Drugs that affect the Nervous System

Question 1

Where does pain originate from?

Answer 1

1. Nociceptive pain - arises from stimulation of superficial or deep nociceptors
   a) Superficial (somatic) Nociceptive pain - skin, mucosa, bones, joints, pleura, peritoneum
   i) Best treated with NSAIDs
   b) Deep (visceral) nociceptive pain - organs and large muscles
   i) Best treated with opioids
   ii) This pain may be referred
2. Neuropathic pain - arises from lesion/dysfunction in somatosensory NS
   a) Associated with paraesthesia, allodynia, and SNS dysfunction
   b) Responds less well to opioids and NSAIDs
   c) Adjunct medication required (e.g. anticonvulsants, antidepressant etc)

Question 2

How is pain generated and transmitted?

Answer 2

1. Nociceptors located on ends of primary afferent neurons and pick up noxious stimuli
2. Types of primary afferent neurons:
   a) Myelinated A-delta fibres - carry sharp, fast pain
   b) Unmyelinated C fibres - slow, dull pain
3. Transmission:
   a) Noxious stimuli are picked up by nociceptors
   b) Signal is taken into spinal cord via afferent nerves
   c) 2nd order neurons at dorsal horn decussate immediately and takes signal to thalamus via spinothalamic pathway
   d) 2nd order neuron synapses with third order neuron at Thalamus and signal continues to higher centres (e.g. somatosensory cortex, prefrontal cortex, other associated areas etc)

Question 3

What is the difference between acute and chronic pain?

Answer 3

1. Onset:
   a) A: Sudden
   b) C: Long duration
2. Characteristics:
   a) A: sharp, localised
   b) C: dull, aching, diffuse
3. Physiological responses:
   a) A: Increased BP, HR, sweating, pallor, dilated pupils, increased muscle tone, tremor
   b) C: often absent
4. Behavioural responses:
   a) A: Increased anxiety, restlessness, cries, grimaces, protects parts
   b) C: Anger, depression, withdrawn, expressionless, exhaustion

Question 4

What are the types of analgesics?

Answer 4

1. Opioid analgesics
2. Non-opioid analgesics
3. Anaesthetics
4. Other (e.g. pregablin, gabapentin, capsaicin, cannabinoids)

Question 5

What are the Opioid analgesics?

Answer 5

1. Opioids are substances that produce morphine-like effects and that are blocked by antagonists

Question 6

Describe the pharmacodynamics of opioids:

Answer 6

1. Opioids bind to receptors located in CNS and PNS
   a) Endorphins and encephalons are the endogenous ligand
2. Opioid receptor types and what they mediate:
   a) Mu receptors: analgesia, euphoria, sedation, decrease GI motility, miosis, respiratory depression, drug dependence
   b) Kappa receptors: analgesia, sedation, miosis, dysphoria
   c) Delta receptors: analgesia, decrease in GI motility
3. Actions of opioids at opioid receptors can include:
   a) Agonists (e.g. morphine)
   b) Antagonists (e.g. naloxone)
   c) Partial agonists (e.g. buprenorphine)
   d) Agonist/antagonists (e.g. pentazocine)

Question 7

Describe the pharmacodynamics of morphine (and all agonists):

Answer 7

1. Opioid receptors are members of the G-protein-coupled family of receptors
2. Morphine binds with G-protein-coupled family of receptors
3. This activates G-protein which leads to inhibition of second messenger systems
4. This results in opening of potassium channels and closing calcium channels
   a) This causes membrane potential to decrease due to potassium leaving (decreased neuronal excitability)
   b) Also causes decrease in neurotransmitters being released due to less calcium
5. As action potentials are prevented from occurring, this inhibits afferent transmission and alters perception/emotion

Question 8

Describe the pharmacokinetics of morphine (and all agonists):

Answer 8

1. Absorption:
   a) Many formulations and routes of administration
   b) Considerable first-pass metabolism (same as all opioids)
2. Distribution:
   a) Widely distributed
   b) 35% bound to proteins (65% free drug)
   c) Quite lipophilic
3. Metabolism:
   a) Commonly metabolised in liver via conjugation with glucuronides (polar substances)
4. Excretion:
   a) Glucuronides attaches with metabolite and is excreted by kidneys

Question 9

What are the pharmacological effects of morphine?

Answer 9

1. Central effects (mediated by CNS):
   a) Analgesia
   b) Suppression of cough reflex
   c) Suppression of respiratory centre
   d) Sedation
   e) Euphoria
   f) Dysphoria
   g) Miosis
   h) Nausea and vomiting
   i) Hypotension and bradycardia
   j) Tolerance/dependence/addiction
2. Peripheral effects (mediated by PNS):
   a) Decreased GI motility (constipation)
   b) Spasms of sphincter muscles
   c) Release of histamine (formication)
3. Adverse effects:
   a) Respiratory depression
   b) Sedation
   c) Circulatory depression
   d) Nausea and vomiting
   e) Constipation
   f) Tolerance

Question 10

What are the contraindications of morphine?

Answer 10

1. Acute respiratory depression
2. Acute alcoholism
3. Head injury
4. Acute asthma
5. COPD
6. Any respiratory impairment (e.g. asthma)

Question 11

What is naloxone?

Answer 11

1. Opioid antagonist used to counter effects of agonist opioids
2. Pharmacodynamics:
   a) Antagonist at opioid receptors
   b) Reversible competitive antagonist
3. Pharmacokinetics:
   a) Only administered parenterally
   b) Very short half-life time (1 hour)
4. Pharmacological effects:
   a) Reverses the effects of opioid agonists
5. Adverse effects:
   a) Nausea and vomiting

Question 12

What are General anaesthesia?

Answer 12

1. A drug that produces a reversible state of unconsciousness over the entire body with absence of pain sensation
2. GA Pharmacodynamics:
   a) Not fully understood
   b) GAs widely varied in chemical structure and concentration necessary to produce anaesthesia
   c) No GA receptor in CNS

Question 13

What are the current theories for how GA work?

Answer 13

1. GAs act at GABA receptors (main inhibitory receptor of CNS)
   a) Causes Cl- channels to open resulting in influx of Cl-
   b) Inside of cell becomes more negative
   c) CNS depression
2. GA opens K+ channels
   a) Leads to hyperpolarisation - CNS depression through no action potentials
3. GA act at NMDA receptors (main excitatory neurotransmitter in CNS)
   a) Ca2+ channels close which stops Ca2+ influx
   b) Inside of cell stays negative
   c) Depresses CNS

Question 14

What are the pharmacological effects of general anaesthesia?

Answer 14

1. Stage 1: Analgesia
   a) Pain and smell abolished immediately
2. Stage 2: Excitement
   a) Individuals in this stage can have responses such as struggling, shouting, frustration, respiratory irregularities
   b) This stage is dangerous and should be moved on quickly
3. Stage 3: Surgical anaesthesia
   a) Loss of reflexes from brain down
   b) Once reflexes are lost, there is decrease in muscle tone, weakened pulse, blood pressure drops
4. Stage 4: Medullary paralysis
   a) Very close to death, it is favourable to stay in Stage 3 where possible

Question 15

What are the types of agents used in general anaesthesia?

Answer 15

1. Inhaled anaesthetics:
   a) Nitrous oxide - commonly used in dentistry and childbirth
   b) Halogenated hydrocarbons (e.g. sevoflurane, methoxyflurane) - used by paramedics during extreme accidents
2. Intravenous anaesthetics:
   a) Ultra-short acting barbiturates (e.g. thiopentone) - not used commonly as is very dangerous
   b) Non-barbiturates (e.g. propofol, ketamine)

Question 16

Describe nitrous oxide:

Answer 16

Inhaled Anaesthetic

1. Pharmacodynamics:
   a) Not known
2. Pharmacokinetics:
   a) How well absorption in lungs occurs is dependent on partial pressures of the lung
   b) Good lung function is therefore critical for effective use
   c) Agents that are lipid soluble transfer to CNS at a quicker rate - however, the higher the lipid solubility the longer it takes to recover from anaesthesia
   d) Minimum Alveolar Concentration (MAC) is the measurement of the anaesthetic that is going from lungs into blood
3. Indications:
   a) Dentistry
   b) Child birth
   c) Minor surgical procedures
4. Adverse effects:
   a) Post operative nausea and vomiting
   b) Mild cardiac depression

Question 17

Describe Sevoflurane:

Answer 17

Inhaled anaesthetic

1. Pharmacodynamics:
   a) Not known
2. Pharmacokinetics:
   a) Approx. 5% of Sevoflurane gets metabolised by liver in into an inactive form
   b) Has a half life of around 15-23 hours
   c) High potency - able to cause anaesthesia very quickly
   d) Low blood and tissue solubility - works quickly but can get ridden of quickly
   e) Most optimal gaseous anaesthetic
3. Indications:
   a) Induction and maintenance of general anaesthesia
   b) Particularly used for children
   c) Day surgery
4. Adverse effects
   a) Post-operative nausea and vomiting
   b) Mild cardiac depression
   c) Shivering and salivation

Question 18

Describe Propofol:

Answer 18

Intravenous anaesthetic

1. Pharmacodynamics:
   a) Unknown
2. Pharmacokinetics:
   a) It is rapidly taken up by brain tissue as it is highly lipid soluble
   b) Equilibrium in blood stream is reached within one arm-brain circulation
   c) Because it doesn’t require lung function, it relies on hepatic metabolism and renal excretion to get rid of it in your system
   d) Short action due to distribution to fat tissue
3. Indications:
   a) Induction and maintenance of general anaesthesia
4. Adverse effects:
   a) Post operative nausea and vomiting
   b) Cardiac depression

Question 19

Describe the administration of general anaesthesia:

Answer 19

1. Induction:
   a) IV anaesthetic (e.g. Propofol)
2. Maintenance:
   a) Inhalation of gas and volatile liquid anaesthetic (e.g. Sevoflurane)
3. In some procedures, TIVA (Total IV Anaesthesia) might be done
4. In paediatrics, ‘Gas-down’ where only inhalation anaesthesia is performed

Question 20

What is a typical drug regiment for surgical procedure?

Answer 20

1. Pre-medication:
   a) Benzodiazepines to decrease anxiety (e.g. midazolam)
   b) Anticholinergics to decrease secretions (e.g. atropine)
   c) Analgesics to prevent pain (e.g. morphine)
2. Induction of GA:
   a) Usually via IV Propofol
3. Maintenance of GA:
   a) Usually inhaled nitrous oxide or sevoflurane
4. Analgesia
   a) Morphine, fentanyl
5. Neuromuscular blocking drugs (e.g. suxamethonium)
6. Post-operative nausea and vomiting (e.g. metoclopramide, prochlorperazine)

Question 21

What is Local Anaesthesia (LA)?

Answer 21

1. Drugs that directly induces the absence of pain sensation in that part of the body
   a) Consciousness is not depressed
2. LAs exist in solution as either charged or uncharged particles
   a) Uncharged form is capable of entering nerve cell and then becomes charged (active)
3. Pharmacodynamics:
   a) LAs block voltage-gated Na+ channels in excitable cells
   b) This decreases Na+ influx
   c) Cells cannot reach threshold and depolarise
   d) No generation of action potential
   e) Decrease in pain sensitivity
4. Pharmacokinetics:
   a) Agent acts on area of administration
   b) Has local disposition - taken up by tissue but metabolism occurs much later on
   c) Most LAs are formulated with adrenaline - this causes vasoconstriction so that LA stays in that area and does not distribute around body
   d) Metabolism and excretion does occur by liver and kidney

Question 22

What are the techniques for applying local anaesthetics?

Answer 22

1. Topical (surface) anaesthesia:
   a) Spray, EMLA cream
   b) Often used in children that are fearful of needles
2. Infiltration anaesthesia:
   a) Injection of LA into tissue to be anaesthetised
   b) Often used to get rid of skin lesions or very minor surgeries
3. Peripheral nerve block anaesthesia:
   a) LA injected into the vicinity of nerve trunk
   b) Often used for dental, eye, or limb procedures
4. Epidural anaesthesia:
   a) LA injected into the space between the dura mater and ligamentum flavum (spinal cord levels C7-T10)
   b) Often used in labour and caesarean section
5. Spinal:
   a) LA injected into CSF in subarachnoid space
   b) Often used for abdominal surgery or surgery to lower extremities

Question 23

What are the pharmacological effects of local anaesthesia?

Answer 23

1. LA are capable of affecting all excitable membranes
2. This means that while pain sensation is abolished, loss of temperature, proprioception, touch, and pressure to the local area is also removed

Question 24

Describe Lignocaine:

Answer 24

Local anaesthetic

1. Pharmacodynamics:
   a) Uncharged form crosses cell membrane
   b) Picks up hydrogen ion
   c) Therefore charged form blocks sodium channel
   d) Reduces action potentials
2. Pharmacokinetics:
   a) Rapid onset of action (5-10 minutes)
   b) Metabolised by liver and excreted by kidneys
   c) Half life of 90-120 minutes
3. Indications:
   a) Various depending on reasoning
4. Adverse effects:
   a) Can have toxic effects on CNS and PNS
   b) Can cause depressed cardiovascular and respiratory system

Question 25

What are the main mechanisms of anti-epileptic drugs?

Answer 25

1. Enhancement of GABA inhibition
   a) Benzodiazepines
   b) Phenobarbital
   c) Tiagabine
   d) Vigabatrine
2. Inhibition of sodium channel function
   a) Phenytoin
   b) Carbamazepine, oxycarbazepine
   c) Lamotrigine
3. Inhibition of calcium channel function
   a) Gabapentin

Question 26

Describe enhancement of GABA inhibition in anti-epileptic drugs:

Answer 26

1. GABA is an inhibitory neurotransmitter which latches on to GABAa or GABAb receptors
2. Action of GABA is terminated by:
   a) Membrane-bound GABA transporters
   b) GABA transaminase

Question 27

What are benzodiazepines?

Answer 27

Enhancement of GABA inhibition anti-epileptic drug

1. Pharmacodynamics:
   a) Act via effects on GABAa receptors (ligand-gated chloride channels)
   b) Benzodiazepines act as allosteric modulators on GABAa receptors - bind to allosteric site of GABAa receptor
   c) This increases affinity of GABA binding to GABAa receptors which increases frequency of chloride channels opening
   d) More chloride enters cell, becomes more negative and leads to more neuronal inhibition
2. Pharmacokinetics:
   a) Absorption - generally well absorbed because they are mainly lipid soluble
   b) Distribution - because they are lipid soluble they are able to cross the blood brain barrier
   i) Have different duration of action
   c) Metabolism - primarily metabolised by enzymes of the GIT and liver
   i) Metabolism decreases with age and so pharmacological effects increase
   d) Excretion - metabolites excreted in urine
3. Indications:
   a) Epilepsy
   b) Anxiety disorders
   c) Sleep disorders
   d) Preoperative medication
   e) Procedural sedation
   f) Preventing muscular spasms
   g) Withdrawal from CNS depressants (e.g. alcohol)
4. Adverse effects:
   a) Commonly; drowsiness, confusion, lack of coordination, double vision, amnesia, vertigo, slurred speech, tolerance/dependence
   b) Less frequently; headache, hypotension, anger, impaired concentration, hallucinations, paradoxical insomnia
5. Drug interactions:
   a) Other CNS depressants (e.g. alcohol, opioids) which can have synergistic effects when mixed together causing depression of CNS
6. Contraindications:
   a) Caution use in children and elderly people because of their lower ability to metabolise and process drug
   b) Many AEDs are potentially teratogenic

Question 28

Describe Tiagabine:

Answer 28

Anti-epileptic drug - GABA enhancer

1. Pharmacodynamics:
   a) Inhibits GAT1 transporter which means less GABA is returned to synaptic vesicles
   b) This means GABA levels at synapse is increased
   c) More GABA is able to bind to receptors and cause neural inhibition

Question 29

Describe Vigbatrine:

Answer 29

Anti-epileptic drug

1. Pharmacodynamics:
   a) Non-competitive inhibitor of GABA transaminase (enzyme that breaks down GABA at synapse)
   b) More GABA at synapse means more GABA is able to bind to receptors and cause longer neural inhibition

Question 30

Describe Phenytoin:

Answer 30

Anti-epileptic drug - Na+ channel blocker

1. Pharmacodynamics:
   a) ‘Use dependent’ blocking action of voltage-gated sodium channels
   b) This means it inhibits high-frequency trains of action potentials
   c) Seizures are caused by way too many action potentials, and so inhibiting the high frequency inhibits seizure discharge
   d) This also inhibits further release of neurotransmitters
2. Pharmacokinetics:
   a) Absorption - usually given orally (but is non-linear pharmacokinetic as it is very unpredictable)
   b) Distribution: 80-90% of drug is protein bound (little amount of free drug)
   i) Certain drugs compete with phenytoin for albumin
   ii) This increases amount of free phenytoin or increases clearance of phenytoin
   c) Metabolism - undergo both oxidation and conjugation in liver but has a saturable metabolism
   i) Phenytoin can also act as an enzyme inducer

Question 31

What are the pharmacological effects of Phenytoin?

Answer 31

1. Indications:
   a) Epilepsy (generalised seizures, status epilepticus)
   b) Provoked seizures
2. Adverse effects:
   a) Drowsiness
   b) Dizziness
   c) Confusion
   d) Hirsutism
   e) Gum hyperplasia
3. Drug interactions:
   a) Can be induced or inhibited by other drugs
4. Contraindications:
   a) It is a pregnancy safety category D

Question 32

Describe Carbamazepine, oxcarbazepine, and lamotrigine:

Answer 32

Anti-epileptic drugs

1. Pharmacodynamics:
   a) ‘Use dependent’ blocking action of voltage-gated sodium channels

Question 33

What are the current treatments for Alzheimer’s disease?

Answer 33

1. Centrally acting anticholinesterases (e.g. donepezil, rivastigmine, galantamine)
2. NMDA antagonists (e.g. memantine)
3. Adjuncts (e.g. antipsychotic agents and antidepressants)
   a) Patients with Alzheimer’s are prone to hallucination and may develop depression early on

Question 34

Describe the centrally acting anticholinesterases:

Answer 34

Neurodegenerative drugs - Donepezil (selective for neuronal acetylcholinesterase), Galantamine, Rivastigmine

1. Pharmacodynamics:
   a) Reversible inhibitors of acetylcholinesterase (AChE)
   b) AChE inhibition means there is more ACh in neurotransmiter
   c) People with dementia have low levels of cholinergic transmitter activity and so drug is increasing levels of transmitter activity
2. Pharmacokinetics:
   a) Available as sustained released formulations or transdermal patches
   b) Metabolised by liver and excreted by kidney
   c) Rivastigmine has slightly longer half life

Question 35

What are the pharmacological effects of anticholinesterases?

Answer 35

1. Effect:
   a) All are equally efficacious
   b) Temporarily improve cognition
2. Indications:
   a) Strict guidelines for prescription - only used for certain Alzheimer’s patients
3. Adverse effects:
   a) Nausea
   b) Vomiting
   c) Diarrhoea
   d) Abdominal pain
   e) Anorexia (not feeling like eating)
   f) Headache
   g) Insomnia
   h) Bradycardia
4. Drug interactions:
   a) Any drug with anti-cholinergic activity
5. Contraindications:
   a) Individuals with significant airway diseases, heart block, or epilepsy

Question 36

Describe the NMDA antagonists:

Answer 36

Neurodegenerative drugs (e.g. memantine)

1. Pharmacodynamics:
   a) NMDA antagonist - main receptor that glutamate binds to
   b) This reduces NMDA receptor-mediated neurotoxicity
2. Indications:
   a) Moderate to severe Alzheimer’s disease
3. Adverse effects:
   a) Headache, agitation, drowsiness

Question 37

What drugs are used to treat Parkinson’s disease?

Answer 37

1. Pathogenesis:
   a) Dopamine deficiency
   b) Acetylcholine/dopamine imbalance
   c) Decrease in other neurotransmitters
2. Types of drugs:
   a) Drugs that increase dopamine levels in brain
   b) Drugs that stimulate DA receptors
   c) Drugs with central anticholinergic activity
   d) Adjuncts
3. Choice of drug depends on symptoms
4. All DA enhancing ages develop tachyphylaxis (tolerance) and so dose has to be either upped in dosage or drug holiday (taken off drug for period of time and put back on)

Question 38

What is levodopa?

Answer 38

Parkinson’s drug - Drugs that increase dopamine level in brain

1. Pharmacodynamics:
   a) Levodopa is a synthetic precursor to dopamine and is converted into dopamine by DDC enzyme
2. Pharmacokinetics:
   a) Absorption - taken orally immediately after meals and is absorbed via active transporters
   b) Metabolism - 99% of levodopa is metabolised by DDC to dopamine and then dopamine is enzymatically degraded by MAO and COMT before it reaches CNS
   i) This causes a problem as DA is rapidly broken down into its metabolites before it reaches the CNS
   ii) 1% of levodopa crosses BBB and is converted to dopamine
   iii) To combat this, peripheral breakdown of levodopa is inhibited by used a second drug (DOPA decarboxylase (DDC) inhibitors) such as carbidopa and benserazide
   iv) DDC inhibitor decreases amount of levodopa being metabolised in peripherals and so more crosses the BBB meaning more dopamine goes to the brain
   v) Important to ensure DDC inhibitor is not lipid soluble so it does not cross BBB or else levodopa will be unable to be converted to dopamine in Brain

Question 39

Describe effects of levodopa-carbidopa:

Answer 39

1. Pharmacological effects:
   a) Increase DA levels in CNS
2. Indications:
   a) Particularly effective against bradykinesia and muscle rigidity that occurs in Parkinson’s disease
3. Adverse effects:
   a) Anxiety
   b) Constipation
   c) Mood changes
   d) Nervousness and confusion
   e) Blepharospasm
   f) Nausea and vomiting
   g) “On-Off” syndrome - patient switches constantly from being free of Parkinson’s to having full effect of Parkinson’s
4. Drug interactions:
   a) Numerous; certain anti-seizure drugs reduce effects of levodopa
   b) Certain anti-depressants mixed with levodopa can increase risk of hypertension
   c) High protein diet can also compete with absorption of levodopa (won’t be absorbed as effectively)
   d) Certain anti-nausea drugs can decrease effects of levodopa
5. Contraindications:
   a) Individuals with severe cardiovascular disease
   b) Individuals with severe asthma
   c) Individuals with severe renal and hepatic diseases

Question 40

What are the different classifications of psychotropic drugs?

Answer 40

1. Anxiolytic and sedative drugs
2. Antipsychotic drugs
3. Antidepressant drugs
4. Drugs to treat mania
5. Psychomotor stimulants
6. Psychotomimetic drugs

Question 41

What are anxiolytics and sedative drugs?

Answer 41

1. Drugs that cause sleep and reduce anxiety
2. Types:
   a) Benzodiazepines
   b) Antidepressants
   c) Zopiclone
   d) Buspirone
   e) Beta antagonists
   f) Antihistamines

Question 42

What are antipsychotic drugs?

Answer 42

1. Drugs that are effective in relieving the symptoms of schizophrenia
   a) Positive: hallucinations, delusions
   b) Negative: ‘Flat’, lack pleasure, apathy
   c) Cognitive: trouble focusing, poor executive function
2. Types:
   a) Typical anti-psychotic drugs - phenothiazines (e.g. chlorpromazine) and haloperidol-like drugs (e.g. haloperidol) which can be used adjunct to anaesthesia
   b) Atypical-anti-psychotic drugs (e.g. clozapine, quetiapine)
3. All anti-psychotics act by blocking dopamine

Question 43

What is olanzapine?

Answer 43

Anti-psychotic

1. Pharmacodynamics:
   a) Antagonist at Dopamine-2 receptor and serotonin 2 receptors
2. Pharmacokinetics:
   a) Available in oral tablet, oral wafer, or intramuscular injection (slowly absorbed)
   b) Initial dose response can be unpredictable depending on individual
   c) Can take several weeks to take effect

Question 44

What is clozapine?

Answer 44

Anti-psychotic

1. Pharmacodynamics:
   a) Competitive blockade of dopamine 1, 2, and 4 receptors - less affinity for D2
   b) Less likely to cause extrapyramidal effects (which occur because dopamine is being blocked in nigrostriatal pathway)
   c) Can also antagonise serotonin, adrenergic, and histamine receptors
   d) More effective than all other anti-psychotic agents
2. Pharmacokinetics:
   a) Oral tablet and is well absorbed
   b) Is 95% protein bound
   c) Narrow therapeutic range - drug monitoring needed
   d) Extensive hepatic metabolism
   e) Half life can range from 4-66 hours

Question 45

What are the adverse effects of anti-psychotic drugs?

Answer 45

1. Extrapyramidal effects:
   a) Dystonias: oculogyric crisis, torticollis, opisthotonus, laryngeal dystonia
   b) Parkinsonism: similar symptoms to Parkinson’s disease, increased muscle rigidity
   c) Tardive dyskinesia: repetitive voluntary movements
   d) Akathisia: motor restlessness
2. Hyperprolactinaemia:
   a) Amenorrhoea
   b) Sexual dysfunction
   c) Galactorrhoea
   d) Gynaecomastia
3. Weight gain
4. Sedation
5. Anti-cholinergic effects
6. Orthostatic hypotension
7. Some are very specific to a certain drug, e.g.:
   a) Clozapine can cause decrease in WBC
   b) Clozapine and elanzepine can increase blood glucose levels

Question 46

What are anti-depressants?

Answer 46

1. Drugs that alleviate the symptoms of depressive illness
2. Types of anti-depressants:
   a) Selective serotonin reuptake inhibitors (SSRIs)
   b) Tricyclic antidepressants (TCAs)
   c) Monoamine oxidase (MAO) inhibitors
   d) Selective noradrenaline reuptake inhibitors (SNRIs)
   e) Noradrenergic and specific serotonergic anti-depressants (NaSSA-type)

Question 47

What is Escitalopram?

Answer 47

Anti-depressants - selective serotonin reuptake inhibitors (SSRIs)

1. Pharmacodynamics:
   a) Inhibits reuptake of serotonin
   b) In doing so, drug competes with serotonin for binding site on serotonin carrier protein
   c) Drug has little affinity for other carriers, only high affinity for serotonin transporters (carrier protein)
   d) Serotonin in synapse maintains feelings of content, the blockage of carrier protein means serotonin stays in synapse and binds to correct receptors to increase feeling of content DIAGRAM
2. Pharmacokinetics:
   a) Oral solution mixed with water or juice, or can be an oral tablet
   b) Presumably well-absorbed
   c) Metabolised by various CYP enzymes in liver
   d) Metabolites are excreted as glucuronides in urine
   e) Half-life of 30 hours (quite short compared to other anti-depressants)

Question 48

What are the effects of SSRIs?

Answer 48

1. Pharmacological effects:
   a) Elevate mood
   b) Reduce social impairment
   c) Treat various anxiety and eating disorders
   d) Can treat pre-menstrual syndrome
2. Adverse effects:
   a) Insomnia
   b) Restlessness
   c) GI distress (nausea, vomiting, diarrhoea)
   d) Suicide risk (most drugs take 5+ days to take effect - sometimes too long for someone with major depression)
3. Drug interactions:
   a) Any drug that increase serotonin levels - can cause ‘Serotonin syndrome’ which occurs when there is excessive amounts of serotonin in synapse leading to confusion, sweats, seizures, death
   b) Any other CNS drugs - can cause CNS depression
4. Contraindications:
   a) Pregnancy category C
   b) Heavy machine operators - due to drowsiness
   c) Generally not indicated in children
   d) Anyone who has hepatic and renal impairment

Question 49

What are tricyclic anti-depressants?

Answer 49

Anti-depressants (e.g. amitriptyline)

1. Pharmacodynamics:
   a) Inhibit reuptake of noradrenaline and serotonin by blocking carrier proteins
2. Indications:
   a) Second-line therapy for major depression
   b) Adjunct in chronic pain management
   c) Prevention of migraine
   d) Urge incontinence (feel the constant need to use bathroom despite not needing to)
3. They were the first successful anti-depressants but are not used often anymore due to two reasons:
   a) Many more side effects because it is not only serotonin reuptake being inhibited but also noradrenaline
   b) Excessively long half life - take too long to take effect

Question 50

What is Mirtazapine?

Answer 50

Anti-depressant - noradrenergic and specific anti-depressants (NaSSA-type)

1. Pharmacodynamics:
   a) Have a dual mode of action - antagonises receptors of noradrenaline and serotonin (can also antagonise histamine)
   i) Alpha2-autoreceptor - increases noradrenaline release
   ii) Alpha2-heteroreceptor
   iii) 5-HT2 and 5HT3 receptors - increases serotonin binding to 5-HT1A receptor which is highly correlated with feelings of content
   iv) H1 receptors
2. Pharmacokinetics:
   a) Rapid onset of action - due to dual action
   b) Available in oral tablet form
   c) 50% oral bioavailability
   d) Extensively metabolised by CYP enzymes in liver
   e) Steady-state reached in 4-6 days
   f) 5% protein-bound
   g) Metabolites excreted in urine and faeces after 4 days
3. Pharmacological effects:
   a) Better efficacy than other anti-depressants
4. Adverse effects:
   a) Increased appetite leading to weight gain
   b) Initial sedation
   c) Impair concentration and alertness

Question 51

What are the drugs affecting cholinergic transmission?

Answer 51

1. Muscarinic agonists
2. Muscarinic antagonists
3. Neuromuscular blocking drugs
4. Anticholinesterases

Question 52

What is Bethanecol?

Answer 52

PNS drug - Muscarinic agonist

1. Pharmacodynamics:
   a) Binds to M3 receptors (M3 agonist) on detrusor muscle of our bladder
2. Pharmacokinetics:
   a) Taken orally
   b) Does not cross BBB
   c) Effects are more prolonged than that of its endogenous ligand (ACh)
   d) Unknown metabolism and excretion
3. Pharmacological effects:
   a) Helps to contract detrusor muscle of bladder
   b) Increases gastric motility and tone
   c) Can restore peristalsis
4. Indications:
   a) Treat urinary retention
5. Adverse effects:
   a) Abdominal pain
   b) Blurred vision
   c) Bronchoconstriction
6. Drug interactions:
   a) Other muscarinic agonists or antagonists

Question 53

What is atropine?

Answer 53

PNS drug - muscarinic antagonist

1. Pharmacodynamics:
   a) Binds to muscarinic receptors and block ACh from binding
2. Pharmacokinetics:
   a) Readily absorbed
   b) Given orally and parenterally
   c) Duration of action is 4-6hours
   d) 50% protein bound
   e) Can cross placenta and BBB
   f) 30-50% is excreted unchanged
3. Pharmacological effects:
   a) Pupil dilation
   b) Inhibition of secretion from lacrimal, bronchial, salivary, and sweat glands
   c) Inhibition of GI motility
   d) Relaxes smooth muscle in urinary tract
   e) Decreases tone of bladder
   f) Low doses decrease HR whilst large doses block vagus nerve causing increased HR
   g) Causes CNS excitement, hallucinations, and irritability
4. Indications:
   a) Use in ocular pharmacology
   b) Sometimes used post- or during surgery in conjunction with general anaesthetics
5. Adverse effects:
   a) Inhibition of sweating
   b) Dry mouth, throat, and skin
   c) Blurred vision
   d) Constipation
   e) Urinary retention
   f) Photophobia
6. Drug interactions:
   a) Tricyclic anti-depressants have an additive effect with atropine
   b) Reduction in GI motility means more drugs are absorbed more readily
7. Contraindications:
   a) Elderly
   b) Individuals with renal and hepatic diseases
   c) Down’s Syndrome

Question 54

What are drugs that affect adrenergic transmission?

Answer 54

1. Influence transmission by:
   a) Stimulating the effect at the adrenergic receptor
   b) Blocking the effect at the adrenergic receptor
2. Achieved by pharmacological agents including:
   a) Alpha-adrenoreceptor agonists
   b) Alpha-adrenoreceptor antagonists
   c) Beta-adrenoreceptor agonists
   d) Beta-adrenoreceptor antagonists

Question 55

What is adrenaline?

Answer 55

PNS drug - drugs affecting adrenergic transmission

1. Pharmacodynamics:
   a) Agonist at alpha and beta adrenoreceptors
2. Pharmacokinetics:
   a) Given SC or IM, if orally it would be rapidly digested in gut
   b) Rapid onset of action
   c) Doses may be repeated
3. Pharmacological effects:
   a) Positive iontrope - increases force of contraction of cardiac muscle
   b) Positive dromotope - speeds up conduction through the AV node
   c) Positive chronotrope - increase heart rate
   d) Dose dependent effects on blood vessels (lower dosage levels - vasodilation; higher levels - vasoconstriction)
   e) Smooth muscle relaxation in GI tract
   f) Detrusor relaxation
   g) Bronchodilation (plus reduces release of inflammatory mediators)
   h) Inhibits insulin secretion
   i) Stimulates lipolysis
4. Indications:
   a) Any systemic shock (e.g. Anaphylaxis)
   b) Adjunct to local anaesthesia
   c) Haemostatic agent in surgical procedures
   d) Heart failure
5. Adverse effects:
   a) Increased nervousness
   b) Restlessness
   c) Tachycardia
   d) Insomnia
6. Drug interactions:
   a) Other adrenergic agonists or antagonists
   b) Digoxin
   c) TCAs
7. Contraindications:
   a) DM
   b) Hypertension
   c) Use in end-arteries

Question 56

What are types of drugs affecting the neuromuscular junction?

Answer 56

1. Blocking action potential generation in motor neuron (e.g. tetrodotoxin blocking sodium channels - Blue-ringed octopus toxin)
2. Inhibiting release of ACh (e.g. botulinum)
3. Neuromuscular blocking drugs
4. Anti-cholinesterase

Question 57

What are the types of neuromuscular blocking drugs?

Answer 57

1. Non-depolarising drugs e.g. pancuromium, rocuronium

2. Depolarising drugs e.g. suxamethonium

Question 58

What is pancuronium?

Answer 58

Neuromuscular blocking drug

1. Pharmacodynamics:
   a) Competitive antagonist of ACh at nicotinic receptors
   b) When >95% of receptors are occupied there is neuromuscular blockade (paralysis)
2. Pharmacokinetics:
   a) Highly water soluble and highly charged - cannot be given orally
   b) Given via IV
3. Pharmacological effects:
   a) Causes muscle relaxation
4. Indications:
   a) Adjunct to general anaesthesia

Question 59

What is suxamethonium?

Answer 59

Neuromuscular blocking drug

1. Pharmacodynamics:
   a) Agonist at nicotinic receptors
   b) Muscle begins to twitch and sodium channels remain open for longer - once there is no more sodium to enter the muscle stops twitching and becomes paralysed
2. Pharmacokinetics:
   a) Parenterally
   b) 2-4 minute half-life
3. Pharmacological effects:
   a) Muscle relaxation
4. Indications:
   a) Electroconvulsive therapy
   b) Tracheal intubation
   c) Orthopaedic manipulations
5. Adverse effects:
   a) Complex effects of CV system
   b) Increased plasma potassium levels
   c) Malignant hyperthermia

Question 60

What are the anti-cholinesterases?

Answer 60

1. Two types:
   a) Reversible anti-cholinesterases - treat various ailments; glaucoma, Alzheimer’s disease, Myasthenia gravis, reversal of neuromuscular blockade after anaesthesia
   b) Irreversible anti-cholinesterases - not pharmacologically viable (chemical warfare or pesticides)

Question 61

What is neostigmine?

Answer 61

Reversible anti-cholinesterase

1. Pharmacodynamics
   a) Reversible inhibitor of AChase
   b) More ACh is able to bind to nicotinic receptor - causes muscular contraction
2. Pharmacokinetics:
   a) Does not cross BBB
3. Indications:
   a) Reversal of neuromuscular blockade
   b) Myasthenia gravis
4. Adverse effects:
   a) Increased parasympathetic effects