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
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
Give an example of a glial cell:
Astrocyte
How do glial cells modulate the shape of post-synaptic response?
Remove the neurotransmitter from the synaptic cleft
Compare the following features of the Nervous system and Endocrine:
Mediator molecules
Cells affected
Time of onset of action
Duration of action
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
How many neuroactive substances can be found in the CNS?
Approx. 40
What type of channels are inotropic receptors?
Ligand-gated ion channels
What type of channels are metabotropic receptors?
GPCRs
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!)
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)
What do neuromodulators do?
They alter the strength of response
What do neurotrophic factors do?
Influences neuronal differentiation and proliferation
(most do this by acting on Tyrosine kinase receptors)
What are the (4) different targets for drug action?
Ion channels
Receptors
Enzymes
Transporter proteins
Name an excitatory neurotransmitter in the CNS:
Glutamate
Name an inhibitory neurotransmitter in the CNS:
GABA
Which drug targets transmitter synthesis in the CNS?And what is the clinical application of this drug?
L- Dopa
Parkinson's disease
Which drug targets transmitter storage in the CNS?And what is the clinical application of this drug?
Reserpine
Hypertension
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)
Name 2 receptor agonists in the CNS?
And what is the clinical application of this drug?
Morphine (analgesia)
Buspirone (Anxiety)
Name 2 receptor antagonists in the CNS?
And what is the clinical application of this drug?
Cloazapine (antipsycotic)
Memantine (alzheimers)
Which 2 drug target reuptake in the CNS?
And what is the clinical application of this drug?
Cocaine (stimulant)
Fluoxetine (depression)
Which 2 drugs target degradation in the CNS?
And what is the clinical application of this drug?
Moclobemide (depression)
Donepezil (alzheimers)
Which drug targets intracellular signalling in the CNS?And what is the clinical application of this drug?
Lithium
Bipolar disorder
Which drug targets nerve growth in the CNS?
And what is the clinical application of this drug?
Myotrophin
Motor neurone disease
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
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)
What may drugs that target glutamate be used to treat? (4)
Learning and memory
Schizophrenia
Mood disorders
Excitotoxicity
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
In which (3) illnesses are GABA B recreptors for GABA targetted?
Epilepsy
Anaesthesia
Cerebral Palsy
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
Treatments for which 5 disorders target dopamine?
Parkinson's disease
Schizophrenia
Drug abuse and addiction
ADHD (attention deficit hyperactivity disorder)
Depression
If drugs such as L-DOPA are given in the wrong situation what can it induce?
Schizophrenia like symptoms & hallucination
What does L-DOPA target? And what is its clinical use?
Bypasses the rate limiting synthetic enzyme for Dopamine
Parkinson's disease
What does Haloperidol target?
And what is its clinical use?
D2 receptor antagonist
Anti-psychotic
What does Domperidone target?
And what is its clinical use?
D2 receptor antagonist
Anti-emetic
What does Selegeline target?
And what is its clinical use?
Monoamine oxidase - B inhibitor (MAO-B)
Neurodegeneration
What does Amantadine target?
And what is its clinical use?
Dopamine releasing agent
Parkinson's disease
What does Amphetamine (methylphenidate) target?
And what is its clinical use?
Re-uptake inhibitor
Attention deficit hyperactivity disorder (ADHD)
What does Buproprion target? And what is its clinical use?
Dopamine/noradrenaline reuptake inhibitor
Anti-craving
What is Pramipexole?
Dopamine partial agonist
Treatments for which (7) disorders target noradrenaline?
Cognition
Depression
Anxiety
Pain
Addiction
Obesity
ADHD
What are the main functional effects of noradrenaline?
Attention
Cognition
Sensory
Homeostasis
Sympathetic output
Sleep-wake cycle
Motivation
What does Amitriptyline target? And what is its clinical use?
Serotonin and Noradrenaline reuptake inhibition
Pain & antidepressant
What does Reboxetine target?
And what is its clinical use?
Noradrenaline reuptake inhibition
Antidepressant
What does Sibutramine target? And what is its clinical use?
Serotonin & Noradrenaline reuptake inhibition
Anti-obesity
What does Mirtazapine target?
And what is its clinical use?
Alpha 2 adrenoreceptor and serotonin receptor antagonist
Antidepressant
What does Atomoxetine target?
And what is its clinical use?
Noradrenaline reuptake inhibiton
ADHD
What does clonidine target?
And what is its 2 clinical uses?
Alpha 2 adrenoreceptor agonist
Anti-hypertensive & epidural anaesthetic
What does Lofexine target?
And what is its clinical use?
Alpha 2 adrenoreceptor antagonist Opiate withdrawal
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
Which (6) diseases are drugs that target serotonin used to treat?
Depression
Anxiety
Pain
Schizophrenia
Migraine
Emesis (vomitting)
What does Clomipramine target?
And what are its 2 clinical uses?
Serotonin reuptake inhibitor
Depression & OCD
What does Amitriptyline target?
And what are its 2 clinical uses?
Serotonin & noradrenaline reuptake inhibitor
Depression & OCD
What does Sibutramine target?
And what is its clinical use?
Serotonin and noradrenaline reuptake inhibitor
Anti-obesity
What does Fluoxetine target?
And what are its two clinical uses?
Serotonin reuptake inhibitor
Depression & eating disorders
What does Nefazedone target?
Serotonin reuptake inhibitor & Serotonin 2 receptor antagonist
What does Risperidone target?
And what is its clinical use?
Serotonin 2 receptor & dopamine 2 receptor antagonists
A-typical anti-psychotic
What does buspirone target?
Serotonin 1A receptor partial agonist
What does Sumatriptan target?
Serotonin 1B/D receptor agonist
What does Ondasetron target?
And what is its clinical use?
Serotonin 3 receptor antagonist
Anti-emetic
What does serotonin 1A receptor effect?
Mood
What does serotonin 1B/D receptor effect?
Vasculature
What does serotonin 2A/C recptor effect?
Behaviour
Why are more isoform selective drugs better?
They have fewer unwanted side-effects
What are anticholinergics used in clinically?
Parkinson's disease
What are acetylcholinesterase (ACHE) inhibitors used for clinically?
Alzheimers disease
What is Acetylchonine involved in in the CNS?
Cognition
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
Give an example of a purine (ATP) receptor anatagonist:
Caffiene
Which 3 things are purine (ATP) receptor agonists used for clinically?
Potentially:
Sedative
Anti-convulsants
Neuroprotection
What are purines (ATP) important for in the CNS?
Neuronal damage to the surrounding tissues when released (can even be neurotoxic)
What is the normal role of cannabinoids in the CNS?
Feedback loop for neurotransmitter release in synapses
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
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
What does an old infarction look like?
Significant tissue loss on the affected side & cystic change
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!
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!
In which 3 ways can we prevent strokes?
- controlling blood pressure
- Aspirin
- Prevent atherosclerosis (low cholestrol diet & excersize)
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)
When do motor neurone diseases onset?
Middle life
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
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)
Name a disease modifying treatment of motor neurone diesease:
Riluzole = inhibits both the release and postsynaptic action of glutamate = protects from exocytotoxicity
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
What 4 things do disorders in the extrapyrimidal system result in?
- Muscular rigidity
- Tremors
- Un-coordinated and abnormal muscle movements
- Disturbances of postural reflexes
What is parkinsons disease?
degenerative disease of basal ganglia
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
What are the causes of Parkinson's disease?
-Often Idiopathic (arising from unknown cause)
- Sometimes follows stroke, viral infection & can be drug induced
Which neurotransmitter loss is associated with parkinsons disease?
Dopamine from the basal ganglia
How do drugs targetting parkinsons disease work?
Counteract the deficiency of dopmine in basal ganglia
OR
blocking muscarinic receptors
How does the mid-brain present differently in parkinsons disease?
Pale substantia nigra due to reduced dopamine level
What is the name of the neurotoxin precursor that causes the permanent symptoms of parkinsons disease?
MPTP (contminant of Meperidine) = destroys dopaminerginc neurones
What are the two actions of dopamine in the body?
A neurotransmitter
Precursor for Noradrenaline!
Which enzyme is responsible for converting dopamine into noradrenaline?
And where is this NOT found?
Beta-hydroxylase
Dopaminergic neurones
How do we tell if dopaminergic neurones are present?
Detect the metabolic products of dopamine (DOPAC, HVA & sulphate conjugates) in urine = present
Which enzyme degrades dopamine?
Monoamine oxidase B (MOA-B)
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
Name 3 drugs used to treat parkinsons disease that mimic the action of dopamine:
Paramipexole
Ropinirole
Bromocriptine
Name a drug used to treat parkinsons disease that causes the release of dopamine:
Amantidine
Name two drugs used to treat parkinsons disease that act as MAO-B (monoaine oxidase beta) inhibitors:
Selegiline
Rasegiline
Name a drug used to treat parkinsons disease that acts as an acetylcholine antagonist:
Benzatropine
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
What is gliosis?
Reactive change of glial cells in response to CNS damage= proliferation & hypertrophy of several different types of glial cells
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)
Which neurotransmitters go wrong in huntingtons disease?
Reduced acetylcholine & GABA in the striatum= hyperactivity of Dopaminergic synapses
How do we treat huntingtons disease?
We treat the physiological issues e.g. decrease muscle tone
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
What are the two classifications of dementia?
Static dementia (fixed degree)
Progressive dementia (can accompany several major brain disorders)
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)
At which age is prevalence of dementia highest?
>80 years old
What is mental retardation?
Common insults that can occur to the developing brain and their consequences
What is alzheimers disease?
Loss of cognitive function
Neurodegeneration of choliginergic neurons and other neurotransmitter systems (NA, 5-HT & Glu) -> mainly cortical areas
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)
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
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
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.)
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
Can amyloid protein aggregants be dissolved?
NO!
What can be used as a good indicator of alzheimers?
The ApoE4 mutation
BUT
Some people with the mutation will not get alzheimers
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
Which two features of alzheimers are neurotoxic?
Amyloid plaques
Neurofibrillary tangles
How do amyloid plaques affect neurones?
They block the network so there is imparired neuronal communication
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
How can some neurotransmitters cause damage to nearby neurones?
Exitotoxicity
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
What are the 2 known risk factors of Alzheimers disease?
Age
Family history/genetic predisposition
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)
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
List 3 cholinesterase inhibitors:
Donepezil
Galantamine
Rivastigmine
What are the side effects of cholinesterase inhibitors?
Abdominal pain
Nausea
Diarrhoea
Name a partial NMDA receptor antagonist:
Memantine
What is CJD (creutzfeld-jacob disease)?
Neurodegenerative prion disease
What is the adverage length of survival for CJD?
6 months
BUT
very long incubation period - could take a decade or longer!
What are the two key clinical expressions of CJD?
- Rapidly progressive dementia
-Loss of motor co-ordination
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)
List some expermimental drugs being used to inhibit aggregation of PrPsc protein;
Quinacrine (antimalarial)
Chlorpromazine (antipsyhchotic)
Pentosan polyphospate (glycosidic polymer)
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
What is the age of onset for Multiple sclerosis?
20-45 years
What is a risk factor for multiple sclerosis?
Vitamin D deficiency (risk higher away from equator)
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
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
Which cells cause remyelination (repair glial cells)?
Glial progenitor cells
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
Which drug is used to treat Multiple scleoris through suppressing inflammation during acute relapse?
Methylprednisolone (corticosteroids -> N.B. no effect on long term outcome)
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)
Which 5 drugs are used to treat multiple sclerosis by controlling muscle tone?
Baclofen
Benzodiazepines
Tizadine
Botulinum toxin
Dantrolene
List 3 anti-obesity drugs that work in the CNS:
Sibutramine
Phentermine
Fenfluramine
What is sibutramine?
A noradrenaline/ serotonin (5-HT) reuptake inhibitor
What is phentermine?
A sympathomimetic
What is fenfluramine?
A serotonin (5-HT) reuptake inhbitor
Which drug is used for anorexia and bulimia?
Fluoxetine (Prozac)
What is fluoxetine?
A selective serotonin reuptake inhibitor
Which other receptor is the target of atypical antipsychotics?
and are these drugs agonists or antagonists of this type of receptor?
5-HT2 antagonism
What is the mode of action for most antidepressants and antipsychotics?
NA or serotonin reuptake inhibiors
What is depression?
A unipolar mood disorder that makes the individual feel down
What is mania?
A unipolar mood disorder that is bad for the patients environment (over-excited) = inappropriate behaviour
What is manic depression?
A bipolar mood disorder causing the individual to fluctuate between feeling down and being over-excited
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)
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
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)
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)
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)
In which two ways can monoamine levels in the CNS be enhanced?
Monoamine re-uptake inhibitors
Monoamine oxidase inhibitors receptor antagonists
Name a post-synaptic receptor agonist that increases monoamine function in the CNS:
Buspirone
Name a pre-synaptic receptor antagonist that increases monoamine function in the CNS:
Mirtazapine
Name four mono-amine oxidase enzyme inhibitors:
Which is reversible and which is irreversible?
Moclobemide (reversible)
Phenylzine (irreversible)
Iproniazid
Tranylcypromine
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
Name two monoamine reuptake inhibitors:
Fluoxetine
Venlafaxine
What are the two different classes of antidepressants?
Typical=
Tricyclic antidepressants (TCAs) & specific reuptake inhibitors
Atypical
= mixed uptake blockers and receptor blocking drugs
What is similar between the two classes?
similar efficacy
delayed onset despite different modes of action
TYPICALName 4 tricyclic antidepressants:
Imapramine
Amitriptyline
Clominpramine
Desipramine
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)
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
TYPICALName 3 Selective Serotonin reuptake inhibitors (SSRI's)
Fluoxetine
Paroxetine
Citalopram
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
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
TYPICALName 1 Selective noradrenalne reuptake inhibitor (NARI)
Reboxetine
ATYPICALName 1 serotonin-noradrenaline reuptake inhibitor (SNRI)
Venlafaxine = used in severly depressed, retarded, hypersomnic, weight gaining, atypical depressives
ATYPICAL Name 1 5-HT2 antagonist + SSRI
Trazodone
ATYPICALName 1 5-HT2 antagonist + SNRI/SSRI
Nefazedone= reduced anxiety, imporved slow wave sleep, reduce sexual dysfunction & sedation
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
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
What is the treatment for mild/moderate depression?
Cognitive therapy
What is the treatment for sever depression?
Drugs
What is the treatment for very severe/drug resistant depression?
Elektroconvulsive therapy & deep brain stimulation (dual or triple therapy)
What are the first line drugs used for depression?
SSRI (selective seretoning reuptake inhibitors)
What are the second line drugs for depression?
Monoamine oxidase inhbitors
After remission from depression a patient should continue taking antidepressants for how long?
6-12 months
What are the 6 other applications for reuptake inhibitors?
Obsessive compulsive disorders
Panic disorder
Social phobia
Anxiety disorders
Eating disorders (bulimia/ binge eating)
Obesity
What are the two other applications for tricylic antidepressants (TCAs)?
Novel analgesic agent (amitryptyline)
Migraine prophylaxis drug (amitryptyline)
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
List the two types of typical antipshycotic drugs:
Phenothiazines (chlorpramazine)Biturophenones (haloperidol)
Name 3 Atypical antipsychotic drugs:
Clozapine
Risperidone
Aripriprazole
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
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
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
why are typical drugs not used so much any more?
Ineffective at relieving negative symptoms
Which 3 drugs are the first line of treatment in schizophrenia?
Quetapine
Zotepine
Risperidone= ATYPICAL ANTI-PSYCHOTIC DRUGS
What is the name of the second line drug?
And which risk is associated with it?
Clozapine (ATYPICAL)
Risk of agranulocytosis
Which drug is widely used in severe psychotic patients?
Haloperidol (TYPICAL ANTI-PSYCHOTIC)
What is the other application for typical antipsychotic drugs?
Psychosis
What are the three other applications for atypical antipsychotic drugs?
Conduct disorders
ADHD non-responders
Behavioural symptoms of alzheimers disease