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Part 2 Flashcards

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1
Q

What is nociception

A

Physiological processes by which pain is perceived

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2
Q

nociceptors are

A

specialised sensory neurones which when activated give Sensation of pain actual/potential

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3
Q

What are thinly and unmyelanted nociceptors called

A

Unmyelinated: terminal axons (C fibre)

Thinly myelinated: terminal exons (Aδ-fibre)

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4
Q

Where are nociceptors found

A

Their cell bodies lie in the dorsal root ganglion in the spinal cord

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5
Q

What do nociceptors do

A

act as transducers that convert noxious stimuli into action potentials which are connected to sensory neurones that connect to the spinal cord
Neurone is connected to dorsal horn neurones that release glutamate (amino acid), a excitatory neurotransmitter

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6
Q

Glutamate can be inhibited by

A

Opioids Cannabinoids γ-aminobutytric acid

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7
Q

What other neurotransmitters can be released by Glutamate

A

Nerve growth factor (NGF), Histamine, Bradykinin, calcitonin gene related peptide (CGRP)

N-methy-Daspartate (NMDA) receptor if high intensity pain/ repetitive noxious stimulation

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8
Q

Describe pain pathway

A 
Stimulus
1. sensory receptors in skin
2. afferent pathway (dorsal route)
3. Integrating centre [CNS]
4. Efferent pathway (verntral route)
5. Effector organs 
Response

1, 2, 4, 5 = PNS

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9
Q

Difference between chronic and acute pain

A

Acute: experienced during surgery/trauma, resolves with healing
Chronic: persists beyond expected period. progressive. non malignant, persists after healing

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10
Q

What is neuropathic pain

A

Chronic pain resulting from damage to the peripheral nervous system. Can be Diabetes, HIV, post-herpetic neuralgia or CNS damage eg spinal cord injury, stroke or MS.

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11
Q

What is Cancer Related Pain

A

Pain associated with tumour growth, metastesis, radiation, chem0therapy

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12
Q

What to assess with pain

A

Location •  Severity •  Quality •  Duration •  Timing •  Pt’s level of function/dysfuntion •  Debilitating?

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13
Q

What is an analgesic and co-analgesic

A

analgesic: relieves pain. Opioid, non opioid
co-analgesic: Drugs that have primary indication other then for pain but act as analgesics in some conditions. E.g. anti-depressants and anticonvulsants (neuropathic oain)

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14
Q

inflammatory reaction consists of the following changed

A
  •   Tissue damage
  •   Cellular – vascular - cellular response
  •   Metabolic changes
  •   Tissue repair
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15
Q

Describe the inflammation pathway

A

tissue injury
release of phospholipids
arachidonic acid
cox 1 (cytoprotective prostaglandins [GI mucosa]) and cox 2 (inflammatory prostaglandins [inflammation])

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16
Q

How does paracetamol work

A

– Mechanism not completely understood
– COX 2 inhibitor
– Limited anti-inflammatory effects
– Suppresses signal transduction in spinal cord

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17
Q

What is the active metabolite of Morphine

A

Morphine-6-glucuronide (M6G) which is anagonist for u receptor

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18
Q

What other metabolite does Diamorphine have

A

6-monoacetylmorphine

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19
Q

Codeine turns into morphine because of

A

CYP2D6

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20
Q

Buprenorphine acts on

A

u receptors. less dependence

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21
Q

Tramadol acts by

A

Weak affinity for υ opioid receptors

Inhibits neuronal uptake of noradrenaline and enhances serotonin release

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22
Q

Nalaxone acts by

A

Competitive antagonist for all opioid receptors

Reverses actions of opioid agonists within minutes

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23
Q

Naltrexone is

A

•  Used in ex drug abusers •  Feel no kick if they take opioid agonists

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24
Q

Name some co analgesics

A

•  Coticoisteroids •  Neuroleptics •  Benzodiazapenes

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25
Adjuvant therapy for neuropathic pain can be
*   Anti-depressants •  Anticonvulsants •  Local anesthetics | *   Capsaicin
26
Which protein do opioids couple with
G Protein Couple receptors which then activate in the spinal cord, PNS and brain
27
What does the peripheral system do?
1. Autonomic - self regulated actions of organs and glands A. Sympathetic: arousing B. Parasympathetic: calming 2. Somatic - voluntary movements of skeletal muscles
28
What kind of things does the sympathetic system do?
dilates pupil, inhibit saliva, accelerate heartbeat, dilates bronchi, inhibit peristalsis/secretion, convert glycogen to glucose, secrete adrenaline/noradrenaline, inhibit bladder contraction
29
What kind of things does the parasympathetic system do?
constrict pupil, stimulate saliva, slow heartbeat, constrict bronchi, stimulates peristalsis/secretion, stimulates bile release, contracts bladder
30
Describe process of Somatic Nervous System
Contains all the sensory and motor neurons outside the central nervous system. It works by: Skin - afferent nerve - spinal cord - efferent nerve - muscle
31
How are nociceptors activated?
spinal cord via dorsal root ganglion sends substance P to mast cells which activate histamine, serotonin prostaglandin, bradykinin, K+
32
Whats the difference between Alpha and C fibres
Alpha-delta (aδ) fibres: Myelinated fibres which conduct much more rapidly, Sharp Pain, Precisely located C-fibres: Non-myelinated fibres with low conduction velocity, diffuse pain, not distinctly localised
33
How to treat neuropathic pain
amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment for neuropathic pain
34
How to treat Trigeminal neuralgia
carbamazepine as initial treatment
35
How do Antidepressants help with pain
- Sodium-channel blockade (TCAs) | - Inhibit reuptake of norepinephrine and serotonin into presynaptic neurones (duloxetine)
36
How do anticonvulsants help with pain
- Sodium-channel blockade (carbemazepine) | - Calcium-channel blockade (gabapentin)
37
How do opioids (oxycodone) help with pain
-Block NT release by nociceptive fibres, thus decreasing transmission of pain producing signals (oxycodone)
38
What is the mechanism for TCA help with pain
Prevents 5HT and Norepinephrine reuptake | tertiary better but more Side effects
39
What is the mechanism for Gabapentin help with pain
not understood possibly ?voltage gated Ca2+ channels
40
What is the mechanism for carbamazapine to help with pain
stabilise inactivated sodium-channels thereby making them less excitable
41
What is the mechanism for tramadol to help with pain
Weakly inhibits serotonin and norepinephrine reuptake
42
Name some opioid receptors and their ligands
δ (delta) - Dynorphin Κ (kappa) - enkephalin υ (epsilon) - β-endorphin
43
Why is diamorhine not given orally
Oral route undergoes metabolism and only morphine metabolite reaches systemic circulation
44
What is methadone used for
maintenance therapy for opioid addicts, reduced cravings, kick, buzz for IV heroin, morphine And in cancer patients and in chronic nonmalignant pain
45
describe innate immunity
``` Innate Response: Does not rely on antigen Quick Onset Does not result in immunological memory Operates from birth Does not change response with subsequent exposure ```
46
describe adaptive immunity
``` Adaptive Response: Requires antigen exposure Delayed Onset Results in immunological memory Acquired after birth Often increases in response to subsequent exposure ```
47
What is the accute innate response
inc blood flow, vasodilation, inc vascular permiability, leakage of fluid to tissue (swelling), activation nociceptors by prostaglandins (pain)
48
When tissue damaged what happens resulting in inflammation
Tissue injury leads to the production of inflammatory mediators: Vasoactive: phospholipids, bradykinin, histamine, serotonin released (and Chemoactive: Cytokines etc) the phospholipids (via phospholipase a2 ) are converted to arachdonic acid which (via cox1 cox2) turn into prostaglandins/thormobaxane cox 1 (mucous protecting stomach) cox 2 (inflammation)
49
What is an autoimmune disease
When immune system can't recognise between ‘self’ and ‘non-self’ antigens eg Coeliac Disease
50
Give examples of inflammation disorders
dermatitis (scalp, face, ears), eczema (neck elbows), acne (face, chest, back), psoriasis (head, ears, elbows), viral wart (hand, feet), skin cancer (exposed skin), fungal/bacterial (all over)
51
What is rheumatoid factor
are proteins produced by your immune system that can attack healthy tissue in your body. High levels of rheumatoid factor in the blood are most often associated with autoimmune diseases, such as rheumatoid arthritis and Sjogren's syndrome
52
How to treat rheumatoid arthiritis
•  Anti-Inflammatory Drugs - Non-steroidal anti-inflmmatory drugs - Corticosteroids •  Disease Modifying Anti Rheumatic Drugs (DMARD) (now first line): - Immunosuppressant's / modulators - Cytokine Blockers - Anti-Rheumatic drugs
53
What does COX 2 cause
•  Produces – Prostaglandins I2 – Prostaglandins E2 •  Effects: – Vasodilation -> inc blood flow -> redness – Potentiates effects of bradykinin, histamine – Increased pain sensation – ‘resets’ bodies thermostat inc fever
54
How to corticosteroids act
*   Mimic the action of steroids produced by the adrenal gland *   Medulla – Secretes catecholamine's *   Cortex – Secretes steroids
55
What are the two types of corticosteroid
•  Mineralocorticoids: – Affect water and electrolyte balance – Aldosterone Na and H2O reabsorption in kidney •  Glucocorticoids (anti inflammatory) – Affects metabolism – Most common produced - Cortisol = hydrocortisone
56
Mechanism of corticosteroid action
1. Binding of steroid hormone to receptor 2. translocation of this complex to nucleus 3. complex binds to DNA regulatory site 4. Transcription 5. translation 6. new protein
57
What affect of corticosteroid
less activation of immune cells, transcription of cox, production of cytokines, prostanoids, interleukins. Inhibits phospholipase 2
58
Name some DMARDS
•  Methotrexate •  Sulfasalazine (Salazopyrin®) •  Hydroxychloroquine (Plaquenil®) •  Leflunomide (Arava®) •  Gold (Myochrisine®) •  Others – Cyclosporine – Azathioprine – Cyclophosphamide
59
Name some combo therapies of DMARDS
*   Triple Therapy – Methotrexate, Sulfasalazine, Hydroxychloroquine *   Double Therapy – Methotrexate & Leflunomide – Methotrexate & Sulfasalazine – Methotrexate & Hydroxychloroquine – Methotrexate & Gold – Sulfasalazine & Plaquenil *  monotherapy
60
How does methotrexate work
Inhibits rapidly dividing cells by: Inhibiting Dihydrofolate reductase which converts dihydrofolic acid to tetrahydrofolic acid. This is found in Thymine (a base of DNA)
61
How does Hydroxychloroquine work
Increases intracellular pH | Interferes with cell’s ability to degrade and process proteins
62
How does sulfasazaline work
treatment of “infective polyarthritis” •  Anti-inflammatory: Salicylic Acid •  Antibiotic: Sulfapyridine •  Sulfasalazine consists of salicylic acid and sulfapyridine
63
In some people with arthritis, a protein called Tumour Necrosis Factor (TNF) is present in the blood and joints in excessive amounts where it increases inflammation (pain & swelling). How should we treat
*   TNF Inhibitors – Adalimumab – Etanercept – Infliximab (Remicade) *   IL-1 Inhibitors – Anakinra (Kineret) *   T-Cell Co-Stimulatory Blockade – Abatacept (Orencia) *   B-Cell Depletion – Rituximab (Rituxan)
64
Histamine release results in
arteriolar dilation increased capillary permeability contraction of nonvascular smooth muscle stimulate nociceptors responsible for the pain response
65
Serotonin release results in
increases vascular permeability dilates capillaries contraction of nonvascular smooth muscle
66
bradykinin release results in
Relaxation of vascular smooth muscle increasing blood flow Makes capillaried more permeable allowing blood components to enter tissue space
67
Leukotrienes release results in
 Chemotactic effect  Increase vascular permeability
68
pancreas has two types of cells
α and β cells – α cells secrete Glucagon – Β cells secrete Insulin
69
How does insuline release from body
*   Glucose binds to GLUT 2 Transporters *   Glucose is metabolised to Pyruvate inc ATP *   Inc in ATP closes KATP Channels, (K+) *   KATP closure depolarisation and opening of Ca2+ channels *   Inc in intracellular Calcium leads to the release of Insulin of βcells into bloodstream
70
How does metformin act
•  Decreases liver glucose production •  Decreases intestinal glucose absorption •  No influence of insulin secretion
71
How do Glitazones, e.g. Roziglitazone, Pioglitazone worl
•  Promoted lipogenesis* and enhances fatty acid and glucose uptake •  Promotes Na+ absorption in tubules??? •  Binds to genes encoding proteins rqd in Insulin Signalling
72
What does angiotensin 2 do?
potent Vasoconstrictor inc BP •  Inc Total peripheral resistance Promotes release of Aldosterone •  Aldosterone causes an increase in Na+ H2O retention inc blood volume *   Promotes release of ADH – Inc in water reabsorption *   Inc Sympathetic activity – Inc heart rate and vasoconstriction
73
How do ACE inhibitors work
Inhibit conversion of Angiotensin I to Angiotensin II By ACE because Angiotensin 2 increases BP ACEi increase Bradykinin (potent dilator) promoting BP to fall further
74
Why dry cough with ACEi
increases [bradykinin], which stimulates the formation of prostanoids and these cause the dry cough
75
ACEi cause
- reduced vasoconstriction, - reduced sodium and water retention -  increased vasodilation (through bradykinin). -  A fall in Blood pressure
76
Why no cough with Losartan etc
Do not interfere with kinin processing
77
How do loop diuretics work
Loop diuretics inhibit the sodium-potassiumchloride co-transporter in the thick ascending limb (25%)
78
How do thiazide diuretics work
inhibit the sodiumchloride transporter in the distal convoluted tubule (5%)
79
How do Potassium Sparing Diuretics work
inhibit the action on epithelial sodium channel
80
How do Aldosterone antagonists work
lower Na absorption
81
How do CaCh Blocker work
•  Target vascular L-type Ca2+ Channels •  Reduce vascular resistance and arterial pressure

Uni (2 decks)

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