Pharmacotherapy Flashcards
(33 cards)
importance of drugs + talk therapy
- 2018 survey found 96.7% of therapists report working with at least 1 client taking psychiatric drugs
- But only 7.3% say training equips them with knowledge to discuss withdrawal
- Tomba et al - withdrawing symptoms likely to be misunderstood as relapse + lead to reinstitution of treatment
Guidence for psychological therapists
- Tomba et al
- Had reduced awareness of barbiturates
- guidence = supported + understand difference between distress . relapse + withdrawal
- DSM-5 refers to a patient population (few drugs) that no longer exists
History of anxiolytic (anti- anxiety) meds - Bromides intro studies
-Lockock - first person to discuss potassium bromide in epilepsy patients improving symptoms
-Behrend- 2 cases of successful treatment of anxiety using potassium bromide
- MacLeod - 8 cases of Bromide sleep: put people to sleep for 5-9 day durations
History of anxiolytic (anti- anxiety) meds - Dr Miles Nervine
- intro in 1884
- contained sodium, potassium + ammonium bromides
- for those suffering from restlessness, sleepless nights + nervousness
- widely available until 1970
History of anxiolytic (anti- anxiety) meds - Bromo-Seltzer
- contained potassium bromide
-Isaac EMerson 1888 - continued over-counter till 1970
-relieves head aches, soothes stomach + calms nerves
History of anxiolytic (anti- anxiety) meds - Barbiturates- Pentobarbital
-Lopez-Munoz (2011)
- Bromides toxic due to 12 day half-life
- gradually replaced with barbiturates as shorter active timespan
- Fischer + von Mering (1903) - reported sedative effects of diethyl-barbituric acid
History of anxiolytic (anti- anxiety) meds - Barbiturates risks
-many variations of og chemical dev
- McNeil laboratories dev sodium butabarbital which is still available
-Johns (1977)- barbiturates alone accounted for 2/3 deaths from poison in 1950-70s
Leo sternbach - inventor of lots of Benzodiazepine drugs
-Held 241 patients + 6 well-known drugs
- worked with Hoffman
-Valium was most prescribed drug in US- 2.3 billion doses
- invented: Librium, Valium (Diazepam) , Mogadon, Palmae, Rohypnol + klonopin
Leo Sternbach: Valium- side effects
- Hesbacher et al - first double blind test of Valium
- simila levels of anti-antiety efficacy to Phenobarbitone but far lower side effects
Pharmacological specificity Benzodiazepins - GABA Receptors
- GABA NT Barbiturates + Benzodiazepines each bind to specific sites on GABA alpha receptor-opening its central channel
- inhibitory chloride ions flood through channel, hyperpolarize it, inhibiting firing
-Barb binds to beta + gamma
-Benzo binds to alpha + gamma
Pharmacological specificity Benzodiazepins alpha subunit variants.
-19 variations of GABA alpha receptor subunits
- common: A1, 2,3 + 5 are sensitive to benozadiazepines
Pharmacological specificity Benzodiazepins alpha subunit- Heterogenous distribution
- Fritschy + Mohler identified heterogenity
- A1 = widespread but intense in cortical + cerebellar regions
- A2: striatum
- A3 = frontal
- A5 = hippocampus
Pharmacological specificity Benzodiazepins - specific functions
- A1 = sedation + anticonvulsant properties but causes amnesia + is addictive
- A2= anxiolysis (anti-aNXiety) + muscle relaxation but is addictive
- A3 = muscle relaxant with no side effects
- A5 = muscle relaxant and amnesia side effect
Pharmacological specificity Benzodiazepins - a 1 receptor sedation test
- Rudolph et al - Diazepam’s clear sedative effects abolished when mice lacked a1 subunit
Pharmacological specificity Benzodiazepins - a1 receptor anxiety test
- Rudolph et al: Diazepams anti-anxiety effects measured in an x maze
- Diazepam increased time on light arms (anxiety- provocking ) because had less antiexy even when lacked a1 subunit
- Anti-anxiety effects not dependent on a 1 subunit
Pharmacological specificity Benzodiazepins - A2 subunit sedation test
- Low et al - Diazepam’s sedative effects just as obvious when mice lacked A 2 subunit
- Diazepam’s sedative effects are independent of a 2 subunit
Pharmacological specificity Benzodiazepins - A2 anxiety test
- Low et al -Diazepam’s anti-antiety effects measured in light/dark x maze
- Diazepam increased time in light arms in control (reduced anxiety) but no effect in those lacking a 2
- Diazepam’s anti-antiexy depends on a 2 subunit
Pharmacological specificity Benzodiazepins - a 1 memory test
- Rudolph et al- passive avoidance memory test, mice normally remembered not to enter dark box with aversive Stimuli
- mice lacked a1 remembered aversive experience + controls
- Anterograde amnesia depends on a 1 subunit
Pharmacological specificity Benzodiazepins -a 5 hippocampus localisation
- Most localised
- largely confined to hippocampus
- plays important role in learning + memory
Pharmacological specificity Benzodiazepins - a 5 sedation test
- crestani et al - removal of a 5 subunit had no effect on diazepam’s sedation
- a5 not involved in sedation
Pharmacological specificity Benzodiazepins - a 5 anxiety test
- crestaini et al - light/dark test in mice
-Diazepam increased time in lighter, anxiety- provoking box regardless of a 5 - a 5 subunit doesn’t mediate anxiety
-Pharmacological specificity Benzodiazepins - a 5 + hippocampal learning
- crestant et al - being able to remember CS before UCs depends on hippocampus
-ppts lacking a 5 do better than controls
Addictive issues of Benzodiazepines - 1960/70s known issues
- Diazepam -> tremorous, agitated t severe withdrawal + death after 3 days of discontinuation
- oxazepam -> toxic delirium, severe agitation + depression
Addictive issues of Benzodiazepines - Ventral Tegmental Area- Dopaminergic Disinhibition by a 1 subunit
- in VTA Al inhibits dopamine neurons
-Benz binds to GABA receptors on neurons + inhibit neurons + GABA release - dopamine are disinhibited + release more dopamine in nucleus accumbens
