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clinical pharmacology and neurosciences Flashcards

1
Q

What is the CATIE study?

A

Study was a nationwide clinical trial that compared the effectiveness of older (first available in the 1950s) and newer (available since the 1990s) antipsychotic medications used to treat schizophrenia.

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2
Q

what happened in phase 1 of CATIE study

A

Phase 1: Phase I compared old and new antipsychotics.
Four of the newer medications to one another, and to an older medication

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3
Q

which four newer and which older antipsychotic were used in which phase of CATIE study

A

Phase 1

olanzapine
quetiapine
risperidone
ziprasidone

or to the older, ‘typical’ medication:

perphenazine

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4
Q

what did the CATIE study phase 1 show?

A

high rates of discontinuation due to intolerable side-effects or failure to adequately control symptoms.

olanzapine, was slightly better than the other drugs but also was associated with significant weight-gain as a side-effect. Patients assigned to olanzapine had the longest successful treatment time, and the fewest hospitalizations as a result of exacerbation of schizophrenia.

Surprisingly, the older, less expensive medication (perphenazine) used in the study generally performed as well as the four newer medications.

Contrary to expectations, movement side effects (rigidity, stiff movements, tremor, and muscle restlessness) primarily associated with the older medications were not seen more frequently with perphenazine than with the newer drugs.

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5
Q

what did PHASE 2 of CATIE trial aim to look at?
what were the study arms?

A

Phase II

To provide guidance on which antipsychotic to try next if the first failed (either due to ineffectiveness or intolerability).

Participants who discontinued their first antipsychotic medication because of :
1. inadequate management of symptoms —> efficacy (clozapine) pathway

  1. intolerable side effects–> tolerability (ziprasidone) pathway.
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6
Q

which medication was found to be effective in phase 2 of catie trial/

A

Clozapine was remarkably effective and was substantially better than all the other atypical medications.

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7
Q

what else did the catie study look at?

A

risk of metabolic syndrome

Central obesity: waist circumference 102 cm or 40 inches (male), 88 cm or 36 inches(female)
Dyslipidaemia: TG 1.7 mmol/L (150 mg/dl)
Dyslipidaemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female)
Blood pressure 130/85 mmHg
Fasting plasma glucose 6.1 mmol/L (110 mg/dl)

MS at baseline in the CATIE group was 40.9%

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8
Q

How are anti-psychotics categorised

A

typical (first generation)
atypical types (second generation)

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8
Q

which other receptor does atypical work on and which medications

A

5-HT1a agonism (some such as clozapine, quetiapine, ziprasidone)

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9
Q

which are typical and atypical?

A

Typical antipsychotics Atypical antipsychotics
Chlorpromazine Clozapine
Flupenthixol Risperidone
Zuclopenthixol Olanzapine
Perphenazine Quetiapine
Trifluoperazine Ziprasidone
Sulpiride Amisulpride
Haloperidol Aripiprazole

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9
Q

how to antipsyhotic works?

A

reduce dopaminergic neurotransmission.

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9
Q

mechanism of typical anti-psychotics

A

defined by the ability to block dopamine (D2) receptors.

They also have in, varying degrees, M1, Alpha-1 and H1 receptor blockade.

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9
Q

mechanism of atypical antipsychotics

A

D2 and 5-HT2a antagonism
Rapid D2 dissociation

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10
Q

how else can anti-psychotics be classified

A

by structure

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11
Q

which medication is Phenothiazines (Aliphatic side chain) associated with

A

Phenothiazines (Aliphatic side chain) Chlorpromazine

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12
Q

which medication is Phenothiazines (Piperidine side chain) associated with

A

Thioridazine, pipothiazine

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13
Q

which medication is Phenothiazines (Piperizine side chain) associated with

A

Trifluoperazine, fluphenazine

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14
Q

Flupenthixol, zuclupenthixol -which structure is associated with these medications

A

Thioxanthenes

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14
Q

what structure is haloperidol associated with

A

Butyrophenones

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15
Q

Pimozide - which structure is associated with this medication

A

Diphenylbutylpiperidines

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16
Q

which structure is associated with this medication

quietapine
sulpiride/amirsulpride
aripiprazole

A

Dibenzothiazepines Quetiapine
Substituted benzamides Sulpiride, amisulpride
Arylpiperidylindole (quinolone) Aripiprazole

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17
Q

which structure is associated with this medication
Clozapine
Risperidone
olanzapine

A

Dibenzodiazepines Clozapine
Benzoxasoles Risperidone
Thienobenzodiazepines Olanzapine

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18
Q

what classification is cloazapine
what is it a deriative off

A

atypical antipsychotic
used when antipsyhotics trialled and failed
classified as a tricyclic dibenzodiazepine derivative.

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19
Q

where is clozapine more active

A

in limbic system rather than striatal

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20
which receptors does clozapine work on?
Clozapine is a D1 (dopamine 1), D2, 5-HT2A, alpha1-adrenoceptor, and muscarinic-receptor antagonist. It has a particularly high affinity for the D4 receptor and exerts only a weak blockade of D2 receptors.
21
clozapine impact on prolactin
nil to little
22
Receptors affected by clozapine
Receptors affected by clozapine Dopaminergic Histaminergic Serotonergic Adrenergic Cholinergic
23
what metabolises clozapine
cYP1A2.
24
what can impact clozapine levels
acco smoke contains polycyclic aromatic hydrocarbons induce CYP1A2
25
what is an inhibitor of this cytochrome what affect does it have on clozapine level
CYP1A2 coffeee caffeine (as inhibitor) of cyp1a2 this leads to increased cloazpine level
26
list the inducers and inhibitors of this cytchrome and the impact it has on clozapine level
Drug Effect on plasma clozapine levels SSRI's Increased Erythromycin Increased Caffeine Increased Carbamazepine Decreased Phenytoin Decreased Tobacco Decreased
27
another important cytochrome with clozapine
CYP2D6.
28
medical word for hypersalivation
(silarrhoea). 1/3 of patients develop this
29
s/e of clozapine
Drowsiness/ sedation Constipation Salivation Weight gain Dizziness Insomnia Nausea Vomiting Dyspepsia
29
active metabolites of clozapine
e main 'active' metabolites (note: some sources regard the metabolites as inactive) are: N-desmethylclozapine (norclozapine) clozapine N-oxide
30
complications of clozapine
Agranulocytosis Myocarditis, pericarditis / pericardial effusion, cardiomyopathy Seizures Severe orthostatic hypotension with or without syncope Increased mortality in elderly patients with dementia related psychosis Colitis Pancreatitis Thrombocytopenia Thromboembolism Insulin resistance and diabetes mellitus (Approx 33 percent developed diabetes mellitus over a ten year period (Henderson, 2005))
31
what is used to help manage excess salivain clozapine patients
Amisulpride (supported by placebo controlled RCT) Atropine (rarely used) Hyoscine hydrobromide (widely used but no published data) Amitriptyline Propantheline (two Chinese RCTs, one positive) Benzhexol (small open study suggests useful)
32
caution with clozapine
prostatic hypertrophy susceptibility to angle-closure glaucoma adult over 60 years
33
what shoudl be noted in patints with seizures on clozapine
Seizures: When using clozapine, valproate should be considered if Using high doses Plasma levels > 0.5 mg/l Patient experiences seizures
34
facts about myocarditis with clozapine
Myocarditis is rarely seen in clozapine use but carries with it a high mortality. 1 in 500 rate, early in the course of clozapine treatment. detected within 16 days (median) of initiating clozapine in a study of 116 cases (Hass, 2007). Approximately 80 percent of cases of clozapine-induced myocarditis occur within four weeks of drug initiation 90 percent occur within eight weeks. Post-mortem examination - damaged myocytes and eosinophilic infiltration suggesting a type I Ig E-mediated acute hypersensitivity reaction. Subsequent use of clozapine in cases with clear clozapine-induced myocarditis leads to recurrence of myocarditis in most cases when the drug is restarted. Features include:- Fever Chest pain Tachycardia Dyspnoea Flu-like symptoms Elevated eosinophil count Elevated cardiac enzyme levels
35
biomarkers for myocarditis
Biomarkers, including creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), myoglobin, and troponin, may all be raised in patients with myocarditis. Troponin T and I are the most specific as they are unique to the myocardium (troponin C is synthesised in skeletal muscle). That said, they are not raised in every case and so often a range of markers are assessed.
36
monitoring clozapine
Clozapine requires differential white blood cell monitoring weekly for 18 weeks, then fortnightly for up to one year, and then monthly as part of the clozapine patient monitoring service. prolactin at 6 months but unlikely to eb raised - be more vigilants for symptoms lood lipids and weight should be measured at baseline, at 3 months (weight should be measured at frequent intervals during the first 3 months), and then yearly with antipsychotics. Patients taking clozapine require more frequent monitoring of these parameters: every 3 months for the first year, then yearly. Fasting blood glucose should be measured at baseline, at 4–6 months, and then yearly. Patients taking clozapine should have fasting blood glucose tested at baseline, after one months’ treatment, then every 4–6 months.
36
he gold standard for diagnosis of myocarditis is
an endomyocardial biopsy,
37
suggested mechanisms of weight gain with clozapine
suggested mechanisms (Dayabandara, 2017) include (presumably mediated through stimulation of appetite): 5HT2a and 5-HT2c antagonism D2 and D3 antagonism H1 and M3 antagonism Hyperprolactinemnia Increased serum leptin (leading to leptin desensitisation) Ghrelin
38
which antipsychotics are at high moderate weight gain risk
Clozapine High Olanzapine High Chlorpromazine Moderate Quetiapine Moderate Risperidone Moderate Paliperidone Moderate
39
if no improvement with lifestyle changes, which antipsyhotics have good support with switching
aripiprazole ziprasidone lurasidone
40
what is good augmentation for clozapine induced weight
Liraglutide
41
which anti-pschotic is associated with death
Thioridazine has pronounced effects on K+ channels and materially prolongs the QTc interval, it is most associated with sudden death.
42
which antipsychotics have highest risk of diabetes what should be considered in prediabetics
Clozapine and olanzapine are associated with the highest risk. Amisulpride, aripiprazole, and ziprasidone are recommended by the Maudsley for patients with a history or predisposition for diabetes.
43
which antipsychotics showed EEG changes
Clozapine 47.1% Olanzapine 38.5% Risperidone 28.0% Typical antipsychotics 14.5% Quetiapine 0.0%
44
what is the steady state with relation to antipsychotics
point at which the amount of drug administered each day is exactly counterbalanced by the amount eliminated. s. Steady-state is when the administration of a drug and the clearance are balanced, creating a plasma concentration that is unchanged over time
45
what are the half life of the following antipsychotics Antipsychotic Amisulpride Aripiprazole Quetiapine Olanzapine Clozapine Risperidone Ziprasidone
Aripiprazole 75 hours Olanzapine 30 hours Risperidone 20 hours Clozapine 12 hours Amisulpride 12 hours Ziprasidone 7 hours Quetiapine 6 hours
46
what are the times to steady state for the list of anti psychotics
aripiprazole 2 weeks olanzapine 1 week the rest 2-3 days
47
which anti psychotics cause postural hypotension
Risperidone Clozapine Olanzapine Paliperidone Quetiapine Ziprasidone
48
which anti psychotic should be considered if postural hypotension
Amisulpride Aripiprazole Haloperidol Sulpiride Trifluoperazine
49
which psychiatric drugs interact with contraceptives
St John's Wort Carbamazepine Phenytoin Topiramate Barbiturates reduced contraceptive effect
50
porphyria symptoms
Abdominal pain Mental state changes Constipation Vomiting Muscle weakness red brown urine seizure anxiety hypertension palpitations
51
what are porphyrias
orphyrias are a group of uncommon disorders that are caused when there are problems with the production of chemicals called porphyrins in the body. Porphyrins are the chemical building blocks of haem, which form haemoglobin, the component of red blood cells that allows oxygen to be carried around the body. An increase in the amount of a specific porphyrin or a porphyrin precursor results in symptoms of porphyria
52
which medications can precipitate prophyria
Barbiturates Benzodiazepines Sulpiride Certain mood stabilizers
53
what are the three phases of steroid use
cycling 4-12 week usage and stopping to minimise side effects stacking more than one at a time, for muscle growth and strength pyramiding increase dose to peak then wean
54
what class of drugs are steriods
class C
55
what psychiatry conditions are associated with steroid use
mania anxiety depression pscyhosis mood instability
56
s/e of steroids
skin -oil skin, acne, male pattern baldness, jaundice muscle hypertrophy cardio -raised bp, hr, LDL, MI Hepatic - cholesterol, malignant liver, sleep apnoea abnormal sperm count, menstruation changes, shrink breast tissue, hypogonadism, deep voice, BPH, Testicular atrophy
57
what is the active metabolite impramine for which antidepressants
lofamriane impramine
58
trazado has an active metabolite named as
MEPP
59
60
who termed antidepressant
Lune
61
which antidepressant most effective by buccal route
fluoxetine
62
which medication give IM has mood evkvating effects
flupentixol
63
what is the concern with citalopram in overdose
torasades de pointes
64
which anti depressant is best for diabetes
SSRI
64
worst antidepressant for discontinuation symptoms
paraxotine venlafaxine
65
best antidepressant for narcolepsy
clopramine
66
best for bulimia
fluoxotine
67
best antidepressant for phobias
clopramine
68
best antidepressant also used for nocturnal enuresis
amitruplline impramine
69
which depo is good for preventing relapse
zuclopenthixol but high risk of s/e
70
71
which are the three atypical antipsychotics
OLANZAPINE ARIPIPRAZOLE RISPERDONE
72
lowest dose for haloperidol
25mg
73
lowest dose for zuclopenthixol
100mg
74
what is post injection syndrome
when antipsychotic is injected into the BV directly person will feel sleepy, confused, anxiety, dizziness
75
lowest dose for flupentixcol
20mg
76
what are the main EPSE
dystonia tardive dyskenesia akathasia pseudoparkinsonism
77
facts about dystonia
multiple types rf: male, neuroleptic naive 10% of patients usually within mins or hours
78
what can be given to counteract dystonia
botox anticholingerics
79
which EPSE is most resistant to treat what is it
akathisia intense sensation of unease or an inner restlessness that usually involves the lower extremities.
80
where do EPSE act on
D2 receptors in basal ganglia
81
triad for Parkinsonism
rigidity -cogwheel bradykinesia fine tremor -pin rolling
82
how common is akathisia
25%
83
what can be used to counteract akathisia
cyprohepadine benzo clomidne propanolol mirtazpine
84
whats risk factor for tardive dyskinesia
elderly female Early EPSE
85
what can be used to manage tardive dyskinesia
stop any anticholingeric gingko. biloba Tetrabenazine
86
name some anticholingerics
procyclidine benztropine orephradine
87
which antipsychotic has the longest half life
aripiprazol 75 hours 2 weeks
88
which depo is good at prevent relapses
zuclopehtnixol but has s/e lots
89
what is used to monitor sexual dysfunction?
arizona sexual experience scale
90
what is pharmacodyanmics
impact of drug on the body biological MoA interactions receptor binding
91
what is pharmokinetics
body on drug Absorption distribution Metabolism elimination
92
highest rate of priapism
trazaone chlorapromazine
93
# ** what are anabolic steriods
synethic derivatives of testosterone they have androgenic properties -masculising anabolic -tissue building
94
which type of steriods are anabolic mostly and what is the reason for this
to reduce adrengic impact such as nandrolone oxandrolone aim is for tissue building
95
wwhat are the functions seen with testosterone
muscle repair amd metabolism sexual cognition function bone/lipid metabolism erythropeosis
96
who discovered forced swim test snd why
porsolt preclinical research looking at depression in rats found those who had antidepressants had more motivation when placed in water
97
Which antidepressants can be given IV
citalopram mirtazpine amitripylline clomipramine
98
what can be given IM with a mood elevating affect
flupenthixol
99
active metabolite of trazdone
MCPP
100
active metabolite for venlafaxine
o-desmethyl-venlafaxine
101
which antidepressant can cause cardiac issue in overdose what is the consequence of thisn
citalopram torsades des pointes
102
which two antidepressants have the worst s/e with stopping
paroxtine venlafaxine
103
which depo is good at preventing relapses but whats the issue with it
zuclothopenthixol increased side effects
104
what is the good thing about fluthixpentol,
can be used in higher doses
105
minimium effective doses for antipsychotics halopderiol zculopehthixol flupenthixol pipothazine fluphenzine
halopderiol - 25mg zculopehthixol 100mg flupenthixol 20mg pipothazine 25mg fluphenzine 12.5mg
106
whare are the antidopaminergic s/e
gyanecomastica galactthorea reduced sperm count reduced libidio ataxia dizziness , TD, akathasia
107
what are the anti histamien s/e
sedation drwosy weight gain
108
what are anti adregenic s/e
postural hypotension ejaculation failure
109
anti cholingeric s/e include
dry mouth blurred vision constipation urinayr retention etc
110
worst antipsychotic for weight gain worst for EPSE
EPSE - haloperidol weight gain - olazapine, sedation and diabetes clozapine also weight gain, sedation wg, diabetes
111
which three antipsychotics dont affect sexual dysufctnion
aripiprazole lurasidone aseniapine
112
what are barbituates
faciitates GABA-A and prolonngs opening of chloride chanells
113
how does baritbuates differ from benzo
benzo increases frequency of chanells
114
how do u remember the difference between barbituates and benzo
BARBIDURATION FRENZODIAZPINE
115
WHAT ARe the two phases of obtaining a biogenic amine from an AA
phase 1: oxidation p450 reduction, hydrlosis phase 2: hydrophilic group added and toxic intermidate is formed then needs to be transferred
116
name some things in phase II
glucuronidation (most common) methylation acetylation sulfation conguation with gluthathione conjucton with amino acids
117
what occurs in phase III
ATP binding caseette activation transport for elimination
118
which is the most common method for phase ii
glucourindation
119
what is carbamazepine used for
1st line for parital seixures bipolar and neuropathic pain
120
who should carbamazepine be ci IN
previous bone marrow suppression MAOI usage combination
121
what is charles bonnet syndrome
they have visual hallycinations and auditory rf : AGE, female, isolated, visual impaiared associated with mascular degeneration
122
what are the new IV anti demenetia medications mechanism
IV adicanumab DISEASE MODIFYING MEDICATIOn in traits with by degrate the plques by using losomones and phagycotysosis also lecaneumab
123
how does ristavigamine and galanatamine differ from donzpezil
galantamine has nictone receptor activity rivastigmine -also has butylcholsterine can be patches
124
half life of donepzil.
70 hours
125
what can affect a medications ability to function
if it is impaired by air or moisture or klight for example zopiclone should not be playced in moisture or light
126
what is used for absent seizure
ethosuximide blockss t type calcium channels
127
what is the half life of lithium
4-6 days
128
half life of rispoderone depo
6-8 weeks
129
what is the half life of olanazapine
7 days
130
what is the half life of TCA
2-3 days
131
what are risk factors for cluster headaches symptoms
male:female 5:1 , smokers pain 1/2 times a day lasting 15 mins to 2 hours intense pain one side around eye eye symptoms sometimes such as swelling, redness, ptosis
132
how do u manage cluster headaches acutely
o2 , nasal subcut triptan
133
prevention of cluster headaches
prednisolone verpamil
134
mx of parxoymal hemioma
indomethacin
135
which nerve ellicts the papillary light reflex
optic oculomotor
136
which nerve ellicit accomodation
optic and oculomotor
137
jaw jerk which nerve ellicit
trigeminal
138
which nerve ellicit corneal reflex
trigmeinal and facial
139
which nerve ellicit gag reflex
glossopharyngeal and vagus
140
what is PrPc and PrPsc
Prion diseases are associated with the conversion of the α-helix rich prion protein (PrPC) into a β-structure-rich insoluble conformer (PrPSc) t
141
kuru dx
associated with cannibalism papa new guniea ate dead ancestors leads to tremors and loss of coordination from neurodegeneration.
142
142
CJD
Creutzfeldt-Jakob disease prior disease two types - sporadic and variant
143
what are the differences in the two types of CJD
variant younge age 20-30s longer duration pulvinar sign in 75% behavioural/MH changes EEG waves not usually present spordiac older 60s shorter duration no pulvinar sign but EEG signs
144
which of the CJD are more common
sporadic 85% older adults
145
which chromosone is associated with prion protein
chromosone 209 methionine homogeneity coldon 129
146
what is Gerstmann–Sträussler–Scheinker syndrome
extremely rare inherited within families few in world autosomal dominant prion disease with slurred speech, nystagmus and rigitity/spacity/blindness
147
what are macroscopic changes seen with LBD
cerebral atrophy Brain weight in normal range though pallor in substanstia nigra - midbrain and The locus coeruleus
148
where are the substanstia nigra and The locus coeruleus what do they produce
substanstia nigra - mid brain and doapmine midbrain and The locus coeruleus - pons and norephedrine
149
what are Lewy bodies made of
alpha synuclein
150
how dO LB differ from pick body
LB have central core and halo Picks don't Pick made of Tau
151
another name for punch drunk syndrome
dementia pugilistica coined by Millspaugh
152
who was punch drunk syndome seen in and symptoms
NFL players boxers neuro trauma slurred speech, impaired hearing, gait ataxis, cognitive dcline, behaviour change, impulse control , irritable
153
what type of condition is punch drunk syndrome
tauopathy affect cortical slucus perivascualr distrubition

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