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Yr 2 - Pharmacology > Treatment of CNS disorders > Flashcards

Flashcards in Treatment of CNS disorders Deck (203):
1

Which channels are opened when a neurotransmitter binds on the post synaptic membrane in excitatory neurones?

And what does this cause?

Na in K out= depolarisation of the membrane

2

Which channels are opened when a neurotransmitter binds on the post synaptic membrane in inhibitory neurones?

And what does this cause?

Cl in = hyper polarisation of the membrane

3

Give an example of a glial cell:

Astrocyte

4

How do glial cells modulate the shape of post-synaptic response?

Remove the neurotransmitter from the synaptic cleft

5

Compare the following features of the Nervous system and Endocrine:

Mediator molecules

Cells affected

Time of onset of action

Duration of action

6

What criteria must a chemical meet before it can be called a neurotransmitter? (3)

Must be synthesised and stored within a pre-synaptic neurone (neurone must contain synthesising enzyme)

Stimulation causes release of the chemical from the nerve terminal (depolarisation)

Must cause the same effect as nerve stimulation on the postsynaptic neurone when applied directly onto the neurone

7

How many neuroactive substances can be found in the CNS?

Approx. 40

8

What type of channels are inotropic receptors?

Ligand-gated ion channels

9

What type of channels are metabotropic receptors?

GPCRs

10

List the (7) major CNS transmitters:

Glutamate

GABA

Acetylcholine

Monoamines (Noradrenaline, Dopamine & Serotonin)

Histamine

Opioids

Nitric Oxide (synthesised on demand & easily crosses the phospholipid bilayer -> its release is not Ca dependant but its synthesis is!)

11

What causes a  neurotransmitter to have a dual response?

It acts on both Ionotropic receptors (faster inital response) AND metabotropic receptors (slower inital response because it takes a while for the second messenger to be synthesised)

12

What do neuromodulators do?

They alter the strength of response

13

What do neurotrophic factors do?

Influences neuronal differentiation and proliferation

 (most do this by acting on Tyrosine kinase receptors)

14

What are the (4) different targets for drug action?

Ion channels

Receptors

Enzymes

Transporter proteins

15

Name an excitatory neurotransmitter in the CNS:

Glutamate

16

Name an inhibitory neurotransmitter in the CNS:

GABA

17

Which drug targets transmitter synthesis in the CNS?And what is the clinical application of this drug?

L- Dopa

Parkinson's disease

18

Which drug targets transmitter storage in the CNS?And what is the clinical application of this drug?

Reserpine

Hypertension

19

Which 2 drugs targets transmitter release in the CNS? And what is the clinical application of this drug?

Amphetamine 

Na & Ca channel blockers

 

Attention Deficit Hyperactivitiy disorder (ADHD)

20

Name 2 receptor agonists in the CNS?

And what is the clinical application of this drug?

Morphine (analgesia)

Buspirone (Anxiety)

21

Name 2 receptor antagonists in the CNS?

And what is the clinical application of this drug?

Cloazapine (antipsycotic)

Memantine (alzheimers)

22

Which 2 drug target reuptake in the CNS?

And what is the clinical application of this drug?

Cocaine (stimulant)

Fluoxetine (depression)

23

Which 2 drugs target degradation in the CNS?

And what is the clinical application of this drug?

Moclobemide (depression)

Donepezil (alzheimers)

24

Which drug targets intracellular signalling in the CNS?And what is the clinical application of this drug?

Lithium 

Bipolar disorder

25

Which drug targets nerve growth in the CNS?

And what is the clinical application of this drug?

Myotrophin 

Motor neurone disease

26

Why is it not a good idea to completely 'knock out' a neurotransmitter?

Give an example:

Bad side effects -> widely spread

e.g. Completely knock out glutamate = coma

27

Name 2 examples of drugs that target Glutamate:

(include their clinical use) 

Ketamine = NMDA channel blocker (one of the inotropic receptors of Glutamate) => dissociative anaesthetic

Memantine = NMDA receptor antagonist => cognitive enhancer (in alzheimers)

28

What may drugs that target glutamate be used to treat? (4)

Learning and memory

Schizophrenia

Mood disorders

Excitotoxicity

29

Name the key 2 examples of drugs that target GABA: What are their clinical uses?

Benzodiazepines: Sedative hypnotic

Barbituates: Sedative hypnotic 

Others:

Vigabatrine: GABA transaminase inhibitor = anti-epileptic

Alphaxalone: steroid general anaesthetic

Baclophen: GABA B angonist = spascticity

GHB: drug of abuse

30

In which (3) illnesses are GABA B recreptors for GABA targetted?

Epilepsy

Anaesthesia

Cerebral Palsy

31

Name the 3 main types of monoamine neurotransmitter:

Dopamine

Serotonin

Noradrenaline 

 

N.b. these are difficult to target individually = aggressive & irritable moods if more than 1 disrupted by drug

32

Treatments for which 5 disorders target dopamine?

Parkinson's disease

Schizophrenia

Drug abuse and addiction

ADHD (attention deficit hyperactivity disorder)

Depression

33

If drugs such as L-DOPA are given in the wrong situation what can it induce?

Schizophrenia like symptoms & hallucination

34

What does L-DOPA target?  And what is its clinical use?

Bypasses the rate limiting synthetic enzyme for Dopamine

Parkinson's disease

35

What does Haloperidol target?

And what is its clinical use?

D2 receptor antagonist

Anti-psychotic

36

What does Domperidone target? 

And what is its clinical use?

D2 receptor antagonist

Anti-emetic

37

What does Selegeline target? 

And what is its clinical use?

Monoamine oxidase - B inhibitor (MAO-B)

Neurodegeneration

38

What does Amantadine target? 

And what is its clinical use?

Dopamine releasing agent 

Parkinson's disease

39

What does Amphetamine (methylphenidate) target? 

And what is its clinical use?

Re-uptake inhibitor

Attention deficit hyperactivity disorder (ADHD)

40

What does Buproprion target? And what is its clinical use?

Dopamine/noradrenaline reuptake inhibitor 

Anti-craving

41

What is Pramipexole? 

Dopamine partial agonist

42

Treatments for which (7) disorders target noradrenaline?

Cognition

Depression

Anxiety

Pain

Addiction

Obesity

ADHD 

43

What are the main functional effects of noradrenaline?

Attention

Cognition

Sensory

Homeostasis

Sympathetic output

Sleep-wake cycle

Motivation

44

What does Amitriptyline target? And what is its clinical use?

Serotonin and Noradrenaline reuptake inhibition

Pain & antidepressant

45

What does Reboxetine target?

 And what is its clinical use?

Noradrenaline reuptake inhibition

Antidepressant

46

What does Sibutramine target? And what is its clinical use?

Serotonin & Noradrenaline reuptake inhibition

Anti-obesity

47

What does Mirtazapine target?  

And what is its clinical use?

Alpha 2 adrenoreceptor and serotonin receptor antagonist

Antidepressant

48

What does Atomoxetine target? 

And what is its clinical use?

Noradrenaline reuptake inhibiton

ADHD

49

What does clonidine target? 

And what is its 2 clinical uses?

Alpha 2 adrenoreceptor agonist

Anti-hypertensive & epidural anaesthetic

50

What does Lofexine target? 

And what is its clinical use?

Alpha 2 adrenoreceptor antagonist Opiate withdrawal

51

What are the (8) functional effects of serotonin in the CNS?

Motor control

Behavioural control

Mood and emotion

Sensory function

Homeostasis

Sleep-wake cycle

Appetite

Vomitting

52

Which (6) diseases are drugs that target serotonin used to treat?

Depression

Anxiety

Pain

Schizophrenia

Migraine

Emesis (vomitting)

53

What does Clomipramine target? 

And what are its 2 clinical uses?

Serotonin reuptake inhibitor

Depression & OCD

54

What does Amitriptyline target? 

And what are its 2 clinical uses?

Serotonin & noradrenaline reuptake inhibitor

Depression & OCD

55

What does Sibutramine target? 

And what is its clinical use?

Serotonin and noradrenaline reuptake inhibitor

Anti-obesity

56

What does Fluoxetine target? 

And what are its two clinical uses?

Serotonin reuptake inhibitor

Depression & eating disorders

57

What does Nefazedone target?  

Serotonin reuptake inhibitor & Serotonin 2 receptor antagonist 

58

What does Risperidone target? 

And what is its clinical use?

Serotonin 2 receptor & dopamine 2 receptor antagonists 

A-typical anti-psychotic 

59

What does buspirone target? 

Serotonin 1A receptor partial agonist 

60

What does  Sumatriptan target? 

Serotonin 1B/D receptor agonist

61

What does Ondasetron target? 

And what is its clinical use?

Serotonin 3 receptor antagonist 

Anti-emetic

62

What does serotonin 1A receptor effect?

Mood

63

What does serotonin 1B/D receptor effect?

Vasculature

64

What does serotonin 2A/C recptor effect?

Behaviour

65

Why are more isoform selective drugs better?

They have fewer unwanted side-effects

66

What are anticholinergics used in clinically?

Parkinson's disease

67

What are acetylcholinesterase (ACHE) inhibitors used for clinically?

Alzheimers disease

68

What is Acetylchonine involved in in the CNS?

Cognition

69

What are the 2 clinical uses of H1 antagonists in the CNS?

give an example

Sedation and Antiemetic(Possible role in cognition and mood)

Modafinil

70

Give an example of a purine (ATP) receptor anatagonist:

Caffiene

71

Which 3 things are purine (ATP) receptor agonists used for clinically?

Potentially:

Sedative

Anti-convulsants

Neuroprotection

72

What are purines (ATP) important for in the CNS?

Neuronal damage to the surrounding tissues when released (can even be neurotoxic)

73

What is the normal role of cannabinoids in the CNS?

Feedback loop for neurotransmitter release in synapses

74

What are the two types of stroke and which % of strokes do they account for?

How is each treated?

How do we determine which type it is?  

Ischaemic (thrombosis) = 85% 

Treatment: Anticoagulants/thrombolytics Haemorrhagic (rupture) = 15%

Treatment: Surgery to clock haemorrhage CT scan

75

Which artery is the most frequently effected in a stroke?

 Middle Cerebral artery (a continuation of the internal carotid artery) 

N.B. it is the only artery supplying this area of the brain -> blockage = death

76

What does an old infarction look like?

Significant tissue loss on the affected side & cystic change  

77

Why is a lack of blood supply to the brain so detrimental?

The blood supplies O2 and Glucose to the brain tissue = metabolism -> the brain does not store glucose!

78

What is the treatment for a stroke?

Fibrinolytics within 3 hours = tissue plasminogen activators = improve blood flow and reduce further damage  :( makes worse if due to haemorrhage! 

79

In which 3 ways can we prevent strokes?

- controlling blood pressure

- Aspirin

- Prevent atherosclerosis (low cholestrol diet & excersize)

80

What is a motorneurone disease?

A chronic progressive degeneration of lower and upper motor neurones in the spinal cord, somatic motor nuclei of the cranial nerves & within the cortex (N.B. does not involve the sensory neurones)

81

When do motor neurone diseases onset?

Middle life 

82

What are the (7) signs of a lower motor neurone lesion?

Muscle wasting

Hypotonia

Reflex Loss

Fasciculation

Contractures of muscle (random contraction of skeletal muscle = spasm/twitch)

Muscle weakness

'Trophic' changes in skin and nail 

83

What is Amyotrophic lateral sclerosis?

Disease of lateral corticospinal tracts = atrophy of muscle 

 

Clinical picture:

progressive spastic tetraparesis or paraparesis with added lower motor neurone signs and fasciulation

Atrophy of the nerve roots & loss of characterisitic large motor neurones (anterior horn cells)

84

Name a disease modifying treatment of motor neurone diesease:

Riluzole = inhibits both the release and postsynaptic action of glutamate = protects from exocytotoxicity

85

What is the extrapyrimidal system involved in (4)? 

Crude movements

Integrates motor and sensory impulses

Co-ordinatwa muscle tone reflexes and movements

Facilitate and restrain anterior horn neurone activity

86

What 4 things do disorders in the extrapyrimidal system result in?

- Muscular rigidity

- Tremors

- Un-coordinated and abnormal muscle movements

- Disturbances of postural reflexes 

87

What is parkinsons disease? 

degenerative disease of basal ganglia     

88

What are the 6 clinical presentations of Parkinsons disease?

- Hypokinesia (muscle rigidity & tremor at rest)

- Mask-like expressionless face  (drooling due to change of muscle tone and reflexes)

- 'pill-rolling' tremor of hands

- Bent posture ('chasing' centre of gravity)

- Stiff shuffling gait

- Difficulty initiating & controlling movements

89

What are the causes of Parkinson's disease?

-Often Idiopathic (arising from unknown cause)

- Sometimes follows stroke, viral infection & can be drug induced 

90

Which neurotransmitter loss is associated with parkinsons disease?

Dopamine from the basal ganglia

91

How do drugs targetting parkinsons disease work?

Counteract the deficiency of dopmine in basal ganglia

OR

blocking muscarinic receptors

92

How does the mid-brain present differently in parkinsons disease?

Pale substantia nigra due to reduced dopamine level 

93

What is the name of the neurotoxin precursor that causes the permanent symptoms of parkinsons disease?

MPTP (contminant of Meperidine) = destroys dopaminerginc neurones

94

What are the two actions of dopamine in the body?

A neurotransmitter

Precursor for Noradrenaline!

95

Which enzyme is responsible for converting dopamine into noradrenaline?

And where is this NOT found?

Beta-hydroxylase 

Dopaminergic neurones

96

How do we tell if dopaminergic neurones are present?

Detect the metabolic products of dopamine (DOPAC, HVA & sulphate conjugates) in urine = present

97

Which enzyme degrades dopamine?

Monoamine oxidase B (MOA-B)

98

Name a drug used to treat parkinsons disease that replaces dopamine:

Which two other drugs is this usually given in combination with?

Levodopa, Carbidopa & Entacopone

99

Name 3 drugs used to treat parkinsons disease that mimic the action of dopamine:

Paramipexole

Ropinirole

Bromocriptine

100

Name a drug used to treat parkinsons disease that causes the release of dopamine:

Amantidine

101

Name two drugs used to treat parkinsons disease that act as MAO-B (monoaine oxidase beta) inhibitors:

Selegiline

Rasegiline

102

Name a drug used to treat parkinsons disease that acts as an acetylcholine antagonist:

Benzatropine

103

What is huntingtons disease?  What causes it?

Neurodegenerative disease of the caudate nucleus

(atrophy = increased size of lateral ventricles & gliosis)= reduced acetylcholine and GABA in the striatumIt is a autosomal dominant genetic disorder

104

What is gliosis?

Reactive change of glial cells in response to CNS damage= proliferation & hypertrophy of several different types of glial cells 

105

What are the 2 clinical features of huntingtons?

- Abnormal choreiform movements (added movements outside of voluntary control)

- Struggle to stop movement - Dementia (onset middle life)

106

Which neurotransmitters go wrong in huntingtons disease?

Reduced acetylcholine & GABA in the striatum= hyperactivity of Dopaminergic synapses 

107

How do we treat huntingtons disease?

We treat the physiological issues e.g. decrease muscle tone

108

Define dementia:

A structurally caused permanent or progressive decline in several dimensions of intellectual function that interferes substantially with the person's normal sca; pr economical activity

109

What are the two classifications of dementia?

Static dementia (fixed degree)

Progressive dementia (can accompany several major brain disorders)

110

What causes dementia?

Static

Following a single major injury

 

Progressive

Primary cerebral cortical degeneration (Alzheimers)

Cerebrovascular disease (Multi infarct dementia)

Primary subcortial degeneration (Parkinsons)

Cerebral infections and inflammation (AIDs)

Prion diseases (CJD)

Toxic and metabolic (alcohol & hypothyroidism)

Tumours and hydrocephalus

Brain injury (subdural haematoma)

111

At which age is prevalence of dementia highest?

>80 years old

112

What is mental retardation?

Common insults that can occur to the developing brain and their consequences

113

What is alzheimers disease?

Loss of cognitive function

Neurodegeneration of choliginergic neurons and other neurotransmitter systems (NA, 5-HT & Glu) -> mainly cortical areas 

114

What are the 3 histological features of azheimers?

(the only way you can 100% diagnose)

- general brain atrophy (brain weight reduced by 30-40%!

also: wider sulci, narrowed gyri mostly over frontal and parietal regions and larger ventricles due to loss of brain tissue)

- extracellular plaques (Beta amyloid)

- Intracellular tangles (tau proteins inside the neurones)

115

What are the 4 mild symptoms of alzheimers?

- confusion and memore loss (losing things & forgetting appointments)

- Disorientation (getting lost in familiar surroundings)

- Problems with routine tasks (e.g. unable to sort out finances)

- changes in personality and judgement

116

What are the 5 moderate symptoms of alzheimers?

- difficulty with activities of daily living (feeding and bathing)

- Anxiety, depression, paranoia, aggression, agitation, halucinations

- Sleep disturbances

- wandering/pacing

- Difficulty recognising family and friends

117

What are the 7 severe symtpoms of alzheimers?

- Aphasia (problems understanding language)

- Apraxia (inability to carry out tasks)

- Agnosia (inability to recognise things)

- Loss of speech- Loss of apetite (weight loss) 

- Loss of bladder and bowel control

- Total dependence on caregiver (against infection pneumonia and stroke etc.)

118

Which 3 enzymes are involved in the cleavage of amyloid precursor protein (APP) to produce amyloid protein (AP)?

Why is the balance between these three enzymes important?

Secretases alpha, beta and gamma

imbalance may be involved in amyloidgenesis

119

Can amyloid protein  aggregants be dissolved?

NO!

120

What can be used as a good indicator of alzheimers?

The ApoE4 mutation

BUT

Some people with the mutation will not get alzheimers

121

What are the two proposed theories of amyloid and neuronal death?

The amyloid may cause the death of the neurones

The death of neaurones may lead to amyloid developing

122

Which two features of alzheimers are neurotoxic?

Amyloid plaques 

Neurofibrillary tangles

123

How do amyloid plaques affect neurones?

They block the network so there is imparired neuronal communication

124

Following neuronal death in alzheimers what intracellular events occur that cause damage to the brain tissue?

Macrophages & the body responds to try and destroy the plaques -> body releases free radicals and enzymes into the area = goes into overdrive & releases cytokines etc. that damage the healthy neurones nearby 

125

How can some neurotransmitters cause damage to nearby neurones?

Exitotoxicity

126

What causes alzheimers disease?

We don't know! 

Some theories:

- APP mutations around beta and gamma secretase sites- Inherited defective gene

- Aluminium intoxication = trace amount -> amyloid has metal binding area = possible shape change

127

What are the 2 known risk factors of Alzheimers disease?

Age

Family history/genetic predisposition 

128

What are the 4 possible risk factors of alzheimers disease?

Head injury

Gender (women may have higher risk)

Educational levels (more years of formal education = less likely to develop)

Diet/lifestyle (high calorie, high fat, cholestrol & lack of excersize)

129

What are the two types of licensed pharmacological therapy for alzheimers disease currently?

- Cholinesterase inhibitors (increase ACh levels)

- Partial NMDA (Ca influx) receptor antagonist = neuroprotective

130

List 3 cholinesterase inhibitors:

Donepezil

Galantamine

Rivastigmine

131

What are the side effects of cholinesterase inhibitors?

Abdominal pain

Nausea

Diarrhoea

132

Name a partial NMDA receptor antagonist:

Memantine 

133

What is CJD (creutzfeld-jacob disease)?

Neurodegenerative prion disease

134

What is the adverage length of survival for CJD?

 6 months

BUT

very long incubation period - could take a decade or longer!

135

What are the two key clinical expressions of CJD?

- Rapidly progressive dementia

-Loss of motor co-ordination

136

What causes CJD?

Prion infection (eating/close contact with BSE infected beef)- brain accumulates abnormal form (PrPsc) of the norally expressed prion protein (PrPc) -> evidence PrPsc is infective agent (not DNA or RNA & = v. resistant)

137

List some expermimental drugs being used to inhibit aggregation of PrPsc protein;

Quinacrine (antimalarial)

Chlorpromazine (antipsyhchotic)

Pentosan polyphospate (glycosidic polymer)

138

What is multiple sclerosis?

A slowly progressive autoimmune CNS disease characterised by disseminated patches of demyelination (damaged glial cells = oligodendrocytes) in the brain and sinal cord = multiple and varies neurological symptoms and signs usually with remissions and exacerbations

139

What is the age of onset for Multiple sclerosis?

20-45 years

140

What is a risk factor for multiple sclerosis?

Vitamin D deficiency (risk higher away from equator)

141

What is the importance on where you live and your susceptibility to multiple sclerosis?

Susceptibility is set by where you lived for the first 8 years of your life

142

Where do the problems in multiple scelrosis stem from? 

Miscommunication in remyelination pathways e.g. osteocytes invade = cytokine release = glial progenitor cells cannot infiltrate = no repair & cell death

143

Which cells cause remyelination (repair glial cells)?

Glial progenitor cells

144

What are the 4 methods of treatment for multiple scleorsis?

- minimization of handicap (physio, occupational therapy & adaptions to work and home environments)

- Suppress inflammation during acute relapse 

- Reduce relapse rates and suppress ongoing disease activity

- Control of muscle tone

145

Which drug is used to treat Multiple scleoris through suppressing inflammation during acute relapse?

Methylprednisolone (corticosteroids -> N.B. no effect on long term outcome)

146

Which 4 drugs are used to treat multiple scleoris through reducing relapsse rates and suppressing ongoing disease activity?

Interferon Beta (may also reduce the rate at which patients progress from a single episode of CNS demyleination progresses to MS)

Glatiramer acetate

Natalizumab

Azothiopine (intravenous IgG)

147

Which 5 drugs are used to treat multiple sclerosis by controlling muscle tone?

Baclofen

Benzodiazepines

Tizadine

Botulinum toxin

Dantrolene

148

List 3 anti-obesity drugs that work in the CNS:

Sibutramine

Phentermine

Fenfluramine

149

What is sibutramine?

A noradrenaline/ serotonin (5-HT) reuptake inhibitor 

150

What is phentermine?

A sympathomimetic

151

What is fenfluramine?

A serotonin (5-HT) reuptake inhbitor

152

Which drug is used for anorexia and bulimia?

Fluoxetine (Prozac)

153

What is fluoxetine? 

A selective serotonin reuptake inhibitor

154

Which other receptor is the target of atypical antipsychotics?

and are these drugs agonists or antagonists of this type of receptor?

5-HT2 antagonism 

155

What is the mode of action for most antidepressants and antipsychotics?

NA or serotonin reuptake inhibiors

156

What is depression?

A unipolar mood disorder that makes the individual feel down

157

What is mania?

A unipolar mood disorder that is bad for the patients environment (over-excited) = inappropriate behaviour

158

What is manic depression?

A bipolar mood disorder causing the individual to fluctuate between feeling down and being over-excited

159

What are the three different causes of mood disorders?

Reactive (response to traumatic life events)

Endogenous (no obvious cause)

Side effect of drug treatment (e.g. rimonabant =put on weight & interferon alpha = hepatitis c or interfering with alzheimers treatment)

160

How long does it take for antidepressants and antipshycotics to start working?

- 6-8 weeks (levels increse gradually & stays in system for several weeks after stop taking)

N.B. cannot just cut off drug as body starts to rely on drug so doesnt function properly without it 

161

What are the 5 main symptoms of mania?

- sleep changes (need less)

- Excessive exuberance, enthusiasm, confidence and grandiosity

- increased libido

- behaviours inappropriate to circumstances

- Disorders of thought (psychosis)

162

What are the 5 things thought to cause depression?

Chemical imbalance (monoamine theory of depression, functional serotonin/NA/DA deficit)

Neurodegeneration (neuronal apoptosis and neurogenesis)

Immune response (sickness behaviour)

Genes

Environment (stress)

163

What are the 3 types of treatments for the depressed?

Pharmacological (enhance monoamine levels in CNS & specific receptor agonists/antagonists)

Cognitive behavioural therapy

Neurological interventions (electroconvulsive shock therapy, deep brain stimulation, vagal nerve stimulation)

164

In which two ways can monoamine levels in the CNS be enhanced?

Monoamine re-uptake inhibitors

Monoamine oxidase inhibitors receptor antagonists

165

Name a post-synaptic receptor agonist that increases monoamine function in the CNS:

Buspirone

166

Name a pre-synaptic receptor antagonist that increases monoamine function in the CNS:

Mirtazapine

167

Name four mono-amine oxidase enzyme inhibitors:

Which is reversible and which is irreversible?

Moclobemide (reversible)

Phenylzine (irreversible)

Iproniazid  

Tranylcypromine  

168

State the key things about Monoamie oxidases and how they work:

Inhibits breakdown of monoamines

Inhibit monoamine oxidase A or B -> (MAOA prefers 5HT & MAOB prefers DA & NA)

Both reversible and irreversible MOA found in all tissues including GI tract Multiple side effects -> M1, alpha 2, H1. 5-HT2, cheese reaction & drug interactions  

169

Name two monoamine reuptake inhibitors:

Fluoxetine 

Venlafaxine

170

What are the two different classes of antidepressants?

Typical=

Tricyclic antidepressants (TCAs) & specific reuptake inhibitors 

 

Atypical

= mixed uptake blockers and receptor blocking drugs

171

What is similar between the two classes?

similar efficacy

delayed onset despite different modes of action

172

TYPICALName 4 tricyclic antidepressants:

Imapramine

Amitriptyline

Clominpramine

Desipramine

173

What are the two mechanism of action of tricyclin antidepressants?

Block NA &/or 5-HT reuptake (relative selectivity varies)

Some block alpha 2 adrenoreceptors 

Many have active metabolites (long lasting effect)

174

What is the main side effect of Tricyclic antidepressants (TCA's)?

  Cardiotoxicity = low theraputic index and cause tachycardia, arrythmias & hypotension

N.B. there are many side effects

175

TYPICALName 3 Selective Serotonin reuptake inhibitors (SSRI's)

Fluoxetine

Paroxetine

Citalopram

176

Which 5 side effect improvements of SSRIs make it preferable to TCAs?

Lack of cholinergic side effects

Less weight gain

Low toxicity in overdose

No food interaction

Reduced drug interaction

177

What are the 5 5-HT related side effects of SSRI's?

Nausea (5-HT3)

Anorexia (5-HT2)

Insomnia (5-HT2)

Sexual dysfunction (5-HT2)

5-HT syndrome = similar to ecstacy overdose

178

TYPICALName 1 Selective noradrenalne reuptake inhibitor (NARI)

Reboxetine

179

ATYPICALName 1 serotonin-noradrenaline reuptake inhibitor (SNRI)

Venlafaxine = used in severly depressed, retarded, hypersomnic, weight gaining, atypical depressives

180

ATYPICAL Name 1 5-HT2 antagonist + SSRI

Trazodone

181

ATYPICALName 1 5-HT2 antagonist + SNRI/SSRI

Nefazedone= reduced anxiety, imporved slow wave sleep, reduce sexual dysfunction & sedation

182

ATYPICALName two alpha 2 adrenoreceptor and 5-HT antagonist

Mianserin

Mirtazapine= increased NA & 5-HT by blockade of pre-synaptic inhibition

 

5-HT antagonist = reduces side effect

183

Which two drugs/chemicals are used as mood stabilsiers to control mania?

Lithium -> mechanism poorly understood (interacts with g proteins & inhibit ability to transduce signal or alter enzynes that interact with second messanger systems):(

Caution: potential toxicicity = careful monitering 

Anti-epileptic drugs:

Valproic Acid - inhibits GABA transaminase = some effect on Na channelsCarbamazepine - use dependent block of Na channelsOlanzapine- Atypical antipsychotic 

184

What is the treatment for mild/moderate depression?

Cognitive therapy 

185

What is the treatment for sever depression?

Drugs

186

What is the treatment for very severe/drug resistant depression?

Elektroconvulsive therapy & deep brain stimulation (dual or triple therapy)

187

What are the first line drugs used for depression?

SSRI (selective seretoning reuptake inhibitors)

188

What are the second line drugs for depression?

Monoamine oxidase inhbitors

189

After remission from depression a patient should continue taking antidepressants for how long?

6-12 months

190

What are the 6 other applications for reuptake inhibitors?

Obsessive compulsive disorders

Panic disorder

Social phobia

Anxiety disorders

Eating disorders (bulimia/ binge eating)

Obesity

191

What are the two other applications for tricylic antidepressants (TCAs)?

Novel analgesic agent (amitryptyline)

Migraine prophylaxis drug (amitryptyline)

192

What are the two major classes of antipsychotic (neuroleptic) drugs = control behavioural disorders such as schizophrenia?

which receptors do they act at?

Typical anti-psychotic drugs = D2 receptor antagonists (with multiple sites of action)

Atypical anti-psychotic drugs = serotonin and dopamine antagonists

193

List the two types of typical antipshycotic drugs:

Phenothiazines (chlorpramazine)Biturophenones (haloperidol)

194

Name 3 Atypical antipsychotic drugs:

Clozapine

Risperidone

Aripriprazole

195

The distinction between typical and atypical antipsychotics depends on which 4 properties?

Receptor profile incidence of extrapyrimidal side effects (fewer in atypical) efficacy in treatment-resistace group of patients (especially clozapine) efficacy against negative symptoms

196

What is the aim of mixed D2 and 5-HT2 antagonists?

Reduce motor side effects and improve treatment of negative symptoms 5-HT2 antagonism = reduced overall D2 blockade through 5-HT DA interactions (reduced extrapyrimidal, hormonal and cognitive side effects)

D2 antagonist = retain sufficient block to counter psychotic symptoms

197

What are the 6 side effects of 5HT2-DA2 receptor antagonists?

Endocrine (hyperprolactinaemia)

Anti-muscarinic (urinary retention, dry mouth & blurred vision) Anti alpha adrenoreceptor (hypotension)

Anti-histamine H1 (sedation)

5-HT2 (weight gain)

Idiosyncratic/Hypersensitivity reactions

198

why are typical drugs not used so much any more?

Ineffective at relieving negative symptoms 

199

Which 3 drugs are the first line of treatment in schizophrenia?

Quetapine

Zotepine

Risperidone= ATYPICAL ANTI-PSYCHOTIC DRUGS

200

What is the name of the second line drug?

And which risk is associated with it?

Clozapine (ATYPICAL)

Risk of agranulocytosis

201

Which drug is widely used in severe psychotic patients?

Haloperidol (TYPICAL ANTI-PSYCHOTIC)

202

What is the other application for typical antipsychotic drugs?

Psychosis

203

What are the three other applications for atypical antipsychotic drugs?

Conduct disorders

ADHD non-responders

Behavioural symptoms of alzheimers disease