Introduction to Clinical Sciences Flashcards
1
Q
What is inflammation
A
cellular reaction to injury involving neutrophils and polymorphs
2
Q
what are neutrophil polymorphs
A
they are white blood cells made in the bone marrow. They have a short lifespan (2-3 days), and are called polymorphs cause they have a polylobed nucleus
3
Q
what do neutrophils contain to remove pathogens
A
contain lysosomes of enzymes which can kill phagocytosed bacteria
4
Q
what types of immune cells are the first to arrive at the site of acute inflammation
A
neutrophils
5
Q
what is the lifespan of macrophages
A
months to years
6
Q
what are features of macrophages
A
they have a circular nucleus, and acts as antigen presenting cells. They have different names dependent on what tissue they reside
7
Q
Define exudate
A
Exudate is fluid that leaks out of blood vessels into nearby tissues. The fluid is made of cells, proteins, and solid materials.
8
Q
what are lymphocytes
A
they are T or B cells which are long lives cells which produce chemicals involved in controlling inflammation and production of antibodies. Lymphocytes are the immunological memory of the body
9
Q
what are plasma cells
A
they are specialised B cells which are antibody producing
10
Q
what are fibroblasts
A
they are cells which produce collagenous connective tissue- spindle shaped cells
11
Q
what are the features of acute inflammation
A
injury or infection
early onset - seconds to minutes
short duration - hours to days
cells involved - neutrophils and then macrophages
12
Q
what are examples of acute inflammation
A
microbial infections - bacteria and viruses
hypersensitivity reactions - parasites
physical agents - trauma, heat, cold
chemicals - corrosives and acids
bacterial toxins
tissue necrosis – ischemic
13
Q
what is the sequence of events of chronic inflammation
A
either progression from acute inflammation or starts as chronic inflammation
there are no or few neutrophils in this case
macrophages and lymphocytes and then fibroblasts involved
can resolve if there is no tissue damage but this often ends up with repair and formation of scar tissue
14
Q
what is an example of primary chronic inflammation
A
infection mononucleosis
15
Q
what is a granuloma
A
it is a particular type of chronic inflammation with collections of macrophages/histiocytes surrounded by lymphocytes
16
Q
what are the reasons for granuloma formation
A
seen in mycobacterial infection such as TB or leprosy, also seen in crohns disease and sarcoidosis
17
Q
what are the features of endothelial cells
A
the line blood vessels and produce nitric oxide to prevent platelets sticking to them.
18
Q
why might an inflamed area be red and swollen
A
because of the larger blood flow to the area - increased capillary action
19
Q
what are the outcomes of acute inflammation
A
resolution
supporation - pus formation
organisation - granulation tissue and fibrosis
progression - excessive inflammaiton - becomes chronic
20
Q
what is resolution
A
where the problem causing inflammation is resolved, inflammation is solved and there is no tissue damage
21
Q
what is first intension healing
A
it is when the edges of the wound can be joint back together, making it much easier for the body to repair the wound.
initial weak fibrin joint and then collagen joint after
22
Q
what is second intension healing
A
when the edges of the wound cant be joint back together which can be either due to trauma or with certain surgeries.. cells have to grow into the wound, with initilal capillary cells, then fibroblasts and then epithelial cells
23
Q
what is granulation tissue
A
where capillary loops are growing into wound (looks a bit like granular tissue)
24
Q
what is tissue repair
A
when there is replacement of damaged tissue that cant regenerate, collagen is therefore produced by fibroblasts, leaving a scar
- original tissue lost
25
what cells regenerate within the body
hepatocytes, blood cells, pneumocytes, gut epithelium, skin epithelium and osteocytes
26
what cells dont regenerate
myocardial cells and neurons
27
what is the steps of acute inflammation
vascular component = dilation of vessels
exudative component = vascular leakage of protein rich fluid
neutrophil polymorph = cells type recruited to tissue
28
what is the appearance of acute inflammation
red in colour, heat, swelling, pain and loss of function
29
what happens during acute inflammation
1. migration of neutrophils; increased plasma viscosity and slowing of flow during injury meaning neutrophils migrate to plasmatic zone
2. Adhesion of neutrophils to the endothelium
3. neutrophil emigration as they pass through the endothelial cells onto the basal lamina
4. diapedesis; RBC may also escape from vessels
30
what are the four outcomes of acute inflammation
1. resolution - complete restoration of tissue to normal w/minimal cell death
2. suppuration - formation of pus, leads to scarring
3. organisation - replacement by granular tissue, new capillaries grow into inflammatory exudate, macrophages migrate and fibrosis occurs
4. progression - causative agents is not removes so there is progression to chronic inflammation
31
what is chronic inflammation
subsequent and prolonged response to tissue injury
32
what are the cells involved in chronic inflammation
lymphocytes, macrophages, plasma cells
33
what are causes of chronic inflammation
primary chronic inflammation, transplant rejection, autoimmune conditions, endogenous and exogenous conditions
34
what is the macroscopic appearance of chronic inflammation
chronic ulcer
crohns abscess cavity
granulomatous inflammation
fibrosis
35
what is the microscopic appearance of chronic inflammation
lymphocytes, plasma cell, macrophages, continuing destruction and possible necrosis
36
what is laminar flow
cells travel in the centre of arterial vessels and dont touch the sides
37
what is a thrombosis
it is the formation of a solid mass from blood constituents in an intact vessel in a living person
38
what is the first stage of thrombosis formation
platelet aggregation - platelets release chemicals when they aggregate which causes other platelets to migrate and stick - starts of a positive feedback cascade
39
what are the three things that can cause thrombosis formation
1. change in the vessel wall
2. change in the blood flow
3. change in the blood constituents
40
what is an embolism
the process of a solid mass in the blood being carried through the circulation to a place where it gets stuck and blocks a vessel
41
what is the most common cause of embolism
a thrombus
42
what are some less common causes of embolism
air, cholesterol crystals, tumours, amniotic fluid, fat
43
what happens if an embolus enters the venous system
will travel to vena cava, through the right side of the heart and lodge in the pulmonary arteries, causing pulmonary oedema
44
what is ischemia
a reduction in blood flow to a tissue
45
what is infarction
a reduction in blood flow to a tissue that results in cell death
46
what is end arterial supply
when an organ/tissue only has a single artery supplying it
47
what are the few organs with a duel arterial supply
the lungs, liver and parts of the brain
48
what are the granules that platelets contain
alpha and dense
49
what is the function of alpha granules
platelet adhesion - fibrinogen
50
what is the function of dense granules
platelet aggregation - ADP
51
How does a thrombus form
a change in the vessel wall will cause a plaque to form there, which will protrude into the lumen and cause some turbulence. this results in the loss of intimal cells. Clumping will occur and fibrin is deposited. this structure will continue to protrude into the lumen
52
do thrombi form in veins
not likely as there is lower pressure in veins - can occurs around valve sites
53
what are the clinical features of arterial thrombi
loss of pulse distal to thrombus, area becomes cold and pale and painful. there could be gangrene
54
what is the fate of thrombi
1. resolution
2. organised - becomes a scar with slight narrowing
3. recanalisation - intimal cells proliferate and capillaries may grow into the thrombus
4. embolus - fragments break off into circulation
55
what could a venous thrombus lead to
DVT
56
what is an atherosclerosis
accumulation of fibrolipid plaques systemic arteries
57
what is the time course of atherosclerosis
birth - none
late teen/early 20s - fatty streaks in aorta, may not progress to established atherosclerosis
30s/40s/50s - development of established atherosclerotic plaques
40s -80s - complications of atherosclerotic plaques
58
what are rick factors of atherosclerosis
hypertension
hyperlipidemia
cigarette smoking
poorly controlled diabetes
59
what is the pathogenesis of atherosclerosis
endothelial damage theory - endothelial cells are delicate and can become damaged by cigarette smoke, shearing forces, hyperlipidemia, glycosylation products
60
what can cumulative damage of the endothelial barrier lead to
it leads to endothelial ulceration, microthrombi and eventual development of established atherosclerotic plaques
61
what are the complications of atherosclerosis
blocked vessels - infarct
embolism leading to cerebral infarction, carotid atheroma, myocardial infarction, aortic aneurysm, peripheral vascular disease and gangrene
62
how does atherosclerosis form
1. endothelial cell dysfunction (lots of cholesterol damages wall)
2. High levels of LDLs will begin to accumulate
3. macrophages are attracted to the site of damage at take up lipid to form foam cells
4. platelet aggregation and the plaque starts to protrude into the artery lumen disrupting flow. thinning of media occurs
5. fibrin mesh and red blood cell trapping occurs
6. fibrous cap forms over smooth muscle cap forming a stable atheroma
63
what are preventative measures for atherosclerosis
smoking cessation
blood pressure control
weight reduction
low dose aspirin
statins - cholesterol reducing
64
what is apoptosis
it is programmed cell death - orderly event without the release of products harmful to surrounding cells
65
what is the purpose of apoptosis
it is a process in normal cell turnover which prevents cells with accumulated genetic damage from dividing and producing cells which might eventually develop into cancer
66
what protein detects DNA damage
p53
67
what is the function of p53
it is a protein in cells which detects the level of DNA damage which will trigger apoptosis if DNA damage is high
68
how does a cell apoptose
the cell triggers a series of proteins which leads to the release of enzymes called caspases which auto digests the cell
69
when does apoptosis occur in health
development - removal of cells during development such as interdigital webs
cell turnover - removal of cells during normal turnover, such as the intestinal villi
70
when does apoptosis occur in disease
cancer - cells in tumours often dont apoptose due to accumulation of genetic mutations, including those in the p53 gene
HIV - HIV can induce apoptosis in CD4 T helper cells to produce an immunodeficient state
71
what is necrosis
it is the traumatic loss of cells - uncontrolled
72
what are clinical examples of necrosis
infarction due to loss of blood supply
frostbite
pancreatitis
73
what are the inhibitors of apoptosis
growth factors, extracellular cell matrix, sex steroids
74
what are the inducers of apoptosis
glucocorticoids, free radicals, ionising radiation, DNA damage
75
what is the intrinsic pathway of apoptosis
this uses pro and anti apoptotic members of the Bcl-2 family. Bax forms Bax-Bax dimers which enhance apoptotic stimuli. the Bcl-2:Bax ratio determines the cells susceptibility to apoptotic stimuli.
it responds to growth factors and biochemical stress.
the p53 gene induces cell cycle arrest and DNA damage repair, and if it cant be fixed it induces apoptosis
76
what is the extrinsic apoptotic pathway
this involves ligand binding to death receptors on the cell surface. this includes the TNFR1, CD95 and the main one the Fas-FasL
the ligand binding causes the clustering of receptor molecules on the cell surface and the initiation of signal transduction cascades
caspases are activated and triggers apoptosis
77
what is coagulative necrosis
most common type - ischemia
78
what is liquefactive necrosis
occurs in brain due to lack of supportive stroma
79
what is caseous necrosis
causes 'cheese' pattern - TB characterised by this
80
what is gangrene
necrosis with rotting tissue - affected tissue is black due to deposition of iron sulphate
81
What is the definition of hypertrophy
It is the increase in cell size without cell division.
82
what is the definition of hyperplasia
Increase in cell number by mitosis - this can only happen in cells that can divide `
83
what cells cant undergo hyperplasia
Myocardial cells or nerve cells
84
what is the definition of atrophy
The decrease in the size of an organ or cell which can be reduction in cell size or number
85
when is there natural atrophy in the body
Occurs during the development of the GU tract
86
what is the definition of metaplasia
the change in differentiation of a cell from one fully differentiated cell type to another
87
what are examples of metaplasia
Barretts oesophagus - squamous epithelium to columnar epithelium
88
what is the definition of dysplasia
morphological changes seen in cells in the progression to becoming cancer
not cancer but could become cancer
89
what is a genetic disease
a disease that occurs primarily from a genetic abnormality
90
what is a single gene disorder
abnormality of a single gene causes a disease - can be recessive or dominant
91
what are the two further classifications of single gene disorder
autosomal or sex linked
92
what is polygenic gene disorder
a genetic disease which is the result of the interaction of several different genes (usually on different chromosomes)
93
what is a congenital disease
a disease which someone is born with - but can also be acquired. This will often be a disease which is due to environmental factors but it may be a strong genetic background
94
what is a homeobox gene
genes which code for particular region of the body and control migration of cells
95
what is benign prostatic hyperplasia
smooth muscle in the prostate divides and causes the prostate to crow and constricts the urethra
96
when do you have combined hypertrophy and hyperplasia
in the uterus during pregnancy
97
what is a classic example of atrophy in aging
dementia
98
What is the limit of aging
number of times a cell can divide
99
what are the limiting factors of cell division
telomerase length - telomeres get shorter after each cell division which then limits the amount of divisions that can occur
100
what things can induce apoptosis in cells
crosslinking or mutation of DNA
accumulation of toxic by products of metabolism
telomere shortening
time dependent activation of aging and death genes
free radical generation
crosslinking of proteins
damage to mitochondrial DNA
loss of DNA repair mechanism
101
what is dermal elastosis
the accumulation of abnormal elastic in the dermis of the skin, which is the result of prolonged or excessive sun exposure. This is because UVB light causes protein cross linking
102
what is osteoporosis
caused by the loss of coupling in the bone remodeling process with increased bone resorption and reduced bone formation. the bone matrix is mineralised as normal but the trabeculae are thinned
103
what is cataracts and its cause
it is the formation of opaque proteins within the lens which usually results in the loss of lens elasticity. It is caused by UVB light causing protein cross linking
104
what causes dementia
plaques and neurofibrillary tangles in the brain
105
what is sarcopenia
it is decreased growth hormone, decreased testosterones and increased catabolic cytokines. This causes involuntary loss of skeletal muscle mass and strength
106
what is the cause of deafness in age
the hair cells cant divide or regenerate in the ear which means once damage occurs it cant be undone
107
What cancer only invades locally
basal cell carcinoma - doesnt metastasize
108
what is the cure for basal cell carcinoma
complete local excision of the cancer
109
what type of cancer is leukemia
it is the cancer of white blood cells
110
what has to happen before cancer removal surgery
they generally do an ultrasound of the area to ensure that there is no growth into surrounding lymph nodes. Can also send a lymph node sample to the lab
111
what cancers commonly spread to the bone
breast, prostate, thyroid, lung and kidney cancers commonly spread to the bone
112
what biopsy can be done to check if cancer is present
a needle core biopsy
113
what is adjuvant therapy
it is extra treatment given after the surgery to help prevent the regrowth of cancer
114
what is the name of the main effector cell in acute inflammation
Neutrophil polymorphs
115
What is the name of the cells that produce collagen in fibrous scarring
fibroblasts
116
what is a common example of acute inflammation
acute appendicitis
117
what is the pattern of differentiation of neoplastic cells lining the bronchi of cigarette smokers
respiratory epithelium to stratified squamous
118
what process is is defined by the formation of a solid mass of blood constituents within an intact vascular system during life
thrombosis
119
what is the definition of carcinogenesis
normal cells to neoplastic cells via permanent genetic mutation or alteration
120
where in the cell do all carcinogens act
the level of the DNA
121
what are the different classes of carcinogen
chemical, viral, radiation, hormones, parasites, mycotoxins and miscellaneous
they all act on DNA
122
what type of neoplasms do carcinogens produce
malignant
cancer causing
123
what is oncogenesis
the formation of benign and malignant tumours
- tumour causing
124
what are carcinogens
agents which are known or suspected to cause tumours
125
what are occupational or behavioral risks for cancer
lung cancer - strong association with smoking
bladder cancer - increased incidence in aniline dye and rubber industries
scrotal cancer - increased incidence in chimney sweeps
126
what are chemical carcinogens
they show no common structural features, where some act directly. Most require metabolic conversation from pro-carcinogens to ultimate carcinogens. Enzymes are required for this which may be ubiquitous or confined to certain organs (meaning you can only get cancer in those organs)
127
what is a tumour
it is any abnormal swelling
128
what are examples of chemical carcinogens
polycyclic aromatic hydrocarbons - found in soot, cigarette smoke and pollution
nitrosamines - processed meats
alkylating agents - used as chemotherapeutic agents to treat other cancers
129
what are examples of viral carcinogens
HepB - liver cancer
HHV8 - Kaposi sarcoma
EBV - Birkett lymphoma, nasopharyngeal carcinoma
HPV - cervix, penis, anus, head and neck
MCV - merkel cell carcinoma
HTLV-1 - leukemia
HCV - hepatocellular carcinoma
130
what type of radiation can cause cancer
UV light - increases all kinds of skin cancer
ionising radiation - can cause cancer over long term exposure
131
what biological agents can cause cancer
oestrogen - breast and endometrial
anabolic steriods - hepatocellular carcinoma
132
what are miscellaneous carcinogens
arsenic, asbestos and metals
133
what host factors can affect cancer risk
ethnicity - more melanin decreases melanoma incidence
diet and lifestyle - alcohol excess increases risk of cancers of the mouth, liver and colon
obesity - breast, oesophagus, colon (exercise reduces this risk)
inherited predisposition - retinoblastoma and FPC
age - increased age increases the risk
biological sex will impact on certain cancer risk
134
what is pre-malignant condition
a localised abnormality which increases the risk of developing cancer such as polyps, ulcerative colitis and undescended testicles
135
what is an example of placental transmission
diethylstilbestrol - was sued for morning sickness which increased the risk of vaginal cancer in the foetus
136
what percentage of all cancer risks are inherited
15%
137
what does in situ mean, in terms of cancer
where the cancer hasnt invaded surrounding tissue, and is still within the area it started. No access to blood or lymphatic vessels
In situ only applies to epithelial neoplasms and the BM is intact
138
how do you treat an in situ cancer
you can excise it
139
what is an invasive carcinoma
where the cancer has invaded the surrounding tissues - has access to blood or lymphatic vessels
140
what is a micro-invasive cancer
one that has invaded surrounding tissues, but not very far
141
what enzymes will cancers need to produce to move through the basement membrane
metalloproteinases - collagenase, cathepsin D
142
what are the stages of metastasis
tumour grows and invades the basement membrane and the extracellular matrix. It will then travel in either the lymphatic or blood vessel, and will then move back into a tissue elsewhere and invade another extracellular matrix to grow there
143
how large must a tumour be for it to need its own blood supply
larger than 1mm
144
what can tumours do to remain undetected by immune cells in the blood
- tumours can aggregate with platelets
- they can shed surface antigens which can be taken up by lymphocytes rather than the tumour cell itself
- they can adhere to other tumour cells to increase size
145
what can tumour cells produce to promote angiogenesis
VEGF and BFGF
146
what cancers commonly spread to the lungs
sarcomas
147
what cancers often invade the liver
colon, stomach, pancreas, carcinoid tumours of the intestine
148
what cancers commonly metasasise to the bone
prostate, breast, thyroid, lung and kidney
149
what are the two types of bone metastasis
sclerotic metastasis (gain of bone)
lytic metastasis (loss of bone)
150
what is a neoplasm
a lesion resulting from the autonomous, or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed (a new growth)
151
what do solid neoplasms contain
neoplastic cells and stroma (supporting network) - except leukemia
152
what are the behavioral classification of neoplasms
malignant, borderline or benign
153
what are the features of benign neoplasms
Localised, non invasive, slow growth rate. They have a low mitotic rate. They have a close resemblance of normal tissue. They are well circumscribes of encapsulated.
154
what is an example of malignant neoplasms
squamous cell carcinoma and prostate cancer
155
what are features of malignant neoplasms
INVASIVE. they can metastases. They have a rapid growth rate and have some varying resemblance to normal tissue. They have a poorly defined boarder.
156
where can neoplasms arise from
epithelial cells, connective tissues, lymphoid or haemopoietic organs
157
what is an adenoma
a benign tumour of glandular or secretory epithelium
- add prefix to add what type it is
158
what is a papilloma
a benign tumour of non glandular non secretory epithelium
-can add a prefix to add what type it is
159
what is a carcinoma
a malignant epithelial neoplasm
- this is a common exam question
160
what is a lipoma
adipocyte neoplasm (benign)
161
what is a chondroma
cartilage neoplasm (Benign)
162
what is an osteoma
a bone neoplasm (benign)
163
what is an angioma
vascular neoplasm (benign)
164
what suffix do benign connective tissue neoplasm have
- oma
165
what suffix do malignant connective tissue neoplasms have
- sarcoma
166
what is a liposarcoma
an adipose tissue neoplasm
167
what is a rhabdomyosarcoma
a striated muscle neoplasm
168
what is a leiomyosarcoma
smooth muscle neoplasm
169
what is a carcinoma in situ
a malignant epithelial neoplasm that has not yet invaded through the original basement membrane
170
How can a metastasis occur
via blood vessels, lymphocytes, across body cavities, along nerves or as a direct implantation of neoplastic cells during surgery
171
what must a tumour have to undergo extravasation
adhesion receptors, collagenases and cell motiity
172
what are examples of angiogenesis inhibitors
angiostatin ,endostatin and casculostatin
173
what are the consequences of a malignant neoplasm
they can cause destruction of adjacent tissue, metastasis, blood loss from ulcers, obstruction of flow, hormone productions, paraneoplastic affects, anxiety
174
what are the consequences of benign neoplasm
They can cause morbidity and mortality cause they can cause obstruction, cause pressure on adjacent structures, produce hormones and can transform. Can cause anxiety
175
what is an anaplastic neoplasm
where the cell - type of origin is unknown
176
what is serum
plasma without fibrinogen and other clotting factors
177
what is the most common white blood cell
neutrophils
178
what white blood cell has a kidney shaped nucleus
monocytes
179
what are the primary lymphoid organs
Bone marrow: origin for all and the B cell maturation site
Thymus: T-cell maturation site
180
what are the secondary lymphoid organs
the lymph nodes: site of DC, B and T cell interactions
Spleen: site of removal or RBC and bacteria
181
what are tertiary lymphoid organs
transient formation of germinal centers which are usually pathology related
182
what is the definition of hematopoiesis
production of all cellular components of blood and blood plasma
183
what stem cell produces all types of white blood cells
hematopoietic stem cells
184
what progenitor cell descendants can be considered as the innate branch of the immune system
the common myeloid progenitor cells
185
what progenitor cell descendants can be considered cells of the adaptive immune response
the common lymphoid progenitor cells
186
what causes ALL
lymphoid progenitors causing increased amounts of immature lymphocytes
187
what causes CLL
increased naive mature B cells
188
what is lymphoma
cancer involving expansion of mature naive T cells and B cells in germinal centres
189
what is multiple myeloma
cancer of the plasma cells
190
what are 7 key points about the innate immune system
1. it is primitive and broad
2. it is fast
3. there is little regulation
4. there is no amplification
5. there is no self discrimination
6. it is short (days)
7. it has no memory
191
what are the 7 key points about the adaptive immune system
1. it is highly specific
2. it is slow
3. it has lots of regulation
4. there is amplification
5. it shows high self discrimination
6. it is long
7. it can produce memory
192
what cells are polymorphonuclear leukocytes
neutrophils, eosinophils, basophils
193
what are mononuclear leukocytes
monocytes, T cells and B cells
194
what immune cell has a kidney shaped nuclei
monocytes
195
what is the role of monocytes in immunity
they play a role in both innate and adaptive immunity as they phagocytose and present antigens.
196
what is the main function of neutrophils in immunity
innate immunity - they have two main intracellular granules. Primary lysosomes kill microbes but secreting toxic substances and secondary granules.
197
what is the main function of macrophages in immunity
they are involved in innate and adaptive immunity. they reside in tissues and have a long lifespan. their main role is removal of foreign and self material as well as antigen presentation to T cells
198
what is the main function of eosinophils
mainly associated with parasitic infections and allergic reactions. they can activate neutrophils, inducing histamine release from mast cells
199
what is the main function of basophils
mainly involved in immunity to parasitic infections and allergic reactions. they bind to IgE and cause de-granulation releasing histamine
200
what is the function of mast cells
they are only found in tissues and induce release of histamine via IgE
201
what are the four main types of T cell
T helper 1 - CD4
T helper 2 - CD4
cytotoxic T cell - CD8
Treg
202
what is the function of natural killer cells
they recognise and kill by apoptosis - tumour cells and viral infected ones
203
what percentage of lymphocytes are natural killer cells
about 15%
204
what are the types of soluble factors in immunity
complement, antibodies and cytokines and chemokines
205
what is compliment function in immunity
direct lysis of pathogen
attraction of leukocytes to sites of infection
opsinisation - coat organisms and aid in phagocytosis
206
what are the five distinct classes of antibodies
1. IgG
2. IgA
3. IgD
4. IgE
5. IgM
207
what is the most predominant antibody
IgG
208
what antibody can cross the placenta
IgG
209
where is IgA antibody found
it is the predominant antibody found in secretions such as saliva, milk, vaginal and bronchiolar secretions
210
where is IgM predominantly found
found in the blood - makes up a pentamer so cant cross endothelium and it is the primary response
211
what are the features of IgE
Basophils and mast cells express an IgE-specific receptor that has high affinity for IgE – binding triggers release of histamine
Associated with allergic response and defence against parasitic infections
212
what is an epitope
it is the part of the antigen that binds to the antibody/receptor binding site
213
what are cytokines
they are proteins secreted by the immune and non-immune cells. they influence the behaviour of cells
214
what do interferons do
they are important in antiviral immunity
215
what do interleukins do
over 30 types - they can stimulate cells to divide, differentiate and secrete factors
216
what is colony stimulating factors
it is involved in directing the division and differentiation on the bone marrow stem cells - precursors of leukocytes
217
what is tissue necrosis factors
it mediates inflammation and cytotoxic reactions
218
what are chemokines
40 proteins that direct movement of leukocytes and attract leukocytes to sites of infection or inflammation
219
what three factors are in the innate immune system
1. physical and chemical barriers
2. phagocytic cells
3. serum proteins
220
what are anatomical barriers to infection
1. skin
2. sebum
3. intact skin
221
What physical barriers are there to infection (mucous membranes)
Saliva, tears, low pH, commensals of vagina, mucous secretions, mucous, cilia, commensal colonies
222
what are physiological barriers to infection
temperature
fever response
pH
Gastric acidity
223
what is inflammation
a series of reactions that brings cells and molecules of the immune system to sites of infection or damage
224
what is the response to a barrier being breached - tissue damage or infection
1. stop bleeding
2. acute inflammation
3. kill pathogens, neutralise toxins and limit spread
4. clear pathogens or dead cells
5. proliferation of cells to repair damage
6. removal of blood cot
7. re-establish normal structure
225
what are the hallmarks of inflammation
increased blood supply, increased vascular permeability and increased leukocyte trans-endothelial migration extravasion
226
what complement factor is required for opsonisation
C3b
227
what are the stages of phagocytosis
1. binding
2. engulfment
3. phagosome formation
4. lysosome fusion
5. membrane disruption
6. antigen presentation/secretion
228
What are MHCs
major histocompatibility complex - displays peptide from self or non self proteins on the cell surface - invasion alert
229
where is MHCI found
found on all nucleated cells
230
where is MHCII found
only on antigen presenting cells
231
what do MHCI do
Intrinsic (intracellular) - this interacts with CD8 cells which then kils the infected cells with intracellular pathogens
232
what do MHCII do
extrinsic - interacts with CD4 T helper cells, which helps to make B cells to make antibodies
233
what interactions need to occur for cell mediated immunity
interaction between antigen presenting cells and T cells. it requires MHC, intrinsic/extrinsic antigens and the recognition of self or non self
234
what is a summary of B cell activation
B cells become activated upon binding with an antigen. These then go to the lymph nodes where clonal expansion takes place with the cells differentiating into plasma cells. These secrete Ab (usually IgM) which later turn into IgG. B cells divide – clonal expansion and differentiate into plasma cells and memory B cells. Re-stimulation of memory B cells lead to secondary response.
235
what are the two types of PRR family
1. secreted and circulating PRRs
2. Cell-associated PRRs (traditional)
236
what are secreted and circulated PRRs
1. antimicrobial peptides secreted in lining fluids from epithelia
2. lectins and collectins (carbohydrate-containing proteins that bind carbohydrates or lipids in microbe walls)
237
what is the function of secreted and circulating PRRs
they activate compliment and improve phagocytosis
238
what are cell associated PRRs
these are receptors that are present on the cell membrane or in the cytosol of the cells. They recognise a broad range of molecular patterns.
239
what are the main cell associated PRRs
TLRs are the main ones
240
other than PAMPs what else can PRRs detect
damage recognition - cellular damage which activates immunity to issue tissue repair (and enhance local antimicrobial signalling)
241
how are PRRs involved in autoimmunity
they can recognise host molecules as foreign
242
what are the 5 cardinal signs
1. Rubor - redness
2. Dolor - pain
3. Calor - Heat
4. Tumor - swelling
5. loss of function
243
what is neutrophil action in acute inflammation
- margination (migration to edge of BV)
- adhesion (selectins bind neutrophils, and cause rolling)
- emigration and diapedesis (movement out of the BV)
- chemotaxis
244
what molecule do granulomas secrete
ACE - blood marker
245
what are the features of an arterial ulcer
punched out holes with little exudate - pale cool skin with low distal pulse
246
what are the features of a venous ulcer
less demarcated with lots of exudate. warm erythematosus skin
- DVT
247
how does a venous thrombosis form
though venous stasis
248
what is found within a plaque
lipid, smooth muscle, macrophages, foam cells, platelets and fibroblasts
249
how are tumours graded
based on the similarity to the parent cell it came from
1. well differentiated - 75% cells like parent
2. 10-75%
3. poorly differentiated - less than 10% resemble parent
250
in staging tumours what does TNM stand for
tumour - node - metastases
251
what cancers are screened for in the UK
cervical, breast and colorectal
252
what is the common mutation associated with colorectal cancer
familial adenomatosis polyposis - a mutated APC gene causing overexpression of c-MYC and KRAS mutation
253
what is transcolemic spread of cancer
when there is spread through the pleural, pericardial and peritoneal effusions (via exudative fluid accumulation)
254
what are the three pathways in the complement system
1. classical
2. lectin
3. alternative
255
what in the compliment system causes direct lysis of cells
the membrane attack complex formation
256
what factors in the compliment system are important for inflammation
C3a and C5a
257
what factor in the compliment system is required for opsonisation
C3b
258
what TLRs are intracellular
3, 7, 8 and 9
259
what does TLR2 detect
gram positive bacteria and TB
260
what does TLR3 detect
intracellular pathogens
261
what does TLR4 detect
LPS - gram negative
262
what does TLR 5 detect
flagellin
263
what does TLR7 detect
single stranded RNA - intracellular
264
what does TLR9 detect
non methylated DNA
265
what type of toxin in LPS
its an endotoxin
266
what 3 things have to occur during immune synapse to activate the T cell
1. receptor binding
2. co-stimulation (another molecule after primary binding)
3. cytokine release
267
what are the best antigen presenting cell
dendritic cells
268
what is thymic tolerance
where T cell in the thymus are checked for self reactivity/to see if they are active to anything
269
what is positive thymic selection
where the T cells are tested to see if they recognise MHC 1 and 2. If they do they are selected for
270
what is negative thymic selection
if the T cells produce to much of a response to self then they are selected against
271
what cytokine is associated with Th1 cells
IFN gamma - activates NK cells and macrophages
272
what cytokine is associated with Th2 cells
IL4 - activates B cells to differentiate into plasma cells
273
what two factors do Th2 cells release to activate B cells
1. IL4 which induces B cell proliferation
2. IL5 which induces B cell differentiation into plasma cells
274
what Ig does IL4 promote class switching to
IgA
275
what Ig does IL5 promote class switching to
IgE
276
what are the four types of hypersensitivity
1. anaphylaxis
2. antigen-antibody complex
3. immune complex deposition
4. T cell mediated
277
describe type 1 hypersensitivity
IgE mediated - IgE binds to basophils and mast cells and causes degranulation and release of histamine which causes vasodilation and increased permeability and bronchoconstriction
278
describe type 2 hypersensitivity
where IgG/M binds to antigens and activates MAC compliment at the site of antigen antibody binding.
- goodpastures
279
describe type 3 hypersensitivity
IgG/A binds to antigen and activates compliment
SLE
280
describe type 4 hypersensitivity
Th1 mediated which are activated by APCs leading to a slow response
281
when treating anaphylaxis what are the steps to take
1. Airway - can they breathe
2. breathing - is it rapid/wheezy
3. circulation - are they pale/cold/clammy
4. disability - are they confused and can they move
5. exposure
282
what is the immediate treatment for anaphylaxis
500mcg of IM adrenaline
283
what else can you give in the case of anaphylaxis
antihistamine or cortisol
284
where is central immune tolerance performed
in the thymus
285
where is peripheral immune tolerance performed
in the secondary lymphoid organs
286
what is autoimmunity
a pathological response to self
287
what are examples of organ specific autoimmunity
type 1 diabetes - endocrine pancreas - beta cells
multiple sclerosis - oligodendrocytes
pernicious anaemia - parietal cells of the stomach
288
what are examples of non organ specific autoimmunity
SLE - affects DNA
Rheumatoid arthritis
289
what are the two ways someone can get immunodeficiency
1. inherited - defect in T cells - SCID
2. acquired - HIV
290
what are patterns of immunodeficiency
1. decreased CD4 in HIV - increases susceptibility of the disease
2. B cells may be deficient
3. Neutrophil and macrophage deficiency
4. complement deficiency (SLE)
5. hyposplenism - lack of function of spleen
291
what are the different types of vaccine
1. live attenuated - MMR
2. antigens
3. toxins - Tetanus
4. constituents - HepB
292
what is natural active immunity
when the body encounters a pathogen and produces memory cells after infection
293
what is active artificial immunity
vaccine mimics encountering pathogen and stimulates immunoglobulin production
294
what is passive natural immunity
maternal Igs pass onto the baby in breast milk or colostrum
295
what is passive artificial immunity
antivenom - infection of Ig from another organism
296
what are the two routes of drug administration
1. Enteral - GIT involved - oral or rectal
2. Parenteral - non GIT - IM, IV, SC, Injections
297
what are the 4 drug targets
1. Receptors
2. Enzymes
3. Transporters
4. Ion channels
298
what are the two types of receptor targeting drugs
1. agonists
2. antagonists
299
what is the most common receptor type
G protein coupled receptor
300
what is the potency of a drug
how much drug is needed to elicit a response in the body - how well the drug works
301
what is drug synergy
when the interaction of drugs is such that the total effect is greater than the sum of the two individual effects
302
what is antagonism
when a substance that acts against and block an action (2 drugs apposing each other)
303
what is summation
this is an additive reaction - where two drugs have the same affect , where the total effect is the sub or the two drugs together
304
what is potentiation
the enhancement of one drug by another - 1+1=1+1.5
305
Define pharmacodynamics
the effect a drug has on the body
306
define pharmacokinetics
what the body does to the drug - deposition of a compound within an organism
307
what must you consider when discussing drug pharmacokinetics
1. Administration/absorption
2. distribution
3. metabolism
4. excretion
308
what is a drugs efficacy
the maximal response a drug can get - how well it activates the receptor
309
what are the properties of an agonist
they have full affinity and full efficacy
310
what are the propertied of an antagonist
they have full affinity but zero efficacy
311
what is an allosteric modulator
a drug which binds to a separate site other than the active site, and increases or decreases normal ligand binding
312
what is an example of an allosteric modulator
benzodiazepine
313
what is a selective drug
a drug that only binds to a specific receptor type in a family - only binding B1
314
what is an example of a non selective drug
propranolol - non selective beta blocker
315
what is a non selective drug
a drug that binds to all receptors within a family
316
what is an example of a selective drug
verapamil - selective beta blocker (only B1)
317
what is an example of an enzyme targeting drug
Cox-1 - NSAIDs
ACE-i - Inhibits conversion of angiotensin 1 to 2
318
What is an example of transporter targeting drugs
Proton pump inhibitors
Diuretics - loop - Furosemide inhibits NKCC2 and Thiazides inhibits NaCl cotransporter
319
What is an example of an ion channel targeting drug
calcium channel blockers - amlodipine, diltiazem
Local anesthetics - lidocaine
320
what is a specific drug
when a drug acts on a certain target
321
what is a selective drug
when a drug acts on a subtype of a target
322
what is bioavailability of a drug
how fast and to what extent a drug reaches systemic circulation
323
what type of drug administration gives 100% bioavailability
intravenous drugs
324
what are the mechanisms of drug administration
the route taken and the entry into the body
325
what are the mechanisms of drug distribution
drugs can be distributed in the plasma according to chemical properties and size, they may be taken up by organs and tissues.
- protein binding will affect how much drug is available and the strength it will act at
326
what are the mechanisms of drug metabolism
drugs are metabolised in the kidneys or liver (CYP450)
- kidneys metabolise mostly small water soluble drugs
- liver hydrophobic molecules: phase 1 and phase 2 reactions
327
what are the mechanisms of drug excretion
through urine (mostly) or feces
- renal will be pH dependent
328
what are some drug interactions to be aware of
Warfarin - lots of interactions causing enzyme induction (increased activity so warfarin has bigger effect quicker)
Acute kidney injury - NSAIDs and ACEi
329
what drugs work at the neuromuscular junction
Botulinum toxin - Ach release inhibited
Curare - nAch receptor antagonist
Ach-ase inhibitors - decreases Ach degradation
330
what happens when there is overstimulation of Ach at the neuromuscular junction
you go into cholinergic crisis
331
what are the symptoms of cholinergic crisis
Salivation
Lacrimation
Urination
Defecation
GI distress
Emesis
332
where are M1, M2 and M3 receptors found in the body
M1 = Brain
M2 = Heart
M3 = Lungs
333
what is the definition of a drug
a medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body
334
what are different types of receptors found in the body
ligand gated ion channels e.g nicotinic Ach receptor
G - protein couples receptors
Kinase - linked receptors e.g growth factors
Cytosolic/nuclear receptors e.g steroid receptors
335
what is tolerance to a drug
where there is reduction in the drug effect over time. This comes from continuous repeated use at high concentrations
336
what is drug desensitisation
this is rapid and comes when either the receptor is uncouples, internalised or degraded
337
what does afferent mean
takes signals toward the brain/spinal cord
338
what does efferent mean
takes signals away from the brain/spinal cord
339
what does adrenergic mean
relating to adrenaline or noradrenaline and either receptors
340
what does cholinergic mean
relating to acetylcholine and its receptor
341
what is the somatic nervous system
1. there are single neurons between the CNS and skeletal muscle 2. innervates skeletal muscle
3. leads to muscle excitation
342
what is the autonomic nervous system
1. a two neuron chain
2. smooth muscle, cardiac muscle, glands and GI
3. leads to excitation or inhibition
343
what separates the two peripheral neurons of the ANS
an autonomic ganglion
344
which branch of the autonomic nervous system (Para or sym) has a longer presynaptic neuron - before ganglion
parasympathetic
345
which branch of the autonomic nervous system (para or symp) has a longer post synaptic neuron - after ganglion
sympathetic
346
what are the two main neurotransmitters of the ANS
acetylcholine and noradrenaline
347
what types of preganglionic receptors does acetylcholine act on
nicotinic receptors
348
what type of postganglionic receptors does acetylcholine act on
muscarinic (PS)
349
what type of postganglionic receptors does noradrenaline act on
alpha and beta receptors (s)
350
in what part of the body is acetylcholine released at sympathetic postganglionic termini
sweat glands
351
in blood vessels what can be released from parasympathetic postganglionic termini
nitric oxide
352
where are the five types of muscarinic receptor found
M1: Brain
M2: Heart
M3: all organs with ps function - most notably the Lungs
M4: Mainly CNS
M5: Mainly CNS
353
what type of receptor are Muscarinic receptors
G coupled protein receptors
354
what does activation of M2 receptors in SAN cause
decrease in heart rate
355
what does activation of M2 receptors in AVN cause
1. decrease in conduction velocity
2. Induces an AV node block (increases PR)
356
What does M3 receptors stimulation in the respiratory system cause
1. mucus production
2. smooth muscle contraction (bronchoconstriction)
357
what does M3 receptor stimulation in the GIT cause
1. increased saliva production
2. increased gut production
3. stimulates biliary secretion
358
what does M3 receptor stimulation in the skin cause
sweating
359
where is the only place in the body where the sympathetic system releases Ach
the skin
360
what does M3 receptor activation of the urinary system cause
1. Contraction of the detrusor muscle
2. relaxation of the internal urethral sphincter (in males)
361
what does muscarinic receptor activation in the eyes cause
1. increases myosis
2. increases drainage of aqueous humour
3. secretion of tears
362
what are pilocarpine eye drops
they are M3 agonists - induce tear secretion and increases drainage of aqueous humour
363
what is atropine used for
used intravenously to increase heart rate, treat bradyarrythmias and AV node block
364
what type of drug is Hyoscine
it is a predominant M3 antagonist
365
what is hyoscine action
it is used in palliative care to treat respiratory secretions and symptoms of bowel obstruction
366
what are examples of inhales antimuscarinics
tiotropium, glycopyrronium, umeclidinium, aclidinium
367
why would you inhale an antimuscarinic
can cause bronchodilation
368
what are side effects of inhaled antimuscarinics
they can cause dry mouth, urinary retention, can worsen existing glaucoma
369
what is solifenacin
a treatment for an overactive bladder
370
how does solifancacin work
blocks M3 receptors in the bladder and inhibits smooth muscle contraction
371
what is mebeverine
a treatment for irritable bowel syndrome
372
how does mebeverine work
it blocks M3 receptors in the gut to slow contractility
373
why might anticholinergics (antimuscarinics) cause memory problems
because Ach is used in CNS as well and implicated in memory
374
what can be used to prevent Ach release in the somatic nervous system
Botulinum toxin
375
what are examples of muscle relaxants given during surgery
Rocuronium, suxamethonium, pancuronium
376
what is the mode of action for rocuronium, suxamethonium and pancuronium
they block nicotinic (N1) receptors to inhibit Ach activity in the somatic nervous system
377
what happens during myaesthenia gravis
there is Ach receptor antibodies which prevents Ach binding to post synaptic neurons. This leads to skeletal muscle weakness with the most notable weakness being on repeated attempts at a movement
378
what is a treatment for myaesthenia gravis
the treatment includes anti-cholinesterase to increase Ach availability at the neuromuscular junction
379
what is the precursor of noradrenaline
dopamine
380
what are the features of alpha 1 receptors
1. Agonist is noradrenaline over adrenaline
2. mechanism of action is increasing intracellular calcium via Gq signalling
3. its activation causes contraction of smooth muscle - mainly in the skin and abdomen
381
what are the features of alpha 2 receptors
1. Agonists are both noradrenaline and adrenaline
2. Mechanism of action is acting through Gi singalling to inhibit cAMP generation
3. causes mixed effects on smooth muscle
382
what are the features of beta 1 receptors
1. agonists are both noradrenaline and adrenaline
2. acts through Gs to raise cAMP
3. causes chronotropic and inotropic effects on the heart
383
what are the features of beta 2 receptors
1. agonist is adrenaline over noradrenaline
2. acts through Gs to raise cAMP
3. relaxes smooth muscles
384
What are the features of beta 3 receptors
1. agonist is noradrenaline over adrenaline
2. acts through Gs to raise cAMP
3. enhances lipolysis and relaxes the bladder detrusor muscle
385
what is given in ITU for shock
IV noradrenaline
386
what is xylometazoline used for
a nasal decongestant - topical alpha activation
387
what is clonidine and what is it used for
it is an alpha 2 agonist and it is used in ADHD to help concentration
388
what is the action of alpha 2 stimulation in blood vessels
it reduces vascular tone and blood pressure
389
what are some examples of alpha 1 blockers
1. doxazosin used to lower blood pressure
2 phenoxybenzamine used in treating a catecholamine secreting tumour
3. tamsulosin used to block alpha 1 receptors in the the prostate during benign prostatic hypertrophy
390
where are beta 1 receptors mainly found
in the heart, kidney and fat cells
391
what does an activation of B1 receptors lead to
1. tachycardia
2. increased stroke volume
3. renin release
4. lipolysis and hyperglycaemia
392
what do beta 1 blockers cause
reduced heart rate, reduced stroke volume, reduced myocardial oxygen demand
393
what are some examples of beta blockers
carvedilol, bisoprolol, atenolol
394
what does beta 2 receptor activation in the bronchi cause
bronchodilation
395
what does beta 2 receptor activation in the bladder wall cause
inhibition of micturition
396
what does beta 2 receptor activation in the uterus cause
inhibition of labour
397
what does beta 2 receptor activation in skeletal muscle cause
increased contraction speed (induces a tremor)
398
what does beta 2 receptor activation in the pancreas cause
insulin and glucagon secretion
399
what are beta 2 receptor agonist drugs used for
asthma i.e salbutamol, and chronic obstructive pulmonary disease
400
what are the steps Ach goes through at the neuromuscular junction
1. synthesis
2. vesicle storage
3. release
4. breakdown
5. reuptake
401
what effects does Ach stimulation have in the parasympathetic nervous system
1. rest and digest
2. pupil constriction
3. decreased HR
4. bronchoconstriction
5. increased gut motility and secretion
6. bladder contraction - detrusor muscles
7. penis erect
402
what effects does noradrenaline stimulation have in the sympathetic nervous system
1. fight or flight
2. pupil dilation
3. increased heart rate
4. bronchodilation
5. decreased gut motility
6. detrusor muscle relaxation
7. ejaculation
403
what is the noradrenergic synthesis pathway
tyrosine - DOPA - dopamine - Noradrenaline - Adrenaline
404
what drug is given in cardiogenic shock
B1 agonist dobutamine
405
what are the two types of Nad receptors
alpha and beta receptors
406
what are dopamine agonists used for
prolactinoma (pituitary tumour), acromegaly, and early in Parkinson's
407
give an example of a dopamine agonist
bromocriptine
408
what are dopamine antagonists used for
they are often used in psychiatric disorders and for nausea and vomiting
409
what are some examples of dopamine antagonists
1. metoclopramide: antiemetic
2. halopemide
410
what are GABA agonists used for
anxiety, sleep disorders, alcohol withdrawal and states epilepticus
411
what is an example of a GABA agonist
benzodiazepines (lorazepam and diazepam)
412
what are histamine H1 antagonists used for
for allergy (T1 IgE anaphylaxis)
413
what is an example of H1 histamine antagonist
loratadine
414
what are H2 histamine antagonists used for
these are second line treatments for GORD or an increased gastric acid after proton pump inhibitors
415
what are examples of a histamine H2 receptor antagonist
ranitidine (main)
Cimetidine
416
what is an irreversible inhibitor
they react with an enzyme and change it chemically (via covalent bond formation)
417
what is a reversible inhibitor
they bind non-covalently and different types of inhibition a produced dependent on whether the inhibitors binds to the enzyme, the enzyme substrate complex or both
418
what are the 4 types of ion channels
1. epithelial - sodium
2. voltage gated - calcium and sodium
3. metabolic - potassium
4. receptor activated - chloride
419
what is the oral bioavailability of opioids
at most about 50%
420
why is oral bioavailability of opioids quite low
due to first pass metabolism in the liver
421
what class of drugs are opioids
class A drugs
422
what are the practical issues with prescribing opioids in hospital
they are stored in locked containers and you must have two people sign them out
423
what is the action of codeine in the body
it is converted into morphine and then acts on the body
424
why must you not proscribe codeine to new mothers or infants
because 5-10% of people have an overactive enzyme which converts codeine to morphine - can lead to respiratory arrect in children (through breast milk)
425
what is the most common form of morphine found in hospitals
oromorph - taken orally
426
what does parenteral drug administration mean
IV administration
427
what does enteral drug administration mean
non-IV
428
how longs does it take an IV drugs, a sub-cutaneous drug and a drug taken orally to go through the body (roughly)
1. IV - minutes
2. Sub-cutaneous - about half an hour
3. Orally - about 1-2 hours
429
what is the difference between morphine and diamorphine
diamorphine is more potent and faster acting
430
how do opioids work
they attach to the opioids receptors in the brain/spinal cord and dampen pain reception.
431
what type of receptor is the opioid receptor
a G protein coupled receptor
432
how do naturally occurring opioids work (ones the body makes)
they inhibit pain transmission at the spinal cord/midbrain and they change the emotional perception of pain. They are part of the bodies fight or flight response and they have short term activity
433
how quicky does opioid tolerance occur
after a couple of days of medication
- receptors lost
434
what are the types of opioid receptor
MOP, KOP, DOP. NOP
435
what is tolerance
the down regulation of the receptors with a prolonged use. You need a higher dose to achieve the same effect
436
what is dependence
the psychological effect - craving, euphoria
437
what is opioid withdrawal
when you stop someones opioid medication - there will be withdrawal within 24 hours and it lasts about 72 hours
need to be careful with this as severe withdrawal symptoms can lead to death
438
why do you get opioid side effects
because you have opioid receptor outside the pain system - in the digestive tract, respiratory control centre etc
439
what are the side effects of opioid use
1. respiratory depression
2. sedation
3. nausea and vomiting
4. constipation
5. itching
6. immune suppression
7. endocrine effects
440
how are opioids metabolised in the body
morphine is metabolised to morphine 6 glucuronide which is more potent than morphine and is renally excreted. With normal renal function this is cleared quickly
441
what is the antidote for morphine
naloxone
442
what are the relative potencies of diamorphine, morphine and pethidine (in an average human)
1. diamorphine - 5mg
2. morphine - 10mg
3. Pethidine - 100mg
443
how do you treat opioid induced respiratory depression
1. ABC; airway, breathing, circulation
2. Give them IV naloxone (slowly - titrate)
444
what is the advice on prescribing opioids in chronic, non-cancer pain
1. before prescribing discuss the risks and features of opioid tolerance, dependence and addiction
2. agree a treatment strategy and when it will end
3. at the end, taper off the medication to help with withdrawal
445
what is the common antibiotic given for community acquired pneumonia
1. Amoxicillin
2. clarithromycin
446
what is the common antibiotic given for COPD
1. Amoxicillin
2. clarithromycin
447
what is the common antibiotic given for TB
RIPE
1. Rifampicin
2. Isoniazid
3. Pyrazinamide
4. Ethambutol
448
what is the common antibiotic given for hospital acquired pneumonia
1. co-amoxiclav 3X daily 500mg or 125mg for 5days
449
what are the side effects of rifampicin
red pee/tears
450
what are the side effects of isoniazid
peripheral neuropathy
451
what are the side effects of Pyrazinamide
can cause hepatitis
452
what are the side effects of ethambutol
can cause optic neuropathy
453
what is the common antibiotic given for cellulitis
flucloxacillin
- if MRSA give vancomycin
454
what is the common antibiotic given for a UTI
Trimethoprim or nitrofurantoin (Give nitrofurantoin)
(if pregnant give folate as well as can be teratogenic - nitrofurantoin preferred)
455
what is the common antibiotic given for pyelonephritis
cefalexin or co-amoxiclav
456
what is the common antibiotic given for chlamydia trachomatis
azithromycin or doxycycline
457
what is the common antibiotic given for Neisseria gonorrhoea
IM ceftriaxone and azithromycin (one off)
458
what is the common antibiotic given for syphilis
benzathine penicillin or benzylpenicillin
459
what is the common antibiotic given for H.Pylori
CAP for 7 days
1. clarithromycin
2. Amoxicillin
3. PPI
460
what is the common antibiotic given for gastroenteritis
campylobacter = clarithromycin
salmonella and shigella = ciprofloxacin
461
what is the common antibiotic given for infective endocarditis
s.aureus = vancomycin and rifampicin
s.vindans = benzylpenicillin and gentamycin
462
what is the common antibiotic given for bacterial meningitis
ceftriaxone in hospital, amoxicillin of listeria suspected and steroids
in the community = benzylpenicillin if meningococcal suspected
463
what is the common antibiotic for C.Difficile
vancomycin - 125mg for 4 times a day for 10 days
464
what neurotransmitter does the parasympathetic system release (commonly)
Ach which acts on muscarinic receptors
465
what neurotransmitter does the sympathetic nervous system release (commonly)
noradrenaline which activates adrenergic receptors (alpha/beta receptors)
466
what do both sympathetic and parasympathetic fibers release pre-ganglionically
Ach which acts on nicotinic receptors
467
what are side effects of anti-cholinergics
worsening or memory and cause confusion. Constipation, drying of the mouth, blurring of vision and worsening of glaucoma
468
what are the different routes of drug administration
1. oral
2. intravenous
3. intra-arterial
4. intramuscular
5. subcutaneous
6. inhalational
7. topical
8. sublingual
9. rectal
10. intrathecal
469
what are the four major metabolic barriers oral drugs must pass through
1. intestinal lumen
2. intestinal wall
3. liver
4. lungs
470
what are the features of intradermal and subcutaneous absorption
1. it avoids the barrier of the striatum corneum
2. it is mainly limited by blood flow
3. only small volume can be given
4. this is used for local effect or to limit the rate of absorption
471
what are the different types of pain
Acute, Cancer, Neuropathic, Chronic non cancer
472
What is the cause of acute pain
nociceptor signaling (Ab, Ad and C fibres) to the thalamus
473
what is the gate control theory
Pain modulated by:
heat - rubbing the site of pain - decreased pain impulses via the ascending tract
medication acting on the same pathway - NSAIDs, Opioids, anesthesia
474
What are the features of adverse drug reactions
ABCDEs
Augmented - is it predictable
Bizarre - is it because of allergy
Chronic - has the drug been used for a long time
Delayed - has the drug been used in the past
End of use - is it because there is withdrawal of drug
475
what are patient factors which must be considered with drug interactions
1. Age
2. Polypharmacy
3. Genetics
4. Hepatitis/renal disease
476
what are the pharmacokinetic influences in drug absorption
acidity, motility and solubility
477
what are the pharmacokinetic influences in drug distribution
influenced by protein binding
478
what are the pharmacokinetic influences in drug metabolism
CYP450 induction and inhibition
479
what are the pharmacokinetic influences of drug excretion
affected by urine pH
- acids cleared faster if urine is weakly basic
- bases cleared faster if urine is weakly acidic
480
what are the antiplatelet drug used in practice
aspirin - COX inhibition
Clopidogrel - P2Y12 inhibition
481
what are the anticoagulant drugs used in practice
Heparin - activates antithrombin 3 and inhibits factor 10
Warfarin - anti vitamin K
DOACs - anti factor Xa
Thrombolytics
482
what is the action of NSAIDs
inhibit COX1 and 2 and prevent prostaglandin production
- needs to be given with PPI now (aspirin)
483
what is the common side effect of NSAIDs
Peptic Ulcer disease
484
What is the common side effect of ACE inhibitors
increased bradykinin accumulation and causes a dry cough
reduces GFR and can cause acute kidney injury
485
what are common side effects of PPIs
prolonged use can increase fracture risk
486
what are common side effects of opioids
respiratory diseases
tolerance and dependence
nausea and vomiting
487
what are common side effects of loop diuretics and thiazides
hypokalemia and dehydration
488
what are common side effects of spironolactone
hyperkalemia
489
what is the common loop diuretic and its action
Furosemide
inhibits the NKCC2 channels in the ascending loop of henle
it increases Cl-, K+ and Na+ and water excretion
490
what is is the common thiazide used and what is its action
Bendroflumethiazide
they inhibit NaCl- channels in the distal convoluted tubule and therefore increase Cl- Na+ and water excretion
491
what is spironolactone and what is its action
it is a diuretic and it inhibits ENaC channels (aldosterone antagonist as well) and therefore increases sodium potassium and water excretion
492
what are the common steroid side effects
Cataracts Increased infection risk
Ulcers Necrosis of bone
Striae Growth restriction
Osteoporosis Increased ICP
DMT2 Myopathy
Adipose hypertrophy Pancreatitis
493
what does intramuscular absorption depend on
blood flow and water solubility with an increase in either enhancing removal of drug from injection site.
494
what are the features of inhalational absorption
there is a larger surface area and blood flow but it is limited by the risks of toxicity to the alveoli
it is largely limited to volatiles such as anesthetics and locally acting drugs
495
what is the most common protein drugs bind to in blood
albumin (reversibly)
496
what happens during phase 1 metabolism of drugs
transforming the drugs to more polar metabolites
- unmasking or adding functional groups
- oxidation reactions catalyzed by CYP450
497
what happens during phase 2 drug metabolism
formation of covalent bonds between the drug and endogenous substrates
- glucuronidation
498
what is first order kinetics
- pharmacokinetics
when an IV drug is given and rapidly distributed into the tissues, the decline in plasma concentration will be exponential
(constant fraction of the drug is eliminated per unit of time)
499
what is zero order kinetics
- pharmacokinetics
if an enzyme that removes a drug is saturated, the rate of removal of the drug is constant and unaffected by any increase in the concentration
500
what are the most common drugs to have allergy to
Antibiotics and NSAIDs
501
what percentage of adverse drug reactions are allergy
5-10%
502
what is the definition of hypersensitivity
objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects and may be caused by immunologic and non immunologic mechanisms
503
what are examples of delayed drug hypersensitivity
rashes, hepatitis and cytopenia's
504
what is a urticarial rash
a fast forming, intensely itchy rash
505
what are the features of anaphylaxis
it occurs within minutes and causes vasodilation, increased vascular permeability, bronchoconstriction, urticaria and angio-oedema, swelling of the lips, face, wheeze.
506
what is the most common cause of anaphylaxis
insect venom, followed by medications
507
what is a biphasic anaphylactic shock
where you have the initial reaction, you are treated for it, and you get the response again (without another stimulus) soon after treatment
508
what percentage of anaphylaxis is biphasic
1-20% of responses
509
what drugs are commonly implicated in hypersensitivity reactions
Aspirin, Penicillin, sulfonamides, antituberculosis drugs, nitrofurans, anticonvulsants, anesthetics, antiarrhythmia agents, antisera and vaccines, heavy metals, antibiotics, phenolphthalein
510
what is non immune anaphylaxis
this is where you need no prior exposure to the allergen, but you still get mast cell degranulation. looks exactly the same as immune mediated anaphylaxis
511
what is the management of anaphylaxis
Common basic life support: ABC
Adrenaline IM 500 micrograms and high flow oxygen
IV fluids and antihistamines
512
what are the actions of adrenaline in anaphylaxis
causes vasoconstriction increasing PVR and BP via alpha 1 receptors
stimulation of Beta 1 receptors causes positive ionotropic and chronotropic effects on the heart
bronchodilation via beta 2 receptors
stops further mast cell and basophil degranulation via cAMP increase
513
what are risk factors of hypersensitivity
medicine factors: protein or polysaccharide based molecules
Host factors: Female, having EBV or HIV, Being in the extremes of life, uncontrolled asthma, previous drug reactions
Genetic factors: certain HLA groups, acetylator status
514
what are the clinical criteria for allergy to drug
1. dont correlate with pharmacological properties of the drug
2. no linear reaction with dose
3. reaction similar to those with other allergens
4. induction period of primary exposure
5. disappearance on cessation
6. re-appears on re-exposure
7. occurs in minority of patients on the drug
515
what are the impacts of adverse drug reactions in healthcare
1. adversely affects patients quality of life
2. increases the cost of care
3. precludes the use of a drug in most patients
4. may mimic disease
5. very common cause of death
516
what is an adverse drug reaction
it is unwanted or harmful reaction following the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to the drug
- has to be noxious and unintended
517
are adverse drug reactions the same as side effects
they can be however not all the time as side affects can be beneficial, but adverse drug reactions are never beneficial
518
what is a toxic affect - adverse drug reaction
when the drug concentration is beyond the therapeutic range
519
what is a collateral effect - adverse drug reactions
when the drug concentration is within the therapeutic range
520
what is a hyper-sensitivity effect - adverse drug reactions
when the drug concentration is below the therapeutic range
521
what are examples of toxic drug effects when the drug concentration is too high
Gentamicin: causes nephropathy or ototoxicity at high concentrations
522
why can toxic drug affects occur
when you have too high drug concentration, you cant excrete the drug correctly, or there are interactions with other drugs
523
what is an example of collateral adverse drug reaction effects
beta blockers causing bronchoconstriction
antibiotics causing clostridium difficile
524
what is an example of hypersensitivity adverse drug reaction
anaphylaxis and penicillin
525
what can the severity of adverse drug reactions be
can range from mild (nausea or drowsiness) to severe (respiratory depression, hemorrhage, anaphylaxis)
526
what are risk factors of adverse drug reactions
Patient risk: female, elderly, neonates, polypharmacy, genetics, hypersensitivity or allergies, hepatic or renal impairment
Drug risk: steep dose response curve, low therapeutic index, commonly causes ADRs
Prescriber risk: human error
527
what are causes for ADRs
1. pharmaceutical variation
2. receptor abnormality
3. abnormal biological system unmasked by drugs
4. abnormal drug metabolism
5. immunological
6. drug-drug interactions
7. multifactorial
528
what is an augmented ADR
it is an extension of the primary effect or the drug (such as propranolol and bradycardia) and has a high morbidity with a low mortality (excludes overdose)
529
what is a bizarre ADR
It is non predictable or related to the pharmacology of the drug and is not dose dependent. It is less common but more serious with low morbidity and high mortality
530
what is idiosyncrasy
where there is an inherent abnormal response to a drug
- enzyme abnormality, deficiency or abnormal receptor activity
531
what are continuous ADRs
it is related to cumulative dose on dose responses to a drug and it occurs over time. It is uncommon
- steroids and osteopetrosis
532
what are delayed ADRs
where the ADR shows itself after the use of the drug. They are uncommon and normally dose related
- Carcinogens
533
what are ending of drug use ADRs
where the ADR occurs once a drug has been withdrawn. they are uncommon
- example is opioid withdrawal
534
what is a failure ADR
This is often caused by drug interactions causing failure of the drug, it is common and dose related
- failure of oral contraceptive and enzyme inducers
535
when do you suspect ADR
1. symptoms occur soon after new drug starts
2. Symptoms appear after increased dose
3. symptoms disappear when drug is stopped
4. symptoms appear when drug is restarted
536
when do you suspect ADR
1. symptoms occur soon after new drug starts
2. Symptoms appear after increased dose
3. symptoms disappear when drug is stopped
4. symptoms appear when drug is restarted
537
what do you do if there is an ADR
1. assess if urgent action is required
2. take history
3. review medication history
4. review adverse effect profile of suspected drug
5. modify dose, stop or swap
6. report
538
what drugs commonly have ADRs
antibiotics, NSAIDs, Cardiovascular drugs, hypoglycemics, CNS drugs
539
what are common ADRs
confusion, Nausea, balance problems, diarrhea, constipation, hypotension
540
how do you gather information on ADRs
pre-clinical trials, post marketing surveillance and yellow card reporting
541
what are the MHRA responsible for
approving medicines for use and watching over them and take actions to protect the public if there is an issue
542
what is the yellow card scheme
it is a ADR reporting scheme which collects spontaneous reports as well as suspected adverse drug reactions - voluntary
543
why would you report an ADR
1. patient safety
2. identify ADRs not seen in clinical trial
3. identify new ADRs quickly
4. compare drugs within the same class
5. identify ADRs in at risk groups
544
what is a black triangle drug
one that is undergoing additional monitoring
545
what are pharmacokinetic issues with immunotherapy
1. immunoglobulins cant be filtered by the kidney: too big
2. FcRn receptor - systemic receptors which absorb IgG into cells protecting them from metabolism dont recognise mouse antibodies resulting in a shorter half life
546
how is insulin currently made
Recombinant Human Insulin
- insulin gene inserted into a plasmid which is transfected into bacteria. The bacteria will then produce insulin during fermentation which can then be purified and used
547
what are examples of recombinant proteins in clinical use
1. insulin
2. EPO
3. growth hormone
4. interleukin 2
5. gamma interferon
548
what are the clinical uses of glucocorticoids (steroids)
asthma, allergic reaction, hives, eczema, COPD, lupus, IBD, MS
549
what is rational drug design
the process of finding new medications based on the knowledge of a biological target
- complementary
550
what is drug re-purposing
a technique where existing drugs are used to treat emerging and challenging diseases
551
what is the monoclonal antibody against TNF alpha
Infliximab
