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Phase 2A > ICS (Part 3) > Flashcards

ICS (Part 3) Flashcards

1
Q

What does sympathetic system regulate?

A

Fight or Flight

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2
Q

What does parasympathetic system regulate?

A

Rest or Digest

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3
Q

State a few examples of what does sympathetic system do?

A
  • Dilate pupils
  • Tear glands maintain eye moisture
  • Inhibition of excess salivary secretion
  • Accelerate heart rate and constrict arterioles
  • Dilate bronchi
  • Inhibit stomach motility and secretion, and inhibit pancreas and adrenals
  • Inhibit intestinal motility
  • Relax bladder
  • Stimulate ejaculation
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4
Q

State a few examples of what does parasympathetic system do?

A
  • Constricts pupil
  • Stimulate tear glands
  • Strong stimulation of salivary flow
  • Slows heart rate
  • Constrict bronchi
  • Stimulate digestive juice secretion
  • Stimulates intestinal motility
  • Contracts bladder
  • Stimulate erection
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5
Q

How is the ganglion different in sympathetic and parasympathetic system?

A
  • In the sympathetic system, the ganglion is within a chain adjacent to the spinal cord
  • In the parasympathetic system, the ganglion is within or very close to the effector organ
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6
Q

In sympathetic system, pre-ganglionic fibre is longer or post-ganglionic fibre is longer?

A

Post-ganglionic fibre

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7
Q

In parasympathetic system, pre-ganglionic fibre is longer or post-ganglionic fibre is longer?

A

Pre-ganglionic fibre

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8
Q

What are the 2 main neurotransmitters?

A
  • Acetylcholine (ACh)
  • Noradrenaline (NAd)
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9
Q

What are the neurotransimtter at pre-ganglionic area?

A
  • Acetylcholine acts on nicotinic receptors (both)
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10
Q

What are the neurotransmitter at the post-ganglionic area?

A
  • Acetylcholine acts on muscarinic receptors (parasympathetic)
  • Noradrenaline acts on alpha and beta receptors (sympathetic)
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11
Q

For some exceptions, some acetylcholine is released at

A

sympathetic post-ganglionic termini

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12
Q

What are the 5 different types of muscarinic receptors?

A

M1: Brain
M2: Heart
M3: All organs with parasympathetic innervation
M4: Mainly CNS
M5: Mainly CNS

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13
Q

For muscarinic receptors, where are they found? and they activate intracellular processes through which protein?

A
  • outside the cells
  • G-protein (formed from 7 transmembrane protein)
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14
Q

What happen when there is Activation of M2 on heart SA node?

A

Decreases heart rate

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15
Q

What happen when there is activation of M2 on the heart AV node?

A
  • Decrease conduction velocity
  • Induces AV node block (increases PR interval)
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16
Q

What does M3 receptors do in
1. Respiratory system
2. GI tract
3. Skin
4. Urinary system
5. Eye?

A
  1. Respiratory system
    - Produces mucus (airways and nasopharynx)
    - Induces smooth muscle contraction (bronchoconstriction)
  2. GI tract
    - Increase saliva production
    - Increases gut motility
    - Stimulates biliary secretion
  3. Skin
    - Only place where Sympathetic system releases ACh
    - Stimulation of M3 causes sweating
  4. Urinary system
    - Contracts detrusor muscle
    - Relaxation of internal urethral sphincter
  5. Eye
    - Causes myosis
    - Increases drainage of aqueous humour
    - Secretion of tears
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17
Q

State the examples of muscarinic poisoning.

A
  1. Meiosis and blurred vision
  2. Hypersalivation
  3. Bronchoconstriction
  4. Bradycardia/heart block
  5. Diarrhoea
  6. Polyuria
  7. hyperhidrosis
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18
Q

Pilocarpine eye drops are M3 agonists. How are they helpful?

A
  • Increases drainage of aqueous humour (on the previous slide)
  • Reduces ocular pressure
  • Treats acute (closed-angle) glaucoma
  • Also used to treat dry mouth (stimulates saliva)
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19
Q

Atropine is a type of muscaranic anatagonist. State how it is helpful in patients with cardiothoracic problems?

A
  • Used intravenously to increase heart rate, treat bradyarrythmias and AV node block
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20
Q

Other than atropine, what are the other muscarinic antagonist?

A
  • Hyoscine
  • (Used in palliative care to treat respiratory secretions and symptoms of bowel obstruction)
  • (patients are uncouncious, hard to clear their respiratory secretion, so have to use the drug hyoscine)
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21
Q

What are examples of inhaled antimuscarinic for airway delivery that can result in bronchodilation?

A
  • Tiotropium
  • Glycopyrronium
  • Umeclidinium
  • Aclidinium
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22
Q

What are the side effects of inhaled antimuscarinic?

A
  • Dry mouth
  • urinary retention
  • can worsen existing glaucoma
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23
Q

Other than atropine and hyoscine, what are the other types of antimuscarinics?

A
  • Solifenacin
    (a treatment for overactive bladder)
    (Blocks M3 receptors in the bladder and inhibits smooth muscle contraction)
  • Mebeverine
  • (a treatment for irritable bowel syndrome)
  • (Blocks M3 receptors in the gut to slow contractility)
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24
Q

Can anticholinergic/antimuscarinic cause memory problems?

A

YES!
ACh also used in CNS receptors and implicated in memory

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25
Q

What are the example of anti-acetylcholine?

A

Clostridium Botulinum
(Botulinum toxin prevents ACh release

Causes flaccid paralysis and death from respiratory muscle involvement

Therapeutically, can treat painful muscle spasms or in cosmetic use if given locally (BoTox)
)

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26
Q

Nicotinic (N1) receptor blockers inhibit ACh activity in the somatic nervous system and they can be used as muscle relaxant in surgery, what are the examples?

A

Rocuronium, suxamethonium, pancuronium

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27
Q

Whats wrong in Myaesthenia Gravis?

A

The ACh system is blocked due to the presence of ACh receptor antibody

Blockage of normal transmission of ACh leads to skeletal muscle weakness

Most notable on repeated attempts at movement (repeated impulses)

Treatment includes anti-cholinesterase (pyridostigmine) to increase ACh availability at neuromuscular junction

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28
Q

Where is noradrenaline released from?

A
  • released from sympathetic nerve fibre ends, often used in the intensive care unit
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29
Q

Where is adrenaline released from?

A
  • released from the adrenal glands (fight or flight, management of anaphylaxis)
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30
Q

What is the precursor of adrenaline and noradrenaline?

A

Dopamine

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31
Q

What are the 5 different types of adrenergic receptors?

A
  1. Alpha 1 - Contracts smooth muscle (pupil, blood vessels)
  2. Alpha 2 - Mixed effects on smooth muscle
  3. Beta 1 - Chronotropic and inotropic effects on heart
  4. Beta 2 - Relaxes smooth muscle (premature labour, asthma)
  5. Beta 3 - Enhances lipolysis, relaxes bladder detrusor
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32
Q

What do you give during anaphylatic?

A

However, adrenaline is stable and available intramuscularly, so useful in anaphylactic shock

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33
Q

What is useful in nasal decongestion?

A

Topical alpha activation useful in nasal decongestion (xylometazoline)

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34
Q

Give an example and usage of Alpha2 receptor.

A

clonidine is alpha-2 agonist used in ADHD to help concentration

Actually reduces vascular tone and reduces blood pressure

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35
Q

What are the different type of alpha 1 blocker?

A
  1. Lower blood pressure e.g. doxazosin (generally less frequently used than modern antihypertensives)

Phenoxybenzamine very useful in treating phaeochromocytoma (catecholamine secreting tumour)

Alpha 1A receptor in the prostate, can be blocked with tamsulosin for use in benign prostatic hypertrophy

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36
Q

What are the examples of alpha2 receptor blocker?

A

Incidentally, tetracyclic antidepressants (mirtazapine) are alpha-2 blockers, but antidepressant effect from other machanisms

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37
Q

Beta 1 receptors main in ? and Agonism to Beta 1 receptors can lead to?

A

Beta 1 mainly in:
- Heart
- Kidney
- Fat cells

Agonism leads to:
- Tachycardia
- Increase in stroke volume
- Renin release (increase in vascular tone)
- Lipolysis and hyperglycaemia

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38
Q

What does beta 1 blocker do?

A

Reduce heart rate
Reduce stroke volume
Reduce myocardial oxygen demand and help remodelling in heart failure or post-myocardial infarction

E.g. carvedilol, bisoprolol, atenolol…
need to be cautious in asthma as they will cause bronchoconstriction

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39
Q

What do you take when there’s beta1 blocker overdose?

A

Glucagon increases heart rate and myocardial contractility irrespective of the presence of beta-receptor blockers

Bypass the beta-adrenergic receptor site and therefore useful as an antidote to beta-blocker overdoses

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40
Q

State a few examples of what does beta 2 receptor do?

A
  1. Bronchi - bronchidilation
  2. Bladder wall - Inhibits micturation
  3. Uterus - inhibition of labour
  4. Skeletal muscles - Increase contraction speed (Induces tremor)
  5. Pancreas - Insulin and glucagon secretion
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41
Q

What is the common use of beta 2 receptor ? state an example

A

Agonist drugs (e.g. salbutamol) are very useful in asthma and chronic obstructive pulmonary disease

Side effects include tremor hyperglycaemia (glucagon release) and tachyarrythmia

Also used in tocolysis (delaying preterm labour)

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42
Q

What are examples of natural occurring opioids?

A
  • Morphine
  • Codeine (weak)
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43
Q

What are the examples of simple opioid chemical modifications?

A
  • Diamorphine
  • Oxycodone
  • Dihydrocodeine
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44
Q

What are the types of synthetic opioids?

A
  • pethidine
  • fentanyl
  • alfentanil
  • remifentanil
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45
Q

What are the types of synthetic partial agonists?

A

Buprenorphine

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46
Q

What is a type of opioid antagonist?

A

Naloxone

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47
Q

Talk about the route of oral administration of opioid prescription.

A

50% bioavailability
- First-pass metabolism by the liver
50% of oral (enteral) morphine is metabolised by first-pass metabolism
Halve the dose if giving it s/c, IM, IV (parenterally) etc.
- 10mg morphine orally is equivalent to 5mg s/c, IM, IV

You will need to write separate prescriptions for oral
compared to s/c / IM morphine

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48
Q

How long does a single dose of morphine last?

A

About 3-4 hours

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49
Q

What are the different route of administration for opioid?

A
  • Parenteral (subcutanoues, intramuscular, intravaneous)
  • IV PCA (Patient controlled analgesia)
  • Epidural/CSF
  • Trans-dermal patches for lipid soluble drugs - fentanyl
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50
Q

Raw opium resin contains up to how many % of morphine?

A

25%

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51
Q

What is a more potent and fast acting opioid?

A

(crosses the blood-brain barrier
quickly)

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52
Q

What is the current Controlled drug legislation?

A

Misuse of Drugs Act 1971

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53
Q

What class of drug is opioid?

A

Class A drug

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54
Q

What are the practical issues of Controlled Drug Legislation?

A
  • Secure Storage
  • Controlled Drug Book - 2 signatures needed
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55
Q

Give some examples and description of synthetic and semi-synthetic opioids?

A
  1. dihydrocodeine - about 1.5x more potent than codeine
  2. oxycodone - developed to try and reduce dependence - about
    1.5x as potent as morphine - reformulated in the 1980s as oxycontin (a slow release formulation) and marketed for non-cancer pain in the US - leading to huge problems with addiction
  3. pethidine - again marketed as being less addictive (it wasn’t!) - and
    had lots of unwanted side effects
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56
Q

How does opioid work?

A
  1. Review of pain pathways - opioid drugs simply use the existing pain
    modulation system
  2. Natural endorphins (endogenous morphine) and enkephalins
  3. G protein-coupled receptors - act via second messengers
  4. Inhibit the release of pain transmitters at spinal cord and midbrain - and modulate pain perception in higher centres - euphoria - changes the
    emotional perception of pain
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57
Q

Simplify how does opioid work?

A
  • Descending inhibition of pain
  • Part of the fight or flight response
  • Never designed for sustained activation
  • Sustained activation leads to tolerance and addiction
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58
Q

What are the different type of opioid receptors?

A

µ, delta and kappa receptors
MOP, KOP, DOP and NOP

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59
Q

What side effects does the kappa agonist of opioid do?

A

Kappa agonists cause depression instead of euphoria

Aim remains to develop opioid analgesics without the side
effects of respiratory depression or addiction

At the moment all the drugs that we use are µ agonists

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60
Q

What is drug potency?

A

Whether a drug is ‘strong’ or ‘weak’ relates to how well the drug binds to the receptor, the binding affinity

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61
Q

What is drug efficacy?

A

Is it possible to get a maximal response with the drug or not?
Or even if all the receptor sites are occupied do you get a ceiling response?
The concept of full or partial agonists

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62
Q

What are the relative potencies for diamorphine, morphine and pethidine that will give the same effect?

A
  • Diamorphine - 5mg
  • Morphine - 10mg
  • Pethidine - 100mg
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63
Q

What is drug tolerance?

A
  • Down-regulation of the receptors with prolonged use. Need higher doses to achieve the same effect
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64
Q

What is drug dependence?

A
  • Psychological - craving, euphoria
  • Physical
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65
Q

For opioid withdrawal, when does it start and how long does it last?

A
  • Starts within 24 hours, lasts about 72 hours
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66
Q

What are the side effects of opioid?

A
  • Opioid receptors exist outside of the pain system too such as digestive tract and respiratory control centre
  • We can sometimes deliver opioids epidurally, but for the most part we have to give them systemically
    > Respiratory Depression
    > Sedation
    > Nausea and Vomiting
    > Constipation
    > Itching
    > Immune Suppression
    > Endocrine Effects
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67
Q

Why should we start with small dose of opioid then titrate up as necessary?

A
  • Different patients have quite a range of sensitivity to opioids
  • You cant retract opioid after you have given them
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68
Q

What do you do when you have opioid induced respiratory depression?

A
  • Call for help
  • ABC (Check Airway Breathing Circulation)
  • Treat with Naloxone (IV is the fastest route)
  • Titrate to effect (Dont have to give all at once, once you have given it, you can’t retract)
  • Short half life of naloxone (beware of drug addict overdose in A&E)
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69
Q

How do you titrate naloxone when there is respiratory depression?

A
  • Titrate to effect - dilute 1ml in
    10ml saline
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70
Q

State the example for opioid use in non-cancer pain?

A

In one large study 50% of patients who were on opioids for non-cancer pain at 12 weeks were still on them 5 years later

  • Addiction to the drug leads to manipulative behaviour - easy to start, but can be very difficult to get patients off them
  • Opioids were marketed aggressively by the drug companies in the US for
    chronic non-cancer pain in the late ‘90s
  • Oxycontin - the drug company involved has admitted: “knowingly and intentionally conspiring with others to aid and abet doctors dispensing medication without a legitimate medical purpose”
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71
Q

What is the MHRA advice for prescribing opioids in chronic, non-cancer pain?

A
  • Before prescribing opioids, discuss with the patient the risks and features of tolerance, dependence, and addiction - use short-term courses
  • Agree a treatment strategy and plan for the end of treatment
  • Warnings have been added to the drug labels and packaging of opioids to support patient awareness
  • At the end of treatment, taper dosage slowly to reduce the risk of
    withdrawal effects - may take weeks
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72
Q

State an example of pro-drug and state its mechanism

A
  • Codeine is a pro-drug
  • It needs to be metabolised by cytochrome CYP2D6 to morphine to work
  • CYP2D6 activity is decreased in 10-15% of the Caucasian population
    • CYP2D6 is absent in a further 10% of this population
  • Codeine will have a reduced or absent effect in these individuals
  • CYP2D6 is overactive in 5% of this population - these individuals may be at increased risk of respiratory depression with codeine - not licensed for children under 12
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73
Q

Talk about metabolism of morphine.

A
  • Morphine is metabolised to morphine 6 glucuronide which is more potent than morphine and is renally excreted. With normal renal function, this is cleared quickly.
  • In renal failure it will build up and may cause respiratory depression
  • Be careful in patients with < 30% renal function (creatinine clearance < 30). Reduce dose and timing interval
  • It will be dangerous to use morphine - use oxycodone instead - if in doubt,
    please ask - or look at the acute pain guidance on the intranet
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74
Q

What is tramadol?

A
  • Tramadol is a weak opioid agonist, slightly stronger than codeine
  • It is also a prodrug - needs to be metabolised by CYP2D6 to o-desmethyl tramadol to be active - and therefore won’t be effective in about 10% of patients
  • It has a secondary effect in analgesia as a serotonin and nor-epinephrine
    reuptake inhibitor
  • So it interacts with SSRIs, tricyclic antidepressants and MAOIs, sometimes fatally - take care prescribing it to patients on antidepressants
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75
Q

Can Naloxone work orally?

A

NO!

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76
Q

To whom you cannot give codeine?

A

Kid and Mothers

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77
Q

Whats the unique part of synthetic opioid drug?

A

faster onset and offset time

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78
Q

Which route of administration is the fastest ?

A
  • Intravenous route
  • how fast does it take to go round of one full circulation? 1 minute
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79
Q

How long does it take for the subcutaneous route of drug administration to work?

A
  • about half an hour before peak, 1-2 hours to get absorped
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80
Q

How do we administer opioid drug into CSF?

A

We can put opiod drugs into CSF into the epidural during lumbar puncture

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81
Q

State the different type of Hypersensitivity reaction.

A
  • Type I (allergy)
    Primarily IgE dependent
  • Type II
    Primarily IgG-dependent cytotoxicity
  • Type III
    IgG/IgM-dependent immune complex formation
  • Type IV (delayed-type hypersensitivity, DTH)
    Cell dependent (Th1/cytotoxic T cells/macrophages)
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82
Q

What are the clinical indications related to allergy?

A
  1. Skin
    - swelling, itching and reddening
  2. Airways
    - excessive mucus production
    - bronchoconstriction
  3. GI
    - abdominal bloating, vomiting, diarrhoea
  4. Anaphylaxis
    - Airway, breathing, circulation…
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83
Q

What is allergy?

A
  • Abnormal response to harmless foreign material (allergens)
  • Atopy = tendency to develop allergies
  • Allergens come in many forms:
    Pollen, house dust mites, animal fur, nickel, foods…..
  • Many ‘allergies’ are actually not allergy:
    Lactose, milk protein (intolerance)
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84
Q

State the examples of some allergic diseases.

A

Anaphylaxis
Allergic asthma
Allergic rhinitis (hay fever)
Atopic dermatitis
Allergic conjunctivitis
Oral allergy syndrome (food allergy)
Angioedema (not idiopathic)

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85
Q

State the percentage/statistics of asthma, rhinitis, atopic dermatitis, and food allergies.

A
  1. Asthma - 1/250 deaths worldwide
    20% of UK population
  2. Rhintis - 500 million currently
  3. Atopic Dermatitis - 10-20% children
  4. Food Allergies - 6% young children
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86
Q

State the pathogenesis of allergy.

A
  1. Usually involved IgE
    - IgG4, IgA also
  2. Genetic factors
    - Strong concordance in twin studies (68%)
  3. Cells
    - Mast, eosinophil, basophil
    - Lymphocytes, dendritic
    - Epithelial cells
    - Smooth muscle, fibroblast
  4. Mediators
    - Cytokines, chemokines, lipids, small molecules
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87
Q

What is the serum half-life of IgE?

A

2.5days

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88
Q

What is serum IgE specific for?

A

Serum IgE specific for allergen indicates sensitisation

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89
Q

What is FcεRI?

A

The high-affinity IgE receptor, also known as FcεRI, or Fc epsilon RI, is the high-affinity receptor for the Fc region of immunoglobulin E, an antibody isotype involved in the allergy disorder and parasite immunity.

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90
Q

Talk about clustering causes signalling in FcεRI.

A
  1. Receptor Cross-Linking
  2. Assembly of Signalling Complex
  3. Amplification
  4. Cellular Responses
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91
Q

Talk about the expression and function of: Low-affinity IgE receptor- FceRII, CD23.

A

Expression: B cells, T cells, monocytes, eosinophils, platelets, neutrophils

Function: Regulation of IgE synthesis;
Triggering of cytokine release by monocytes; Antigen presentation by cells

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92
Q

What are the FcεRI expressing cells out there?

A
  • eosinophils, mast cells, basophils
  • These are the major cell types that express a high affinity IgE receptor
    Involved in host defence against parasites
  • Basophils (1%) and eosinophils (2.3%) circulate as mature cell types with short half-lives;
    mast cells exist only in tissues
  • Eosinophils express a different range of granule contents to mast cells and basophils
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93
Q

Talk about mast cells

A
  • IgE-mediated immunity
    Main effector cells
  • Heterogeneity
  • Primary role in innate and acquired immunity
  • Involved in many disease processes
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94
Q

Where is Mast cells produced? Talk about its development.

A
  1. Mast cells produced by a specific cell lineage in bone marrow
    - Despite similarity to basophils, development appears to be separate
  2. Characterised by the requirement for c-kit protein
    - CD117 (c-kit) is a cell surface receptor for Stem Cell Factor (SCF)
    - Systemic mastocytosis caused by c-kit mutations
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95
Q

Talk about mast cell morphology.

A

monolobed nucleus, narrow surface folds and numerous electron-dense cytoplasmic granules.

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96
Q

Talk about the immediate response of mast cells

A

Immediate:
> Preformed Compounds
*Histamine:
Arteriolar dilation, capillary leakage
Induces cholinergic reflex bronchoconstriction (bronchospasm)
*Chemotactic factors
Some cytokines (e.g. IL-4, SCF)
*Proteases
Tryptase (serum marker)
Chymase
*Proteoglycans
chondroitin sulphate (?)
heparin (protease packaging?)

Mast cell chemotactic factors typically lead to eosinophil attraction and activation

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97
Q

Talk about the minutes response of mast cells:

A

> Lipid derived mediators
* Leukotrienes e.g. LTC4, D4, E4
Capillary endothelial contraction with vascular leakage: Increased permeability
* Prostaglandin D2
Potent inducer of smooth muscle contraction
* Platelet Activating Factor (PAF)
Increases platelet aggregation, degranulation; Increases vascular permeability; Activates neutrophil secretion

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98
Q

Talk about the hour effect of mast cells:

A

> Transcription/translation
Cytokines
IL-8, IL-5, IL-4, IL-13, RANTES

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99
Q

What can lead to B cells class switching - IgE production

A

Mast cell derived cytokines promote a Th2 response and can lead to B cell class switching – IgE production

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100
Q

What are the direct activators of mast cells?

A
  • Cold/mechanical deformation (asthma?)
  • Aspirin, tartrazine, preservatives, NO2, latex, proteases…….
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101
Q

What are the indirect activators of mast cells?

A

> Allergens
- Latex, wasp/bee venoms, foods, drugs, pollens, house dust mite faeces, animal dander
- Prior sensitization is required (generally through mucosal surface)
Bacterial/viral antigens
- Protein L of Pneumococci; protein A of S. aureus
superantigens
- gp120 of HIV-1

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102
Q

What cells and antibodies are resistant to parasitic infections?

A
  • E.g. hookworms, pinworms, flukes
  • Multicellular organisms
  • Immune response characterised by Th2 cytokines
    IL-3, IL-4, IL-5, IL-10
    IgE response
  • Local mast cell activation by cross-linkage of IgE leads to the recruitment of eosinophils, macrophages and neutrophils.
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103
Q

What is atopy?

A

a hereditary predisposition to the development of immediate hypersensitivity reactions against common environmental antigens.

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104
Q

It has also been suggested that the relative absence of bacterial and viral infections in western society has lead to an imbalance in the ?

A

Th1/Th2 pathways for T cell response

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105
Q

What are the other cells involved in allergy?

A

> Lymphocytes
- Typically Th2

> Dendritic Cells
- Antigen presentation

> Neurons
- Cholinergic/adrenergic

> Other non-immune cells
- Epithelial (compromised barrier function)
- Fibroblasts, smooth muscle

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106
Q

What makes an allergen?

A

> Particulate delivery of antigens
HDM faeces are 20-40μm

> Presence of weak pathogen-associated molecular patterns (PAMP)
- Weak innate immune activation

> Nasal/skin delivery
Oral delivery desensitizes

> Derp2)
High doses desensitise (Cat ownership)

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107
Q

What makes an allergen ? direct contact with mast cells?

A

-contact of allergen with dendritic cells
- T cells and B cells activate mast cells

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108
Q

Talk about anaphylaxis

A
  1. Rapid (within minutes)
    > Airway, Breathing, Circulation, Disability, Exposure (ABCDE)
    > Mast cell or basophil activation
    - IgE or direct activation (idiopathic)
    - Serum tryptase, histamine elevated
    > CV
    - Vasodilation, increased vascular permeability, lowered BP
    > Respiratory
    - Bronchial SM contraction, mucus
    > Skin
    - Rash, swelling
  2. Slow (within hours)
    GI: Pain, vomiting etc
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109
Q

Talk about allergic disease: asthma

A

> Complex inflammatory disease of the bronchi

> Commonly triggered by allergens
- House dust mites, aspergillus

> Can involve eosinophil influx into lungs

> Often involves IgE

> Not everyone with atopy develops asthma

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110
Q

Talk about chronic asthma

A

> Non-Th2 T cell mechanisms in chronic asthma

> CD8 (regulatory) T cells control eosinophil responses

> Similar to type IV hypersensitivity

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111
Q

What are the treatment strategies for allergy?

A
  • Avoid allergens!
  • Desensitisation to allergen
  • Prevent IgE production
  • Prevent IgE interaction with receptor
  • Prevent mast cell activation
  • Inhibit mast cell products
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112
Q

What is desensitisation?

A

In medicine, desensitization is a method to reduce or eliminate an organism’s negative reaction to a substance or stimulus.

In pharmacology, drug desensitization refers to two related concepts. First, desensitization may be equivalent to drug tolerance and refers to subjects’ reactions (positive or negative) to a drug reducing following its repeated use.

This is a macroscopic, organism-level effect and differs from the second meaning of desensitization, which refers to a biochemical effect where individual receptors become less responsive after repeated application of an agonist.

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113
Q

Talk about the mechanism of desensitisation.

A

> Immunotherapy
- Increasing doses of antigen
* Sub-lingual
* Sub-cutaneous (SCIT)

> Risk
- 23% moderate reactions; 3% life-threatening

> Limited use
- Atopic eczema, asthma no benefits

> Usually used only for severe allergies

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114
Q

Talk about preventing IgE production

A

> Th2 responses be suppressed
- Delivery of suppressive cytokines
* IL-12 Reduces eosinophilia, Th2 responses in mice
* IL-18 Reduces IgE production in mice

  • Blockade of cytokines
  • IL-4 antagonist (pitrakinra) Reduction in late-phase response

> Anti-CD23 antibodies can decrease IgE levels

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115
Q

State an example of anti-IgE therapy

A

Xolair (Omalizumab) is a recombinant DNA-derived humanized IgG1κ monoclonal antibody that selectively binds to human immunoglobulin E (IgE).
Xolair inhibits the binding of IgE to the high-affinity IgE receptor (FcεRI)

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116
Q

What are the anti-cytokines antibodies?

A
  • IL-5 antibody (Mepolizumab)
  • IL-5 receptor antibody (Reslizumab, benralizumab)
  • Anti-IL-4/IL-13 receptor antibody (Dupilumab)
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117
Q

What are the 5 factors of Mast cells activation?

A

> Mast cell stabilisers (sodium cromoglycate)
- Reduce mediator release

> Beta2 agonists (Salmeterol, etc)
- Increase cAMP

> Glucocorticoids (e.g. Budesonide, prednisolone)
- Inhibit gene transcription
- Some long-term effects

> Calcium channel blockers

> Signalling inhibitors
E.g. Syk kinase, Map kinase inhibitors

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118
Q

State the 5 different models of current drug development stages

A
  1. lead compound identification
  2. pre-clinical research
  3. filing for regulatory status
  4. clinical trials on humans
  5. marketing the drug
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119
Q

What can the plant poppy produce?

A

morphine

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120
Q

What can the plant deadly nightshade produce?

A

Atropine

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121
Q

What can the plant periwinkle produce?

A

Vincristine

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122
Q

What does lower molecular weight mean?

A

<500D

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123
Q

What are the examples of drugs with Sulphonamide Nucleus(Unreactive and rigid)?

A
  • Bendroflumethazide (hypertension)
  • diazoxide
  • tolbutamide
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124
Q

What drug is developed from noradrenaline?

A

Propanolol
- B-adrenoceptor antagonist
Cardiovascular disease : Angina

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125
Q

What drug is developed from histamine?

A

Cimetidine
Histamine H2 receptor Antagonist
Duodenal Ulcer

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126
Q

State a type of antibody that is non-specific.

A

Polyclonal

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127
Q

State a type of antibody that is specific.

A

Monoclonal

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128
Q

What are the benefits of humanised antibody?

A

have less non-self issues

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129
Q

What does monoclonal antibody with “murine” end with?

A

omab

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130
Q

What does monoclonal antibody with “chimeric” end with?

A

ximab

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131
Q

What does humanised antibody end with?

A

zumab

132
Q

What does human antibody end with?

A

umab

133
Q

What can infliximab treat?

A

Rheumatoid Arthritis – chemical inhibition by extracellular neutralisation of TNF alpha

Inhibits lymphocyte proliferation

IV infusion every 6-8 weeks

Mouse chimeric *monoclonal antibody against TNF alpha

134
Q

What is an example of a receptor antagonist?

A

Etanercept

135
Q

What is the first fully humanised TNF alpha antibody ?

A

Adalimumab (Humira)

136
Q

What are the 3 pharmacokinetic issues for immunotherapy?

A

Immunoglobulin (IgG MW 150kD) – not filtered by kidney

FcRn Receptor - systemic receptors which absorb IgG into cells protecting them from metabolism

Mouse antibodies not substrates for human FcRn receptor – result shorter half-life in man than human antibodies.

137
Q

What is the example fo drug from animal source?

A

Insulin/Thyroxine/Steroid

138
Q

What are the examples of recombinant protein in clinical use?

A
  • Insulin
  • Erythropoetin
  • Growth hormone
  • Interleukin 2
  • Gamma interferon
  • Interleukin 1 receptor antagonist
139
Q

What are the clinical uses of glucocorticoids?

A
  • Asthma
  • Allergic rhintis and hayfever
  • Atopic eczema
  • COPD
  • painful and inflammed muscles, joints and tendons
  • IBD
  • multiple sclerosis
140
Q

State the drug which is the structural analogues of folic acid?

A

Methotrexate

141
Q

State the example of protein kinase inhibitor.

A

vemurafinib

142
Q

What is gene therapy?

A
  • Replacing a mutated gene that cause disease with a healthy copy of gene
  • Inactivating/knocking out a mutated gene that is functioning improperly
  • introducing a new gene into the body to help fight a disease
143
Q

What are the examples of adeno-associated virus vector-based gene therapy that delivers a fully functional copy of the human SMN gene into the target motor neuron cells.

A

Zolgensma

144
Q

What are the importance of Adverse Drug Reactions?

A

Account for 6 -7% of all hospital admissions

Occur in 10-20% of hospital inpatients

2% patients admitted with an ADR die

Cause deaths in 0.1% of medical and 0.01% of surgical inpatients

5th most common cause of hospital death

WHO state 60% preventable

Adversely affect patients’ quality of life

Increase costs of patient care

Preclude use of drug in most patients, although they may occur in only a few patients

May mimic disease

Very common cause of death, behind heart disease, cancer and stroke

145
Q

What is adverse drug reaction?

A

Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug.

Has to be noxious and unintended

146
Q

What is the main difference between side effect and adverse drug reactions?

A

Side effect might be beneficial sometimes but adverse drug reaction wont !!

147
Q

What is side effect?

A

Side effect is an unintended effect of a drug related to its pharmacological properties and can include
unexpected benefits of treatment

(Minoxidil for hypertension led to hair growth)

148
Q

What are the three different names of the graph portion - “beyond therapeutic range”, “Within therapeutic range” and “Below therapeutic range”?

A
  1. Toxic effects (beyond therapeutic range)
  2. Collateral effects (therapeutic range)
  3. Hyper-susceptibility effects (below therapeutic range)
149
Q

Talk about collateral effects.

A

Standard therapeutic doses

Beta blockers causing bronchoconstriction

Broad spectrum antibiotics causing clostridium difficile and pseudomembranous colitis

149
Q

Talk about toxic effects.

A

Nephrotoxicity or ototoxicity with high doses of aminoglycosides e.g. gentamicin
Dysarthria and ataxia with lithium toxicity
Cerebellar signs and symptoms with xs phenytoin

Can occur if dose is too high or drug excretion is reduced by impaired renal or hepatic function or by interaction with other drugs

150
Q

Talk about hypersusceptibility reactions

A

Sub therapeutic doses
Anaphylaxis and penicillin

151
Q

What are the severity level of adverse drug reactions?

A
  • Can be mild eg nausea, drowsiness, itching rash
  • Can be severe eg respiratory depression, neutropenia, catastrophic haemorrhage, anaphylaxis
151
Q

What are the severity level of adverse drug reactions?

A
  • Can be mild eg nausea, drowsiness, itching rash
  • Can be severe eg respiratory depression, neutropenia, catastrophic haemorrhage, anaphylaxis
151
Q

What are the severity level of adverse drug reactions?

A
  • Can be mild eg nausea, drowsiness, itching rash
  • Can be severe eg respiratory depression, neutropenia, catastrophic haemorrhage, anaphylaxis
152
Q

What are the risk factors for adverse drug reactions?

A

Patient risk
-Gender (F>M)
-Elderly
-Neonates
-Polypharmacy (21% 5 or more drugs)
-Genetic predisposition
-Hypersensitivity/allergies
-Hepatic/renal impairment
-Adherence problems

Drug Risk
- Steep dose-response curve
- Low therapeutic index
- Commonly causes ADR’s

153
Q

What are the potential causes for adverse drug reactions?

A
  1. Pharmaceutical variation
  2. Receptor abnormality—
  3. Abnormal biological system unmasked by drug
  4. Abnormalities in drug metabolism
  5. Immunological—penicillin induced anaphylaxis
  6. Drug-drug interactions—increased incidence of hepatitis when isoniazid is prescribed with rifampicin
  7. Multifactorial
154
Q

Time-dependent reaction in adverse drug reactions?

A

Rapid reactions
First dose reactions
Early reactions
Intermediate reactions
Late reactions
Delayed reaction

155
Q

What are the 6 different types of Rawlins Thompson classification?

A
  1. Type A (Augmented pharmacological)– predictable, dose dependent, common (morphine and constipation, hypotension and antihypertensive) 80% all ADRs
  2. Type B (Bizarre or idiosyncratic)– not predictable and not dose dependent (anaphylaxis and penicillin)
  3. Type C (Chronic) – osteoporosis and steroids
  4. Type D (Delayed) – malignancies after immunosuppression
  5. Type E (End of treatment) – occur after abrupt drug withdrawal eg opiate withdrawal syndrome
  6. Type F (Failure of therapy) – Failure of OCP in presence of enzyme inducer
156
Q

Talk about Rawlin Thompson Type A Classification.

A

Extension of primary effect (bradycardia and propranolol, hypoglycaemia and insulin, haemorrhage due to anticoagulants, respiratory depression and opiates)

Secondary effect (bronchospasm with propranolol B2 blocking effect)

High morbidity, low mortality

Excludes drug abuse and overdose

157
Q

Talk about Rawlin Thompson Type B Classification.

A

Not predictable or related to pharmacology

Not dose dependant

Can’t be readily reversed

Less common but often serious

Life threatening

Can be idiosyncrasy

Can be allergy or hypersensitivity (I-IV hypersensitivity)

Low morbidity, high mortality

158
Q

What does idiosyncracy mean?

A

Inherent abnormal response to a drug

Genetic abnormality, enzyme deficiency

May be due to abnormal receptor activity

159
Q

Talk about allergy and hypersensitivity.

A

Antigen/antibody reaction
First dose acts as antigen
Antibody produced
Second dose causes antibody-antigen reaction

160
Q

What are the different types of hypersensitivity?

A

Type 1 immediate anaphylactic IgE eg penicillin allergy

Type 2 cytotoxic antibody IgG, IgM eg methyl dopa and haemolytic anaemia

Type 3 eg procainamide induced lupus

Type 4 delayed hypersensitivity T cell eg contact dermatitis

161
Q

Talk about Rawlin Thompson Type C Classification.

A

Continuous/Chronic
- Uncommon
- Related to cumulative dose
- Time-related
- Steroids and osteoporosis
- Analgesic nephropathy
- Colonic dysfunction due to laxatives

162
Q

Talk about Rawlin Thompson Type D Classification.

A

Uncommon
- Usually dose related
- Shows itself some time after the use of the drug
- Teratogenesis – drugs taken in the first trimester eg thalidomide
- Carcinogenesis eg cyclophosphamide and bladder cancer
- Use 1959-1961 for its mild sedative effects and morning sickness
- This led to tougher testing and drug approval

163
Q

Talk about Rawlin Thompson Type E Classification.

A

Ending of drug use
- Uncommon
- Occurs soon after drug withdrawn
- Opiate withdrawal
- Glucocorticoid abruptly withdrawn leads to adrenocortical insufficiency
- Withdrawal seizures when anticonvulsants are stopped

164
Q

Talk about Rawlin Thompson Type F Classification.

A

(Failure)
- Common
- Dose related
- Often cause by drug interactions
- Failure of oral contraceptive pill with enzyme inducers
- Failure of therapeutic effect in patients taking warfarin leading to CVA

165
Q

When should we suspect an ADR?

A
  • Symptoms soon after a new drug is started
  • Symptoms after a dosage increase
  • Symptoms disappear when the drug is stopped
  • Symptoms reappear when the drug is restarted
166
Q

What should we do if there is an Adverse Drug Reaction?

A

Assess if urgent action is required
Take a history
Review medication history
Review the adverse effect profile of suspected drug
Modify dose, stop or swap
Report

167
Q

What are the examples of the most common drugs to have ADR’s?

A

Antibiotics
Anti-neoplastics (cancer drug)
Cardiovascular drugs
Hypoglycaemics
NSAIDS
CNS drugs

168
Q

What are the common system to be affected by adverse drug reaction?

A

GI
Renal
Haemorrhagic
Metabolic
Endocrine
Dermatologic

169
Q

What is the drug that cause most death due to adverse drug reaction?

A

Clozapine

170
Q

What are the common symptoms of adverse drug reactions?

A

Confusion
Nausea
Balance problems
Diarrhea
Constipation
Hypotension

171
Q

Can ADRs be avoided?

A

30-50% are preventable
Drug interactions
Inappropriate medication
Unnecessary medication

172
Q

How do we gather information on ADRs?

A

Pre-clinical phase 1 trials
Clinical phase 1 to 3 trials
Post-marketing surveillance
Yellow card reporting

173
Q

Which authority is responsible for approving medicine and device uses?

A

Medicines and Healthcare products Regulatory Agency (MHRA)

174
Q

What is yellow card scheme used for?

A

To identify ADRs not identified in clinical trials
To identify new ADRs ASAP
To compare drugs in the same therapeutic class
To identify ADRs in ‘at risk’ groups

175
Q

What to report to a yellow card?

A
  • All suspected reactions for
    herbal medicines
    black triangle ▼ drugs
  • All serious suspected reactions for
    established drugs, vaccines and contrast media drug interactions
176
Q

What is black triangle drug?

A

The black triangle ▼ indicates a medicine is undergoing ‘additional monitoring’
It is assigned to any preparation that:

contains a new active substance; new medicines or vaccines authorised on or after January 2011

is a biological medicine, such as a vaccine or a medicine derived from plasma (blood);

has been given a conditional approval or approved under exceptional circumstances

the company that markets the medicine is required to carry out additional studies: for instance, to provide more data on long-term use of the medicine, or on a rare side effect seen during clinical trials.

177
Q

What is a serious reaction?

A

A reaction that
- is fatal
- is life threatening
- is disabling or incapacitating
- results in hospitalisation
- prolongs hospitalisation
(If in doubt, report)

178
Q

Who can report to a yellow card?

A

Doctors, dentists, coroners, pharmacists, nurses, including midwives and health visitors, radiographers, optometrists.
Patients

179
Q

4 critical pieces of information that must be included on the report ?

A

Suspected drug(s)
Suspect reaction(s)
Patient details
Reporter details

180
Q

What is drug hypersensitivity?

A

Hypersensitivity is broadly defined as ‘objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects’ and may be caused by immunologic (allergic) and non‐immunologic mechanisms’

181
Q

Different duration classification of drug hypersensitivity?

A

Immediate <1hr (urticarial, anaphylaxis)

Delayed >1hr (other rashes, hepatitis, cytopenias)

182
Q

What are the different types of hypersensitivity reactions?

A

Type 1 – IgE mediated drug hypersensitivity
Type 2 – IgG mediated cytotoxicity
Type 3 – Immune complex deposition
Type 4 – T cell mediated

183
Q

Talk about Type 1 Hypersensitivity - acute anaphylaxis?

A
  • Prior exposure to the antigen/drug
    IgE antibodies formed after exposure to molecules
  • IgE becomes attached to mast cells or leucocytes, expressed as cell surface receptors
  • Re-exposure causes mast cell degranulation and release of pharmacologically active substances such as histamine, prostaglandins, leukotrienes, platelet activating factor etc
184
Q

Symptoms of anaphylaxis?

A
  • Occurs within minutes and lasts 1-2 hours
  • Vasodilation
  • Increased vascular permeability
  • Bronchoconstriction
  • Urticaria
  • Angio-oedema
  • Drug anaphylaxis majority of deaths due to anaphylaxis
  • Insect venom most common cause followed by medications
  • 1-20% have biphasic response
185
Q

Talk about type 2 hypersensitivity reaction.

A
  • Drug or metabolite combines with a protein
  • Body treats it as foreign protein and forms antibodies (IgG, IgM)
  • Antibodies combine with the antigen and complement activation damages the cells e.g. methyl-dopa-induced haemolytic anaemia, pemphigus
186
Q

Talk about type 3 reaction - immune complex mediated.

A

Antigen and antibody form large complexes and activate complement

Small blood vessels are damaged or blocked

Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process

Includes glomerulonephritis, vasculitis

187
Q

What is type 4 reaction? (Lymphocyte mediated)

A

Antigen specific receptors develop on T-lymphocytes

Subsequent admin, adminstration leads to local or tissue allergic reaction

E.g. contact dermatitis

E.g. Stevens Johnson syndrome (TEN)

188
Q

What are the drugs commonly implicated in hypersensitivity reactions?

A
  • Aspirins
  • Penicillin
  • Anesthetics
  • Antipsychotic transquilizer
  • Antihypertensive agent
  • Heavy metal
  • Vaccine
189
Q

Talk about non-immune anaphylaxis.

A

Previously called Anaphylactoid reactions

Due to direct mast cell degranulation

Some drugs recognised to cause this

No prior exposure

Clinically identical

190
Q

What are the main features of anaphylaxis
?

A

Exposure to drug, immediate rapid onset

Rash (absent in 10-20%)

Swelling of lips, face, oedema, central cyanosis

Wheeze / SOB

Hypotension (Anaphylactic shock)

Cardiac Arrest

20 deaths per year in the UK

191
Q

What are the management of anaphylaxis?

A
  • Commence basic life support. ABC
  • Stop the drug if infusion
  • Adrenaline IM 500micrograms(300mcg epi-pen)
  • High flow oxygen
  • IV fluids – aggressive fluid resuscitation
  • If anaphylactic shock may need IV adrenaline with close monitoring
  • Antihistamines not first line treatment but can be used for skin symptoms
  • Corticosteroids no longer recommended
192
Q

Why do we use adrenaline when there is anaphylaxis?

A

Vasoconstriction - increase in peripheral vascular resistance, increased BP and coronary perfusion via alpha1-adrenoceptors

Stimulation of Beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart

Reduces oedema and bronchodilates via beta2-adrenoceptors

Attenuates further release of mediators from mast cells and basophils by increasing intracellular c-AMP and so reducing the release of inflammatory mediators

193
Q

State some examples of mycobacterium and relate the different diseases.

A
  1. M tuberculosis - Tuberculosis
  2. M. avium complex (MAC) - Disseminated infection in AIDS, chronic lung infection
  3. M. kansasii - chronic lung infection
  4. M.marinum - fish tank granuloma
  5. M.ulcernas - Buruli ulcer
  6. Rapidly growing microbacteria (M. fortuitum complex) - Skin anf soft tissues infection
  7. M. leprae - Leprosy
194
Q

Which mycobacterium is some neglected tropical area diseases?

A

M ulcerans

195
Q

Mycobacterium that causes TB is similar to the mycobacterium that causes which disease?

A

Leprosy

196
Q

How can we treat Buruli ulcer?

A

By providing antibiotic

197
Q

State the different stages of the Buruli ulcer.

A

Nodule > Small Ulcer > Large Ulcer > Deforming + Bone destruction

198
Q

How many death of TB in the last 20 years?

A

1000,000,000

199
Q

For tuberculosis, what is the
1. annual death
2. Infected case
3. New cases per year
4. antibiotic resistance

A
  1. 1.5 million death per year
  2. 2.5 billion infected
  3. 10.4 million new case per year
  4. more than 500 k per annum
200
Q

What type of bacteria is mycobacterium?

A

Acid Fast Positive bacteria ( Ziehl-Neelsen stain positive)

201
Q

Normal bacteria takes 30-60 minutes to culture but mycobacterium is different, how long does it take?

A

24 hours

202
Q

Describe the structure of Mycobacterium.

A
  • Slightly curved, beaded bacilli
  • High lipid content with mycolic acids in cell wall makes mycobacteria resistant to gram stain
203
Q

How much bacilli do we need per ml to diagnose TB?

A

10K bacilli per ml

204
Q

3 points about Ziehl Neelsen stain

A
  • Carbol fuchsin
  • Acid alcohol (AFB are resistant to destaining)
  • Methylene blue
205
Q

Talk about the microbiology part of mycobacterium

A
  • Aerobic, non-spore
    forming, non motile
    bacillus
  • Cell wall: high molecular
    weight lipids +++
  • Slow growing: M. tuberculosis generation
    time 15-20h vs. 1h for
    common bacterial
    pathogens
206
Q

What does the key components of the mycobacterium include?

A
  • Mycolic acids
    – Lipoarabinomannan
207
Q

What are the challenges of treating TB?

A
  • Thick lipid rich cell wall making immune cell killing and penetration
    of drugs challenging
  • slow growth:
    a. gradual onset of disease
    b. takes much longer to diagnose
    c. takes longer to treat
208
Q

How does tuberculosis spread?

A

spitting, coughing and sneezing

209
Q

What are the different types of tuberculosis?

A
  1. Primary tuberculosis
  2. Latent tuberculosis
  3. Pulmonary tuberculosis
210
Q

Talk about primary tuberculosis

A
  • Initial ‘contact’ made by
    alveolar macrophages
  • Bacilli taken in lymphatics to hilar lymph nodes
211
Q

Talk about latent tuberculosis

A
  • Cell-mediated immune response from T cells
  • Primary infection contained, but CMI persists
  • no clinical disease detectable CMI to TB on tuberculin skin test
212
Q

Talk about pulmonary tuberculosis?

A
  • Granulomas forms
    around bacilli that have
    settled in apex
  • In the apex of the lung, there are more air and less blood supply (fewer defending white cells to fight)
  • necrosis results in abscess forming and caseous material coughed up
  • Could occur immediately following
    primary infection (post-primary)
    or after later reactivation
  • TB may spread in lung
    causing other lesions
213
Q

What does primary complex in TB consist of?

A

Granuloma + Lymphatics + Lymph nodes

214
Q

TB spreads beyond lung, what are the examples?

A
  • TB Meningitis
  • Miliary TB
  • Pleural TB
  • Bone and joint TB
  • Genito urinary TB
  • Bacilli in lymph nodes
  • Bacilli in the lung apex

-

215
Q

What will be caused if there is TB in the spine?

A

Gibbus formation
(collapse of one or more vertebral bodies, which results in kyphosis )

216
Q

How does TB infect us?

A
  • Aerosol transmission
  • Primary TB in lung
  • Latent TB can remain for decades
  • Can spread beyond lungs
217
Q

What does our body do to protect us from TB?

A
  • Mycobacteria are phagocytosed by macrophages and traffic to a phagolysosomes
  • The bacterium has adapted to the intracellular environment and aims to withstand phagolysosomal killing and escape to the cytosol
  • Effective immunity requires CD4 T-cells which generate interferon gamma and this helps activate intracellular killing by macrophages.
218
Q

Which type of people is more likely to get TB?

A
  • People living with HIV are m 20X times more likely to get TB
  • TB is the leading cause of death in people living with HIV
219
Q

What is the key feature of TB?

A

– key feature of latent TB is the macrophage is holding the TB in the central location, TB bacteria response by turning on central function, steady state with all other cell types surrounding the bacteria, called as granuloma
- we may or may not get a stable granuloma, in the middle, the cell dies, and there are necrotic tissues, “caseous appearance” look like cheese, goes from microscopic to nodules known as tubercles, and it can get bigger in the lung and can become cavity, and can break into the larger tube, can be coughed up and infect somewhere else

220
Q

What does our body do to protect us from TB (4 points simplified version please)?

A
  • Primarily controlled by macrophages
  • Requires a CD4 T cell response to be controlled
  • Involves many cells of immunity- formation of granulomas
  • Granuloma stability controls reactivation of TB
221
Q

Talk about the hallmark formation of TB (the consequence if granuloma works and granuloma fails)?

A

If the granuloma works: Mycobacteria shut down metabolically in order to survive – dormancy

But if fails, e.g. in the lung, this can result in the formation of a cavity full of live mycobacteria and eventual disseminated disease (consumption)

222
Q

What does macrophage and Type 1 helper T lymphocytes capable of synthesising?

A

IFN-γ and other
cytokines such as TNFα

223
Q

Which 2 ways cause granuloma to become unstable?

A
  • CD4 depletion
  • TNFα depletion
224
Q

Is mycobacterium fastidious ?

A

YES!

225
Q

Which step is needed when we are growing mycobacterium in agar culture?

A

First need decontamination steps to kill off other rapid growing bacteria
(lipid coat protects mycobacteria)

226
Q

What are the 2 different culture of mycobacterium?

A
  1. Solid culture L.J. SLOPE
    * Egg-based Lowenstein Jensen
    * Agar-based Middlebrook 7H11
    * 2-8 weeks
  2. Liquid culture
    * Automated systems BACTEC
    Mycobacterial growth indicator
    tube (MGIT).
    * Fluorometric detection in liquid
    media
    * 1-3 weeks
227
Q

Talk about nucleic acid detection for mycobacterium.

A
  • GeneXpert MTB/RIF cartridge-based test
  • Nucleic acid amplification test using PCR
  • Purifies and concentrates MTB, sonicates to release genomic material and then performs PCR
  • Rapid result for MTB and detects Rifampicin resistance using fluorescence
  • Sensitivity 88%, Specificity 98%
  • Can detect 131 bacilli/ml
  • Recommended for rapid diagnosis in TB endemic countries
228
Q

Talk about how can we utilise TB immunity in real life?

A
  • The highly immunogenic nature of mycobacterial lipids stimulates T-cell responses in 3-9 weeks after exposure to M. tuberculosis
    a) +ve effects; macrophage killing of mycobacteria, containment of infection, formation of tissue
    granulomata.
    b) -ve effects; hypersensitivity reactions with skin lesions, eye lesions and swelling of joints
  • This reactivity is measured in the tuberculin skin test where intradermal injection of purified protein derivatives induces skin swelling and redness.
229
Q

What is the name for the Tuberculin skin test?

A

(Mantoux)

230
Q

Talk about treatment for TB or anti-TB drugs

A
  • Standard therapy: isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (ETH) x 2 months
    followed by isoniazid and rifampicin for further 4 months
  • Second line: injectable agents (streptomycin, cycloserine, capreomycin)
  • Side effects are wide-ranging and severe, including liver damage
  • TB treatment- 4-9 months of combination therapy!
231
Q

What are the different resistance mechanism out there?

A
  • Drug inactivation:
    (Mtb produces beta- lactamase)
  • Drug titration:
    (Target overproduction)
  • Alteration of drug target:
    ( Missense mutations)
  • Altered cell envelope:
    (Increased permeability
    and drug efflux)
232
Q

What is multiple drug resistant TB?

A

XDR-TB: resistant to four commonly used TB drugs. 6%
of all TB cases
* Resultant from inadequate TB therapy and failure to
clear patients of bacteria
* Treatment is lengthy and expensive

233
Q

What do we use to treat XDR - TB?

A

BPaL regimen:
– Bedaquiline
– Pretomanid
– Linezolid

All oral treatments for 6 months

These can fail too with totally drug
resistant (TTR) TB. No known solution as
yet.

234
Q

How can we study TB?

A

Using different animal models
- Mouse
- Rabbit
- Zebrafish
- Guinea Pig

Animal models a way to understand complex immunology
* Mouse not a natural host of TB
* Fish have their own mycobacterial species that can be used to
help investigate host-directed therapies

235
Q

Talk about zebrafish as a model to study immunity in TB.

A
  • Embryos are visually transparent
  • Genetically manipulable
  • Pharmaceuticals can be added to
    the embryo water
236
Q

Talk about Hypoxia Inducible Factor (HIF) in TB.

A

What activates white blood cells?
- INJURY > loss of blood
> HYPOXIA (low oxygen)
- Can we trick our white blood
cells into thinking they are in
hypoxia during infections?
- HIF decreases infection

237
Q

How many people does spanish flu cause?

A

50-100 million people deaths

237
Q

How many people does spanish flu cause?

A

50-100 million people deaths

238
Q

How many cases and death of Sars-cov-2 (ie covid) from 2019 until now?

A

604M cases
6.5M deaths

239
Q

What are the viruses importantly related to miscarriage and birth defects?

A

e.g. Cytomegalovirus (CMV),Varicella Zoster Virus (VZV),Herpes Simplex Virus (HSV),
Rubella

240
Q

What are the viruses importantly related to outbreaks?

A

e.g. Influenza, Measles, Mumps, Norovirus, SARS-CoV-2

241
Q

What are the viruses related to cancer?

A

e.g. Epstein Barr Virus (EBV) + lymphoma,Hep B/C + hepatocellular carcinoma,Human Papilloma Virus (HPV) + cervical/anal cancer, HIV + many!

242
Q

What are the viruses related to immunocompromised patients?

A

Reactivation of latent viruses: EBV, CMV, HHV6, HHV7, JC virus, BK virus

243
Q

Are viruses a common and significant cause of human disease globally, and nationally in the UK

A

yes!

244
Q

Can virus be seen on light microscope?

A

viruses couldn’t be seen on light microscopy when it was discovered

Electron microscopy introduced in 1939

245
Q

What is the range of virus size and what is the biggest virus as of now?

A

Human viruses range in size from 20 to 260nm in diameter

Poxvirus is the biggest virus

246
Q

Whatis a virus?

A

An infectious, obligate intracellular parasite

Comprising genetic material
(DNA or RNA) surrounded by aprotein coat and/or a membrane

247
Q

Whatis a virus?

A

An infectious, obligate intracellular parasite

Comprising genetic material
(DNA or RNA) surrounded by a protein coat and/or a membrane

Obligate intracellular – totally dependant on living cells for their replication and existance

All have a receptor binding protein to “dock” to cells

All contain genetic material

248
Q

Does virus have
1. Cell wall
2. Organelle
3. DNA and RNA
4. Dependent on host cells?
5. Alive?

A
  1. Cell wall - no
  2. Organelle - no
  3. DNA and RNA - no
  4. Dependent on host cells? - yes
  5. Alive? -no
249
Q

Does bacteria have
1. Cell wall
2. Organelle
3. DNA and RNA
4. Dependent on host cells?
5. Alive?

A
  1. Cell wall - yes
  2. Organelle - yes
  3. DNA and RNA - yes
  4. Dependent on host cells? - no
  5. Alive? -yes
250
Q

What are the different shapes of virus?

A
  • Helical
  • Icosahedral
  • complex
251
Q

What are the different structures of viruses?

A

Can be enveloped or non-enveloped (envelope= lipid coat derived from plasma membrane of the host cell)

  • the nucleocapsid (protein coat of a virus + genetic material) is either helical (spiral staircase e.g.influenza), or icosahedral (cubic e.g. adenovirus) in symmetry
252
Q

What are the different structures of viruses?

A

Can be enveloped or non-enveloped (envelope= lipid coat derived from plasma membrane of the host cell)

  • the nucleocapsid (protein coat of a virus + genetic material) is either helical (spiral staircase e.g.influenza), or icosahedral (cubic e.g. adenovirus) in symmetry
253
Q

Talk about viruses outside of the host cells.

A

When not inside an infected cell, viruses exist as virions. These consist of:
Genetic material (DNA or RNA)
Protein coat (capsid)

Virions can exist outside of a host for a variable amount of time (depending on the virus and the environment), but cannot replicate unless they are within a host.

254
Q

Are viruses very small, and consist of genetic material surrounded by a protein coat ?

A

Yes!

255
Q

The virus genome can be examined through?

A

The viral genome can be examined through “sequencing”. Different methods can be used to find out the DNA or RNA sequence of the virus.

256
Q

How do viruses replicate?

A
  1. Attachment to specific receptor
  2. Cell entry
  3. Host cell interaction + Replication
  4. Assembly of virion
  5. Release of new virus particles
  6. Viral and cell receptors viruses need specific receptors to attach to cells and enter cells- this dictates the type of cells that viruses can infect
  7. Only central viral ‘core’ carrying the nucleic acid and some associated proteins enter host cell.
    • Migration ofgenome tocell nucleus
    • Transcription to mRNA using host materials
    • Use cell materials (enzymes, amino acids, nucleotides) for their replication; subvert host cell defence mechanisms.
  9. Occurs in different locations depending on virus
    Nucleus (e.g. herpes viruses)
    Cytoplasm (e.g. poliovirus)
    At cell membrane (e.g. influenza virus)
  10. a) bursts out - cell death
    e.g. rhinovirus
    b) b) budding/exocytosis
    e.g. HIV, influenza
  • Occurs in different locations depending on virus
    > Nucleus (e.g. herpes viruses)
    > Cytoplasm (e.g. poliovirus)
    > At cell membrane (e.g. influenza virus)
257
Q

A virus is completely dependent on its host cell’s machinery to replicate
(True/False?)

A

True!

258
Q

How do viruses cause disease?

A
  1. Direct destruction of host cells
  2. Modification of host cell
  3. “Over-reactivity” of immune system
  4. Damage through cell proliferation
  5. Evasion of host defences
  6. e.g. poliovirus  host cell lysis and death after a viral replication period of 4 hours - cause paralysis
  7. e.g. rotavirus  atrophies villi and flattens epithelial cells:
    > decreases small intestine surface area
    > nutrients incl. sugar not absorbed
    > hyperosmotic state
    > profuse diarrhoea
  8. eg Hepatitis B
    - Symptoms: Jaundice, Pale stool, Dark urine, RUQ pain, Fever + Malaise, itching
    - In chronic HBV, there is sustained viral replication and liver cell destruction but at a lower level, therefore fewer clinical symptoms
  9. SARS-CoV-2
  10. e.g. human papillomavirus  cervical cancer
    - HPV associated with cervical, penile, anal, vaginal, vulval and head/neck cancer
    5.
    a) Cellular level :
    > Latency: e.g. herpesviridae
    > Cell-cell spread: e.g. measles, HIV
    b) Molecular level:
    > Antigenic variability e.g. influenza, HIV, rhinovirus
    > Prevention of host cell apoptosis e.g. herpesviridae, HIV
    > Downregulation of interferon and other intracellular host defence proteins e.g. many!
    > Interference with host cell antigen processing pathways e.g. herpesviridae, measles, HIV
259
Q

Relate latency and Varicella Zoster Virus (VZV)

A
  • Primary infection CHICKENPOX
  • Reactivation SHINGLES / HERPES ZOSTER
260
Q

Direct cell-to-cell spread has multiple advantages, for example?

A
  • Avoids random release into the environment
  • Increased speed of spread within tissues
  • Avoiding immune system
261
Q

What does the fact below explain?
“Ability to change the surface antigens in order to evade the host’s immune system”?

A

Explains:
- how a host can be re-infected with the same virus e.g. common cold

  • why with influenza vaccination is required annually, as each season a different viral strain is circulating
262
Q

Recognising how viruses cause disease allows us to?

A
  • Understand transmission and natural history
  • Know who is most at risk
  • Develop treatments and “preventative” drugs
263
Q

Viruses vary wildly in the - range of clinical syndromes they can cause, due to?

A
  • Different host cells and tissues that they can infect
  • Different methods of interaction with the host cell
264
Q

What kind of virus can be obtained if you eat undercooked meat?

A

Hepatitis C virus

265
Q

Talk about passive immunity.

A
  • Protection provided from the transfer of antibodies from immune individuals
  • Most commonly cross-placental transfer of antibodies from mother to child (e.g. measles, pertussis)
  • Or, via transfusion of blood or blood products including immunoglobulin (e.g. Hep B)
  • Protection is temporary – usually only a few weeks or months.
266
Q

Explain more about passive immunisation?

A
  • Passive immunity provided by injection of human immunoglobulin containing antibodies to the target infection
  • Temporarily increases person’s antibody level to that specific infection. Protection gained within a few days but lasts only a few weeks.
  • Human normal immunoglobulin (HNIG) derived from the pooled plasma of donors and contains antibodies to infectious agents that are currently prevalent in the general population.
  • Used to protect immunocompromised children exposed to measles and of individuals after exposure to hepatitis A.
  • Specific immunoglobulins available for tetanus, hepatitis B, rabies and varicella zoster.
267
Q

Talk about active immunisation

A

Vaccination stimulates immune response and memory to a specific antigen/infection

  • Vaccines made from
    inactivated (killed) (e.g. pertussis, inactivated polio)
  • attenuated live organisms (e.g. yellow fever, MMR, polio, BCG)
  • secreted products (e.g. tetanus, diphtheria toxoids)
  • the constituents of cell walls/subunits (e.g. Hep B) or
  • recombinant components (experimental)
268
Q

What is vaccine failure and what are the 2 types of vaccine failure?

A
  • No vaccine offers 100% protection
  • Small proportion of individuals get infected despite vaccination.
    > Primary vaccine failure – person doesn’t develop immunity from vaccine.
    > Secondary vaccine failure – initially responds but protection wanes over time.
269
Q

What are the example of vaccine-preventable diseases?

A
  1. Diphtheria
    - Corynebacterium diphtheriaebacteria
    - “Bull neck”
    - Cutaneous diphtheria
  2. Tetanus
    - Clostridium tetani bacteria
    - Tetany
  3. Pertussis
    - Bordetella pertussis bacteria
    - “Whooping cough”
  4. Polio
    - Poliovirus
    - Poliomyelitis
  5. Haemophilus influenzae type B
    - Haemophilus influenzae bacteria
    - Acute epiglottitis
    - Periorbital cellulitis
  6. Meningococcal disease
    - Neisseria meningitidis bacteria
    - Meningococcal sepsis
    -
270
Q

How to prevent further cases of infectious disease?

A
  • Notification
  • Contact tracing
  • Antibiotic chemoprophylaxis
  • Vaccination
271
Q

What is contact tracing?

A

Contact for meningitis is taken to be any person having close contact with a case in the past 7 days

Close contact includes kissing, sleeping with, spending the night together or spending in excess of eight hours in the same room

272
Q

Diseases, infections and conditions specifically listed as notifiable under which act?

A
  1. the Public Health (Control of Disease) Act 1984
  2. theHealth Protection (Notification) Regulations 2010
273
Q

Notifiable diseases examples:

A

Anthrax
Cholera
Plague
Rabies
SARS
Smallpox
Viral haemorrhagic fever
Yellow fever

Acute encephalitis
Botulism
Brucellosis
Enteric fever (Typhoid & Paratyphoid fever)
Haemolytic Uraemic Syndrome
Legionnaires Disease
Ophthalmia neonatorum
Leprosy
Leptospirosis
Malaria
Relapsing fever
Typhus fever

274
Q

What are the examples of diseases that are preventable by vaccine?

A

Acute poliomyelitis
Diphtheria
Measles
Mumps
Rubella
Tetanus
Whooping cough
Acute Meningitis / Meningococcal septicaemia

275
Q

What are the exampels of notifiable disease that require specific control measures?

A

Acute infectious hepatitis
Foodborne
Food poisoning
Botulism
Enteric fevers
Infectious bloody diarrhoea
Scarlet fever
Tuberculosis

276
Q

Why should we notify infectious diseases? what are the role of surveillance?

A

Detection of any changes in a disease
Outbreak detection
Early warning
Forecasting

Track changes in disease
Extent and severity of disease
Risk factors

Allows development of interventions targeted at vulnerable groups

277
Q

How do we protect the community from infectious disease?

A

Investigate: contact tracing, partner notification, lookback exercises, etc…

Identify and protect vulnerable persons: e.g. chemoprophylaxis, immunisation, isolation

Exclude high risk persons or from high risk settings

Educate, inform, raise awareness, health promotion

Coordinate multi-agency responses

278
Q

What are the route of disease transmission?

A

Source > Pathway > Receptor

279
Q

Talk about Group A streptococcus bacteria

A

Scarlet Fever
‘Sandpaper rash’
‘Strawberry tongue’

Think of
risk settings e.g. schools
co-infections e.g. chickenpox

280
Q

Talk about typhoid fever

A

Think
- Risk factors e.g. travel
- Risk groups e.g. food handlers, health & care staff, young children, doubtful hygiene

  • Salmonella typhi bacteria
281
Q

Talk about Hepatitis B

A

Think
- Risk factors e.g. travel, medical procedures, infected mother-to-child, blood products
- Risk groups e.g. MSMs, sex workers, IV drug users, health workers, prisoners

  • Hepatitis B virus
282
Q

Talk about Legionnaires disease.

A

Legionella pneumophila bacteria
- Think
> Travel
> Water-related exposures (aerosol)

283
Q

State how a sporadic disease becomes pandemic and endemic.

A

Sporadic disease > Cluster > Outbreak > Epidemic >Pandemic > Endemic

284
Q

What are the public health countermeasures?

A
  • Hygiene
  • Social distancing
  • Isolation / quarantine
  • Personal protective equipment
  • Treatment as prevention
  • Chemoprophylaxis
  • Vaccination
285
Q

State the examples of diseases and viral cause?

A
  1. Common cold (Rhinitis, Sinusitis)- rhinoviruses
  2. Sore throat (Pharyngitis/Tonsillitis) - Adenoviruses,
    Epstein-Barr Virus
  3. Influenza - Influenza A and B
  4. Laryngo-tracheobronchitis/
    “croup” (<1yrs) - Parainfluenza viruses
  5. Acute Bronchitis - Adenoviruses
  6. Chronic Bronchitis - RSV, Rhinoviruses
    Parainfluenza viruses
  7. Bronchiolitis (<2yrs)
    Pneumonia - RSV, Adenoviruses
286
Q

What is influenza? Talk about influenza.

A

Influenza or ‘flu’ is an acute respiratory illness caused by infection with influenza viruses.

3 separate genera: influenza A, B and C Influenza A viruses subdivided by 2 key surface antigens:
> Haemagglutinin
- 15 subtypes
- Helps virus bind and enter cells: i.e. the “Grappling Hook”
> Neuraminidase ()
- 9 subtypes
- The “Bolt Cutters” for getting out; cuts newly formed virus loose from infected cells

287
Q

What are the main human pathogens in influenza?

A

Influenza A and B are the main human pathogens

288
Q

Talk about viral genome.

A

Viral genome consists of 8 single-stranded RNA segments.

Because the genome is segmented, gene re-assortment can occur in infections.

Genes swapping can occur during co-infection with human and avian flu virus
Also, no proofreading mechanism, so very prone to mutation.

289
Q

What causes
1. Seasonal flu
2. Pandemic

A
  • Minor antigenic variation (antigenic drift) causes seasonal epidemics.
  • Gene re-assortment & major antigenic variation (antigenic shift) may be associated with pandemics.
290
Q

Talk about influenza A, B and C.

A

Influenza A
- Can infect pigs, cats, horses, birds and sea mammals
- Causes the severe and extensive outbreaks and pandemics

Influenza B
- Like Influenza A, also prone to mutation
- Tend to cause sporadic outbreaks (e.g. schools, care homes, garrisons) that are less severe
- More often seen in children

Influenza C
- Relatively minor disease: mild symptoms or even asymptomatic

291
Q

Talk about influenza transmission.

A

Transmission mainly via aerosols generated by coughs and sneezes.

However, also possible via hand-to-hand contact, other personal contact or fomites.

292
Q

Talk about influenza infection and its potential complications.

A

Characterised by upper and/or lower respiratory tract symptoms, as well as fever, headache, myalgia and weakness.

Complications include bacterial pneumonia, and can be life threatening.

293
Q

Mortality risk higher in persons with underlying medical conditions, such as ?

A
  • Chronic cardiac and
  • pulmonary diseases
  • Old age
  • Chronic metabolic diseases
  • Chronic renal disease
  • Immunosuppressed
294
Q

Treatment options for influenza.

A
  1. Supportive care
    - oxygenation
    - hydration/nutrition
    - Maintain homeostasis
    - Prevent/ treat secondary infections
  2. Role of antiviral infection
    - Reduce the risk of transmission to others
    - Reduce severity and duration of symptoms
295
Q

Talk about seasonal flu.

A

Every year the virus changes a little bit (‘Antigenic Drift’)

Means it can infect some people who were immune to last year’s variant.

Influenza occurs most often in the winter months and usually peaks between December and March in the northern hemisphere.

Illnesses resembling influenza may occur in the summer months but they are usually due to other viruses.

Annual flu vaccination of at risk groups and children offers some protection against infection.

296
Q

Talk about avian influenza.

A

Strictly an avian pathogen but can pass from birds to humans

H5N1 started circulating in SE Asia before 1997

Mild disease in birds, but mutation to highly pathogenic form 100% mortality

Human cases reported.

Inter-species spread possibly due to
Due to close proximity of poultry and people
50-80% of poultry in small rural households

297
Q

What are the measures out there to control avian flu?

A
  • Cull affected birds
  • Biosecurity and quarantine
  • Disinfecting farms
  • Control poultry movement
  • Vaccinate workers – seasonal influenza vaccine
  • Antivirals for poultry workers
  • Personal Protective Equipment (PPE)
  • Try to reduce chance of co-infection
298
Q

Talk about pandemic influenza.

A

Virus mutates markedly (‘Antigenic shift’)

Large proportion of the population is susceptible.

Often created by the strain “jumping” from another species e.g. Flu virus found in ducks, chickens, horses, pigs, whales, seals…

Pandemic flu likely to cause:
High morbidity
Excess mortality
Social disruption
Economic disruption

299
Q

H1N1 history time period

A
  1. Spanish Flu 1918
  2. Pandemic influenza 2019
300
Q

Talk about the spanish flu

A

H1N1 flu subtype, derived from an avian source.

Killed between 50-100 million people worldwide.

~ 40% of the world’s population became ill.
Of those who died, many felt ill in the morning and were dead by nightfall.

It killed more people than WWI.

Believed that the movement of soldiers helped to spread the virus further afield.
It killed mostly young people (20- 40 years).

301
Q

Talk about the pandemic flu.

A

Short incubation period 1-4 days
Infectious from onset of symptoms to 4-5 days after 10% infectious before symptom onset.

Little warning? 2-4 weeks from first case to first introduction to UK??

First wave last 3-5 months. Subsequent waves may be worse.

What age groups will be affected?

Will take 4 – 6 months (or more) before vaccine available.

Effectiveness of anti-virals??

Unknown attack rate and case fatality rate

302
Q

Will we get more pandemics?

A
  • More travel
  • More people
  • Intensive farming
  • More animal contacts with people
  • Factory farming breeding grounds for viruses

BUT on the plus side
- Better nutrition, overall healthier population
- Better supportive care options
- Vaccination
- Antivirals?

303
Q

Talk about the infection controls for infectious disease.

A

Hand hygiene, cough etiquette
Universal precautions and PPE (mask, apron, gown, gloves)

Surgical masks OK for non aerosol generating procedures

Segregation of patients

Reduce social contact

Flu surgeries

Environmental cleaning

304
Q

Talk about antiviral drugs?

A

UK stockpiled 30 million courses of antivirals for H1N1 pandemic in 2009

Would cover a 50% attack rate

Mostly Oseltamivir (Tamiflu), with some Relenza

Oseltamivir needs to be given with 24-48 hours of contact to have maximum effect

Evidence from seasonal flu is that it reduces hospitalisation by 50% and duration of disease by approximately 24hours (drug company studies…)

Issues:
- What happens if the virus develops resistance?
- What about side effects?
- Who do we give them to?
- How do we distribute them?

305
Q

Talk about vaccines.

A

Could take 6 -10 months, hopefully quicker

When to switch from producing normal seasonal flu vaccine to the pandemic strain?

Capacity:
will take time to manufacture
who do you allocate it to first?

How many doses are required?
Who should be prioritised for it?
How long does protection last?
How good is the protection?

306
Q

What are the possible population-wide interventions.

A
  • Travel restrictions
  • Restrictions of mass public gatherings
  • Schools closure
  • Voluntary home isolation of cases
  • Voluntary quarantine of contacts of known cases
  • Screening of people entering UK ports
307
Q

What causes SARS Cov (Severe Acute Respiratory Syndrome)

A

Caused by a SARS Coronavirus (SARS CoV)
New member of the Coronavirus family
Animal origin/reservoir: Bats
Intermediate host: Civet cats

308
Q

Talk about SARS signs, symptoms and outcomes.

A

Incubation period believed to be 2-7 days

Symptoms:
High fever, cough, shortness of breath, myalgia, diarrhoea

Chest x-ray shows pneumonia or respiratory distress syndrome

Case fatality rate:
Age under 24 years <1%,
Rising to >50% in those over 65 years

No vaccine & no specific treatment

309
Q

Talk about superspreading in SARS Cov.

A

Up to 75% of infections in Hong Kong and Singapore were linked to super-spreaders.

In Singapore, 5 people caused more than half of the 205 cases.

310
Q

What are the control measures for SARS?

A

Surveillance, isolation & quarantine

311
Q

Talk about MERS Cov?

A

Also caused by a coronavirus

First reported in Saudi Arabia in 2012 and has since spread to several other countries

Also presents like SARS with severe acute respiratory disease

Again, bat origin, with camels as intermediate host

Outbreak of MERS in May - July 2015 in South Korea

Largest known outbreak of MERS outside the Arabian Peninsula.

186 cases – 185 in S Korea, 1 in China, 36 deaths

312
Q

When did WHO declare the COVID19 outbreak a Public Health Emergency of International Concern (PHEIC)?

A

30 January 2020

313
Q

Speed of COVID 19 spreading

A

R0~2.6 for wildtype (2020),
higher for some of the later variants

Asymptomatic spread

Pre-symptomatic spread

Superspreading events

314
Q

Talk about the common symptoms, Severe symptoms and Transmission for COVID -19.

A

Common symptoms:
- Fever
- After 2-7 days, cough develops
- Mild breathing difficulties
- GI issues
- Diarhhea
- General body aches

Severe Symptoms
- High fever
- Pneumonia
- Kidney Failure
- Death

Transmission
- Cough or sneezes from an infected person or touching contaminated objects

315
Q

Talk about the incubation period, infectious period, and symptomatic period.

A

Incubation period - Time from exposure to symptom onset, ranges from 14 days, but is typically 5 days

Infectious period - Typically start 2 days before symptoms to 10 days after symptoms onset

Symptomatic period - The duration and type of symptoms can vary between individuals

316
Q

Risk factors for COVID-19 death?

A

Age
Gender
Obesity
Co-morbidities

317
Q

Is covid-19 higher rate in younger people or older people?

A

Older people

318
Q

What are the risk settings for COVID-19?

A

Household & workplace clusters dominate

High risk settings: e.g. hospitals and care homes

Links with deprivation: high density housing, unsafe workplaces

Superspreading events: mass gatherings, night clubs, choirs

319
Q

Potent enablers of disease transmission.

A

Close contact
Crowds
Confined spaces

320
Q

Talk about intervention for COVID-19

A
  1. Detect
  2. Track
  3. Trace
  4. Isolate
  5. Support
321
Q

What is the of pandemic defense, recognising that no single intervention is perfect at preventing speed.

A

The swiss cheese theory

322
Q

Talk about COVID-19 vaccine.

A

Vaccines highly effective at protecting against severe outcomes (e.g., severe disease requiring hospitalisation, death)

Not so good at protecting against getting infected in the first place

Ongoing research into “nasal vaccines”

Unsure how long protection lasts or how good it is, especially against new emerging variants

The vulnerable remain vulnerable so will benefit from vaccination programmes, boosters.

Need to immunize health and care staff, as well as carers too.

323
Q

Talk about pandemic response for COVID-19.

A

Local, national and global surveillance
Epidemiological surveillance
Wastewater surveillance
Genomic surveillance
Research
Reinfections
Durability of immunity
Long Covid
Population behaviour
Rapid evidence reviews
Vaccine efficacy studies

Phase 2A (11 decks)

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