Pharmacology Flashcards
(186 cards)
1
Q
Name 4 non-steroidal anti-inflammatory drugs (NSAIDs)
A
- Ibuprofen
- Aspirin
- Diclofenac
- Naproxen
2
Q
Name 2 COX2- selective NSAIDs
A
- Celecoxib
2. Etoricoxib
3
Q
Name 2 drugs used in management of opioid addiction
A
- Methadone
2. Buprenorphine
4
Q
Codeine and dihydrocodeine are examples of what class of drug?
A
Weak opioid analgesics
5
Q
Name 3 drugs used to treat neuropathic pain
A
- Gabapentin
- Pregabalin
- Carbamazepine
6
Q
Name 5 general anaesthetics
A
- Isoflurane
- Propofol
- Nitrous oxide
- Sevoflurane
- Ketamine
7
Q
Name 3 local anaesthetics
A
- Lidocaine
- Bupivacaine
- Levobupivacaine
8
Q
Naloxone and naltrexone are examples of what class of drug?
A
Opioid receptor antagonists - used in management of opioid overdose
9
Q
Name a weak analgesic/antipyretic
A
Paracetamol
10
Q
What are the 3A’s that make up consciousness?
A
- Alertness (controlled by upper brainstem reticular formation)
- Awareness (controlled by cerebral cortex)
- Attention (controlled by limbic system)
11
Q
In which state does the patient show reduced movement and consciousness, which can be readily reversed by external stimulaiton? Anaesthesia/Coma/Sedation/Sleep
A
Sleep
12
Q
What is restless leg syndrome?
A
Disorder causing uncontrollable, erratic movements or sensations in the legs that normally occur during sleep. Anaesthesia reduces movment.
13
Q
Where is the glabellar tap performed?
A
Forehead; the glabellar region is the region between the eyebrows and above the nose; quick repeated taps here will elicit a blink reflex/should trigger rapid eye opening in sedated patients.
14
Q
What are the 3 main scales used to determine and maintain correct levels of sedation?
A
- The Ramsay scale
- The Richmond Agitation Sedation Scale (RASS)
- The Riker Sedation Agitation Scale (SAS)
15
Q
Which class of drug is haloperidol?
A
First generation (classical) antipsychotic
16
Q
What is the primary mechanism of action of haloperidol?
A
Dopamine (D2) receptor antagonist
17
Q
Name the 2 groups of symptoms associated with and used to diagnose schizophrenia
A
Positive and negative symptoms
18
Q
Name 5 positive symptoms of schizophrenia
A
- Hallucinations
- Delusions
- Agitation
- Exaggerated/disorganised speech
- Exaggerated/disorganised and bizarre behaviour
19
Q
Name the 4 negative symptoms of schizophrenia
A
- Affective blunting
- Ahedonia (inability to feel pleasure in normally pleasurable activities)
- Alogia
- Apathy
The 4A’s
20
Q
What biological causes are thought to be involved in schizophrenia?
A
- Imbalance of neurotransmitter levels (increased dopamine release in mesolimbic pathways)
- Degeneration within the grey matter, particularly in medial temporal lobes
- Enlarged ventricles and sulci
- Cerebral blood flow reduced in basal ganglia and frontal lobes
21
Q
What are the two groups of antipsychotics?
A
- First generation (aka classical) antipsychotics
- Second generation (aka atypical) antipsychotics
22
Q
Describe the action of first generation antipsychotics
A
Primarily potent antagonists at the D2 receptor (but alos act on muscarinic, histamine and adrenergic receptors)
- Have low efficacy (30% patients are non-responders)
23
Q
Name 2 examples of first generation antipsychotics
A
Chlorpromazine
Haloperidol
Both selective dopamine (D2) receptor antagonists
24
Q
Name 3 examples of second generation antipsychotics
A
Amisulpride
Risperidone
Clozapine
Seretonin and dopamine (D2) receptor antagonists
25
Describe the action of second generation antipsychotics
Serotonin and dopamine antagonism (but complex and may interact with other receptors)
- Better at dealing with negative symptoms than first generation
26
What is the gold-standard antipsychotic?
Clozapine (serotonin-dopamine antagonist with high efficacy but has the most side effects of all atypicals)
27
What are the majority of side effects seen with antipsychotics?
Extrapyramidal symptoms (seen in 75% of patients)
Include:
- Dystonias (sustained or repetitive muscle contractions)
- Akathisia (inability to stay still)
- Parkinsonism
28
What is a specific problem seen with clozapine?
Agranulocytosis (dangerously low WBC count)
29
Why do second generation antipsychotics have less side effects?
Second generation antipsychotics have a higher affinity for the mesolimbic and cortical pathways than the nigrostriatal dopaminergic pathways
30
What is neuroleptic malignant syndrome?
Side effect associated with antipsychotics in patients with a genetic polymorphism of the D2 receptor (12-15% of patients).
Leads to fever, autonomic problems and altered consciousness
31
How is neuroleptic malignant syndrome treated?
Immediate withdrawl of the antipsychotic
Dopamine agonists and benzodiazepines
32
What is a common side effect of prolonged first generation antipsychotic use?
Tardive dyskinesia
- Irreversible in many cases
- Characterized by disabiling involuntary movements including tongue protruding, choreiform movements grimacing and twisting
33
How should tardive dyskinesia be treated?
Stop antipsychotic
Stop any anticholinergics being used
Switch to atypical antipsychotic
34
Name some symptoms of parkinsonism
1. Stiffness, cog wheel rigidity
2. Tremor (pill rolling; 10Hz)
3. Mask-like face
4. Clumsiness
5. Festinant gait
35
What is the name of the late stage side effects associated with long term treatment for parkinsonism?
'On-off' effects
36
Which dopamine pathways are involved in the pathogenesis of schizophrenia?
Mesolimbic
| Mesocortical
37
Which dopamine pathways are involved in the pathogenesis of parkinson's?
Striatonigral
38
What are the 3 A’s of consciousness?
1. Alertness
2. Awareness
3. Attention
39
What are the 3 components of the Glasgow coma scale?
1. Best eye response (1-4)
2. Best verbal response (1-5)
3. Best motor response (1-6)
40
Name the eye response for the GCS
```
4= Opens spontaneously
3= Opens to speech
2= Opens to painful stimulus
1= no response
```
41
Name the verbal responses for the GCS
```
5= oriented to time, place and person
4= confused
3= inappropriate words
2= incomprehensible sounds
1= no response
```
42
Name the motor responses for the GCS
```
6= obeys commands
5= Moves to localised pain
4= flexion withdrawal from pain
3= Abnormal flexion (decorticate)
2= abnormal extension (decerebrate)
1= no response
```
43
What score would a comatose patient have on the GCS?
8 or less
44
What score would a totally unresponsive patient have on the GCS?
3
45
What would a minor head injury score on the GCS?
13 or more
46
What would a moderate head injury score on the GCS?
9-12
47
What would a severe head injury score on the GCS?
8 or less
48
What is anaesthesia?
Describes a lack of feeling.
| Generally a drug induced and predictable reversible form of coma.
49
What is coma?
State of extreme unresponsiveness, in which an individual exhibits no voluntary movement or behaviour.
50
What is sedation?
State that allows patients to tolerate unpleasant diagnostic or surgical procedures and to relieve anxiety and discomfort, during which verbal contact can be maintained with the patient.
51
What is sleep?
Period of rest for the body and mind, during which volition and consciousness are in abeyance (disuse) and bodily functions are partially suspended.
52
In which state does the patient show reduced movement and consciousness, which can be readily reversed by external stimulation?
Sleep
53
In which state does restless leg syndrome occur most commonly?
Sleep
54
A patient is admitted to the ED with a dislocated finger, they are very distressed and in pain. Doctor administers s drug which allows finger reduction but they can still understand what the doctor is saying. What state are they in?
Sedation
55
What level of sedation should be used for minor procedures e.g. shoulder reduction?
Conscious sedation
56
What are the 3 main scales used to determine and maintain correct levels of sedation?
1. The Ramsay scale
2. The Richmond agitation sedation scale
3. The Riker sedation agitation scale
57
How can you tell using the eyes that a patient is anaesthetised?
The corneal and pupil reflexes will be reduced
58
What are the most commonly used classes of drugs for sedation?
- Benzodiazepines
- Opiates
- Entonox
- Other: Dexmedetomidine
- Anaesthetics
59
Name 3 benzodiazepines
1. Lorazepam
2. Diazepam
3. Midazolam
60
Name 3 opioid receptor agonists
1. Alfentanil
2. Fentanil
3. Remifentanil
61
Name 3 local anaesthetics
1. Lidocaine
2. Bupivacaine
3. Levobupivacainw
62
Name 5 general anaesthetics
1. Propofol
2. Nitrous oxide
3. Ketamine
4. Sevofulrane
5. `Isoflurane
63
What is the mechanism of action of benzodiazepines?
Positive allosteric modulator
Act at GABA receptor as co-agonists to increase chloride entry into the cell, leading to hyperpolarisation, which reduces neuronal firing.
64
Which property do benzodiazepines not have?
No analgesic properties so do not reduce pain sensation
65
Which disorders can benzodiazepines be used for?
- Epilepsy
- Anxiety
- Insomnia
66
Why are benzodiazepines only used for short-term treatment of disorders?
Longer-term use may lead to the development of tolerance and dependance
67
How do barbituates work?
Work in an identical way to benzodiazepines, as postivie allosteric modulators of the GABA receptor.
The only difference is that they bind at the juncture of the beta-subunit of the receptor (benzodiazepines bind at the gamma- subunit juncture)
68
Name 3 barbituates
1. Primidone
2. Phenobarbitone
3. Pentobarbitone
69
What are the 2 main routes of administration for general anaesthetics?
1. Intravenous
| 2. Inhalation
70
What properties of the nerve affect the speed/effectivness of a local anaesthetic?
Local anaesthetics work more easily on smaller, un-myleinated or lightly-myelinated nociceptive sensory fibres and unmyelinated autonimic fibres, because access to the Na+ channels via the membrane is easier than across the larger and more myelinated proprioceptive fibres. The least affected by local anaesthetics are the large, myelinated motor fibres.
71
Why don't local anaesthetics work as well if the tissue is inflamed?
Their ability to work is pH dependant and the inflammatory 'soup' in the damaged tissue is generally acidic.
Local anaesthetics ionise in acidic pH which reduces their ability to cross the neuronal membrane to attach to the Na+ channel.
72
What are the two chemical structure groups that local anaesthetics are grouped into?
1. Amino esters (mainly metabolised in plasma)
| 2. Amino amides (mainly metabolised in the liver)
73
What is the half-life of local anaesthetic amino amides in circulation?
Up to 3 hours (usually 1-3 hours)
74
What class are bupivacaine, lidocaine and levobupivacaine?
Amino amides; local anaesthetics
75
What do general anaesthetics do?
Reversibly block nerve conduction causing a loss of sensation affecting the whole body but also resulting in a loss of consciousness.
76
What are Isoflurane, Sevoflurane and nitrous oxide and what is their normal route of administration?
General anaesthetics
| Inhalation
77
What are Ketamine and propofol and what is their normal route of administration?
General anaesthetics
| Intravenous
78
How is the potency of an inhalational anaesthetic calculated?
By calculating the minimum alveolar concentration (MAC) required to immobilise 50% of patients during noxious stimulation (normally a skin incision)
79
Is an inhalational anaesthetic with a high MAC more potent than one with a lower MAC? Why?
No, becuause a high MAC indicates a low potency as it means that more drug is required to immobilise the patient.
80
How long does it take for intravenous drugs to induce anaesthesia?
Unconsciousness is induced in most people within 30 seconds
81
What is the current view on how intravenous anaesthetics act?
No one MOA; thought to suppress consciousness through reduction of activity within the CNS, with agents acting on both inhibitory (GABA) and excitatory (glutamate) pathways
82
How does ketamine act?
Ketamine is an NMDA (glutamate) receptor antagonist, which blocks the ion channel preventing movement of sodium and calcium into the cell.
It is a general anaesthetic.
83
How does Midazolam act?
It is a benzodiazepine
| Positive allosteric modulator of the GABA receptor (y-subunit)
84
What type of anaesthetic is most commonly used for short-term dental anaesthesia? Which drug would be appropriate?
Local anaesthetic
Lidocaine (half-life 1-2 hours)
85
When injecting a local anaesthetic (lidocaine) for a filling in an upper right incisor using the right anterior superior alveolar nerve, which cranial nerve is being injected?
Trigeminal, maxillary branch (Vb) as this carries sensation to the maxilla and upper teeth
86
What type of anaesthesia is epidural?
Local; injection of anaesthetic into the epidural space between the vertebral column and the spinal cord
87
How does epidural differ from spinal anaesthesia?
Epidural only enters the epidural space between the vertebral column and the outer meningeal layers of the spinal cord (dura)
Spinal anaesthesia enters the enlarged subarachnoid space located below the level of the spinal cord, the lumbar cistern
88
What type of surgical procedures is epidural most commonly used for?
Lower genitourinary procedures; obs and gyn procedures and orthopedic work on the lower limb.
Can also be used for pain control
89
Give an example of a scale used to determine the level of epidural block
Bromage scale; assesses and grades the patient ability to move their legs folllowing induction of the block. Has 4 levels:
0: No block - patient can flex the knees and feet fully
1: Partial block - patient can partially flex the knees and resist gravity and has movement of the feet
2: Almost complete block - patient demonstrates an inability to flex the knees but ability to flex the feet
3: Complete block - patient is unable to move knees or feet
90
Which 2 local anaesthetics are commonly used for epidural anaesthesia?
Lidocaine
| Bupivacaine
91
What do neuromuscular blockades do?
Relax muscle by blocking the activity at the neuromuscular junction (NMJ)
92
What are the two groups of NMB?
1. Depolarising
| 2. Non-depolarising
93
Name 2 depolarising neuromuscular blockades
1. Suzamethonium
| 2. Neostigmine
94
Name 2 non-depolarising neuromuscular blockades
1. Vecuronium
| 2. Atracurium
95
How do depolarising NMB's work?
Bind to the Ach receptor causing prolonged depolarisation (causes the receptor to close and repolarise even though the agonist is still bound to it) and then block the site, preventing further depolarisation and muscle contraction.
The inital depolarisation causes fasciculation of the muscles prior to relaxation occuring and is associated with increased likelihood of muscle pain post-operatively
96
How do non-depolarising NMB's work?
Non-depolarising NMB compete with ACh to bind to the ACh receptors.
Once bound, they prevent depolarisation (i.e. non-depolarising), thus blocking the effect of ACh.
Also act presynaptically to reduce calcium entry, whcih reduces release of transmitter from presynaptic vesticles.
Have a slower onset than depolarising NMB, randing from 2-5 minutes, with duration between 15-90 mins.
Water soluble and show no accumulation with repeated doses, making them more suitable for long-term use than depolarising NMB.
97
How do anticholinesterases work?
Work non-competitively to increase the levels of ACh in the junctional cleft by blocking acetylcholinesterase (AChE) breakdown of ACh.
Cause muscle paralysis by overloading the system, activating all the ACh receptors at maximum and leaving no room for additional movement; simialr to depolarising NMBs.
98
Do depolarisng or non-depolarising have faster onset?
Depolarising
99
Which of depolarising and non-depolarisng are competitive?
Non-depolarising
100
Which 2 drugs are used to reverse the effects of NMB?
1. Neostigmine (anticholinesterase)
| 2. Sugammadex (a selective relaxant binding agent)
101
A 42 yeard old woman is given atracurium as an NMB during abdominal surgery. What type of NMB is atracurium and what is its MOA?
Atracurium is a non-depolarising NMB which competitively blocks the ACh receptor to prevent depolarisation and muscle contraction
102
What are the 3 main effects of anaesthetics?
1. Unconsciousness (via action on the reticular formation)
2. Loss of reflexes (by affecting the sensory input to the reflex arc)
3. Analgesia (reduced transmission of conscious sensation)
103
Which class of drug are avoided for surgical interventions?
NSAID's as they may lead to increased bleeding
104
Name 3 drug groups used as adjuncts for anaesthesia
1. Antimuscarinic
2. Adrenergics
3. Antihistamines
105
What does the process of general anaesthesia include?
1. Premedication (usually with benzodiazepine to reduce anxiety)
2. Induction (inhalation or intravenous administration of anaesthetic)
3. Muscle relaxation and intubation (with a NMB - to relax the muscles during long surgical procedures for abdominal and thoracic surgery and for mechanical ventilation during NMB block)
4. Maintenance (Inhaled/IV adminstration)
5. Analgesia (adminstration of agents to reduce pain on recovery from surgery)
6. Reversal (of both NMB and anaesthesia - via metabolic breakdown/exhaaltion), return of consciousness
106
Name and describe the 2 types of pain seen clinically
1. Nociceptive (result of tissue damage, often acute, short-term and relatively easy to treat)
2. Neuropathic (result of damage to neurons, often chronic and difficult to treat)
107
Give 4 exampels of nociceptive pain
1. Low-back pain
2. Myofascial pain
3. Arthirits
4. Visceral pain (pancreatitis, endometriosis)
108
Name some symptoms of neuropathic pain
Shooting/burning pain
Paraesthesias (pins and needles)
Numbness
109
Give 4 examples of neuropathic pain
1. Phantom limb pain
2. Trigeminal neuralgia
3. Post-stroke pain
4. Post-herpetic pain
110
Name 5 forms of headache
1. Tension (bilateral, frontal lobes, back of neck)
2. Sinus (butterfly pattern)
3. Migraine (unilateral)
4. Cluster (sympathetic involvement, focus behind eye)
5. Medication overuse headache
111
If a patient came in complaining of the 'worst ever headache' what does this indicate?
Sub arachnoid haemorrhage - red flag - send to CT
112
How is a tension headache treated?
NSAIDs
| Diary to determine trigger factors
113
How is a sinus headache treated?
Decongestant
Antihistamine
Steroid
114
How is a migraine treated?
NSAIDs + Antiemetic (against vomiting and nausea)
| Anti-migraine drugs - triptans
115
Define addiction
A relapsing-remitting disorder comprising behaviours that are performed in a compulsive manner in spite of the potential for self-harm.
116
Describe the difference between addiction and dependence
Addiction is the compulsive need for the substance
| Dependence is characterised by a state of withdrawl when the substance of abuse is removed
117
Name 5 things that people can become dependent upon
```
Analgesics (painkillers)
Tobacco
Alcohol
Gambling
Stimulants (including caffeine)
Opioids
Sedatives/hypnotics
```
118
What are the 3 categories which behaviours associated with dependence fall into?
1. Drug seeking/craving behaviours (anticipation of obtaining/taking a drug prior to its use)
2. Binging/intoxication behaviours (taking the substance, the 'highs' and also includes issues of tolerance and dependence)
3. Withdrawl behaviour (negative rffects of removal of the drug)
119
What are the 2 categories dependence can be divided into?
1. Psychological dependence
| 2. Physical dependence
120
What is psychological dependence?
The need to keep performing the compulsive behaviours; characterised by emotional distress on stopping these behaviours
121
What is physical dependence?
The need for the functional effect of the drug on the body itself, characterised by physical symptoms on withdrawl of the drug.
122
Name 3 psychological indicators of someone suffering from dependence on prescription drugs
1. Behavioural changes e.g. stealing
2. Personality changes e.g. lying
3. Positive reinforcement of use of the drugs e.g. they make you feel better
123
Define tolerance
The requirement for an increasing amount of the drug/behaviour to elicit the same level of positive reinforcement ('high') as that experienced during previous exposures to the substance/behaviour
NB. Tolerance does not mean addiction/dependence - it is a decreased sensitivity
124
What are the 3 main types of tolerance?
1. Acute
2. Chronic
3. Learned
125
What is acute tolerance?
Example: Cocaine
Usually caused by repeated exposure to a drug over a relatively short period of time e.g. repeatedly using cocaine over a single night results in a rapid decrease in the 'highs' percieved.
126
What is chronic tolerance?
Example: Opioids
Chronic tolerance develops as a result of constant exposure to a substance over a prolonged period of time e.g. prescription opioid use that over weeks or months can lead to increasing doses needed
127
What is learned tolerance?
Example: Alcohol
Results from frequent exposure to substances that become integrated into the normal behavioural routines e.g. some people who use alcohol often seem unaffected by the substance, learning to compensate for the effects of alcohol over time
128
Why does the 'crash' following a drug occur?
Not due to changes in plasma levels as occurs before this - most likely due to changes in regional neuronal activation; once the 'high' in the striatum, thalamus, nucleus accumbens and cortical regions begins to subside, other areas involved (stiatum and amygdala) in the negative aspects become more dominant
129
Name 4 common psychological symptoms of withdrawl
1. Anxiety
2. Dysphoria
3. Irritability
4. Anhedonia
Confusion
Fatigue
Headache
130
What is anhedonia?
Inability to feel pleasure in normally pleasurable activities
131
What is dysphoria?
A state of unease or generalised dissatisfaction with life
132
Name 4 common physical symptoms of withdrawl
1. Tachycardia
2. Hyperhidrosis
3. Confusion
4. Tremor
Tachypnoea
Lacrimation
Rhinorrhea
133
What is the receptor target of Ketamine?
Ketamine blocks the NMDA type of glutamate receptor
134
What is the receptor target of Heroin?
Heroin (diamorphine) is a synthetic opioid, originallly developed to use against opium addiction.
135
What is the receptor target of ecstasy (MDMA)?
Ecstasy is a serotonin (5HT) receptor agonist
136
What is the receptor target of cocaine?
Cocaine targets all monoamines, but the effect on the reward pathway occurs via the interaction with dopamine
137
What is the recpeotr target of marijuana?
Marijuana (cannabis) binds to cannabinoid receptor
138
Alcohol slows down the way the body functions. Which two transmitters can be over released in an attempt to return the body to a normal functioning state?
Adrenaline and noradrenaline
These are produced in increased amounts to increase activity in the autonomic nervous system, increasing HR and BP to offset the depressant effects of alcohol.
When the alcohol wears off, this excess adrenaline and noradrenaline results in shaking, sweating and anxiety associated with withdrawl
139
What type of inheritance pattern would you predict dependence follows?
Likely the result of polygenic inheritance (most behaviours are moderate to highly heritable, but triggered and reinforced by personal choice (behavioural mimicking and environmental factors)
140
Why does route of administration a factor in the development of dependence?
The speed with which the drug reaches the CNS will have a huge effect on the likelihood of asssociations between drug taking and any positive effects forming
141
Place these in order of speed of increasing concentration of the drug in the brain: Ingestion, Injection, Snorting, Inhalation
1. Inhalation (fastest)
2. Injection
3. Snorting
4. Ingestion (slowest)
142
Which psychological model do individuals go through when going through a change related to their addiction?
The transtheoretical model (Precontemplation, contemplation, preparation, action, maintenance, relapse?)
143
A patient comes to you after a number of weeks spent planning the start of his detoxification. He has not taken any drug for 24 hours and is feeling anxious and shaky. What stage of the transtheoretical model is he in?
Action
144
What type of drug is nicotine classed as?
Parasympathomimetic
145
What type of receptor does nicotine bind to?
Nicotinic cholinergic receptors (nAChR)
146
What does nicotine trigger the release of?
At low doses, it triggers the release of acetylcholine, noradrenaline and adrenaline via the ANS. These associated with the stimulant effects of smoking.
Also triggers endorphins, dopamine and serotonin. These account for the positive mood effects and addictive quality of the substance.
147
What do MAOIs do?
MAOIs are monoamine oxidase inhibitors; these stop the enzyme responsible for breaking down dopamine, noradrenaline and serotonin from working, so there are more of these substances around.
Tobacco contains MAOIs which further increases the positive effects of the nicotine and contributes to the formation of addictive behaviours
148
Name 3 pharmacological interventions used to increase adherence to smoking cessation
1. Nicotine replacement therapy (patches/inhalation/spray/lozenge)
2. Bupropion (atypical antidepressant)
3. Varenicline (partial agonist at the nicotine receptor - NB there is link to this and suicidal thoughts so requires monitoring)
149
Name 3 suggestions for how alcohol works on the CNS
1. Enhances GABA activity
2. Inhibits glutamatergic NMDA receptors
3. Inhibits voltage dependent calcium channels (VDCC)
Chronic use of alcohool leads to the inverse effects occuring, which may be linked to increased anxiety and insomnia assocated with dependence.
150
What does AUDIT stand for (screening tool for potential alcohol misuse)?
Alcohol Use Disorder Identification Test
| A score of 5 or more is AUDIT positive
151
What type of depression has recurrent low levels of depression and mod-high mood for >2 years?
Cyclothymia
152
What is the biggest 'red flag' that indicates severe depression?
Thoughts of suicide
153
What is the most common side effect with the 'gold standard' treatment for severe depression?
Memory loss
| ECT
154
Which atypical drug acts as a partial agonist at 5HT1A receptors?
Buspirone
155
Which common antidepressant can be used to treat neuropathic pain?
Nortriptyline
| Amitriptyline
156
Which dietary amine should be kept to a minimum if you're on MAOIs?
Tyramine
(cheese reaction)
Also tyrosine
157
What are the 2 patterns of depressive states?
1. Unipolar
| 2. Bipolar
158
What is the name for clinical depression?
Major depressive disorder (MDD)
159
What is dysthymia?
Low level of depression (altered moods), chronic
But not yet major depressive disorder
160
What is bipolar?
Recurrent episodes/cycles of mania and depression. Includes bipolar disorder and cyclothymia (low level, not as extreme as bipolar)
161
Name the 2 key symptoms of depression
1. Persistent sadness or low mood
| 2. Marked loss of interests or pleasure
162
Name some additional symptoms of depression (in addition to key ones)
- Disturbed sleep
- Decrease or increase in appetite
- Fatigue/loss of energy
- Poor concentration, indecisiveness
- Feelings of worthlessness
- Suicidal thoughts or acts
163
What are the 3 grades of major depressive disorder?
1. Mild depression --> 4/5 symptoms only, result in only minor functional impairment
2. Moderate depression
3. Severe depression --> most symptoms, and these markedly interfere with functioning
All at least for 2 weeks
164
How many symptoms does DSM V require for a diagnosis of mild depression?
> 5 symptoms
| For nearly every day for 2 weeks
> 2 years for chronic depression
165
How many symptoms does ICD-10 require for a diagnosis of mild depression?
> 4 symptoms
| For nearly every day for 2 weeks
> 2 years for chronic depression
166
Describe the biological basis of depression (brain structures)
Decrease in hippocampal volume/activity
Decreased activity in prefrontal cortex
Increase in amygdala (controls negative emotions)
Increased activity in hypothalamus
167
Name 4 theories for depression
1. Monoamine theory (neurotransmitter)
2. Neurohormonal (e.g. HPA axis)
3. Immune/autoimmune
4. Circadian
168
Name 5 functions serotonin is involved in
1. Mood
2. Nausea and vomiting
3. GI function
4. Sexual function
5. Appetite
169
What is the main site of production of serotonin?
Raphe nuclei in the brainstem
| but gut also produces serotonin
170
What are the main sites of production of noradrenaline?
```
Locus coeruleus (nucleus in the pons of the brainstem related to physiological responses to stress and panic)
Lateral tegmental area (also in pons)
```
171
Name some functions of noradrenaline
- Energy homeostasis
- Emotions
- Blood pressure
- Heart rate
- Bladder control
- Motor functiion
- Depression
172
Describe the role of inflammation in depression
Inflammation/damage in CNS can lead to microglia activation, cell dysfunction and cell death.
These can lead to neurological disorders.
173
What is the gut-brain axis?
There is significant communication between the enteric nervous system, ANS and CNS.
- Inflammation in the gut can trigger altered activity in the brain
- The gut microbiome acts as a protectant so nothing gets through the barrier to affect brain function, but if damage here then substances can penetrate and access CNS to change function
- Probiotics shown to reduce anxiety/improve mood
174
Describe the role of neurogenesis in depression
- Depression is associated with decreased dendritic arborisation
- Also associated with decreased number of synapses (decreased boutons on neurons)
- Overproduction of receptors (to try and catch the little neurotransmitter that there is)
- Can be reversed by neuronal growth factors e.g. BDNF and antidepressants
175
What are the 4 major groups of drugs used to treat depression?
1. Selective serotonin reuptake inhibitors (SSRIs)
2. Tricyclic antidepressants (TCAs)
3. Monoamine oxidase inhibitors (MAOI-A)
4. Atypical antidepressants
176
Name some treatment types for depression
1. Cognitive behavioural therapy (CBT)
2. Pharmacological
3. Transcranial magnetic stimulation (TMS)
4. Transcranial direct current stimulation (tDCS)
5. Electroconvulsive therapy (ECT)
6. Exercise?!
177
Name 2 selective serotoin reuptake inhibitors
1. Citalopram
| 2. Sertraline
178
How do SSRIs act?
Increase levels of serotonin/5HT by inhibiting the re-uptake pump, so more is left in the synaptic cleft
179
How do 5HT partial agonists act as anti-depressants?
Partial agonists slow down activity of the neurons to allow things to reset (allows neurotransmitter to build up in vesicles in the pre-synaptic terminal and allowing reduction in overproduced receptors on post-synaptic membrane), so when neuron is next active, it will be more effective
Indirect approach to depression
180
What are the 5 main actions of tricyclic antidepressants?
1. 5HT reuptake blocker
2. Noradrenaline reuptake blocker
3. a1 adrenoreceptor antagonist
4. H1 receptor antagonist
5. M1 receptor antagonist
181
Name some common side effects of TCAs
- Sedation
- Confusion
- Visual problems
- Cardiac dysrhythmia
- Mania
Many drug interactions
182
How do Monoamine oxidase inhibitors act?
Stops the breakdown of neurotransmitter after it is re-uptaken into the pre-sunaptic terminal
Therefore increases the levels of serotonin and noradrenaline (also dopamine as it is a monoamine)
e.g. Moclobemide, which is a reversible inhibitor of MAO
183
Name some side effects of MAOIs
- Many cross drug reactions (cannot use with SSRIs or TCAs)
- Convulsions
- Sleep disorders
- 'Cheese reaction' - tyramine
184
How does mirtazapine work?
a-2 antagonist
Blocks a2 receptors
Noradrenaline and serotonin would normally bind to these receptors.
By blocking, prevents noradrenaline and serotonin from becoming bound to the nerve cells.
More free serotonin/noradrenaline
185
Name a mood stabiliser
Lithium
186
Name 2 side effects of electroconvulsive therapy
1. Memory loss
2. Short term muscle aches
Stigma!
