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PharmacologyPHARMA BOARD
AnxietyFear, apprehension and worryAccompanied by physical sensations such
as anxiety, nausea, chest pain and/or shortness of breath
NeurotransmittersExcitatory NTs
Key words: sodium, calcium, depolarization
Inhibitory NTs Key: chloride, GABA, hyperpolarization
Excitatory neurotransmitters
opens Na or Ca channels/ influx depolarization (more positive) nerve impulse
e.g. Norepinephrine, Dopamine, Acetylcholine, Glutamate, Aspartate
Inhibitory neurotransmitters
opens Cl channels hyperpolarization (more negative) no nerve impulse
e.g. glycine, gamma-aminobutyric acid (GABA)
1. Panic disorder- recurrent unexpected panic attacks that can occur with agoraphobia in which patients fear places in which escape might be difficult.
2. Specific phobia- intense fear of particular objects or situations (e.g. snakes, heights);most common psychiatric disorder
3. Social phobia-intense fear of being scrutinized in social or public situations (e.g., giving a speech, speaking in class).
4. Generalized anxiety disorder- intense pervasive worry over virtually every aspect of life
5. Post-traumatic stress disorder- persistent reexperience of a trauma, efforts to avoid recollecting the trauma, and hyperarousal
6. Obsessive-compulsive disorder- recurrent obsessions and compulsions that cause significant distress and occupy a significant portion of one’s life
Sedatives-Hypnotics Benzodiazepines
Increase the frequency of GABA-mediated chloride ion channel opening
Barbiturates Increase the duration of GABA-mediated
chloride ion channel opening
Classes of Anxiolytic and Hypnotic drug
Benzodiazepines 5-HT1A-receptor agonists β-adrenoceptor antagonists
Benzodiazepines Act by binding to a specific regulatory site
on the GABA A-receptor enhances the inhibitory effect of GABA. Subtypes of the GABA A-receptor exist in
different regions of the brain differ in their sensitivity to benzodiazepines.
Anxiolytic benzodiazepines are agonists at this regulatory site.
Receptor Empty
Intra cellular
GABA
GABA Receptor
- CL
+++++++
- - - - -
Na
Channel
Na
Channel
Intra cellular
GABA
GABA Receptor
- CL
+ + + +
- - - -
Na
Channel
Na
Channel
- - - -
Use of The DrugsClinical indications for the use of the
anxiolytics, sedatives and hypnotics 1. Prevention of anxiety 2. Formation of sedative state 3. Induction of sleep
ACTIONS Reduction of anxiety Sedative – hypnotics Anticonvulsant Muscle relaxant
The BENZODIAZEPINES
The benzodiazepines are the most frequently used anxiolytic drugs.
These agents prevent anxiety states without causing much sedation, with less physical dependence than other agents.
The BENZODIAZEPINES
Long Acting Intermediate Acting Short Acting
Long Acting (1-3 days) Charlie Chaplein Died From Q-fever
Long Acting (1-3 days) Charlie - Chlorazepate Chaplein - Chlordiazepoxide Died - Diazepam From - Flurazepam Q-fever - Quazepam
Intermediate L A T E
Intermediate L - Lorazepam A - Alprazolam T - Temazepam E - Estazolam
Short Acting O- Oxazepam T- Triamzolam
Uses: Anxiety- alprazolam, diazepam Seizures- diazepam, clonazepam,
lorazepam Insomnia- flurazepam, midazolam Pre-operative sedation- midazolam
The BENZODIAZEPINESSpecial uses
Diazepam(Valium)
Status epilepticus
Chlordiazepoxide (Librium)
Alcohol withdrawal
Alprazolam (Xanax)
Panic attack
The BENZODIAZEPINES
These agents are indicated for the treatment of
1. anxiety disorders2. alcohol withdrawal3. hyperexcitability, and agitation4. pre-operative relief of anxiety and tension
and in induction of balanced anesthesia.
The BENZODIAZEPINESPharmacodynamics: The adverse effects CNS effects= drowsiness,
depression, lethargy, blurred vision GIT= dry mouth, constipation, nausea,
vomiting
. sedation,
CVS= Hypotension or hypertension, arrhythmias, palpitations, and respiratory difficulties.
Hematologic= blood dyscrasias and anemia
GU= urinary retention, hesitancy, loss of libido and sexual functions changes.
The BENZODIAZEPINES
Instruct to avoid consuming ALCOHOL while taking the drug.
The BENZODIAZEPINES
Have available FLUMAZENIL as an antidote for benzodiazepine overdose.
5-HT1A Agonists as Anxiolytic Drugs Buspirone
potent (though non-selective) agonist at 5HT1A-receptors.
Lacks anti-seizure and muscle relaxant properties as benzodiazepines
Headache, minimal tolerance and withdrawal Anxiolytic effects take days or weeks to develop.
Ipsapirone and Gepirone are similar. Side effects include dizziness, nausea, headache, but
not sedation or loss of coordination
The BARBITURATES These are also anxiolytics and
hypnotics with a greater likelihood of producing sedation, with increase risk of addiction and dependence.
Barbiturates
Non-selective CNS depressants Sedation and unconsciousnessBind to the GABA receptor and enhances activity
potent inducers of hepatic drug-metabolising enzymes
Tolerance and dependence occur.
Barbiturates
Non-selective CNS depressants Sedation and unconsciousnessBind to the GABA receptor and enhances activity
potent inducers of hepatic drug-metabolising enzymes
Tolerance and dependence occur.
MODE OF ACTION Interferes with Na and K transport Potentiates GABA action on Cl
ACTIONS Depression of CNS Respiratory depression Enzyme induction
CLASSIFICATION ULTRA – SHORT Thiopental Thiamylal Methohexital Duration: 30min
SHORT ACTING Hexobarbital Pentobarbital Secobarbital Duration: 2hrs
INTERMEDIATE ACTING Amobarbital Butabarbital Duration: 3 – 5hra
LONG ACTING Barbital Phenobarbital Duration: > 6hrs
The BARBITURATES
Pharmacodynamics: The Adverse effects CNS= CNS depression, somnolence, vertigo,
lethargy, ataxia, paradoxical excitement, anxiety and hallucinations.
GIT= nausea, vomiting, constipation/diarrhea and epigastric pain
CVS= bradycardia, Hypotension and syncope.
Respi= serious hypoventilation, respiratory depression and laryngospasms
Others= hypersensitivity and Stevens-Johnson syndrome.
Other Notes Benzodiazepines have no analgesic
properties Fatality of alcohol and benzodiazepines Hypnotics does not induce REM so less
restful than normal sleep Longer acting drugs are easier to dose so
effective in alcohol withdrawal
Sedative-Hypnotics: BarbituratesDrug Interactions Additive effects:
ETOH, antihistamines, benzodiazepines, narcotics, tranquilizers
Inhibited metabolism: MAOIs will prolong effects of barbiturates
Increased metabolism: Reduces anticoagulant response, leading to
possible clot formation
Benzodiazepines vs. BarbituratesCriteria BZ Barb.
Relative Safety High Low
Maximal CNS depression Low High
Respiratory Depression Low High
Suicide Potential Low High
Abuse Potential Low High
Antagonist Available? Yes No
Ion channel that contains the GABA receptor:
A. sodiumB. calciumC. chloride D.potassium
Anxiolytic drug acting through serotonin receptors:
A.diazepam (Valium) B. buspirone (BuSpar) C. triazolam (Halcion) D. phenobarbital
A comatose patient is brought to the emergency department with severe respiratory depression caused by diazepam overdosage. Reasonable intervention at this point include:
A. administer naloxone (Narcan) to block the drug's effect at the receptor B. provide supportive therapy until the drug effect wears off. C. administer flumazenil D. B & C
Short-acting benzodiazepineA. diazepam (Valium) B. flurazepam (Dalmane)C. triazolam (Halcion) D. buspirone (BuSpar)
Most useful in reversing symptoms of benzodiazepine overdosage:
A. amphetamine B. buspirone (BuSpar) C.flumazenil (Romazicon) D. naltrexone (ReVia)