danger?
Anxiety
What are the general medical conditions that cause anxiety?
MI, asthma, hyperthyroidism (usually when tx the anxiety improves), migraine, pain
What are the psychiatric disorders that cause anxiety?
Mood disorders, schizophrenia, delirium, dementia, substance abuse
What are the medication induced causes of anxiety?
Depressants, stimulants
When does anxiety become pathological?
- Pathological anxiety occurs when safe stimuli acquire a meaning of danger
- Anxiety is excessive, inappropriate or generalized
- Responses to feared stimuli are maladaptive
When does anxiety become a disorder?
Becomes a DISORDER when source of significant subjective distress or functioning impaired
What are the neurochemical theories?
--Noradrenergic Model Hypersensitive autonomic nervous system --Benzodiazepine Receptor Model Inhibitory pathway Deficit in patients with anxiety disorders --Serotonin Model Primarily an inhibitory neurotransmitter May help to reduce ANS hyperactive state
What are the anxiety associated neurotransmitter systems?
GABA
Norepinephrine model
Serotonin model
What is the gamma-aminobutyric acid (GABA) receptor?
High affinity sites, adjacent to GABA receptors, for benzodiazepine and barbiturates on the cell membrane in the CNS.
What is the MOA of benzodiazepines?
The binding of benzodiazepines enhances the action of GABA, resulting in a greater entry of chloride ion
What are the anxiety disorders?
Panic disorder (+/-) Social anxiety disorder (SAD) Specific phobia Generalized anxiety disorder (GAD) Obsessive-compulsive disorder (OCD) Posttraumatic stress disorder (PTSD)
What is literally the fear of market place or open spaces, also anxiety about being in situations that escape is difficult?
Agoraphobia
What do people with agoraphibia avoid?
Driving, bridges, tunnels, elevators, airplanes, malls, long lines, sitting in middle of row
Are males or females more affected by anxiety?
Females
What are panic attacks?
Sudden onset with no warning Usually last no more than 20-30mins Can occur at anytime Overwhelming sense of doom Fear of dying or losing control Physical sx
What is a panic attack under the DSM-IV criteria?
Period of intense fear or discomfort, in which at least 4 of the following sx developed abruptly and peaked w/in 10 minutes: Palpitation Sweating Trembling Sensations of SOB Feeling of choking CP or discomfort Nausea or abd distress Dizziness, lightheadedness, feeling faint Fear or losing control or going crazy Fear of dying Numbness or tingling Chills or hot flashes Derealization of depersonalization
What is Generalized anxiety disorder (GAD)?
Excessive anxiety and worry about a number of events or activities on most days for at least 6 mo.
Associated w/ 3 or more sx- restlessness, easily fatigued, difficulty concentration, irritability, muscle tension, sleep disturbance.
Significant distress at work and socially
Typically present with somatic complaints
What are the nonphamarcologic therapy options for GAB?
Lifestyle changes
CBT
What are the pharmacotherapy tx for GAD?
Antidepressants Benzodiazepines Buspirone Pregabalin Beta Blockers
What should patients with GAD avoid?
Caffeine
OTC cold preparations
Marijuana
Excess alcohol or use for sleep
What are the advantages of CBT?
It works It may have low relapse rate when d/c MOst people like it TIme-limietd Overall low price few side effects
What are the disadvantages of CBT?
Harder to admin than meds Limited availability More effort than taking meds Lack of 3rd party coverage Not all patients willing or able
What are the benzodiazepines used to tx anxiety?
Alprazolam (Xanax) Clonazapam (Klonopin) Chlordiazepoxide (Librium) Cloraze[ate (Tranxene) Diazepam (Valium) Halazepam (Paxipam) Lorazepam (Ativan) Oxazepam (Serax)
What are the most effective and safe medications for acute anxiety sx?
Benzodiazepines
Benzodiazepines (-pams)- ROA and absorption
Route of Admin Oral, IV, IM, rectal Absorption Rapidly and completely Lipophilic agents-distributed throughout the body
Benzodiazepines (-pams)- duration of action and metabolism
Short, intermediate, long Long-acting form active metabolites with long half-lives Metabolism Hepatic (active metabolites) Excreted in urine; redistributed
What are the long acting 1-3 day benzodiazepines?
Clorazepate- not used often don’t worry about this one.
Chlordiazepoxide
Diazepam
Flurazepam
What are the intermediate 10-20 hour acting benzodiazepines?
Alprazolalm
Lorazepam
Temazepam
What are the short acting 3-8 hour acting benzodiazepines?
Oxazepam
Triazolam
Benzodiazepine (-pams)- MOA
Potentiate the inhibitory activity of GABA
Binds to the GABA-BDZ receptor complex
-Facilitates the opening of Cl- channels
Prevents further release of excitatory neurotransmitters (hyperpolarization)
*Bind to the allosteric site!
What should dosing of benzos be related back to?
Lorazepam
What is the onset of high potency benzos?
Fast
Benzodiazepine (-pams)- ADRs
SEDATION
Fatigue
Weakness
Psychomotor impairment (decreased memory and decreased recall, ataxia and mental confusion)
Paradoxical reactions (mostly in special populations like elderly, brain injured, MR, kids)
Rebound anxiety and insomnia
Benzodiazepines (-pams)- tapering
<10-25% every 1-2 wks
At 50% initial dose, slow taper further
Maintain multiple dosing to minimize taper-related plasma level fluctuations
Discontinuation is less difficult over the first 50% of the dose
A longer taper period is needed for the final 50% of the dose to avoid potentially severe withdrawal sx
Benzodiazepines (-pams)- drug interactions
–Other CNS depressants – ETOH, opiates
–Cimetidine –Inhibits metabolism of longer acting BZDs
–Fluoxetine–Decreases clearance of diazepam
–CYP3A4 inhibitors (fluoxetine, fluvoxamine, grapefruit juice, ketoconazole, nefazodone)
Decrease clearance of alprazolam
What are the three big disadvantages of benzodiazepines?
Physiologic dependence
Risk for withdrawal reactions with abrupt discontinuation
Concern over abuse potential
What results from abrupt withdrawal from benzodiazepines?
Abrupt withdrawal results in withdrawal symptoms– confusion, anxiety, agitation, restlessness, insomnia, tension
Long-acting tend to withdrawal themselves
Short-acting more severe withdrawal treatment = long t1/2 benzo
When is a benzo overdose lethal?
Benzo overdose seldom lethal unless combined with other central depressants ie., ETOH
What is The antidote for a benzodiazepine overdose?
FLUMAZENIL** rapidly reverses effects of benzos
IV
May require frequent administration
May precipitate withdrawal in dependent patients or cause seizures in epileptics
Are barbutrates used for insomnia and anxiety?
No
Barbiturates- ADRs
Induce tolerance, physical dependency, severe withdrawal symptoms
Potentially Fatal Respiratory Depression
Suppresses hypoxic and chemoreceptor response to CO2
narrow therapeutic range
Why do barbiturates have alot of drug interactions?
They are p450 inducers
Barbiturates- indications
Ultra-short t1/2: IV General Anesthesia
thiopental
Sedative/hypnotic
At low doses, sedation (calming, reduced excitement) higher doses hypnosis anesthesia coma and death
Amobarbital (amytal), pentobarbital, secobarbital
Anticonvulsant
–Treatment of tonic-clonic, status epilepticus, eclampsia
–DOC in children with recurrent febrile SZ
Phenobarbital
What is the drug of choice for a child with recurrent febrile sz?
Phenobarbital
Barbiturates- MOA
Potentiates GABA action on chloride entry into neuron ->hyperpolarization
Barb receptor on GABA different than Benzo
Block excitatory glutamate receptors
Anesthetic concentrations block Na+ channels
What are the long acting (1-2days) barbiturates?
Phenobarbital
What are the short-acting (3-8 hours) barbiturates?
Pentobarbital
Secobarbital
Amobarbital
What are the ultra short-acting (20 min) barbiturates?
Thiopental
Barbiturates- pharmakokinetics
PO Redistribute in body from brain to splanchnic areas to skeletal muscle then adipose tissue Metabolized in liver P450 inducer drug-drug interactions Renal excretion
Barbiturates- ADRs
Drowsiness, impaired concentration, mental/physical sluggishness
Synergizes ETOH
Drug hangover
Nausea and dizziness
Are barbiturates a P450 inducer?
Increase porphyrin synthesis contraindicated in patients with acute intermittent porphyria
What happens with abrupt withdrawal of barbiturates?
Abrupt withdrawal-> tremors, anxiety, weakness, restlessness, N/V, SZ, delerium, cardiac arrest
More severe than opiate withdrawal, can result in death
What occurs with OD of barbiturates?
Severe respiratory depression coupled with CV depression-> shock; shallow, infrequent breathing
What is the tx of a barbiturate OD?
No antagonist available
Ventilation; purge stomach; hemodialysis; alkalinization of urine with phenobarbital
What components of anxiety does a beta blocker help with?
Physiologic component of anxiety:
tachycardia, palpitations, tremor, sweating
No CNS depression
non-addicting, no drowsiness
Do not use in asthma, diabetes, CHF
monitor BP, pulse
Helpful for performance anxiety:
propranolol 10 mg prn
When should beta blockers be used to tx anxiety?
When you have a patient that has stage fright or anxiety in front of a crowd. Not a regular medication to manage anxiety
Buspirone (Buspar®)- indications
Treat anxiety d/o
Buspirone (Buspar®)- MOA
Reduce 5-HT transmission by acting as partial agonist at these receptors
Some affinity for DA receptors also
Buspirone (Buspar®)- advantages and disadvantages
Advantages:
Dependence unlikely; minimal sedation
Disadvantages:
Only effective in GAD; doesn’t work in severe anxiety
Slow onset of action
CAUSES HYPOTHERMIA; INCREASED PROLACTIN/GH
P450 metabolism- chance of drug interactions.
Buspirone (Buspar®)- ADRs
HA, dizziness, nausea
How long does it take for buspirone to start working?
1 week
Pregabalin-MOA
Similar to gabapentin
Site of action- Alpha(2) delta subunit of voltage dependent calcium channels
Reduces calcium influx into the neuron and inhibits neuronal excitability
Reduces the release of glutamate, NE, and substance P
Pregabalin- ADRS (in GAD)
Dizziness Somnolence Dry Mouth Abnormal Thinking Blurred vision Diarrhea Incoordination Ataxia
What type of antidepressant is able to be used in all anxiety disorders?
SSRIs
What is considered the DOC for GAD?
SSRI
What is DOC for panic disorder?
SSRI (FLX, SERT, PAR)
What can a combination of benzos and antidepressants cause?
Jitteriness syndrome or hyperrsensitivity reaction– jitteriness, shakiness, increased anxiety, and insomnia.
Start low and go slow!
What are the advantages of SSRI/VLFX in panic disorder treatment?
Effective for comorbid depression
Effective in managing mixed patients- especially with PD, GAD, OCD
Lower risk in suicidal patients
Generally well tolerated and no abuse potential
Once daily dosing
Relapse prevention
What are the disadvantages of SSRI/VLFX for treating panic disorder-GAD?
Delayed onset (days to weeks)
Transient activation early in therapy
SE: GI, sexual dysfunction, discontinuation syndrome
Withdrawal reactions when discounted
What is SSRI induced anxiety?
Enhanced 5-HT release or have supersenstive 5-HT2 receptors, which increases glutamate
High potency BZDs have rapid anxiolytic effects and also reduce early SSRI-induced anxiety
Who needs long term medications for anxiety?
The majority of anxiety and panic disorder patients need long-term tx
Relapse rates after discontinuation of medication are significant
Tapering needs to be very gradual (3-6mo)
What antihistamines are used to tx anxiety and insomnia?
Diphenhydramine (Benadryl)
Hydroxyzine (Atarax)
What are the side effects of antihistamines?
Non- addicting
Some anticholinergic effects
ETOH- MOA
Antianxiety and sedative effects
CNS depressant producing sedation then hypnosis with increasing doses
Shallow dose-response curve
Sedation over wide dose range
ETOH- pharmacokinetics
PO; readily absorbed Vd close to total body water Metabolized by liver ETOH->acetaldehyde-> acetate Eliminated via kidneys and lungs Synergizes other sedative agents Severe CNS depression with barbs and antihistamines
ETOH- ADRs
Chronic consumption: gastritis, nutritional deficiencies, severe liver disease, cardiomyopathy
What medications are involved with the treatment of alcohol withdrawal?
-Benzodiazepines
-Carbamazepine for SZ during withdrawal
-Disulfiram (Antabuse)
Conditioned avoidance response
Blocks oxidation of acetaldehyde to acetate
Accumulation of acetaldehyde flushing, TACHY, hyperventilation, nausea
