NPP 1 Flashcards
1
Q
What is the primary focus of neuropharmacology?
A
Drug actions and effects on the CNS
Neuropharmacology studies how drugs affect the nervous system, particularly in terms of neurotransmission.
2
Q
What is psychopharmacology concerned with?
A
Clinical application of drugs affecting emotion, experience, and cognition
It evaluates the efficacy, safety, and tolerability of drugs in treating diseases.
3
Q
What are the two main functions of neurones?
A
Generation and propagation of electrical impulses
Neurones transmit signals through electrical impulses across synapses.
4
Q
What process primarily occurs during synaptic transmission?
A
Chemical transmission
The majority of synaptic transmission involves the release of neurotransmitters.
5
Q
What triggers the release of neurotransmitters from vesicles?
A
Depolarising surface impulse causing exocytosis
Exocytosis is the process by which vesicles release their contents into the synaptic cleft.
6
Q
How does a neurotransmitter cross the synapse?
A
By simple diffusion
Neurotransmitters move from high to low concentration across the synaptic cleft.
7
Q
What happens when a neurotransmitter attaches to its receptor?
A
Causes local de/hyperpolarisation
This change in polarization can affect the likelihood of generating an action potential in the postsynaptic neuron.
8
Q
What is the role of autoreceptors in neurotransmission?
A
They modify activities within presynaptic neurones
Autoreceptors help regulate neurotransmitter release and synthesis.
9
Q
What are the three methods for clearing excess neurotransmitter from the synapse?
A
- Intrasynaptic metabolism by enzymes
- Active re-uptake into presynaptic neurone
- Vesicular storage of recycled transmitter
These processes ensure neurotransmitter levels are balanced and prevent overstimulation.
10
Q
What are G-proteins involved in?
A
Transferring receptor activity to intracellular organelles
G-proteins play a crucial role in signal transduction pathways in neurons.
11
Q
What is the foundational psychiatric pharmacopoeia?
A
- Antidepressants
- Antipsychotics
- Mood stabilisers
- Sedative/hypnotics
- Antimuscarinics
- Cognitive enhancers and immunotherapies
- ‘Illicit’ substances
These categories encompass the primary classes of medications used in psychiatric treatment.
12
Q
What are the types of antidepressants?
A
- Monoamine oxidase inhibitors (MAOIs)
- Tricyclics (TCAs)
- Newer compounds: SSRIs, SNRIs, NaSSAs
Different classes of antidepressants work through various mechanisms to alleviate depressive symptoms.
13
Q
What characterizes monoamine oxidase inhibitors (MAOIs)?
A
Non-selective and irreversible
MAOIs inhibit the enzyme monoamine oxidase, affecting neurotransmitter levels.
14
Q
What are the two isoenzymes of monoamine oxidase?
A
MAOA and MAOB
They are encoded on the X-chromosome and have different substrate specificities.
15
Q
What is the significance of flavin adenine dinucleotide (FAD) in monoamine oxidases?
A
It mediates redox reactions
FAD acts as a cofactor in the enzymatic reactions catalyzed by monoamine oxidases.
16
Q
Which neurotransmitters do MAOA and MAOB preferentially oxidize?
A
- MAOA: serotonin, adrenaline, noradrenaline, melatonin
- MAOB: phenylethylamine, benzylamine
Each isoenzyme has specific substrate preferences that impact their clinical effects.
17
Q
What type of inhibitors are tranylcypromine and phenelzine?
A
Irreversible non-selective MAO inhibitors
These drugs irreversibly inhibit monoamine oxidase activity.
18
Q
What is a unique characteristic of the MAO isoenzymes?
A
They are membrane-bound
This unique feature influences their function and interaction with substrates.
19
Q
What are Monoamine Oxidase Inhibitors (MAOIs)?
A
A class of antidepressants that are non-selective and irreversible.
20
Q
Name a hydrazine-based MAOI.
A
Phenelzine.
21
Q
What type of MAOI is isocarboxazid?
A
Hydrazine-based.
22
Q
What is the mechanism of action for tranylcypromine?
A
Amphetamine-based MAOI.
23
Q
True or False: MAOIs are frequently used today.
A
False.
24
Q
What major adverse effect can result from MAOIs?
A
Hypertensive crises due to uninhibited absorption of pressor amines.
25
What syndrome can occur with interactions from MAOIs?
Serotonin syndrome.
26
Name a reversible, selective MAO-A inhibitor.
Moclobemide.
27
What is selegiline classified as?
Irreversible, selective MAO-B inhibitor.
28
What is a key characteristic of selective MAOIs?
They have a low risk of serious interactions.
29
Fill in the blank: MAOIs have a _______ mode of action.
[novel]
30
What does the term 'mechanism-based' refer to in MAOIs?
Enzymes seek out drugs combining covalently to form inactive adducts.
31
What is the difference between reversible and irreversible MAOIs?
Reversible MAOIs can be displaced from the enzyme, while irreversible ones cannot.
32
What is the role of neurotransmitter sodium symporters (NSS)?
They facilitate the uptake of biogenic amines like dopamine and serotonin.
33
What is the effect of reuptake inhibition by tricyclic antidepressants?
It maintains high levels of neurotransmitters in the synaptic cleft.
34
Name a tricyclic antidepressant.
Amitriptyline.
35
True or False: Tricyclic antidepressants are selective blockers of biogenic amine transporters.
False.
36
What does a Ki value indicate?
The binding affinity of a drug to a receptor.
37
Fill in the blank: MAOIs can lead to _______ crises.
[hypertensive]
38
What does the grading system for Ki values indicate?
Affinity levels of drugs based on their binding strength.
39
What are common side effects of MAOIs?
Hypertensive crises and interactions with certain medications.
40
What is the pharmacokinetic aspect dissociated from in MAOIs?
Pharmacodynamics.
41
What is the grading system for receptor binding affinity?
++++ : < 1
+++ : 1-10
++ : 11 – 100
+ : 101 – 1000
(+) : > 1000 (of little/no clinical significance)
- : no activity
blank : no/inadequate information
42
What is the pharmacological classification of all tricyclic antidepressants?
'SNRIs'
43
What are the major metabolites of amitriptyline?
nortriptyline
44
What is the first tricyclic antidepressant (TCA) introduced?
imipramine
45
Which tricyclic antidepressant is known for its powerful antihistamine properties?
doxepin
46
What side effect is commonly associated with the cholinergic receptor interactions of TCAs?
dry mouth
47
Fill in the blank: SSRIs are relatively selective blockers of the _______.
serotonin transporter (SERT)
48
What is a common side effect of TCAs related to histamine receptor interaction?
sedation
49
Which TCA is known to be dangerous in overdose?
dosulepin (dothiepin)
50
What is the significance of Ki values in receptor binding studies?
Figures (nM) should be taken as relative, not absolute.
51
True or False: All tricyclic antidepressants interact with a wide range of central and peripheral receptor types.
True
52
What is the receptor profile for clomipramine?
pharmacologically an SSRI
53
What are the common receptor types that TCAs interact with?
*histamine (H1)
*cholinergic (M1-5)
*noradrenergic (α-1)
54
What is the effect of TCAs on postural hypotension?
caused by noradrenergic (α-1) receptor interactions
55
What are the effects of TCAs on sexual function?
sexual problems (especially in males)
56
What is the mechanism of action of G-protein-coupled inwardly rectifying potassium channels?
activated by M2 muscarinic, A1 adenosine, D2 dopamine, μ-, δ-, κ- opioid, serotonergic, m-Glu, CB1, CB2 cannabinoid
57
Which TCA is metabolized to desipramine?
lofepramine
58
What are the principles of neurotransmission involving?
*presynaptic neurone
*postsynaptic neurone
*synapse
*transmitter
*postsynaptic receptor
59
What are the potential ECG changes caused by TCAs?
QTc /antiarrhythmic
60
Fill in the blank: The pharmacology of tricyclic antidepressants includes strong interactions with _______.
biogenic amine transporters
61
Which TCA has the highest rates of sedation/anxiolysis due to its histaminic antagonism?
trimipramine
62
What is the effect of TCAs on urinary function?
urinary hesitancy
63
What is the role of second messengers in neurotransmission?
they mediate the effects of neurotransmitters after binding to receptors
64
What is the importance of understanding the pharmacological profiles of antidepressants?
to anticipate side effects and therapeutic efficacy
65
What does SSRI stand for?
Selective Serotonin Reuptake Inhibitors
## Footnote
SSRIs are a class of antidepressants used to treat depression and anxiety disorders.
66
What is the primary action of SSRIs?
Selective blockers of the serotonin transporter (SERT)
## Footnote
This action increases serotonin levels in the synapses.
67
List three examples of SSRIs.
* Citalopram
* Fluoxetine
* Sertraline
## Footnote
These are commonly prescribed SSRIs.
68
Which SSRI is known for having the longest half-life?
Fluoxetine
## Footnote
Its active metabolite, norfluoxetine, has a half-life of ~72-96 hours.
69
What is a common side effect of SSRIs related to gastrointestinal issues?
Nausea
## Footnote
Other GI symptoms include vomiting, abdominal pain, and changes in appetite.
70
True or False: All SSRIs can cause a withdrawal syndrome upon sudden cessation.
True
## Footnote
Paroxetine has the highest risk of withdrawal symptoms, while fluoxetine is less likely to cause them.
71
Fill in the blank: SSRIs can cause _______ dysfunction as a side effect.
sexual
## Footnote
This may include loss of interest or other sexual side effects.
72
What is the mechanism of action for antipsychotics?
Impedes central dopaminergic activity
## Footnote
Antipsychotics primarily act as post-synaptic dopamine (D2) receptor antagonists.
73
List the four traditional classes of antipsychotics based on chemical type.
* Phenothiazines
* Thioxanthenes
* Butyrophenones
* Substituted benzamides
## Footnote
These classifications are based on their chemical structure.
74
What distinguishes atypical antipsychotics from typical ones?
Lower liability to cause parkinsonism
## Footnote
Atypical antipsychotics are modeled on clozapine.
75
True or False: Large studies have consistently supported the idea that newer antipsychotics are more effective than older ones.
False
## Footnote
Studies have often failed to support this assumption.
76
What hypothesis may be oversimplified according to pharmacodynamic data?
Biogenic Amine Hypothesis
## Footnote
This hypothesis relates to neurotransmitter function in mood disorders.
77
What are NMDA receptors composed of?
Heterotetrameric channels from different isoform subunits
## Footnote
They include GluN1 and GluN2 subunits.
78
What ion is known to block the NMDA receptor?
Mg²⁺
## Footnote
Magnesium ions block NMDA receptors in a resting state.
79
What is the action of aripiprazole and cariprazine in relation to dopamine receptors?
Partial agonism
## Footnote
These drugs achieve their effect differently from typical antipsychotics.
80
Define the term 'discontinuation syndrome'.
Withdrawal symptoms following sudden cessation of SSRIs
## Footnote
Symptoms can include nausea, agitation, and insomnia.
81
What does the term 'affinity' refer to in pharmacology?
The strength of binding between a drug and its receptor
## Footnote
It is a measure of how well a drug can bind to its target.
82
Fill in the blank: G-protein coupled receptors (GPCRs) include _______ receptors.
D2
## Footnote
D2 receptors are a type of GPCR involved in neurotransmission.
83
What is the role of GTP in GPCR signaling?
Activates the receptor
## Footnote
GTP binding turns the receptor 'on' while GDP binding turns it 'off'.
84
List the three different protein subunits found in G-proteins.
* Alpha
* Beta
* Gamma
## Footnote
These subunits contribute to the diversity of GPCR signaling.
85
What is the role of guanosine diphosphate (GDP) in G-protein signaling?
GDP is associated with the 'off' state in G-protein signaling.
86
What is the role of guanosine triphosphate (GTP) in G-protein signaling?
GTP is associated with the 'on' state in G-protein signaling.
87
What are D2 receptors?
D2 receptors are G-protein coupled receptors (GPCRs) that bind guanosine diphosphate (GDP) and guanosine triphosphate (GTP).
88
List some common 'old' antipsychotics.
* benperidol
* chlorpromazine
* flupentixol
* haloperidol
* levomepromazine
* pericyazine
* perphenazine
* pimozide
* prochlorperazine
* promazine
* sulpiride
* trifluoperazine
* zuclopentixol
89
What is the primary pharmacological action of antipsychotics?
Antipsychotics primarily act as postsynaptic dopamine (D2) antagonists.
90
What are the major G-protein alpha subunits?
* Gαs
* Gαi
* Gαq11
* Gα12, Gα13
91
What is the role of phosphodiesterases (PDEs) in neurotransmission?
PDEs specify the site, duration, and amplitude of cyclic nucleotide signaling.
92
Fill in the blank: All antipsychotics are of equal efficacy but vary greatly in _______.
tolerability
93
What are common side effects of 'broad spectrum' antipsychotics?
* sedation
* (postural) hypotension
* (mild) tachycardia
* urinary symptoms
* sexual dysfunction
94
What is the significance of 'tight' binding in antipsychotic pharmacology?
'Tight' binding can affect motor function and is associated with a resting state of the D2 receptor.
95
What are some examples of neurotransmitters classified as biogenic amines?
* dopamine
* noradrenaline
* serotonin
* histamine
96
True or False: Clozapine is known for its high extrapyramidal side effects liability.
False
97
What are the potential side effects of high potency 'narrow spectrum' drugs?
* acute dystonia
* akathisia
* parkinsonism
* tardive dyskinesia
98
What is the effect of G-protein coupled receptors on intracellular signaling?
They activate gene networks and modulate intracellular signaling pathways.
99
What does the term 'neuroleptics' refer to?
Neuroleptics refer to antipsychotic medications.
100
Fill in the blank: The __________ hypothesis suggests a shift from postsynaptic to presynaptic 'hyperdopaminergia'.
Dopamine
101
What is the first messenger in neurotransmission?
Dopamine
102
What is the role of cyclic adenosine monophosphate (cAMP) in neurotransmission?
cAMP acts as a second messenger that activates protein kinase A.
103
What is the main difference between 'tight' and 'loose' binding in the context of antipsychotics?
'Tight' binding leads to a stronger effect and potential for motor side effects, whereas 'loose' binding may reduce these side effects.
104
What are high potency drugs more likely to cause?
Extrapyramidal neurological side-effects such as acute dystonia, akathisia, parkinsonism, and tardive dyskinesia.
105
Which drugs are examples of high potency antipsychotics?
* Haloperidol
* Risperidone
* Amisulpride/Sulpiride
106
Are all antipsychotics of equal efficacy?
Yes, but they vary greatly in tolerability.
107
What is the guideline for starting antipsychotic medication?
'Start low: rise slow.'
108
What are the two categories of pharmacological actions?
* Direct pharmacological actions
* Indirect unpredictable actions
109
What are examples of direct pharmacological actions?
* Central actions
* Peripheral actions
110
What can indirect unpredictable actions be based on?
* Chemical properties (toxic effects)
* Idiosyncratic host response (allergic effects)
111
What are common cardiovascular adverse effects of antipsychotic drugs?
* Increased heart rate
* Hypotension
* Lengthening of QT interval
* ST depression
* T-wave flattening
112
What does QTc stand for?
QTc is an ECG measure of cardiac repolarization time corrected for heart rate.
113
What factors can affect QTc measurements?
* Gender
* Time of day
* Family history
* Cardiovascular disease
* Other drugs that prolong QT interval
114
What is the risk of potentially fatal tachyarrhythmias with a QTc above 600 msecs?
Approximately 1:4000.
115
What is a significant issue for psychiatrists regarding antipsychotic drugs?
QTc prolongation.
116
What should be monitored in patients taking antipsychotic drugs?
* Serum potassium
* ECG in high-risk groups
117
What is hyperprolactinaemia associated with?
Older antipsychotic drugs, especially benzamides.
118
What are some endocrine adverse effects of antipsychotic drugs?
* Galactorrhea
* Amenorrhea
* Gynaecomastia
119
What is the metabolic syndrome also known as?
'Dysmetabolic syndrome' or 'Syndrome X.'
120
What are the criteria for metabolic syndrome according to NCEP?
* Abdominal circumference >40” (males) / >35” (females)
* Fasting triglycerides ≥150 mg/dL
* HDL <40 mg/dL (males) / <50 mg/dL (females)
* Blood pressure ≥130/85 mmHg or on antihypertensives
* Fasting glucose ≥110 mg/dL
121
What was the prevalence of metabolic syndrome found in the CATIE study?
* Males: 40.9%
* Females: 36.0%
* Overall: 51.6%
122
What is the relationship between antipsychotic drugs and weight gain?
Weight gain is very common, especially with Olanzapine and Clozapine.
123
What is the association between antipsychotics and glucose intolerance?
Common, especially with Olanzapine.
124
What is the main concern regarding antipsychotic polypharmacy?
Evidence for polypharmacy per se is weak, but prolonged QTc is generally dose-related.
125
What does the systematic review of RCTs indicate about Sertindole?
It is the only SGA associated with significant worsening effect on mean QTc.
126
What should be done in cases of rapid tranquillisation with antipsychotics?
Particular care is needed due to the major risk of sudden death.
127
Fill in the blank: The risk of prolonged QTc is in general _________.
dose-related.
128
What is the effect of D2 antagonism on tuberoinfundibular function?
Absent/unsustained.
129
What are common sexual symptoms associated with antipsychotic drugs?
Loss of libido, impaired erection, anorgasmia.
130
What is a significant adverse effect of antipsychotic drugs in women?
Loss of bone density.
131
What condition can occur due to D2 antagonism?
Galactorrhoea.
132
What is amenorrhoea potentially caused by?
Complex mechanisms related to D2 antagonism.
133
What is a rare side effect of antipsychotic drugs related to hormonal imbalance?
Gynaecomastia.
134
What metabolic syndrome effect is common with olanzapine?
Hyperglycaemia.
135
Which antipsychotic drugs are associated with significant weight gain?
Olanzapine, clozapine.
136
What is the mortality gap between schizophrenics and the general population in Finland (2006)?
22.5 years.
137
What is associated with a significant reduction in mortality compared to no antipsychotic?
Use of antipsychotics.
138
Which antipsychotic has a reduced mortality risk compared to perphenazine?
Clozapine (-26%).
139
What is the association of polypharmacy with mortality from ischemic heart disease?
Moderate mortality but no higher than drugs individually.
140
What does not predict the risk of acute death during antipsychotic treatment?
QTc interval.
141
What is a very common gastrointestinal adverse effect of antipsychotics?
Dry mouth/angular stomatitis.
142
Which antipsychotic is associated with hypersalivation?
Clozapine.
143
What is the risk associated with large bowel hypomotility from clozapine?
Up to 40% mortality.
144
What is a common neurological effect of antipsychotics?
Impaired temperature regulation.
145
What is the incidence of CVA/TIA associated with antipsychotic drugs?
Increased risk, especially with risperidone.
146
What is the estimated incidence of stroke for unexposed individuals?
12 per 1000 patient-years.
147
What factor doubles the crude incidence of stroke over 80 years?
Age.
148
What is a rare genitourinary side effect of antipsychotic drugs in males?
Urinary hesitancy/retention.
149
What is a common side effect related to sedation from antipsychotics?
Non-specific sedation.
150
What is the relationship between antipsychotics and stroke risk in the elderly?
Increased risk with different types.
151
What is the risk ratio for stroke with phenothiazines compared to non-exposed controls?
5.26 unadjusted.
152
What common dental issue can result from antipsychotic use?
Dental caries.
153
What neurological effect is characterized by EEG changes?
Decreased alpha, increased theta/delta.
154
Fill in the blank: Clozapine is the most _______ drug utilized in psychiatric practice.
toxic.
155
True or False: Clozapine's benefits are considered objectively significant.
False.
