Anxiolytic Flashcards
What are the neurotransmitter changes associated with with anxiety? Name 3
Increase GABA
Decrease serotonin
Decreased dopamine
Does insomnia improve with age ?
No it worsens with age
Insomnia is more common in which gender?
Women
Which receptor does benzodiazepines bind to?
A1 GABA A receptors increasing the frequency of chloride influx.
What does alpha1 GABAa receptor affect?
Aborts seizures
Anterograde amnesia
Sedation
What does a2 GABAa receptors affect?
Anxiety reduction
Hypnosis
GABAb
Bound by BACLOFEN in the spinal cord to relax spastic musculature.
Benzodiazepines increase the ……….. of opening of …………… channel.
Frequency, chloride channels.
- What are the long-acting benzodiazepines (half-life of 25-100 hrs)?
Diazepam Chlodiazepoxide Flurazepam Ketazolam Halazepam Prazepam Clonazepam Clobazam Nitrazepam Quazepam
What are the intermediate-acting benzodiazepines (half-life 10-15 hrs)?
Temazepam Lorazepam Alprazolam Oxazepam Estazolam
What are the short-acting benzodiazepines (half-life <10hrs)?
Triazolam
Midazolam
What is sleep ?
Sleep is a state of circadian, physiological depression of consciousness with cyclical EEG and REM changes.
What are the 2 types of sleep?
Rapid eye movement ( REM)
Non rapid eye movement(NREM)
What are the features of REM sleep?
Erection Dreams Muscle relaxation skeletal Flatuating resp bp and hr. Cerebral blood flow increases
What are the features of NREM sleep?
Night terrors
Muscle relaxation
Bp hR and respiratory decline or steady
Somnambulism
Growth hormone levels are maximal.
What is the half life of the following groups of benzodiazepines?
Long acting
Intermediate
Short acting
Long acting 25 to 100hrs
Intermediate 30hrs
Short acting 8hrs
- Which benzodiazepines are preferred for long-term treatment of anxiety?
Lorazepam
diazepam
Clonazepam
Which benzo is most commonly used to treat short-term anxiety but is also highly addictive?
ALPRAZOLAM intermediate acting benzodiazepines
How do benzodiazepines affect REM and slow wave sleep?
The reduce REM sleep and slow wave sleep.
Which benzodiazepines would be useful in a patient complaining of insomnia
Triazolam short acting
Flurazepam long acting.
Temazepam intermediate
What are the drugs of choice for the termination of a seizure?
Diazepam long acting benzo
Lorazepam intermediate
Which benzos can be used in the treatment or prevention of alcohol withdrawal?
• Diazepam
•oxazepam
• Chlordiazepoxide
Clorazepate
When does delirium tremens usually start?
It’s 48- 96 ei. 2 to 4 days after the last drink.
What is the mortality rate of delirium tremens?
5%
What are the signs of DT?
Fever Hypertension Diaphoresis Agitation Disorientation Incoherence of speech Hallucinations
Which benzodiazepine is commonly used in anesthesia induction and in conscious sedation?
MIDAZOLAM
Do benzodiazepines cross the placental barrier?
Most benzodiazepines have a category D rating This means that there is some positive evidence of human fetal risk, but the potential benefits may warrant use of benzodiazepines in pregnant women.1 There are also several benzodiazepine medications that currently have a category X rating. This means that the risk involved with their use clearly outweigh the potential benefits and they are contraindicated during pregnancy. These drugs include:2 Flurazepam (Dalmane) Estazolam (ProSom) Temazepam (Restoril) Quazepam (Doral) Triazolam (Halcion)
All classes of benzodiazepines rapidly cross the placenta and can consequently affect the baby.9 Symptoms of benzodiazepine toxicity have been reported in newborns, including sedation, decreased muscle tone (floppiness), and breathing problems.9
These symptoms are not commonly seen and are likely to occur in women taking higher doses of benzodiazepines. There have also been reports of benzodiazepine withdrawal occurring in newborns exposed to benzodiazepines during pregnancy.10 Symptoms of neonatal benzodiazepine withdrawal include irritability, sleep disruption, restlessness, depression, tremors, and seizures.10
- What are the symptoms of benzodiazepine withdrawal？
Agitation Restlessness Disorientation Diphoresis Hallucinations etc Seizures
What are the adverse effects of benzodiazepines
Drowsiness
Rebound anxiety
Risk of injury in the elderly
Respiratory distress
In which patients are benzodiazepines contraindicated
Asthmatic
Closed angle glaucoma (benzodiazepines (BZDs) can narrow the iridocorneal angle and induce acute angle-closure glaucoma (AACG).
Concomitant use with alcohol causes CNS depression.
Liver dx
Psychoses
- What medication is used to reverse the effects of benzodiazepines
FLUMAZENIL and IMIDAZODIAZEPINE
Which inverse agonist blocks the effect of classic Agonist and causes anxiety and seizures if administered alone?
Beta carbolines
- Buspirone works on which receptors?
5HT1a
D2
What is Buspirone used for ?
General anxiety disorders.
What the adverse effects of BUspirone use? And explain Why increase in PRL
Less sedation since it does not work on gaba receptor
Increased prolactin prod. Due to inhibition of D2 receptor stimulation which antagonises dopamine release and dopamine inhibits PRL.
Increased growth hormone
Headaches.
Why are benzodiazepines the DOC for sedation and hypnosis?
They have a large therapeutic index.
Low risk of drug interactions base on drug induction
Slow elimination which can favor CNS desired effects
. What is the primary side effect of hydroxzyzine
Drowsiness
Which class of drug is hydroxyzine?
H1 receptor blocker.
What’s the mechanism of action of BARBITURATES?
Barbiturates bind to the GABAa receptors increasing the duration of opening of CL channels by binding directly to GABA receptors.
The also block kainate receptors( ionotropic glutamate receptor ) inhibit excitation of glutamate as well as AMPA ( transmembrane ionotropic receptors for glutamate)
Blocks neuronal Acetylcholine receptors as well
In higher doses blocks High frequency sodium channels.
It also blocks 5HT3 which is a ligand gated channel unlike the other 5Ht receptor which are Gcoupled increasing Na potassium and Ca conductance.
How can Barbiturates affect the cardiovascular system?
Decreases blood pressure and heart rate by blocking ganglionic receptor stimulation at high doses
Toxic doses cause circulatory collapse due to depression of the medullary vasomotor centre
Effects of barbiturates in respiratory ?
Causes respiratory distress by depressing the respiratory centres in brain
Inhibits the hypoxic and chemoreceptors receptor sensors from detecting CO2 ( CO2 is the stimulant of the respiratory mechanism) thus causing respiratory depression
Skeletal muscle effects of barbiturates
Large doses cause curare like effects resulting in flaccid paralyses.
What is the effects of barbiturates on kidney?
There is decrease urine formation due to hypotension and ADH release.
Effects of barbiturates on liver?
Barbiturates are liver enzyme enhancers and increase the degradation of barbiturates and other medications thus creating the chance for tolerance.
It also increases the inactivation of anticoagulants Phenytoin Theophylline Digoxin Glucocorticoid.
What are the clinical uses of barbiturates
Anxiety
Hypnosis
Convulsions
Induction of anaesthesia
Used in the management of cerebral edema, ICP and ischemia reason( by inhibiting all excitatory activities of the brain reduces the vascular tones as well as metabolic activity which demands increase cerebral blood flow. This reduces the overall cerebral blood volume and reduces the ICP.
MONITOR ICP ROUTINELY WHEN USING HIGH DOSE PHENOBARBITAL FOR ICP.
Why is barbiturates effective in management of CRIGLER NAJJAR unc, GILBERT SYNDROMEunc Rh incompatible?
(ROTOR SYNDROME conj
DUBIN JOHNSON SYNDROMEconj. )
Crigler najjar type 2 responds to phenobarbital because it stimulates the liver to produce glucoronyl transferase which is the enzyme deficient in the above dx. Note that it only effective in type 2. Type one NJ requires aggressive phototherapy to prevent kenicterus
What are the adverse effects of barbiturates?
Dependency
Decrease REM sleep
Respiratory depression
Withdrawal symptoms
Porphyria due to increase production of porphyrin. Reason barbiturates induce other enzymes, notably δ-aminolevulinic acid (ALA) synthetase. ALA synthetase is involved in the porphyrin production pathway, and therefore barbiturates are contraindicated in patients with acute intermittent porphyria (AIP) or variegate porphyria because they may precipitate an attack, manifested by severe abdominal pain, nausea, vomiting, psychiatric disorders, and neurologic abnormalities.
What is the management of barbiturates overdose?
Alkaline urine to enhance excretion
Hemodialysis and peritoneal dialysis
Induce diuretic
Respiratory support and circulation
Contraindications for barbiturates?
Acute intermittent porphyria (PoPhobilinogen deaminases)
Variegate porphyria (PPO )
Asthma
Shock
Kidney and renal failure.
What are the long acting barbiturates? PMB
Phenobarbital t1\2 1 to 2 days
Mephobarbital
Barbital
Intermediate acting barbiturates 3 to 5 hours ACTA
Aprobarbital
Cyclobarbital
Talbutal
Amobarbital
Short acting barbiturates about 2 hours
Secobarbital (quinabarbital)
Pentobarbital
Hexobarbital
Ultra short acting barb 30min TMT.
Thiopental
Methohexital
Thiamylal
Benzodiazepines effective in managing panic attacks?
Alprazolam
The duration of barbiturates action mainly depends on?
Lipid solubility and time to distribute through out the body for
Drug choice Petit mal and myoclonus seizures
Clonazepam
How long does it take for BUSPIRONE to be start its therapeutic effect
2 to 3 weeks delay before.
Which long acting. Benzodiazepines is associated with suicide ideation?
Chlordiazepoxide
