ICS - Pathology, Immunity and Pharmacology

Question 1

Define inflammation.

Answer 1

A local physiological response to tissue injury.

Question 2

Give a benefit of inflammation.

Answer 2

Inflammation can destroy invading micro-organisms and can prevent the spread of infection.

Question 3

Give a disadvantage of inflammation.

Answer 3

Inflammation can produce disease and can lead to distorted tissues with permanently altered function.

Question 4

Define exudate.

Answer 4

A protein rich fluid that leaks out of vessel walls due to increased vascular permeability.

Question 5

What are the 5 cardinal signs of inflammation?

Answer 5

Rubor - redness - due to dilation of small BV

Dolor - pain - from stretching and distortion of tissues due to inflammatory oedema and pus putting pressure in an abscess cavity

Calor - heat - due to increased blood flow (hyperaemia) and systemic fever

Tumor - swelling - resulting from oedema and to a lesser extent the inflammatory cells migrating into the area

Loss of function

Question 6

What are the stages of acute inflammation?

Answer 6

Increase vessel calibre - inflammatory cytokines and endogenous chemical mediators (bradykinin, prostcyclin and NO) mediate vasodilation.

Fluid exudate - Vessels become leaky and protein rich fluid is forced out of the vessel leading to swelling

Cellular exudate - neutrophils become abundant in this exudate

Question 7

What is neutrophil action in acute inflammation?

Answer 7

1. Margination - Due to increase in plasma viscosity and slowing of flow due to injury, neutrophils migrate to plasmatic zone
2. Adhesion - selectins bind to neutrophil and cause rolling along the blood vessel margin
3. Emigration and diapedesis - Movement of neutrophils out of the blood vessel through or in between the endothelium and basal lamina (other inflammatory cells follow)
4. Chemotaxis - movement towards site of inflammation along chemical gradients

Question 8

What is the action of neutrophils at the site of inflammation?

Answer 8

Bind to the pathogen and start phagocytosis
Lysosomes move to fuse with the neutrophil to form the phagolysosome
This releases lytic enzymes to kill the pathogen.
Macrophages then clear the debris

Question 9

What are the outcomes of acute inflammation?

Answer 9

Resolution - initiating factor is removed and the tissue can return to normal structure and function

Suppuration - formation of pus (collection of leukocytes) surrounded by a pyogenic membrane to start the healing process (leads to scarring)

Organisation - Granulation tissue forms and you get the development of fibrosis

Progression - Excessive recurrent inflammation can become chronic and you get fibrotic tissue forming.

Question 10

What are granulomas?

Answer 10

Aggregates of epitheliod histocytes (mainly macrophages) at the site of inflammation to contain the pathogen

Question 11

How can acute inflammation be diagnosed histologically?

Answer 11

By looking for the presence of neutrophil polymorphs.

Question 12

Give 3 endogenous chemical mediators of acute inflammation.

Answer 12

1. Bradykinin.
2. Histamine.
3. Nitric Oxide.

Question 13

What are 4 systemic effects of acute inflammation?

Answer 13

1. Fever.
2. Feeling unwell.
3. Weight loss.
4. Reactive hyperplasia of the reticuloendothelial system.

Question 14

Give 6 causes of acute inflammation.

Answer 14

1. Microbial infections (bacteria and viruses).
2. Chemicals (corrosives, acids/alkalis).
3. Physical agents (trauma, burns, frost bite).
4. Hypersensitivity reactions (TB).
5. Bacterial toxins.
6. Tissue necrosis.

Question 15

What cells are involved in chronic inflammation?

Answer 15

Macrophages and plasma cells (B and T lymphocytes).

Question 16

What cell can form when several macrophages try to ingest the same particle?

Answer 16

Multinucleate giant cell.

Question 17

Give 4 causes of chronic inflammation.

Answer 17

1. Primary chronic inflammation.
2. Transplant rejection.
3. Recurrent acute inflammation.
4. Progression from acute inflammation.

Question 18

What can cause primary chronic inflammation?

Answer 18

1. Infective substances having resistance to phagocytosis e.g. TB, leprosy.
2. Endogenous materials e.g. uric acid crystals. necrotic tissue
3. Exogenous materials e.g. asbestos.
4. Autoimmune diseases e.g. chronic gastritis, rheumatoid arthritis etc.
5. Other chronic inflammatory diseases e.g. chronic inflammatory bowel disease.

Question 19

What are some macroscopic features of chronic inflammation?

Answer 19

1. Chronic ulcer.
2. Chronic abscess cavity.
3. Granulomatous inflammation.
4. Fibrosis.

Question 20

What is the Microscopic appearance of chronic inflammation?

Answer 20

Characteristically lymphocytes, plasma cells and macrophages
Exudation is not a common feature
Evidence of continuing destruction
Possible tissue necrosis

Question 21

What is granulation tissue?

Answer 21

Granulation tissue is composed of small blood vessels in a connective tissue matrix with myofibroblasts.
It is important in healing and repair of chronic inflammation

Question 22

What condition causes granulomas with central necrosis?

Answer 22

Caseous granuloma (soft cheese like)
Caused by TB

Question 23

What conditions cause granulomatous inflammation without central necrosis?

Answer 23

Sarcoidosis, leprosy, vasculitis, chrons disease

Question 24

What blood marker is released from granulomas?

Answer 24

ACE

Question 25

What is the difference between resolution and repair?

Answer 25

Resolution is when the initiating factor is removed and the tissue is able to regenerate. In repair, the initiating factor is still present and the tissue is unable to regenerate.

Question 26

Name 5 types of cells capable of regeneration.

Answer 26

1. Hepatocytes. 2. Osteocytes. 3. Pneumocytes. 4. Blood cells. 5. Gut and skin epithelial cells.

Question 27

Name 2 types of cells that cannot regenerate.

Answer 27

Myocardial cells Neurons

Question 28

Define abscess.

Answer 28

Acute inflammation with a fibrotic wall.

Question 29

Define thrombosis.

Answer 29

Formation of a solid mass from blood constituents in an intact vessel in the living.

Question 30

Give 2 reasons why thrombosis formation is uncommon.

Answer 30

Laminar flow of blood Endothelium is non-sticky

Question 31

What are the 3 factors that can lead to thrombosis formation (virchow's Triad)

Answer 31

1. Change in vessel wall. (endothelial injury) 2. Change in blood constituents. (platelet aggregation, thrombus formation or fibrin deposition) 3. Change in blood flow. (stasis of blood flow)

Question 32

Define embolus.

Answer 32

A mass of material (often a thrombus) that is carried in the vascular system that is able to become lodged in a vessel and block it.

Question 33

Define ischaemia.

Answer 33

Decreased blood flow to tissues w/o other complications

Question 34

Define infarction.

Answer 34

Decreased blood flow to a tissue that results in subsequent cell death.

Question 35

Define Acute inflammation

Answer 35

Initial Response to tissue injury Inflammation that is: sudden onset, lasts for a short duration and usually resolves Involves Neutrophils and Monocytes

Question 36

How do bacteria and viruses cause harm?

Answer 36

Bacteria - release exo/endotoxins that initiate the inflammatory pathways Viruses - Intracellular replication causes cell death

Question 37

What processes do the endogenous chemical mediators lead to?

Answer 37

Vasodilation chemotaxis increased vascular permeability itching and pain

Question 38

What are the main cell types in acute inflammation?

Answer 38

Neutrophil polymorphs Macrophages Fibroblasts Endothelial cells Lymphocytes

Question 39

What are the main cell types in chronic inflammation?

Answer 39

Macrophages Lymphocytes Plasma cells

Question 40

What is a multinucleated giant cell?

Answer 40

The cell that forms when several macrophages try to ingest the same pathogen and end up fusing together.

Question 41

What are some differences between acute and chronic inflammation?

Answer 41

Chronic is persistent and the causative agent is often not removed There tends to be less swelling Inflammation and repair occurs at the same time Fibrosis is a key feature

Question 42

What is resolution?

Answer 42

Tissue restored to normal pre injury state tissue architecture is undamaged tissue initiating factor is removed

Question 43

What is lobar pneumonia

Answer 43

A bacterial infection caused by strep pneumonia one lobe of the lungs filled with pus and neutral polymorphs fill alveoli of the lungs this is resolved through antibiotics

Question 44

What is healing by first intention?

Answer 44

1. Edges of incision are brought together using stitches? 2. The incision wound fills up with blood and a thrombus forms 3. Exudation of fibrinogen causes the formation of weak fibrin. 4. Epidermal growth, and collagen synthesis leads to a strong collagenous joint. 5. Epidermis grows over the top.

Question 45

What is healing by second intention?

Answer 45

When there is a gap or whole in the skin and there is tissue loss. 1. small blood vessels move in from the edges of the gap 2. fibroblasts enter the site of trauma and make collagen - granulation tissue 3. fibroblasts organise tissue to form organised collagen fibrils 4. early thrombus scar forms 5. Epidermis grows over the top and leaves a scar.

Question 46

What are the constituents of a thrombus?

Answer 46

Platelets. Red blood cells, fibrin.

Question 47

What are the stages of thrombosis?

Answer 47

Vasospasm Platelet aggregation - VWF binds exposed collagen and platletes bind to this via GP1b. Then platelets aggregate by binding to each other through GP2a/3b Clotting cascade.

Question 48

What clotting facotrs make up the intrinsic, extrinsic and common coagulation cascade?

Answer 48

Intrinsic - 12, 11, 9, 8 Extrinsic - 3, 7 Common - 10 , 5, 2, 1

Question 49

What is the Role of platelets?

Answer 49

No nucleus, derived from megakaryocytes Contain alpha granules and dense granules Alpha granules are involved in platelet adhesion, e.g. fibrinogen Dense granules cause platelets to aggregate, e.g. ADP Platelets are activated, releasing their granules when they come into contact with collagen If this happens within an intact vessel, a thrombus is formed

Question 50

What stimulates platelet aggregation?

Answer 50

Endothelial damage changes localised blood flow from laminar to turbulent. Platelets come into contact with the endothelium and stick.

Question 51

What are the different types of thrombosis and what causes them?

Answer 51

Arterial thrombosis - atherogenesis Venous thrombosis - venous stasis

Question 52

How would you treat an arterial and venous thrombosis?

Answer 52

Arterial thrombosis - Antiplatelets Venous Thrombosis - Anticoagulants

Question 53

What are the clinical features of an arterial and venous thrombus?

Answer 53

Arterial thrombi: Loss of pulse distal to thrombus Area becomes cold, pale and painful Possible gangrene Venous thrombi: Tender Area becomes reddened and swollen

Question 54

What are the fates of a thrombosis?

Answer 54

Resolution - thrombus degrades and returns to normal Organisation - Leaves scar tissue behind Embolism - fragments of thrombi break off and get lodged in the circulation

Question 55

Define embolism.

Answer 55

A solid mass in the blood vessel which causes a blockage to the vasculature.

Question 56

What happens to an embolus if it enters the venous system?

Answer 56

- Filtered by the lungs - Travels through the vena cava, though the right hand side of the heart and lodge somewhere in the lungs depending on size - Blood vessels in the lung split down to capillary size so act as a sieve

Question 57

What happens to an embolus if it enters the arterial system?

Answer 57

It will travel anywhere downstream of its entry point

Question 58

Where may an infarct have a reduced impact?

Answer 58

on areas with a dual blood supply Brain, Liver Lungs

Question 59

what is an atheroma?

Answer 59

Focal thickening of the tunica intima arteries produced through the movement of ldls from the lumen.

Question 60

How is an atheroma formed?

Answer 60

The ldls caused a cascade of events which, mediated through inflammatory response and smooth muscle cells proliferation leads to the development of obstructive fibrolipid plaque.

Question 61

What is atherosclerosis?

Answer 61

Atheromas are plaque build-ups which obstruct that flow of blood. Atherosclerosis is the condition caused by atheromas, marked by arteries narrowed with and hardened by plaque causing CV complications, such as angina, myocardial/ cerebral infarction

Question 62

What is a foam cell?

Answer 62

Where a macrophage has phagocytosed LDL

Question 63

What is an atherosclerotic plaque made up of?

Answer 63

Fibrous tissue Lipid component - Cholesterol Lymphocytes FOAM cells

Question 64

What are the stages of atherosclerotic plaque formation?

Answer 64

1. Endothelial cell dysfunction - Lots of cholesterol damages wall - Endothelial cells directly injured 2. High levels of LDL in the blood - Can freely pass in + out of the wall - At high concentration LDLs accumulate in the arterial wall and undergo oxidation 3. Oxidised LDLs active the endothelial cells to: - Release cytokines and growth factors - Express adhesion molecule for **leukocytes** - Attract macrophages + T helper cells - Take up LDLs 4. Macrophages - Engluf oxidised LDLs to form foam cells (inflammatory response) 5. Foam cells promote migration of smooth muscle cells from tunica media to tunica intima - Increased population of smooth muscle cells leads to the increased sythesis of collagen (VIII) → hardened fibrous cap 6. When foam cells die their lipid content is released, causing the formation of a collagenous lipid plaque 7. Plaque occludes the lumen → leads to angina 8. Eventually the plaque ruptures → leads to thrombosis and complete occusion of the vessel lumen

Question 65

How does Atherosclerosis compare in a high and low-pressure vessel?

Answer 65

Atherosclerosis is never present in low pressure systems (pulmonary circulation) -but will form in high pressure vessels such as the systemic circulation

Question 66

Name some system specific complications of atherosclerosis.

Answer 66

- Obstruction/ occlusion of arteries in the head and neck = cerebral infarction - Obstruction/ occlusion of coronary artery = myocardial infarction - Obstruction/ occlusion of artery in the limbs = peripheral vascular disease or gangrene - Obstruction/ occlusion og renal arteries = increased renin release → increased blood pressure - Atherosclerosis in the aorta can cause an aortic aneurysm, a result of excessive dilation of the aorta to the point that it rupture. Results in sudden death

Question 67

why does aspirin help a patient if they have atherosclerosis?

Answer 67

Aspirin inhibits platelet aggregation, therefore reducing plaque formation.

Question 68

What are the risk factors for atherosclerosis?

Answer 68

Age gender FHx smoking sedentary lifestyle High cholesterol Hyperlipidaemia Hypertension Diabetes

Question 69

Define apoptosis

Answer 69

Non inflammatory programmed cell controlled death.

Question 70

What are the steps of apoptosis?

Answer 70

Pyknosis - nucleus condenses Blebs form - cell membrane becomes irregular Apoptotic bodies form cell membrane breaks off into fragments for easy phagocytosis

Question 71

What are the mediators of apoptosis?

Answer 71

Caspases

Question 72

What regulates the activity of caspases?

Answer 72

Intrinsic: Bcl2 family of enzymes: Bcl2 - inhibits apoptosis Bax - promotes apoptosis Extrinsic: Fas Binding of Fas ligand to the fas receptor induces apoptosis

Question 73

What is necrosis?

Answer 73

Inflammatory unprogrammed traumatic cell death that induces inflammation and repair.

Question 74

What are the different types of necrosis?

Answer 74

Coagulative necrosis: Most common type Can occur in most organs Cause by ischaemia Liquefactive necrosis: Occurs in the brain due to its lack of substantial supporting stroma Caseous necrosis: Causes a ‘cheese’ pattern TB is characterized by this form of necrosis Gangrene: Necrosis with rotting of the tissue Affected tissue appears black due to deposition of iron sulphide (from degraded haemoglobin)

Question 75

Give 3 differences between apoptosis and necrosis.

Answer 75

Apoptosis is programmed cell death whereas necrosis is unprogrammed. Apoptosis tends to effect only a single cell whereas necrosis effects a large number of cells. Apoptosis is often in response to DNA damage. Necrosis is triggered by an adverse event e.g. frost bite.

Question 76

Define genetic disease.

Answer 76

A genetic disease is one that occurs primarily from a genetic abnormality.

Question 77

Define congenital disease.

Answer 77

A disease which is present at birth.

Question 78

Define inherited disease.

Answer 78

Caused by inherited genetic abnormality, it may not manifest itself until later life.

Question 79

Define an acquired disease.

Answer 79

Caused by non genetic environmental factors that usually occurs after birth.

Question 80

Define atrophy.

Answer 80

Decrease in tissue size caused by the decreased in number of constituent cells or a decrease in their size.

Question 81

Define hypertrophy.

Answer 81

Increase in tissue size caused by an increase in the size of the constituent cells.

Question 82

Define hyperplasia.

Answer 82

Increase in tissue size caused by an increase in the number of the constituent cells.

Question 83

Define metaplasia.

Answer 83

Change in differentiation of a cell from one fully differentiated type to a different fully differentiated type.

Question 84

Define dysplaysia.

Answer 84

Morphological changes seen in cells in the progression to becoming cancer.

Question 85

Define carcinogenesis

Answer 85

The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations This is a multistep process

Question 86

What is a carcinogen?

Answer 86

A mutagenic agent known to cause cancer

Question 87

Define carcinogenic?

Answer 87

Cancer causing

Question 88

Define Oncogenic?

Answer 88

Tumour causing

Question 89

Define oncogenesis?

Answer 89

The process by which normal cells transform into neoplastic cells

Question 90

What is a neoplasm?

Answer 90

An autonomous abnormal persistent new growth that continues to grow after the initial growth stimulus has been removed.

Question 91

What can neoplasms arise from?

Answer 91

They can only arise from nucleated cells (eg. not RBCs but could arise from their precursors)

Question 92

What is a tumour?

Answer 92

Any abnormal swelling

Question 93

What percentage of cancer risk is environmental?

Answer 93

85%

Question 94

What host risk factors will increase the risk of cancer?

Answer 94

Race Diet Sex Age Inherited predisposition premalignant conditions Transplacental exposure

Question 95

Give examples of how race can affect cancer risk?

Answer 95

Oral cancer increase risk in SE asia releated to chewing betal nut and reverse smoking Skin cancer risk is decreased in people with black skin as an increase in melanin is protective against UV.

Question 96

Give some examples of inherited predispositions that will increase cancer risk?

Answer 96

Familial polyposis coli - increase risk of bowel cancer

Question 97

Give some examples of premalignant conditions that will increase the risk of cancer?

Answer 97

Colonic polyps Ulcerative colitis Undescended Testis

Question 98

Give an example of how transplacental exposure increased the risk of cancer

Answer 98

The daughters of moths who took diethylstilboestrol for morning sickness had and increased risk of developing vaginal cancer

Question 99

Name 5 different categories of carcinogens?

Answer 99

Viral Chemical Ionising and non-ionising radiation Hormones, parasites and mycotoxins Miscellaneous

Question 100

Give some examples of viruses that cause cancer?

Answer 100

Hepatitis B anda C - HCC HHV8 (human herpes virus 8) - kaposi sarcoma HPV - Squamous cell carcinoma EBV - Burkitts Lymphoma HIV - cerebral lymphoma

Question 101

How can hormones cause cancer?

Answer 101

increase in oestrogen can cause endometrial cancer

Question 102

What parasite can cause cancer?

Answer 102

Shistosoma causes bladder cancer

Question 103

What miscellaneous materials can cause cancer?

Answer 103

Asbestos Metals - arsenic

Question 104

What type of cancer do polyaromatic hydrocarbons cause and what exposes people to these?

Answer 104

Lung and skin cancer Smoking and mineral oils

Question 105

What cancer do aromatic amines cause?

Answer 105

bladder cancer People who work with dye or rubber

Question 106

What cancer do nitrosamine cause?

Answer 106

Gut cancer

Question 107

What type of cancer do alkylating agents cause?

Answer 107

Leukaemias

Question 108

Define Neoplasia?

Answer 108

A lesion resulting from new and abnormal tissue growth which persists independent of its initiating stimulus.

Question 109

What are the two types of neoplasia?

Answer 109

Benign and malignant

Question 110

How can neoplasias be classified?

Answer 110

By behaviour By histogenesis

Question 111

What is a benign tumour?

Answer 111

Slow growing - low mitotic activity Well circimuscribed - no invasion to surrounding tissue Resemble cell origin - rarely necrose or ulcerate Exophytic - grow outwards

Question 112

what are some long-term effects of benign tumours?

Answer 112

Pressure on adjacent tissues Obstruction of ducts/hollow organs produce hormones Can be pre-malignant Anxiety

Question 113

What are the features of a malignant tumour?

Answer 113

Fast growing - high mitotic activity and division rate Poorly defined, irregular infiltrative borders - invasion of surrounding tissues (metastasis) Variable resemblance to cell of origin - commonly necrosing or ulcerating Endophytic growth - grow inwards.

Question 114

What are some complications of malignant tumours?

Answer 114

Pressure on adjacent structures form secondary tumours Obstructory very painful blood loss

Question 115

What is the structure of a neoplasm?

Answer 115

Neoplastic cell Stroma

Question 116

What are neoplastic cells?

Answer 116

Always derived from nucleatedcells Usually monoclonal Growth pattern related to parent cell Synthetic activity related to parent cell - eg. hormone producing.

Question 117

What is the stroma of a neoplasm?

Answer 117

Supported by connective tissue framework that provides mechanical and nutritional support. usually blood vessels.

Question 118

What factors promote angiogenesis?

Answer 118

VEGF Fibrobalst growth factor

Question 119

What is the behavioural classification of neoplasms?

Answer 119

Benign Borderline - defy precise classification Malignant

Question 120

What are the main histological classifications of tumours?

Answer 120

epithelial Connective tissue Lymphoid Haematopoietic

Question 121

What cancer does not have a stroma?

Answer 121

Leukaemia

Question 122

What is a benign non-glandular eplithelial neoplasm called?

Answer 122

Papilloma

Question 123

What is a benign glandular epithelial neoplasm called?

Answer 123

Adenoma

Question 124

What is a malignant epithelial neoplasm?

Answer 124

Carcinoma

Question 125

What is a carcinoma?

Answer 125

A malignant epithelial neoplasm

Question 126

What is the suffix for malignant connective tissue neoplasms?

Answer 126

Sarcoma

Question 127

What is a benign neoplasm of adipocytes?

Answer 127

Lipoma

Question 128

What is a benign neoplasm of adipocytes?

Answer 128

Lipoma

Question 129

What is a benign neoplasm of Cartilage?

Answer 129

Chondroma

Question 130

What is a benign neoplasm of bone

Answer 130

Osteoma

Question 131

What is a benign neoplasm of vasculature?

Answer 131

Angioma

Question 132

What is a benign neoplasm of striated muscle

Answer 132

Rhabdomyoma

Question 133

What is a benign neoplasm of smooth muscle

Answer 133

Leiomyoma

Question 134

What is a benign neoplasm of nerves

Answer 134

Neuroma

Question 135

What is a well-differentiated tumour?

Answer 135

A tumour that closely resembles normal tissue. These have a lower grade and tend to have a better prognosis.

Question 136

If a neoplasm doesnt resemble normal tissue what is it said to be?

Answer 136

Poorly differentiated higher grade and would carry a worse prognosis

Question 137

What does the term anaplastic mean?

Answer 137

When the cell type of origin is unknown the tumour is anaplastic

Question 138

What is a melanoma?

Answer 138

A malignant neoplasm of melanocytes

Question 139

What is a mesothelioma?

Answer 139

A malignant neoplasm of mesothelial cells

Question 140

What is a lymphoma?

Answer 140

A malignant neoplasm of lymphoid cells

Question 141

What is burkitts lymphoma?

Answer 141

A B cell malignancy caused by EBV

Question 142

What is kaposi sarcoma?

Answer 142

A vascular endothelial malignancy caused by Human herpes virus 8 and related to HIV

Question 143

What is ewings sarcoma?

Answer 143

A bone malignancy

Question 144

is a teratoma?

Answer 144

A cancer of all 3 embryonic germ layers

Question 145

What is a blastoma?

Answer 145

A tumour of an embryo

Question 146

What is the pathway of metastasis?

Answer 146

1. Detachment from primary tumour 2. Invasion of surrounding connective tissue 3. Intravasation into the lumen of blood vessels 4. Evasion of host defence 5. Adherence to blood vessel wall 6. Extravasation to a distant site 7. Proliferation of cells in new site/environment

Question 147

What are the different methods of spread of a metastasis?

Answer 147

Haematogenous - via blood Lymphatic - secondary formation in the lymph nodes Transcolemic - via exudative fluid accumulation. spread through pleural, pericardial and peritoneal effusions. along nerves Iatrogenic

Question 148

What are the characteristics of a neoplastic cell?

Answer 148

Autocrine growth stimulation - overexpression of GF and mutations of tumour suppressor genes (p53) Evasion of apoptosis Telomerase - prevents telomeres shortening with each replication Sustained angiogenesis - provides nutritional support.

Question 149

What cancers commonly spread to bone?

Answer 149

BLT KP Bladder Lung Thyroid Kidney Prostate

Question 150

What is a neoplasm in situ?

Answer 150

When a neoplasm has proliferated but has not broken through the basement membrane to other tissues

Question 151

When is a cancer considered to be invasive?

Answer 151

When it has breached its own tissue type into another area

Question 152

What is a micro-invasive carcinoma?

Answer 152

A carcinoma that has only just broken through the basement membrane

Question 153

What is invasion of a cancer dependent on?

Answer 153

Decreased cellular adhesion abnormal increased cellular motility Production of lytic enzymes to breakdown surrounding tissue

Question 154

Define metastasis

Answer 154

The process by which a malignant neoplasm spreads from its primary site to produce secondary neoplasms at distant sites.

Question 155

How do tumours invade surrounding tissues?

Answer 155

Proteases break down tissue surrounding neoplasm tumour cell derived motility factors allow it to invade

Question 156

How do tumours enter and exit blood vessels (intravasion)

Answer 156

Collagenases break down the blood vessel wall and allow the neoplasm to enter Adhesion receptors allow the tumour to stick to a specific area. collagenases again break the BV wall so the tumour can exit

Question 157

How do neoplasms evade host defenses?

Answer 157

Aggregation with platelets Shedding of surface antigens Adhesion to other tumour cells

Question 158

Why do malignant tumours often have a necrotic centre?

Answer 158

If neoplasms become too big and are too fast growing then they will outgrow the blood supply and so the centre of the tumour does not get enough nutrition and hence it will necrose.

Question 159

What are some angiogenesis inhibitors?

Answer 159

Angiostatin Endostatin Vasculostatin

Question 160

Describe the process for metastasis to the lung?

Answer 160

- If the carcinoma enters the venous system, it will travel through the blood vessels to the vena cava, right atrium, right ventricle and onto the pulmonary circulation - From there, as the lung blood vessels act as a sieve, it will get stuck at some point (same process as thrombosis) - If this new neoplasm site then grows into the venous system of the pulmonary circulation, it can travel anywhere in the body

Question 161

Describe the process for metastasis to the liver?

Answer 161

- Liver receives 100% of blood from colorectal (remember first pass metabolism) - Neoplasm may break off from digestive system and travel in the blood stream to the liver through the portal venous system - Again, the liver blood vessels act as a sieve as they go down to capillary level - Neoplasm will imbed at some point in the vasculature tree.

Question 162

What cancers are screened for in the UK?

Answer 162

Cervical Breast Colorectal

Question 163

Eosinophillic granulomas would be an indication of what?

Answer 163

Parasitic infection

Question 164

What cells are polymorphonuclear leukocytes?

Answer 164

Neutrophils Eosinophils Basophils

Question 165

What cells are the mononuclear leukocytes?

Answer 165

Monocytes T cells B cells

Question 166

Where is complement secreted from?

Answer 166

The liver

Question 167

What are the 3 modes of action for complement?

Answer 167

Direct lysis - MAC Chemotaxis - attract more leukocytes Opsonisation - coat invading organisms

Question 168

How can antibodies circulate in the blood

Answer 168

Bound to B cells Free in plasma

Question 169

Which part of the strucutre of an antibody is responsible for antigen binding?

Answer 169

FAB regions Variable in sequence Bind to specific antigens

Question 170

What part of the structure of an antibody is responsible for antigen elimination?

Answer 170

Fc region Constant sequence binds to complement, Fc receptors on phagocytes or NK cells

Question 171

What are the 5 classes of antibodies?

Answer 171

IgG IgM IgA IgE IgD

Question 172

What is the structure, where it is found and its function for the IgG class of antibody?

Answer 172

Monomer - 2 heavy and 2 light chains Most abundant in serum and tissues Main Ab involved in adaptive immune response for secondary and memory responses. Can cross the placenta

Question 173

What is the structure, where it is found and its function for the IgM class of antibody?

Answer 173

Pentamer - dependent on J chain Mainly found in the blood as they are too big to cross the vascular endothelium Initial contact with Ag for immune response High affinity low specificity Ab

Question 174

What is the structure, where it is found and its function for the IgA class of antibody?

Answer 174

Dimer Found at mucosal surfaces (secretory Ig) also found in serum First line of defence

Question 175

What is the structure, where it is found and its function for the IgE class of antibody?

Answer 175

50% found in blood. the rest bound to mast cells or basophils Responsible for hypersenitivity reactions and anaphylaxis. Important in parasitic infections

Question 176

What is the structure, where it is found and its function for the IgD class of antibody?

Answer 176

Found on mature B cells No effector functions identified

Question 177

What are the different mechanisms of action of antibodies?

Answer 177

Agglutination - bind together in a clump Neutralisation - antibodies cover the toxic sites of Ag to stop it binding Lysis - Some antibodies can attack the cell membrane directly to rupture it. Activate the classical complement pathway

Question 178

What are cytokines?

Answer 178

Proteins secreted by immune and non-immune cells

Question 179

What do interferons do?

Answer 179

Induce a stateof viral resistance in uninfected cells and limit the spread of viral infection

Question 180

What are the 3 types of interferons and which cells secrete them?

Answer 180

IFN alpha and beta produced by virus-infected cells IFN gamma Produced by activated Th1 cells and this activates Macrophages

Question 181

What do interleukins do?

Answer 181

Can be proinflammatory or anti-inflammatory Cause cells to divide, differentiate and secrete factors

Question 182

What do colony stimulating factors do?

Answer 182

Direct the division and differentiation of bone marrow stem cells

Question 183

what do tumour necrosis factors do?

Answer 183

TNF alpha and beta Mediate inflammation and cytotoxic reactions

Question 184

What are chemokines?

Answer 184

proteins that direct the movement of cells from the blood stream to the tissues.

Question 185

What is innate immunity

Answer 185

Primitive non-specific rapid response no memory is used or produced Typically involves neutrophils and macrophages and complement activation along with physical and chemical barriers

Question 186

What physical and chemical barriers are involved in the innate immune response

Answer 186

Physical barriers - skin, mucus, cilia Chemical barriers - lysozymes in tears, stomach acid

Question 187

What are pattern recognition receptors?

Answer 187

Receptors on immune cells that detect the presence of PAMPs

Question 188

PAMPS and DAMPS?

Answer 188

Pattern-associated molecular patterns Damage associated molecular patterns

Question 189

What are Toll-like receptors?

Answer 189

A type of PRR that recognise structurally conserved molecules derived from microbes.

Question 190

What is the TLR responsible for detecting Gram +tve Bacteria and Lipoteichoic acid/peptidoglycan?

Answer 190

TLR 2

Question 191

What is the TLR Responsible for detecting Gram Negative Bacteria and Lipopolysaccharide (LPS)

Answer 191

TLR-4

Question 192

What components make up the innate immunity?

Answer 192

Physical and chemical barriers Phagocytic cells -neutrophils, macrophages Blood proteins - complement, acute phase proteins.

Question 193

How can physical barriers be breached for allowing pathogens to entre the body?

Answer 193

Tissue trauma Infection

Question 194

What are the steps to the whole inflammatory response?

Answer 194

- Bleeding - acts to flush bacteria out of the site - Coagulation - plugs the site to stop further antigens entering the system - Acute inflammation - leukocyte recruitment - Kill pathogens, neutralise toxins, limit pathogen spread - Phagocytosis - clear debris - Proliferation of cells to repair damage - Remove thrombus - remodel extracellular matrix - Re-establish normal function/structure of the tissue

Question 195

What are 3 features of inflammation?

Answer 195

Increased blood supply Increased Vascular permeability Increased leukocyte extravasation

Question 196

What cells detect presence of antigens in the blood?

Answer 196

Monocytes neutrophils

Question 197

What cells detect the presence of antigens in the tissues?

Answer 197

Macrophages DCs

Question 198

What are the 3 activation pathways for the complement system?

Answer 198

Classical - antibody binds to microbe Alternative - C' binds to microbe Lectin - activated by mannose-binding lectin bound to a microbe.

Question 199

What are the 3 mechanisms of action of complement?

Answer 199

Direct lysis - Membrane attack complex (MAC) Chemotaxis - C3a and C5a Opsonisation - coat microbes to make them easier to phagocytose (C3b)

Question 200

Describe the process of Extravasation of neutrophils in acute inflammation

Answer 200

1. E-selectin (an adhesion molecule on the capillary endothelium), is activated by IL-1 and TNF-α from damaged cells and binds to the glycoprotein CD15 on neutrophils in blood. 2. This causes neutrophils in the blood to slow down and roll along the endothelium lining. 3. ICAM-1 on endothelium (induced by LPS, IL-1, TNF-α) binds to integrin on neutrophil; the neutrophil stops. 4. Diapedesis: neutrophil squeezes through endothelium (holes caused by C3a, C5a, chemokines, histamines, prostaglandins, leukotrienes (causing smooth muscle contractions in the bronchioles))

Question 201

What are 3 ways phagocytosis can be initiated?

Answer 201

Antibodies bound to antigens on microbes C3b opsonised on microbes binds to complement receptor Mannose receptor binds to carbohydrates on bacterial wall

Question 202

What are the main steps in phagocytosis?

Answer 202

Binding Engulfment (phagosome) Phagolysosome bacterial killing clear debris

Question 203

What are the 2 pathways that neutrophils and macrophages use to kill microbes?

Answer 203

Oxygen dependent Oxygen independent

Question 204

What is oxygen dependent killing of microbes?

Answer 204

Uses ROI (reactive oxygen intermediates) Superoxide ions are converted to H2O2 and then to a hydroxide free radical

Question 205

What is the oxygen independent mechanism of killing microbes?

Answer 205

Enzymes - lysozymes proteins - defensins pH TNF

Question 206

What are the 3 outcomes of phagocytosis?

Answer 206

Debris gets secreted by the phagocytic cell cell components are converted to energy Antigens are presented on cell surface via MHC II

Question 207

What cells are APCs (antigen presenting cells)?

Answer 207

Dendritic cells Macrophages B cells

Question 208

What is the function of a neutrophil?

Answer 208

70% of all WBC key mediator of acute inflammation Follow chemotaxic gradients of IL-8 (CXCL8) Will eat and kill microbes

Question 209

What is the function of macrophages?

Answer 209

Activated by IFN-y from Th1 Will phagocytes microbes and debris to remove them. Secrete TNF-a, IL-1 and IL-2 Can act as APCs Can either be circulating or resident to tissues

Question 210

What is the function of eosinophils?

Answer 210

Contain MBP Often in response to a parasitic infection.

Question 211

What is the function of Basophils and mast cells?

Answer 211

IgE binding and upon re-exposure IgE crosslinking via FceR1 Degranulate to release histamine in Type 1 hypersensitivity reactions, Mast cells are fixed at tissues Basophils circulate in the blood.

Question 212

What is the function of a natural killer cell?

Answer 212

NKs cells are a key role in viral cell killing CD16 Fc receptors When activated they release perforin to kill infected cells or malignant cells.

Question 213

What is the function of a dendritic cell?

Answer 213

These cells act as APCs and provide an interface between the innate and adaptive immune system.

Question 214

What are the 3 conditions that must be met to enable antigen presenting to function?

Answer 214

Primary receptor binding co-stimulation molecules Cytokine release

Question 215

What does TLR 1 detect?

Answer 215

Gram positive bacteria

Question 216

What does TLR 2 detect?

Answer 216

Gram positive bacteria such as lipopeptides, lipoteichoic acid

Question 217

What does TLR 3 detect?

Answer 217

Endogenous viral infection and tissue necrosis Responds to ds RNA

Question 218

What does TLR 4 detect?

Answer 218

Gram Netagive Bacteria detects endotoxin such as LPS

Question 219

What does TLR 5 detect?

Answer 219

Flagellin

Question 220

What does TLR 7 detect?

Answer 220

Single stranded RNA

Question 221

What does TLR 8 detect?

Answer 221

Viral and bacterial pathogens Important for detecting pyogenic bacteria

Question 222

What does TLR 9 detect?

Answer 222

Non-methylated DNA

Question 223

What is the adaptive immune response?

Answer 223

Specific and slower response Needs to be activated first but then the second exposure has a much larger response Provides immunological memory Killing is usually antibody-mediated Involves T and B lymphocytes.

Question 224

Why do we need an adaptive immune response?

Answer 224

Microbes can evade innate immune responses Intracellular viruses and bacteria hide from the innate immune system Memory to specific antigens allows a faster response upon subsequent exposure to clear infection more effectively.

Question 225

Which part of the immune system deals with intracellular and extracellular microbe

Answer 225

B cell (humoral - antibody) - extracellular T cell (cell-mediated) - Intracellular

Question 226

To recognise self from non-self what is required?

Answer 226

MHC proteins

Question 227

What do T lymphocytes respond to?

Answer 227

Intracellular presented antigens

Question 228

Where do T cells mature?

Answer 228

In the thymus

Question 229

Where do B cells mature?

Answer 229

In the bone marrow

Question 230

What is Thymic central tolerance?

Answer 230

Where T cells are tested to see if they recognise self antigens . if they produce an immune response they they are selected against and killed by T regulatory (Treg) cells

Question 231

What is the common T cell marker? What is the Marker of T cell activation?

Answer 231

CD3 CD25

Question 232

Where is MHC I found?

Answer 232

On all nucleated cells

Question 233

Where is MHC II found?

Answer 233

On APCs Only

Question 234

For intrinsic antigens (i.e. virus): which MHC class presents them, where is the MHC expressed, which T cells bind, what is the function of this T cell?

Answer 234

- MHC Class I - All cells express MHC Class I (except for red blood cells) (every**one** expresses MHC Class **one** - Tcytotoxic (CD8) cells - Kill infected cell with intracellular pathogen directly

Question 235

For extrinsic pathogens (i.e. extracellular pathogen): which MHC class presents them, where is the MHC expressed, which T cells bind, what is the function of this T cell?

Answer 235

- MHC Class II - Only antigen presenting cells express MHC Class II - Th (CD4) cells - Help B cells make antibodies to extracellular pathogen and can help directly kill pathogen

Question 236

What is required for full T cell activation?

Answer 236

Co-stimulatory molecules CD28 on the T cell binds to CD80/CD86 on the APC to fully activate the T cell

Question 237

What is secreted from an activated T cell?

Answer 237

IL2 binds to the T cell receptor (autocrine)

Question 238

What does T cell activation lead to?

Answer 238

Division Differentiation (to CD4 or CD8) Effector functions Memory

Question 239

What determines whether a T cell will differentiate into a Th1 or Th2 CD4 T cell?

Answer 239

Levels of IL-12 High IL-12 = Th1 Low IL-12 = Th2

Question 240

What is the function of a Th1 CD4 T cell?

Answer 240

Travel to secondary lymphoid tissue Secrete IFN gamma to help kill intracellular antigens

Question 241

What is the function of a Th2 CD4 T-cell?

Answer 241

Binds to a B cell presenting an antigen and stimulates B cell divide (clonal expansion) and differentiation Secretes IL-4 to stimulate differentiation

Question 242

What is the function of a Cytotoxic CD8 T cell?

Answer 242

Kills cell directly. Formation of perforin and granulysin which induce apoptosis in infected cells, Secrete IFN gamma to inhibit viral invasion of neighboring cells to prevent viral spread Secretion of chemokines to recruit more immune cells. Express Fas-ligand to initiate apoptosis

Question 243

Which membrane bound antibodies do B cells Express?

Answer 243

IgM or IgD monomers

Question 244

How many types of antibodies can an individual B cell make?

Answer 244

1 Antibody specific to 1 antigen.

Question 245

What happens if a B cell recognises self?

Answer 245

The B cell is killed in the bone marrow

Question 246

How do B cells act as APCs?

Answer 246

Phagocytose the pathogen Present the epitope on MHC II Tcell binds to MHC II lots of costimulatory molecules required such as CD80 and CD86

Question 247

How is a B cell activated?

Answer 247

Th2 T cell binds to antigen presented via MHC class II Co-stimulatory molecules bind CD80/CD86 T cell releases IL-4 and IL6 IL-4 induces B cell proliferation (clonal expansion) IL-6 induces B cell differentiation into a plasma cell or memory cell

Question 248

What is the Mature B cell marker?

Answer 248

CD20

Question 249

What is B cell somatic hypermutation?

Answer 249

A cellular mechanism where the immune system adapts to new foreign elements that confront it

Question 250

What is B cell class switching?

Answer 250

Where an activated B cell changes its Ab production from IgM to either IgE, IgA or IgG depending on the functional requirements

Question 251

What causes Somatic hypermutation?

Answer 251

AID Activation induced Cysteine deaminase

Question 252

What interleukin promotes class switching from IgM to IgA and IgE?

Answer 252

IL-4

Question 253

What chromosome is the MHC protein found on?

Answer 253

Chromosome 6

Question 254

What is the role of Tregs?

Answer 254

Regulatory T cells These are important in immune tolerance and ensuring T cells are not autoreactive

Question 255

What interleukin stimulates a naive T cell to become a Treg?

Answer 255

TGF-b and IL-2 Tregs secrete IL-10 which is anti-inflammatory

Question 256

What Interleukin stimulates a naive T cell to become a Th17?

Answer 256

IL-17

Question 257

What is passive immunisation?

Answer 257

The transfer of pre-formed antibodies

Question 258

What are the two types of passive immunisation?

Answer 258

Natural - Transfer of preformed maternal antibodies across the placenta or through breast milk Artificial - Treatment with pooled normal human IgG (immunoserum)

Question 259

What would artificial immunisation be effective against?

Answer 259

Individuals with immunocompromisation No time for active immunisation - against pathogens with a short incubation time Anti-toxins or anti-venoms

Question 260

What are the disadvantages of passive immunisation?

Answer 260

Does not provide immunological memory - no long term protection IgG is cleared form the circulation

Question 261

How do toxins act on a nerve cell to produce toxic effects?

Answer 261

Toxin prevents fusion of vesicles at the synapse so the neurotransmitters cannot get into the synapse

Question 262

How does tetanus toxin act on the synapse?

Answer 262

Tetanus toxin inhibits the release of inhibitory neurotransmitters GABA and Glycine which prevents muscle relation It causes muscle contraction and spasticity

Question 263

How does Botulinum toxin act on the synapse?

Answer 263

Botulinum vesicles contain ACh which prevents muscle contraction It causes muscle relaxation and flaccidity

Question 264

What is active immunisation?

Answer 264

Manipulation of the immune system to generate a persistent protective response against pathogens by mimicking natural infection

Question 265

What is the difference between innoculation and active immunisation?

Answer 265

Inoculation refers to the introduction of viable microorganisms into the individual to evoke an immune response

Question 266

What are the advantages of active immunisation?

Answer 266

- Mobilises immune system to generate immunological memory - B and/or T cell memory - Learned immunological behaviour → faster response

Question 267

What are the stages of active immunisation?

Answer 267

Engage innate immune system Mimicking agent elicits danger signals that TLRs etc Activation of specialist APCs Engage the adaptive immune system to generate memory T and B cells

Question 268

What are the primary and secondary responses of active immunisation?

Answer 268

Initial response: Relies on innate system IgM predominates Low affinity Secondary response: Rapid and large High affinity IgG Somatic hypermutation

Question 269

Give an example of an artificial active immunity

Answer 269

Vaccinations

Question 270

What are the different antigen options used in vaccines?

Answer 270

Whole organism - live attenuated or killed/inactived Subunit - toxoids, antigenic extracts, recombinant protein Peptides DNA/RNA Engineered virus

Question 271

Give examples of a whole organism vaccination

Answer 271

Live attenuated - TB, Typhoid Killed/inactivated - Influenza, Hep A

Question 272

What are the advantages and disadvantages of Live attenuated vaccinations?

Answer 272

Adv: Activates full natural immune response Produces memory T and B cells Long lasting and comprehensive protection Often only requires a single immunisation Disadv: Immunocompromised at risk of infection Complications could occur Can lead to outbreaks in areas with poor sanitation Require specific storage methods such as freezing

Question 273

What are the advantages and disadvantages of dead/inactivated Vaccinations?

Answer 273

Adv: No risk of infection Storage is less important Strong immune response is still possible Disadv: Tends to activate humoral response without T cell involvement Immune response is weaker than live attenuated Booster vaccinations required as a lack of memory is produced

Question 274

What is an adjuvant

Answer 274

Any substance added to a vaccine to stimulate an enhanced immune response

Question 275

Give an example of an adjuvant and explain how it functions

Answer 275

Aluminium salts: Activate macrophages and lymphocytes help APCs absorb antigen extend the presence of antigen in the blood potentiate opsonised phagocytosis

Question 276

What cells are involved in the cell mediated immune repsonse?

Answer 276

Neutrophils and monocytes Lymphocytes (T and B cells)

Question 277

What is involved in the non-cellular humoral immune response?

Answer 277

Immunoglobulins (antibodies) complement Surfactant proteins

Question 278

What immunoglobulin is made at the beggining of an infection?

Answer 278

IgM

Question 279

What immunoglobulin is in high abundance upon second exposures?

Answer 279

IgG specific antibodies

Question 280

What immunoglobulin is often involved with an allergic reaction?

Answer 280

IgE

Question 281

What are the common features of anaphylaxis?

Answer 281

Rapid onset Blotchy rash Swelling of face and lips Hypotension Wheeze Cardiac arrest if severe

Question 282

What drugs can commonly cause hypersensitivity reactions?

Answer 282

Amiodarone Bleomycin Methotrexate NSAIDs Nitrofurantoin Novel Ig treatments

Question 283

Describe a Type 1 hypersensitivity Reaction

Answer 283

> 1️⃣ B-cells are stimulated (by CD4 and TH2 cells) to produce IgE antibodies specific to an antigen > 2️⃣ IgE binds to mast cells and basophils via FcεRI - this is known as sensitisation. > 3️⃣ Later exposure to the same allergen causes IgE cross-linking, resulting in anaphylactic degranulation of mast cells, therefore the release of inflammatory mediators - notably histamine, as well as leukotrine, prostaglandins, IL-4 ,IL-13, TNFa > 4️⃣ Leads to acute anaphylaxis.

Question 284

Give example of type 1 hypersensitivity reactions

Answer 284

Allergic Rhinitis (hayfever) asthma Nut,food and drug allergies

Question 285

What is Atopy?

Answer 285

An inherited tendency to produce an exaggerated IgE response to an antigen (hayfever, eczema, Asthma)

Question 286

How are type one hypersensitivity reactions diagnosed?

Answer 286

Skin prick tests Radioallergosorbent Tests (RASTs)

Question 287

What is the treatment for hayfever?

Answer 287

Prevent exposure Anti-histamines steroids - reduce local inflammation Desensitisation therapy - controlled, gradually increased exposure to the antigen

Question 288

What is the treatment for acute anaphylaxis

Answer 288

Adrenaline 500mg IM (intramuscularly) if necessary: Antihistamines - Chlorphenamine Cortisol - hydrocortisone

Question 289

Describe a Type 2 hypersensitivity reaction

Answer 289

Antigen-Antibody complex on cell surface IgG and IgM are directed against the self allergen. leads to cell lysis, tissue damage and loss of function through the classical complement pathway. Antibody dependent cytotoxicity.

Question 290

What can cause Type 2 hypersensitivity reactions?

Answer 290

Transplant rejection Autoimmune diseases

Question 291

Describe a Type 3 Hypersensitivity reaction?

Answer 291

Immune Complex Deposition: Occur when immune complexes have not been adequately cleared by innate immune cells IgG/IgA bind to free floating antigens giving rise to complement activation and leukocyte recruitment. Complexes are deposited in the tissue resulting in tissue damage

Question 292

Give examples of Type 3 hypersensitivity reactions?

Answer 292

Systemic Lupus Erythematosus (SLE) Post strep glomerulonephritits Rheumatoid Arthritis

Question 293

Describe a Type 4 hypersensitivity reaction?

Answer 293

> 1️⃣ CD4 and T-helper cells recognise antigens in complex with MHC class II on the surface of APCs. > 2️⃣ The APC (commonly macrophages or monocytes) secrete IL-12 which stimulates the proliferation of CD4+TH-1 cells and their release of IL-2 and INF-y > 3️⃣ IL2 and INF induce further TH-1 cytokine release. > 4️⃣ Immune response leads to the activation of; CD8 T-cells - destroy target cells on contact; macrophages - produce hydrolytic enzymes and transform into multinucleated giant cells on presentation with certain intracellular pathogens

Question 294

Give examples of Type 4 hypersensitivity reactions?

Answer 294

TB Contact dermatitis Sarcoidosis

Question 295

What is involved in the diagnosis of drug hypersensitivity reactions?

Answer 295

Lung function tests CT scans Chest X rays

Question 296

What is involved in the treatment of drug hypersensitivity reactions?

Answer 296

Withdraw offending drug Give steroids for severe respiratory failure

Question 297

What is autoimmunity?

Answer 297

Pathological response verses self antigens. Caused by faulty immune tolerance or molecular mimickry

Question 298

Give examples of organ specific Autoimmune disease?

Answer 298

T1DM - endocrine pancreas - beta cells MS - oligodendrocytes of CNS Pernicious anaemia - Parietal cells of the stomach - Loss of intrinsic factor - not Vit B12 absorption Hashimoto's Thyroiditis - Anti-TPO Ab Graves disease - TSH-R antibodies Myasthenia Gravis - Anti ACh receptor antibodies

Question 299

Give some non organ specific autoimmune diseases

Answer 299

Systemic Lupus Erythematosus Autoimmune Haemolytic Anaemia Immune Thrombocytopenic purpura Rheumatoid Arthritis

Question 300

Name different types of drug interactions

Answer 300

Synergism Antagonism Summation Potentiation

Question 301

Define synergism?

Answer 301

Interaction of 2 compounds leads to a greater combined effect (1+1>2)

Question 302

Define Antagonism

Answer 302

Interaction of 2 compounds where one may block another from working so the overall net effect is 0 (1+1=0)

Question 303

Define Summation

Answer 303

Interaction of 2 compounds with similar pharmacodynamics combine to give an increased expected effect (1+1=2)

Question 304

Define Potentiation

Answer 304

Where one compound may increase the potency of another drug without affecting its own state (1+1=1+1.5)

Question 305

What are some host risk factors for drug interactions?

Answer 305

Old age Polypharmacy Genetics Hepatic Disease Renal Disease

Question 306

What are some drug risk factors for drug interactions?

Answer 306

Drugs with a narrow therapeutic index Drugs with a steep dose response curve Drugs with a saturable metabolism

Question 307

Name some mechanisms through which drug interactions can take place?

Answer 307

Pharmacokinetic mechanism Pharmacodynamic mechanism

Question 308

What are the 2 major routes of drug administration?

Answer 308

Enteral - Gut involved (eg. oral) Parenteral - Bypasses the gut (eg. IV, IM, SC)

Question 309

Define Pharmacokinetics

Answer 309

What happens to the drug within the body

Question 310

What are the different pharmacokinetic mechanisms?

Answer 310

ADME Absorption Distribution Metabolism Excretion

Question 311

What factors affect a drugs absoprtion?

Answer 311

Gut motility Acidity Solubility Complex formation Direct action on enterocytes

Question 312

What factors affect drug distribution?

Answer 312

Protein binding Chemical properties (water soluble/lipid soluble) Blood flow to area

Question 313

What factors affect a drugs metabolism?

Answer 313

Drugs are metabolised by the liver or the kidneys Liver - hydrophobic compounds - CYP450 enzymes - Phase1/2 metabolism Induction or inhibition of CYP450 Kidney - small water-soluble compounds

Question 314

What factors affect a drugs excretion?

Answer 314

Renal factors Its pH dependent Weak bases are cleared faster if urine is acidic Weak acids are cleared faster if urine is basic (can use this to aid overdose eg. treat aspirin overdose with bicarbonate)

Question 315

How are drugs metabolised?

Answer 315

By the liver mostly Phase 1 - microsomal enzymes increase reactivity by adding groups Phase 2 - non-microsomal enzymes conjugate compounds to increase hydrophilicity

Question 316

What is CYP450 induction/inhibition and what can affect this?

Answer 316

Induction - Drug A induces CYP450 = Increased metabolism of drug B - so drug B has reduced effects Inhibition - Drug C blocks metabolism of drug D = increase free drug D in plasma - increases drug Ds effects Can be inhibited by food or drugs

Question 317

Give an example of compounds that will inhibit CPY450/enzymes?

Answer 317

Metronidazole - inhibits Alcohol Dehydrogenase - prevents ethanol metabolism - increases drunkenness

Question 318

How do Avocado and grapefruit affect drug pharmacokinetics?

Answer 318

Avocado - affects solubility - High fat content increases absorption of warfarin (anticoagulant) Grapefruit juice - Inhibits CYP3A4 which increases the bioavailability of drugs with a high first pass metabolism

Question 319

Define Pharmacodynamics

Answer 319

The effect that a drug has on the body

Question 320

What do drugs usually target? Give examples of different types?

Answer 320

PROTEINS!! Receptors Enzymes Transporters Ion Channels

Question 321

What are the different effects of a ligand?

Answer 321

Agonists Partial Agonist Antagonist - Competitive or non-competitive

Question 322

Give examples of receptor based drug interactions

Answer 322

Agonists - Alcohol + benzodiazepine at a GABA A receptor causes a summative effect Antagonists - Beta Blockers and asthma - make asthma worse

Question 323

Give examples of how signal transduction can lead to drug interactions?

Answer 323

Giving beta blockers to a diabetic At B3 receptor - alters blood glucose control At B2 receptor - suppresses hypoglycaemia So a diabetic would lose their hypoglycaemic awareness

Question 324

Define Bioavailability?

Answer 324

Amount of drug taken up into systemic circulation unaltered as a proportion of the amount administered

Question 325

How can we avoid drug interactions?

Answer 325

Prescribe rationally BNF/NICE guidelines Ward pharmacists Patient information leafles

Question 326

What are some important drug side effects to know?

Answer 326

Simvastatin - Rhabdomyolysis Warfarin - bleeding SSRIs - Serotonin syndrome NSAID + ACEi + Furosemide - renal failure

Question 327

Define a receptor?

Answer 327

A component of a cell that interacts with a specific ligand and initiates a change in biochemical events leading to ligand-observed effects

Question 328

What is the difference between a target cell and non-target cell?

Answer 328

> Target cell → contains receptors required for a specific ligand to bind and elicit a response > Non-target cell → does not contain receptors required for specific ligands to being and elicit a response

Question 329

What are the different types of receptors targeted by drugs?

Answer 329

Ligand gated ion channels G-protein coupled receptors (GPCRs) Kinase-linked receptors Cytosolic/nuclear receptors

Question 330

How do ligand gated ion channels work and give an example?

Answer 330

Ion channels are opened through the the binding of a ligand (e.g. neurotransmitter) to an orthosteric site → triggers a conformational change resulting in the conducting state. Nicotinic ACh Receptor

Question 331

How do GPCRs work?

Answer 331

1️⃣Binding of ligand to the extracellular binding domain causes the Gα-subunit to undergo a conformational change. 2️⃣Change allows Gα to bind GTP (release GDP) 3️⃣Binding of GTP causes the another conformation change which results in the separation of the G-protein into a Gα and Gβγ-subunit 4️⃣Gα and Gβγ-subunits are able to actively continue the signal transduction pathway 5️⃣Activate effector molecules to initiating signal cascades via secondary messengers Adenylate cyclase - cAMP pathway Phospholipase C - phosphatidylinositol pathway

Question 332

What are the 3 types of GPCR?

Answer 332

Gs - stimulatory - activates Adenylate cyclase Gi - Inhibitory - Inhibits Adenylate Cyclase Gq - Activates PLC - increases IP3 and DAG

Question 333

Give examples of different GPCRs

Answer 333

Muscarinic 3 receptor - Gq GPCR B2 Adrenoceptor - Gs GPCR

Question 334

How do kinase linked receptors work and give an example?

Answer 334

1️⃣Ligand binding causes or stabilises receptor dimerisation 2️⃣This allows tyrosine in the cytoplasmic portion of each receptor monomer to be transphosphoylated by its partner receptor 3️⃣Phosphorylation of specific tyrosine residues within the activated receptor creates ligand-specific signalling protein binding sites (e.g. a phospholipase C binding site) 4️⃣Binding to these binding sites causes signalling protein phosphorylation and activation → initiation of signal transduction pathway Receptors for Growth Factors

Question 335

How do cytosolic/nuclear receptors work and give an example?

Answer 335

1️⃣Steroid ligand freely move into the cell cytoplasm 2️⃣Steroid ligand binds to receptor on nuclear membrane - often form dimers 3️⃣In the nucleus, the steroid complex acts as a transcriptional factors, functioning to augment or supress transcription of particular genes by binding to DNA Breast cancer drugs - Tamoxifen

Question 336

What is an agonist?

Answer 336

A compound that binds to a receptor to activate it It has both affinity and efficacy

Question 337

What is an antagonist?

Answer 337

A compound that binds to a receptor but shows no response at the receptor It has affinity but no Efficacy These block the effects of agonists

Question 338

What is a partial agonist?

Answer 338

A agonist which, no matter how much it is exposed to the receptor, a maximal response is never reached Does not have full efficacy

Question 339

What are the 2 types of antagonist?

Answer 339

Competitive - Binds to the active site. (Decreases Potency but does not affect efficacy) Non-competitive - Binds to an allosteric site (Decreases both potency and efficacy)

Question 340

What is the Emax?

Answer 340

The maximum response that can be achieved (The Efficacy)

Question 341

What is the EC50?

Answer 341

The concentration of a drug that gives half the maximal response It tells us about potency

Question 342

What does the EC50 tell us about?

Answer 342

How potent a drug is

Question 343

Would a drug with a lower EC50 have a lower or greater potency?

Answer 343

Greater Potency

Question 344

Which is more efficacious, a full agonist or partial agonist?

Answer 344

A full agonist is more efficacious as a full agonist has the capability of inducing a 100% response.

Question 345

Define efficacy?

Answer 345

How well a ligand activates a receptor how well it induces a conformational change

Question 346

Define Affinity

Answer 346

How well a ligand can bind to a receptor

Question 347

What are the two subtypes of Cholinergic receptors and what are their respective agonists and antagonists?

Answer 347

- Muscarinic (mAchR) - GPCR Agonist → muscarine Antagonist → atropine - Nicotinic (nAchR) - Ion channel Agonist → nicotine Antagonist → curare

Question 348

What is the effect of fewer receptors on drug potency?

Answer 348

Fewer receptors will shift the dose-response curve to the right → potency reduced

Question 349

What is a receptor reserve?

Answer 349

Where an agonist needs to activate only a small fraction of the existing receptors to produce the maximal system response

Question 350

What is the effect of less signal amplificiation on drug response?

Answer 350

Less signal amplification gives a reduced drug response

Question 351

Describe allosteric modulation?

Answer 351

An allosteric modulator binds to a different site (the allosteric site) on a receptor and influences the role of an agonist.

Question 352

What is inverse agonism?

Answer 352

When the binding of a drug to the same receptor as the agonist induces an opposite pharmacological response to that of the agonist - the inverse agonist changes the function of the receptor.

Question 353

Define tolerance?

Answer 353

A reduction in the effect of a drug overtime Due to continuous use, repeated use or use at high concentrations

Question 354

Describe the difference between tolerance and desensitisation

Answer 354

- Tolerance - reduction in drug effect over time (continuously repeated high conc) - Desensitisation - receptors become degraded / uncoupled / internalised

Question 355

What 3 ways can a receptor become desensitised?

Answer 355

Uncoupled - agonist unable to interact with the GPCR Internalised - The receptor is taken into the cell via endocytosis Degraded

Question 356

What is the drug target for statins?

Answer 356

HMG-CoA reductase

Question 357

What is the action of statins?

Answer 357

Block the rate limiting step in the cholesterol pathway

Question 358

what is the end effect of statin use?

Answer 358

Lipid lowering Prevent CVD Reduce CVD and mortality of those at risk

Question 359

What is the Renin-angiotensin aldosterone system responsible for?

Answer 359

Blood pressure control

Question 360

What is the function of ACE inhibitors?

Answer 360

Reduces the production of angiotensin II Reduces blood pressure

Question 361

What is the function of L-DOPA in parkinsons?

Answer 361

It is a dopamine precursor It can freely cross the BBB and thus be given as part of a treatment for parkinsons

Question 362

What are the mechanisms of action of Co-Careldopa (carbidopa)?

Answer 362

DOPA decarboxylase inhibitor Reduces L-DOPA metabolism to dopamine in the periphery More can pass into the brain to be metabolised here (carbidopa does not cross the BBB)

Question 363

What is the mechanism of action of tolcapone and entacapone?

Answer 363

Catechol-O-methyl transferase (COMT) inhibitor prevents breakdown of L-DOPA and dopamine

Question 364

Can tolcapone cross the BBB?

Answer 364

Yes

Question 365

What is the mechanism of action of selegiline and rasagiline?

Answer 365

Monoamine oxidase - B (MOA) inhibitors Prevent the breakdown of dopamine

Question 366

What are the 3 types of protein ports?

Answer 366

uniporters - use ATP to move molecule through Symporters - use the passive transport of one molecule to pull another through Antiporters - use the passive transport of one molecule to move another molecule the opposite way

Question 367

What does amiloride act on and what is its function?

Answer 367

Epithelial sodium channel (ENaC) Stops reabsorption of water in the kidney Used as an antihypertensive

Question 368

What does thiazide act on and what is it function?

Answer 368

NaCl cotransporter Stops reabsorption of water in the DCT of the nephron Used as an antihypertensive

Question 369

What class of drug is amlodipine?

Answer 369

Angioselective calcium channel blocker

Question 370

What is the mechanism of action of amlodipine?

Answer 370

Blocks the activation of calcium channels Inhibits the contraction of cardiac muscle and vascular smooth muscle Reduces TPR and leads to a decrease in overall BP

Question 371

What is the mechanism of action of lidocane and what class of drug is it?

Answer 371

Anaesthetic use-dependent blockage of VG-Na channels Sodium channels need to activate in order for lidocaine to act on them Blocks transmission of APs Reduces Arrhymthmias

Question 372

How do potassium channel blockers help in T2DM?

Answer 372

Block of potassium cause membrane depolarisation in pancreatic beta cells opens calcium channels which cause exocytosis of insulin

Question 373

Give 3 examples of potassium channel blockers used to treat T2DM?

Answer 373

Repaglinide Nateglinide Sufonylureal

Question 374

What do barbiturates do and give an example of a drug in this class?

Answer 374

Phenobarbitone GABA receptor agonists GABA is an inhibitory ionotropic receptor

Question 375

What is the mechanism of action of digoxin?

Answer 375

Blocks the action of NA/K/ATPase mainly in myocardial tissue this increases level of Na in the cell Decreases the action of Na-Ca exchanger Increases amount of Ca in the cell Increases the length of contraction and reduces heartrate

Question 376

What do proton pump inhibitors do an give an example?

Answer 376

Omeprazole Act on the stomach by decreasing gastric acid production by irreversible inhibition. Decrease the pH of gastric acid

Question 377

What does the rate of metabolism determine?

Answer 377

Duration and intensity of a drugs pharmacological action

Question 378

What is Cytochrome P450?

Answer 378

Major microsomal enzyme in the liver Most drugs are inactivated by CYP however some require CYP to be activated

Question 379

What are the different categories of opioids?

Answer 379

Naturally occurring Simple chemical modifications Synthetic opioids Synthetic partial agonists

Question 380

What are the naturally occurring opioids?

Answer 380

Morphine (from the opium poppy) Codeine

Question 381

What are the simple chemical modifications class of opioids?

Answer 381

Diamorphine (2x stronger than morphine) Oxycodone (1.5x more potent than morphine) Dihydrocodeine (1.5x more potent that codeine)

Question 382

What are the modern synthetic opioids?

Answer 382

Fentanyl Alfentanil Remifentanil

Question 383

give an example of a synthetic partial agonist opioid?

Answer 383

Buprenorphine

Question 384

What drug is the antagonist to opioids and is important to treat overdose with?

Answer 384

Naloxone - acts on the u receptor

Question 385

What percentage of oral morphine is metabolised in first pass metabolism?

Answer 385

50% Hence, you would half the dose if giving by s/c; IM; IV etc 10mg oral morphine = 5mg s/c;IM;IV - you will need to write two separate prescriptions!

Question 386

What are the main routes of administration of opioids?

Answer 386

Parenteral: IM SC IV (fastest) Epidural Transdermal patches - fentanyl

Question 387

What is important about IV PCA?

Answer 387

Intravenous patient-controlled analgesia important that only the patient administers the dose as this is a protective mechanism against respiratory distress. If the patient administers too much then they will fall asleep before they get to respiratory distress and hence prevent them administering more drug.

Question 388

What is the difference between potency and efficacy?

Answer 388

Potency: Strength of binding affinity of the drug for the receptor Efficacy: is it possible to get a maximal response with the drug or not?

Question 389

What is the difference between tolerance and dependence?

Answer 389

Tolerance: ↓ regulation of receptors with prolonged drug use Dependence: what happens when you stop: physical and psychological effects

Question 390

What is the mechanism of action of opioids?

Answer 390

They use the existing pain modulation system - endorphins and enkephalins Work via GPCRs Inhibit the release of pain neurotransmitters at the midbrain and spinal cord Can modulate pain perception (euphoria) to change the emotional aspect of pain.

Question 391

What is the main opioid receptor?

Answer 391

u, Mu or MOP

Question 392

What are the main side effects of opioids?

Answer 392

1. Respiratory distress 2. Sedation 3. Nausea and Vomiting 4. Constipation 5. Itching 6. Immune suppression 7. Endocrine effects

Question 393

How would you treat opioid induced respiratory depression?

Answer 393

With Naloxone

Question 394

What enzyme metabolises codeine and what is it metabolised to?

Answer 394

CYP2D6 metabolises codeine to morphine (codeine is a prodrug)

Question 395

What is morphine metabolised to?

Answer 395

Morphine-6-glucoronide (more potent than morphine)

Question 396

Describe the dose response curve to morphine

Answer 396

As dose increases response increases. This association is initially rapidly and then the graph plateaus. It is not sigmoidal!

Question 397

What is tramadol?

Answer 397

A weak opioid agonist (slightly stronger than codeine) Also acts as a SSRi and noradrenaline reuptake inhibitor.

Question 398

What systemic effects can be controlled by manipulating cholinergic and adrenergic pathways?

Answer 398

Control blood pressure; raise in shock, lower in hypertension Control heart rate; speed up lethal bradycardias, slow down dangerous tachycardias Anaesthetic agents; muscle relaxants Regulation of airway tone; treat life-threatening bronchospasms Control GI functions; treat diarrhoea and constipation Reduce pressure in the eye; prevent glaucoma causing blindness

Question 399

How does the structure of the Somatic NS and the Autonomic NS differ?

Answer 399

- Somatic Nervous System - a neurone comes from CNS to innervate skeletal muscle - Autonomic Nervous System - there are two nerves in the series; the pre- and postganglionic fibres. The parasympathetic ganglia have short postganglionic fibres (near target); the sympathetic ganglia have long postganglionic fibres (near spinal cord)

Question 400

What nerves are the PNS made up of?

Answer 400

- Oculomotor (CN III) - Facial (CN VII) - Glossopharyngeal (CN IX) - Vagus (CN X) - Further outflow via *sacral nerve* innervations of the pelvis

Question 401

What neurotransmitter and receptor are associated with the Parasympathetic nervous system?

Answer 401

Acetylcholine acting on muscarinic receptors

Question 402

What neurotransmitter is released by the preganglionic nerve fibres within the ANS?

Answer 402

Acetylcholine acting on N2 receptors

Question 403

What neurotransmitter is released by the post ganglionic nerve fibres within the sympathetic NS?

Answer 403

Noradrenaline acting on alpha/beta adrenoceptors

Question 404

What neurotransmitter is released in the somatic NS at the effector cells?

Answer 404

Acetylcholine acting on N1 receptors

Question 405

give examples of non-adrenergic/cholinergic autonomic transmitters?

Answer 405

Sympathetic - ATP, Neuropeptide y Parasympathetic - NO, VIP

Question 406

What nervous system pathway does cholinergic pharmacology deal with?

Answer 406

Manipulation of the parasympathetic pathway

Question 407

What does nicotine stimulate?

Answer 407

Stimulates all automimic ganglia via preganglionic nicotinic receptors Activates both the SNS and PNS

Question 408

What does muscarine stimulate?

Answer 408

Activates the muscarinic receptors specific to the PNS

Question 409

What type of receptor are muscarinic and nicotinic receptors?

Answer 409

Muscarinic - GPCR - M1-5 Nicotine - Ligand gated ion channels

Question 410

Where are the different subtypes of muscarinic receptors found?

Answer 410

M1 - Brain M2 - Heart M3 - Glandular and smooth muscle (lungs and GI tract) M4 - Mainly CNS M5 - Mainly CNS

Question 411

What is the effect of muscarinic agonists at the M2 receptors?

Answer 411

Slows the heart rate

Question 412

What is the effect of muscarinic agonists at the M3 receptors?

Answer 412

Causes bronchoconstriction of smooth muscle Will increase sweating, saliva and GI motility.

Question 413

What is the difference between a selective and non-selective drug?

Answer 413

A selective drug will act on a specific subunit of a receptor type (eg. B2 receptors only) A non-selective drug will act on all receptors of a certain type (eg. B1 and B2 receptors)

Question 414

What is pilocarpine?

Answer 414

A muscarinic agonist Stimulates salivation - treats Sjogrens syndrome Contracts iris smooth muscle - treats glaucoma by draining aqueous humour

Question 415

What is a side effect of pilocarpine?

Answer 415

Slows the heart (non-selective muscarinic agonist)

Question 416

What is atropine?

Answer 416

A muscarinic antagonist Prevents bradycardia - used to treat bradycardia in cardiac arrest Dry secretions perioperatively

Question 417

What drugs are used in the treatment of bronchoconstriction?

Answer 417

Drugs that block the M3 receptors - anticholinergics/anti-muscarinics Short acting (SAMA) - Ipratropium bromide Long acting (LAMA) - Tiotropium

Question 418

What other roles can anticholinergics play?

Answer 418

Solifenacin - treat overactive bladder Mebeverine - Treat IBS

Question 419

Give 2 examples of ACh action in the CNS?

Answer 419

Motion sickness - ACh stimulates vomiting centre in the brain Worsen Parkinsons symtpoms - ACh increases dopamine re-uptake

Question 420

How is ACh synthesised?

Answer 420

Acetyl CoA combined with Choline; mediated by Choline Acetyl Transferase

Question 421

What enzyme is responsible for ACh breakdown in the synaptic cleft?

Answer 421

Acetylcholinesterase

Question 422

What is the action of the botulinum toxin at the NMJ?

Answer 422

Botulinum inhibits Ach release at the NMJ → Cause paralysis/decrease muscle contractions - cosmetic and antispasmodic uses

Question 423

What is the purpose of competitive antagonists at the NMJ?

Answer 423

Competitive antagonists block Ach receptors → muscle relaxants, adjuncts to general anaesthesia (pancuronium)

Question 424

What is the action of depolarising agonists?

Answer 424

Act as blockers as they cause receptor desensitisation

Question 425

What are AChE inhibitors used for?

Answer 425

prevent the breakdown of Ach in the synaptic cleft. Used to increase the amount of Ach available in the synaptic cleft to compete with depolarising blockers or receptor deficiencies

Question 426

What is Myasthenia Gravis and how is it treated?

Answer 426

A diseases associated with the autoimmune destruction of nAchR, resulting in weakness; treated using acetylcholinesterase inhibitors to increase the amount of Ach available to limited nAch receptors

Question 427

What are some side effects of anticholinergics?

Answer 427

- Worsening memory/ confusion - Constipation - Dry mouth - Blurred vision

Question 428

What are organophosphates?

Answer 428

Used in insecticides and nerve gases They are irreversible AChE inhibitors Cause muscle tremors, twitching, salivation and confusion.

Question 429

Give some examples of AChE inhibitors?

Answer 429

Neostigmine Pyridostigmine Rivastigmine

Question 430

What is Curare and Pancuronium?

Answer 430

An nACh-R antagonist

Question 431

What does overstimulation of Ach at the NMJ lead to?

Answer 431

Cholinergic Crisis (SLUDGE) Salivation Lacrimation Urination Defecation GI distress Emesis

Question 432

What nervous system pathway does adrenergic pharmacology deal with?

Answer 432

Sympathetic nervous system

Question 433

What are the principle catecholamines involved in the sympathetic nervous system?

Answer 433

- **Noradrenaline**; released from sympathetic nerve fibre ends → important in the management of shock in ICU - **Adrenaline;** released from adrenal glands → important for management of anaphylaxis - **Dopamine;** precursor of noradreanline, which is the precursor of adrenaline

Question 434

What is the synthetic pathway of catecholamines?

Answer 434

Tyrosine DOPA Dopamine Noradrenaline Adrenaline

Question 435

What is the primary function of α1 adrenoceptors?

Answer 435

Vasoconstriction (contraction of BV) Bladder contraction Dilation of pupils

Question 436

What is the primary function of α2 adrenoceptors?

Answer 436

Responsible for pre-synaptic inhibition - prevents NAd release Used in analgesia

Question 437

What neurotransmitter predominates in α1 and α2 interactions?

Answer 437

α1 - Noradrenaline α2 - Adrenaline = noradrenaline

Question 438

What is the primary function of β1 adrenoceptors?

Answer 438

Increased cardiac effects to increase SV and CO Increase ionotropy (force of contraction) Increase chronotropy (heart rate) Increase Dromotropy (electrical conduction) Increase renin secretion

Question 439

What neurotransmitter predominates in β1, β2 and β3 interactions?

Answer 439

β1 - Noradrenaline = adrenaline β2 - Adrenaline β3 - Noradrenaline

Question 440

What is the primary function of β2 adrenoceptors?

Answer 440

Decrease SM tone - Bronchodilation Vasodilation (partly)

Question 441

What are the primary functions of β3 adrenoceptors?

Answer 441

Increased Lipolysis Bladder - detrusor muscle relaxation

Question 442

Where are the various adrenoceptors located?

Answer 442

α1 - Vascular smooth muscle, pupil α2 - Presynaptic neurone (CNS Acting) β1 - Heart β2 - Lungs β3 - Bladder detrusor muscle (and increase lipolysis)

Question 443

What is the role of adenylate cyclase?

Answer 443

Converts ATP to cyclic AMP (cAMP) to activate PKA

Question 444

What do α1 adrenergic agonists do?

Answer 444

Vasoconstriction; used for treatment of septic shock

Question 445

What do α1 adrenergic antagonists (alpha blockers) do?

Answer 445

Vasodilation; lowers blood pressure (doxazosin)

Question 446

What disease could an α1 adrenergic antagonist be used in the treatment of?

Answer 446

Benign prostatic hyperplasia; tamsulosin blocks α1 receptors in the prostate

Question 447

What drugs act on Alpha 2 receptors and what could they be used for?

Answer 447

Conidine/ alpha-methyldopa CNS acting vasodilators

Question 448

What do β1 adrenergic agonists do?

Answer 448

Increase heart rate and chronotropic effects; used for treating conditions like septic shock (dobutamine)

Question 449

What do β1 adrenergic antagonist do?

Answer 449

Reduce CO and reduce renin secretion; lower blood pressure (Bisoprolol, Atenolol, Metoprolol)

Question 450

What diseases could an β1 adrenergic antagonist be used in the treatment of?

Answer 450

Hypertension, angina and arrhythmia.

Question 451

What do β2 agonists do?

Answer 451

Muscle relaxation; life-saving treatment for asthma and delay onset of premature labour

Question 452

What do β3 agonists do?

Answer 452

Smooth muscle relaxation; relaxation of detrusor muscle to reduce over-active bladder symptoms

Question 453

Give examples of cardioselective beta blockers and non-selective beta blockers?

Answer 453

Cardioselective (against B1) - Atenolol, Metoprolol Non-selective - Propanolol

Question 454

What is the suffix for: Murine Antibodies Chimeric Antibodies Humanised Antibodies Human Antibodies

Answer 454

Murine Antibodies - omab Chimeric Antibodies - ximab Humanised Antibodies - zumab Human Antibodies - umab

Question 455

Where are DA (dopamine receptors) most found?

Answer 455

Nucleus accumbens in the brain

Question 456

What is the main excitatory and main inhibitory neurotransmitter in the CNS?

Answer 456

Excitatory - glutamate Inhibitor - GABA

Question 457

Give an example of a GABA agonist and what it may be used to treat?

Answer 457

Benzodiazepines (eg. Diazepam, Lorazepam) Treats: Anxiety Sleep disorders Alcohol withdrawal

Question 458

Give an example of a Histamine (H1 and H2) receptor antagonist and what they would be used to treat?

Answer 458

H1 Antagonist - Loratidine - treats allergy (T1 hypersensitivity) H2 antagonist - cimetidine, Ranitidine - Treats GORD/reflux (Reduces gastric acid)

Question 459

What is an adverse drug reaction (ADR)?

Answer 459

An unwanted, harmful reaction following the administration of a drug or combination of drugs under normal conditions of use, and is suspected to be related to the drug Rxn has to be noxious and unintended

Question 460

Are side effects and ADRs the same?

Answer 460

No! side effects are predictable A side effect is an unintended effect of a drug related to the pharmacological properties and can include unexpected benefits of treatment (e.g. PDE5 inhibitors (viagra), used for erectile dysfunction, is also found to improve urinary flow).

Question 461

What are the patient risk factors for ADRs?

Answer 461

- Gender (F>M) - Elderly - Neonates - Polypharmacy - Genetic predisposition - Hypersensitivity/ allergies - Hepatic/ renal impairment - Adherence problems

Question 462

What are the drug risk factors for ADRs?

Answer 462

- Steep dose-response curve - Low therapeutic index

Question 463

What are some potential causes for ADRs?

Answer 463

- Pharmaceutical variation - Receptor abnormalities - Abnormal biological system unmasked by drug - Abnormalities in drug metabolism - Immunological - Drug-drug interactions - Multifactorial

Question 464

What drugs commonly cause ADRs?

Answer 464

- Antibiotics (penicillin) - Anti-neoplastics - Cardiovascular drugs - Hypoglycaemics - NSAIDs - CNS drugs

Question 465

What body systems are commonly affected by ADRs?

Answer 465

- Gastrointestinal - Renal - Haemorrhagic (i.e. NSAIDs in patients on warfarin can cause gastric ulcer causing a catastrophic bleed) - Metabolic - Endocrine - Dermatologic

Question 466

Give examples of common ADR presentations

Answer 466

- Confusion - Nausea - Balance problems - Diarrhoea - Constipation - Hypotension

Question 467

How are ADRs categorised?

Answer 467

- Toxic effects - above therapeutic range - Collateral effects - at normal therapeutic range - Hypersusceptibility effects - below therapeutic range (e.g. tiny does of penicillin causing anaphylaxis)

Question 468

What is the Rawlins Thompson System of ADRs?

Answer 468

Type A - Augmented Type B - Bizarre Type C - Chronic Type D - Delayed Type E - End of use Type F - Failure

Question 469

Describe a Type A ADR

Answer 469

*Augmented (or pharmacological).* - Common and predictable from physiological effects of the drug; often dose related. (eg. Anticoagulants causing haemorrhage) Treatment is reduce drug dose

Question 470

Describe a Type B ADR

Answer 470

*Bizarre (or idiosyncratic).* - Not predictable, not dose dependent and cannot be readily reversed - For example, immunological mechanisms and hypersensitivity reactions such as anaphylaxis to penicillin Tx is to withdraw drug immediately

Question 471

Describe a Type C ADR?

Answer 471

*Chronic.* - Occurs after long term therapy (eg. Nephropathy caused by long term NSAID use)

Question 472

Describe a Type D ADR?

Answer 472

Delayed Occurs many years after treatment (eg. teratogenesis caused by thalidomide)

Question 473

Describe a Type E ADR?

Answer 473

End of use Complications of stopping medication (withdrawal) eg. opioids

Question 474

Describe a Type F ADR?

Answer 474

Failure of therapy (eg. Failure of the oral contraceptive pill in the presence of enzyme inducer drugs)

Question 475

What does the acroyn DoTS mean?

Answer 475

Dose relatedness - Toxic, collateral or hypersusceptibility Timing - fast rxns, or late Rxns Susceptibility - Patient factors

Question 476

When should you suspect an ADR?

Answer 476

- Symptoms after a new drug is started - Symptoms after dosage increase - Symptoms disappear when drug is stopped - Symptoms reappear when drug is restarted

Question 477

Define Drug hypersenstivity?

Answer 477

Reproducible symptoms or signs that are initiated by the exposure to a drug at a dose tolerated by normal subjects

Question 478

Give explanations for the main features of anaphylaxis?

Answer 478

- Occurs within minutes of drug exposure and lasts 1-2 hours - Vasodilation - flushing - Increased vascular permeability - fluid centrally shifted peripherally; swelling and oedema - Angio-oedema - swelling of the face and throat - Central cyanosis - bluish discolouration of the hands or feet - Bronchoconstriction - wheeze, SOB - Urticaria - itchy, aggressive rash (80-90%) - Hypotension - known as anaphylactic shock - Cardiac arrest

Question 479

What is non-immune anaphylaxis?

Answer 479

- Anaphylaxis occuring with no prior exposure - due to the direct degranulation of mast cells - Clinically identical as immunological anaphylaxis and the treatment is the same.

Question 480

How is anaphylaxis managed?

Answer 480

- Commence basic life support (ABCDE) - Stop the drug if currently being infused - Adrenaline (IM) 500mg - second dose after five miuntes if patient is not initially responding. - High flow oxygen - IV fluids - fluid shifts peripherally; IV fluids maintain intravascular volume - IV Antihistamine (Chlorphenamine 10mg) - IV Hydrocortisone (100 to 200mg)

Question 481

What does adrenaline do during anaphylaxis Treatment?

Answer 481

- Vasoconstriction - increases peripheral vascular resistance; increases BP and coronary perfusion via α1-adrenoreceptors - Stimulation of β1-adrenoreceptors; produces positive ionotrophic (strength) and chronotropic (speed) effects on heart - Stimulation of β2-adrenoreceptors; reduces oedema and bronchodilation - Attenuates further release of mediators from mast cells and basophils by increasing intracellular cAMP → reduced release of inflammatory mediators

Question 482

Define Absorption (pharmacokinetics)

Answer 482

The process of transfer from the site of administration into the general or systemic circulation

Question 483

What are the routes of drug administration?

Answer 483

po - oral iv - intravenous pr - rectal sc - subcutaneous im - intramuscular in - intra-nasal top - topical sl - sublingual inh - inhaled neb - nebulised et - endotracheal

Question 484

How do drugs cross membranes to reach their target sites?

Answer 484

Passive diffusion Facilitated diffusion Active transport non-ionic diffusion Pinocytosis

Question 485

What is drug ionisation?

Answer 485

A property of a drug: they can be weak acids (e.g. aspirin) or weak bases (e.g. propranolol). Drugs with ionisable groups exist in equilibrium between charged ionised and uncharged forms

Question 486

What is the strength of drug ionisation dependent on?

Answer 486

The strength of the ionisable group pH of the solution

Question 487

What are other terms used to describe ionised drugs vs. unionised drugs?

Answer 487

Water soluble vs. lipid soluble respectively

Question 488

What is the pKa of a drug?

Answer 488

The pH at which half of the substance is ionised and half is unionised

Question 489

Drugs that are weak acids are best absorbed where?

Answer 489

The stomach (eg. Aspirin is a weak acid and so becomes less ionised in the stomach due to the low gastric pH.)

Question 490

Drugs that are weak bases are best absorbed where?

Answer 490

The intestines

Question 491

What is the effect of an increase in pH on a weak acid?

Answer 491

The weak acid will become more ionised

Question 492

What is the effect of an increase in pH on a weak base?

Answer 492

The weak base will become less ionised.

Question 493

What is the effect of a decrease in pH on a weak acid?

Answer 493

The weak acid will become less ionised

Question 494

What is the effect of a decrease in pH on a weak base?

Answer 494

The weak base will become more ionised

Question 495

What route of drug administration has a bioavailability of 1?

Answer 495

IV - all the drug administered will go into the plasma

Question 496

Explain what would happen to the bioavailability of aspirin if gastric pH increased.

Answer 496

The bioavailability would decrease. Aspirin would be more ionised and so wouldn’t diffuse across the gut into the plasma as rapidly this would mean aspirin uptake would decrease.

Question 497

How many litres of water are there in the following body compartments: a) Plasma. b) Interstitial space. c) Intracellular space.

Answer 497

a) 3L. b) 11L. c) 28L

Question 498

What equation can be used to determine the degree of ionisation at a specific pH?

Answer 498

Henderson Hasselbach. pH = log[A-]/[HA] + pKa.

Question 499

What can enhance non ionic diffusion?

Answer 499

Non ionic diffusion can be enhanced if adjacent compartments have pH difference.

Question 500

Give an example of a proton pump inhibitor.

Answer 500

Omeprazole

Question 501

Give an example of a statin

Answer 501

Simvastatin Atorvostatin

Question 502

Give an example of an ACE inhibitor?

Answer 502

Enalapril

Question 503

Give an example of a COX inhibitor?

Answer 503

Aspirin Ibuprofen

Question 504

Give an example of a beta 2 adrenoceptor agonist?

Answer 504

Salbutamol

Question 505

Give an example of a beta 1 adrenoceptor antagonist?

Answer 505

Atenolol

Question 506

Give an example of a Calcium channel blocker?

Answer 506

Amlodipine

Question 507

Give an example of a broad spectrum antibiotic?

Answer 507

Amoxicillin

Question 508

Give an example of a phosphodiesterase inhibitor?

Answer 508

Dipyridamole - stimulates prostacyclin and inhibits thromboxane A2

Question 509

Give an example of an opiate analgesic?

Answer 509

Tramadol

Question 510

Give an Example of a Direct Factor Xa inhibitor?

Answer 510

DOACs Apixaban Rivaroxaban

Question 511

Give an Example of an indirect Anti-thrombin inhibitor?

Answer 511

Heparin - activates anti-thrombin to inhibit thrombin and Factor Xa

Question 512

Give an example of a Vitamin K antagonist?

Answer 512

Warfarin Decreases Factor II (prothrombin) and is an antagonist to Vitamin K Therefore reduces Vit K dependent clotting factors (2, 7, 9, 10)

Question 513

What pharmaceutical properties can affect the rate of drug absorption?

Answer 513

Pharmaceutical form - syrup/pill Ability to disintegrate Ability to dissolve

Question 514

What physiochemical properties of a drug affects the rate of drug absorption?

Answer 514

Solubility pH Molecular weight

Question 515

What physiological variables can affect the rate of drug absorption?

Answer 515

Available Surface area Contact time of drug with receptors Concentration of drug at absorption site Absorption site - level of blood flow Drug interactions Transporter systems

Question 516

What is first pass metabolism?

Answer 516

Where a drug is metabolised at a specific site prior to reaching its site of action or the systemic circulation that results in an overall reduced dose/bioavailability

Question 517

Define distribution (pharmacokinetics)

Answer 517

The process by which the drug is transferred (reversibly) from the general circulation to the tissues as the blood concentration increases and then returns from the tissues to the blood when the blood concentration falls.

Question 518

What is important about drugs binding to proteins in the plasma?

Answer 518

Binding lowers the free conc of a drug and acts as a depot releasing the bound drug when the plasma conc drops through redistribution or elimination.

Question 519

What is the most common protein that drugs bind to?

Answer 519

Albumin

Question 520

What type of drugs pass easily into the brain?

Answer 520

Lipid soluble Some drugs use SLC (solute carrier) transporters that supply the brain with carbohydrate and AAs e.g. L-DOPA used in Parkinson's

Question 521

How are water soluble and lipid soluble drugs eliminated?

Answer 521

Water soluble: directly by the kidney Lipid soluble: must be metabolised to water soluble products

Question 522

What are the phases of metabolism?

Answer 522

Phase 1: Transform the drug to a more polar molecule by unmasking or adding functional groups through oxidation, reduction or hydrolysis reactions. This is usually carried out by CYP450 microsomal enzymes Phase 2: Conjugation reactions where there is a major increase in hydrophilicity to make the drug easily excreted via the kidney. Often uses conjugates such as glucuronic acid, glutathione.

Question 523

What is first order kinetics?

Answer 523

Rate of metabolism is directly proportional to Drug concentration Where a constant fraction of drug is eliminated per unit time

Question 524

What is zero order kinetics?

Answer 524

If an enzyme system that removed a drug is saturated the rate of removal of the drug is constant and unaffected by an increase in concentration e.g. ethanol follows zero order kinetics once alcohol dehydrogenase has been saturated.

Question 525

Define half-life

Answer 525

The time taken for a concentration of a drug to reduce by half.

Question 526

What would be the bioavailability of an oral drug?

Answer 526

F<1 as they are incompletely absorbed and undergo incomplete first pass metabolism.

Question 527

If a drug has an oral bioavailability of 0.1, and the IV dose has a bioavailability of 1, what is the oral dose needed to be to be effective?

Answer 527

10x the oral dose

Question 528

What is the volume of distribution and how is it calculated?

Answer 528

A measure of how widely a drug is distributed between various body fluids and tissues. Amount of drug in the body / Measured plasma concentration

Question 529

Do water soluble or lipid soluble drugs have a higher volume of distribution?

Answer 529

Lipid soluble - these will move into the tissues more readily Water soluble - highly protein bound and will be confined to the blood

Question 530

Define Clearance?

Answer 530

The volume of plasma from which a drug is completely removed per unit time The rate at which a plasma drug is eliminated per unit plasma concentration

Question 531

Give the equation for renal clearnace?

Answer 531

Renal clearance = Rate of appearance in urine / plasma concentration.

Question 532

Define hepatic extraction ratio (HER).

Answer 532

The proportion of a drug removed by one passage through the liver.

Question 533

What is the limiting factor when a drug has a high HER?

Answer 533

Hepatic blood flow, perfusion limited

Question 534

What is the limiting factor when a drug has a low HER?

Answer 534

Diffusion limited. A low HER is slow and not efficient.

Question 535

What happens to high and low HER drugs when enzyme induction is increased?

Answer 535

The clearance of low HER drugs increases. There is minimal effect on high HER drugs.

Question 536

What is steady state?

Answer 536

A balance between drug input and elimination

Question 537

What is the role of the lymphatic system in acute inflammation?

Answer 537

Lymphatic channels dilate and drain away oedematous fluid therefore reducing swelling. Antigens are also carried to lymph nodes for recognition by lymphocytes.

Question 538

What are APUDomas?

Answer 538

Neuroendocrine tumours

Question 539

Describe T cell Activation

Answer 539

Naive T cell with the TCR binds to the epitope of the antigen presented via MHC on the APC Co stimulatory molecule CD28 binds to CD80/CD86 on the APC to allow for full activation of the T cell. The T cell will release IL-2 which then rebinds to the T cell IL-2-R to initiate T cell differentiation via autocrine mechanism. The T cell will divide into Th1 or TH2 depending on the IL-12 concentration present at the time of differentiation.

Question 540

What cytokines are released from Th1 cells and Th2 cells

Answer 540

Th1 - IL2 and INFy Th2 - IL-4, IL-5, IL-6, IL-10

Question 541

Give 3 functions of antibodies.

Answer 541

1. Neutralise toxins. 2. Opsonisation. 3. Activate classical complement system.

Question 542

Give 3 examples of O2 dependent mechanisms of killing.

Answer 542

1. Killing using reactive oxygen intermediates. 2. Superoxides can be converted to H2O2 and then to hydroxyl free radicals. 3. NO leads to vasodilation and increased extravasation and so more neutrophils etc are in the tissues to destroy pathogens.

Question 543

What is the role of NO in killing pathogens?

Answer 543

NO leads to vasodilation and increased extravasation. This means more neutrophils etc pass into the tissues to destroy pathogens.

Question 544

Why can superoxides be used to destroy pathogens?

Answer 544

Superoxides can be converted to H2O2 and then to hydroxyl free radicals. Hydroxyl free radicals are highly reactive and can destroy pathogens.

Question 545

What is the function of these complement proteins: MAC C3a and C5a C3b

Answer 545

MAC - Lyse microbes directly C3a /C5a - Chemotaxis C3b - Opsonisation

Question 546

What is the function of MAC in a pathogens' membrane?

Answer 546

MAC is a leaky pore like channel. Ions and water pass through the channel and disrupt the intracellular microbe environment -> microbe lysis.

Question 547

Which complement plasma proteins are pro-inflammatory and cause chemotaxis and activation of neutrophils and monocytes etc?

Answer 547

C3a and C5a.

Question 548

Which complement plasma proteins have opsonic properties when bound to a pathogen?

Answer 548

C3b and C4b.

Question 549

Name 3 receptors that make up the PRR family.

Answer 549

1. Toll-like receptors (TLR). 2. Nod-like receptors (NLR). 3. Rig-like receptors (RLR).

Question 550

What is the main function of TLR's?

Answer 550

TLR's send signals to the nucleus to secrete cytokines and interferons. These signals initiate tissue repair. Enhanced TLR signalling = improved immune response.

Question 551

What is the main function of NLR's?

Answer 551

NLR's detect intracellular microbial pathogens. They release cytokines and can cause apoptosis if the cell is infected.

Question 552

What disease could be caused by a non-functioning mutation in NOD2?

Answer 552

Crohn's disease.

Question 553

What is the main function of RLR's?

Answer 553

RLR's detect intracellular double stranded RNA. This triggers interferon production and so an antiviral response.

Question 554

TLR's are adapted to recognise damaged molecules. What characteristic do these damaged molecules often have in common?

Answer 554

They are often hydrophobic.

Question 555

What kind of TLR's can be used in vaccine adjuvants?

Answer 555

TLR4 agonists.

Question 556

What is extravasation?

Answer 556

Leukocyte (WBC) migration across the endothelium.

Question 557

What do macrophages at the tissues secrete to initiate extravasation?

Answer 557

TNF alpha.

Question 558

Describe the process of extravasation.

Answer 558

1. Macrophages at tissues release TNF alpha. 2. The endothelium is stimulated to express adhesion molecules (eg. GAG) and to stimulate chemokines. 3. Neutrophils bind to adhesion molecules (ICAM-1); they roll, slow down and become stuck to the endothelium. 4. Neutrophils are activated by chemokines. 5. Neutrophils pass through the endothelium to the tissue to help fight infection.

Question 559

Define Adsorption and give an example

Answer 559

Where a compound clings to the surface of another molecule eg. In paracetamol overdose you could prescribe activated charcoal to stick to the paracetamol to prevent its absorption from the gut.

Question 560

How would you treat paracetamol overdose?

Answer 560

If less than 1hour since ingestion: Give Activated charcoal with N-acetylcysteine If longer than an hour since ingestion: give N-acetylcysteine

Question 561

Which common condition often diagnosed in childhood is a contraindication of beta-blockers and why?

Answer 561

Asthma Beta blockers cuase bronchoconstriction

Question 562

What is the role of p53 protein?

Answer 562

p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.

Question 563

Define chronic inflammation.

Answer 563

Subsequent and prolonged tissue reactions to injury.

Question 564

Why is adjuvant therapy often used in the treatment of carcinomas?

Answer 564

Micrometastes are possible even if a tumour is excised and so adjuvant therapy is given to suppress secondary tumour formation.

Question 565

What kind of drugs can be used in targeted chemotherapy?

Answer 565

Monoclonal antibodies (MAB) and small molecular inhibitors (SMI).

Question 566

What enzymatic cascade systems does plasma contain?

Answer 566

1. The complement system. 2. The kinin system. 3. The coagulation system. 4. The fibrinolytic system.

Question 567

Give examples of 3 extracellular PRR.

Answer 567

1. Mannose receptors. 2. Scavenger receptors. 3. TLR's.

Question 568

What are the 7 hallmarks for cancer?

Answer 568

1. Evade apoptosis. 2. Ignore anti-proliferative signals. 3. Growth and self sufficiency. 4. Limitless replication potential. 5. Sustained angiogenesis. 6. Invade surrounding tissues. 7. Escape immuno-surveillance.

Question 569

What are the two types of tumour antigens and where are they found?

Answer 569

1. Tumour specific antigens; only found on tumour cells. Due to point mutations. 2. Tumour associated antigens; found on normal cells and over expressed on tumour cells.

Question 570

What is cancer immunosurveillance?

Answer 570

When the immune system recognises and destroys transformed cells, this is an important host protection process.

Question 571

What are the 3 E's of cancer immunoediting?

Answer 571

1. Elimination. 2. Equilibrium. 3. Escape.

Question 572

Which infection is most often seen in patients with hypogammaglobulinemia?

Answer 572

Streptococcus penumonia sinusitis.

Question 573

Give 5 examples of PAMPs.

Answer 573

1. Lipopolysaccharides. 2. Endotoxins. 3. Bacterial flagellin. 4. Peptidoglycans. 5. dsRNA.

Question 574

What class of biological agent is often used in the treatment of rheumatoid arthritis when DMARDs fail?

Answer 574

TNF blockers - they bind to TNF to prevent it interacting with its receptors.

Question 575

Give a side effect of using TNF blockers.

Answer 575

Increased susceptibility to TB.

Question 576

How do IL-6 blockers work?

Answer 576

IL-6 is an inflammatory cytokine. The biological agent binds to IL-6 so as to prevent it interacting with its receptor.

Question 577

Name an IL-6 blocker.

Answer 577

Tocilizumab.

Question 578

When are IL-6 blockers used?

Answer 578

They're used in the treatment of rheumatoid arthritis when TNF blockers fail.

Question 579

What factors govern drug action?

Answer 579

Receptor related: Affinity Efficacy Tissue Related: Receptor number Signal amplification

Question 580

Give 4 properties of the 'ideal drug'.

Answer 580

1. Small Vd (high bioavailability) 2. Drug broken down effectively by enzymes. 3. Predictable dose:response relationship. 4. Low risk of toxicity.

Question 581

Give an advantage of a drug having a low Vd.

Answer 581

It is easy to reach steady state and plasma concentration is ‘responsive’ to dose rate.

Question 582

Give examples of adverse muscarinic agonist effects.

Answer 582

DUMBELS: 1. Diarrhoea. 2. Urination. 3. Miosis. 4. Brachycardia. 5. Emesis (vomiting). 6. Lacrimation. 7. Salivation.

Question 583

Which enzymes inactivate catecholamines?

Answer 583

MAO and COMPT.

Question 584

Define pain.

Answer 584

An unpleasant sensory and emotional experience associated with actual or potential tissue damage.

Question 585

Give 3 advantages of pain.

Answer 585

1. Gives a warning for tissue damage. 2. Immobilisation for healing. 3. Memory establishment.

Question 586

Define acute pain.

Answer 586

Pain caused by nociceptor activation. It is of short duration,

Question 587

Define chronic pain.

Answer 587

Pain that is on-going or persistent, it lasts for >3-6 months.

Question 588

Define neuropathic pain.

Answer 588

Pain caused by a primary lesion or dysfunction of the nervous system.

Question 589

Define nociceptive pain.

Answer 589

Pain caused by actual or potential damage to non neural tissue, it is due to nociceptor activation.

Question 590

Describe the gate control theory.

Answer 590

Non-noxious stimuli trigger larger A beta fibres, these override smaller pain fibres and 'close the gate' to pain transmissions to the CNS.

Question 591

Give 4 risk factors for hypersensitivity.

Answer 591

1. Protein based macromolecules. 2. Female > male. 3. Immunosuppression. 4. Genetic factors.

Question 592

Why are drug interactions such a big problem today?

Answer 592

1. Ageing population. 2. Polypharmacy. 3. Increased use of over the counter drugs.

Question 593

What is dobutamine used in the treatment of and at what receptor is it an agonist?

Answer 593

Dobutamine is a beta 1 agonist. It is used in the treatment of heart failure.

Question 594

What are the 3 actions of NSAIDS?

Answer 594

1. Anti-inflammatory. 2. Analgesic. 3. Anti-pyrexic. (AAA).

Question 595

Give examples of Non-selective NSAIDs?

Answer 595

Diclofenac Ibuprofen Naproxen High Dose Aspirin Inhibit both COX1/COX2 to reduce conversion of Arachidonic acid to prostaglandins

Question 596

Give Examples of Selective NSAIDs?

Answer 596

Celecoxib Specifically Targets COX2 Low dose Aspirin - Targets COX1

Question 597

What are the effects of a competitive antagonist?

Answer 597

Decreases potency of a drug but does not affect the efficacy

Question 598

What are the effects of a non-competitive antagonist?

Answer 598

Decreases both the potency and efficacy.

Question 599

Give examples of alpha 1 blockers and what they can be used to treat

Answer 599

Doxazosin - Decrease BP Phenoxybenzamine - Treats phaeochromocytoma

Question 600

What drugs are CYP450 Inducers and what does that do to drug effects?

Answer 600

Drug effects reduced PCBRAS: Phenytoin Carbamazepine Barbiturates Rifampicin Alcohol (chronic use) Sulfonylureas

Question 601

What drugs are CYP450 Inhibitors and what does that do to drug effects?

Answer 601

Drug effects increased ODEVICES: Omeprazole Disulfiram Erythromycin Valproate Isoniazid Ciprofloxacin Ethanol (acute) Sulphonamides

Question 602

What is the Role of platelets?

Answer 602

No nucleus, derived from megakaryocytes Contain alpha granules and dense granules Alpha granules are involved in platelet adhesion, e.g. fibrinogen Dense granules cause platelets to aggregate, e.g. ADP Platelets are activated, releasing their granules when they come into contact with collagen If this happens within an intact vessel, a thrombus is formed