ICS Flashcards
1
Q
What is inflammation?
A
A reaction to an injury or infection involving cells such as neutrophils and macrophages.
2
Q
How is inflammation classified?
A
Acute and Chronic
3
Q
What cells are common in acute inflammation?
A
Neutrophils
4
Q
What cells are common in chronic inflammation?
A
Lymphocytes & macrophages
5
Q
Features of acute inflammation?
A
- Sudden onset
- Short duration
- Usually resolves
6
Q
Features of chronic inflammation?
A
- Slow onset or sequel to acute
- Long duration
- May never resolve
7
Q
What do neutrophil polymorphs do in inflammation?
A
- Short lived
- First on scene
- Cytoplasmic granules containing enzymes
- Die at scene of inflammation -Releases yellowy puss
- Releases chemicals that attract other inflammatory cells eg. macrophages
8
Q
What do macrophages do in inflammation?
A
- Long life (weeks to months)
- Phagocytic
- Carry debris away (eg. to lymph nodes)
- Present antigens to lymphocytes
- Don’t always die
9
Q
What do lymphocytes do in inflammation?
A
- Memory cells
- Long life (years)
- Produce chemicals which attract inflammatory cells
10
Q
What do endothelial cells do in inflammation?
A
- become sticky
2. become porous (precapillary sphincters open = more blood flows through = more inflammatory cells)
11
Q
Why is there redness and swelling in inflammation?
A
Red = increased blood flow
Swelling = more protein out, less/no liquid in
12
Q
What cells are involved in chronic inflammation?
A
Lymphocytes, plasma & macrophages
13
Q
What is a granuloma?
A
Aggregate of epitheliod histiocytes (macrophages) surrounded by lymphocytes.
14
Q
Systemic effects of inflammation?
A
- Fever (pyrexia)
- Weight loss
- Amyloidosis
15
Q
How do you treat inflammation?
A
Aspirin
NSAIDs - stop prostaglandin synthase
Betnovate cream
16
Q
What is betnovate cream?
A
Corticosteroid
Can cause skin to atrophy
Powerful/potent anti inflammatory
Binds to DNA to upregulate inhibitors of inflammation and downregulate chemical mediators of inflammation.
17
Q
What is prostaglandin synthase?
A
It is a chemical mediator of inflammation.
18
Q
When is cell damage resolved?
A
When initiating factor is removed.
Tissue is undamaged or able to regenerate.
19
Q
When is cell damaged repaired?
A
Initiating factor is still present. Tissue damaged and unable to regenerate.
20
Q
What causes cirrhosis?
A
Architectual damage –> fibrous scarring –> regenerative nodules –> cirrhosis
21
Q
How do skin abrasions heal?
A
Scab forms over surface, root hair cells and weat glads still there, grows up under the scab.
22
Q
How do 1st intention (edges together) wounds heal?
A
Fibrin from blood - fibroblasts produce collagen.
23
Q
How do 2nd intention (edges can’t be pulled together) wounds heal?
A
Fibroblasts grow from the edges of the wound.
24
Q
What cells regenerate?
A
- Hepatocytes
- Pneumocytes
- All blood cells
- Gut epithelium
- Skin epithelium
- Osteocytes
25
What cells don't regenerate?
- Myocardial cells
| - Neurones
26
What is ischaemia?
Reduction in blood flow
27
What is infarction?
Death of cells due to ischaemia.
28
What is a reperfusion injury and why are they caused?
When blood is reintroduced after ischaemia cells produce damaging chemicals eg. superoxides.
29
Features of RCA obstruction?
- Inferior obstruction
- ECG changes in leads II, III, aVF
- Can involve post. septum
- 30% of cases
30
Features of LAD obstruction?
- Artery of sudden death
- Anterior infartion
- ECG changes in anterior chest leads
- 50% cases
31
Features of circumflex obstruction?
- Lateral infaction
- ECG changes in I, aVL and lateral chest leads (V4-6)
- 20% cases
32
What is a thrombosis?
Solid mass of blood constituents formed within intact vascular system during life.
33
What are the three components that make up thrombosis risk?
- Change in vessel wall
- Change in blood flow
- Change in blood constituents
34
How do you prevent thrombosis?
- Exercise
- Tight elastic stockings/socks
- Wiggle toes
- Aspirin = anti-platelet = stops platelet aggregation
35
What is an embolus?
Mass of material in the vascular system able to become lodged within a vessel and block it.
The most common is a piece of thrombus but can be others eg. gas.
36
What is hypertrophy?
Increase in size of a tissue caused by an increase in size of the constituent cells.
37
What is hyperplasia?
Increase in size of a tissue caused by an increase in number of the consituent cells.
38
What is atrophy?
Decrease in size of a tissue caused by a decrease in number of the constituent cells OR a decrease in their size.
39
What is metaplasia?
Change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type.
40
What is dysplasia?
Imprecise term for the morphological changes seen in cells in the progression to becoming cancer.
(Not yet but could become cancer)
41
What is apoptosis?
Programmed cell death.
42
What causes cells to apoptose?
DNA damage
43
How do cell apoptose?
- Enzymes released which kills nucleus
- Nucleus condenses
- Cells shrink
- Nucleus fragments
- Cleaned by macrophages
44
What is p53?
A protein which detects DNA damage and produces chemicals to cause apoptosis.
45
What is necrosis?
Mass death of cells.
46
What are the two types of necrosis?
Coagulative - thick and goey
| Liquifactive - goes liquidy
47
What is caseous necrosis?
Has holes in it - common in TB
48
What are telomeres?
Section at the end of chromosomes, each time a cell divides the telomere shortens.
49
What affects how quickly a cell wears out?
-Cross-linking/mutations of DNA
-Loss of Ca2+ influx controls
-Cross-linking of proteins
-Telomere shortening
-Accumulation of toxic by-products of metabolism
-Free radical generation
-Peroxidation of membranes
etc.
50
What does UVB light cause?
Protein cross linking - makes collagen no longer elastic
51
What is osteoporosis in women?
Lack of aestrogen = increased bone resorption and decreased bone formation.
52
How are cataracts caused?
UV-B light causes protein cross linking which makes the proteins opaque.
53
What causes sarcopaenia (lack of muscle)?
Decreased growth hormones, decreased testosterone, increased catabolic cytokines.
Increasing testosterone does decrease sarcopaenia but increased GH doesn't.
54
When does atheroschlerosis occur?
- In more deprived area
| - Age 50+
55
Where is there rarely atherosclerosis?
Low pressure systems.
56
What's in plaque?
- Fibrous tissue
- Lipids, cholesterol
- Lymphocytes, chronic inflammation
57
What are risk factors of atherosclerosis?
- Smoking cigarettes = free radicals, nicotine, carbon monoxide which cause damage to endothelial cells
- Hypertension = shearing forces
- Poorly controlled diabetes = superoxide anions, glycosylation products
- Hyperlipidaemia
58
Why does atheroslerosis form?
Endothelial cell damage.
They are delicate and metabolically active cells.
59
What is acute inflammation?
The initial and often transient series of tissue reactions to injury.
60
What is chronic inflammation?
The subsequent and often prolonged tissue reactions following the initial response.
61
What is tissue necrosis?
Death of tissues from lack of oxygen or nutriients resulting from inadequate blood flow.
62
Treatment for basal cell carcinoma?
Complete local excision
63
Breast cancer treatment:
| It has spread to the axilla.. treatment?
Axillary node clearance
64
Breast cancer treatment:
| It has spread to the rest of the body.. treatment?
Systemic chemo therapy
65
Breast cancer treatment: it hasn’t spread to the rest of your body or axilla.. treatment?
Surgery with or without axillary lymph node clearance.
66
What is adjuvant therapy?
Treatment given after surgical treatment.
67
What is carcinogenesis?
Transformation of normal cells to neoplasticism cells through permanent genetic alterations or mutations.
68
What is oncogenesis?
Formation of benign and malignant tumours.
69
What’s the difference between carcinogenic and oncogenic?
Carcinogen: agents thought to cause rumours
Oncogen: cancer tumour causing
Both act on DNA
70
What percentage of cancer risk is environmental?
85%
71
What are the carcinogens for hepatocellular carcinoma?
Hep B/C and mycotoxins
72
What are the carcinogens for Oesophageal carcinoma?
Linhsien chickens and very very hot coffee.
Increased incidence in Japan, China , Turkey, Iran
73
What are the carcinogens for Lung cancer?
Smoking
35,000 deaths/year
74
What are the carcinogens for Bladder cancer?
Anyone dye and rubber industries
75
What are the carcinogens for Scrotal cancer?
Higher risk in chimney sweeps. Polycyclic aromatic hydrocarbons.
76
What is Thorotrast?
- Colliidal suspension of thorium
- radiographic contrast medium 1930-1950
- 1947 post-thorotrast angiosarcoma
- it is radioactive
77
What are the classes of carcinogens?
- Chemical
- Viral
- ionising and non-ionising radiation
- hormones, parasites and micro toxins
- misc
78
What can polycyclic hydrocarbons cause?
Lung & skin cancer
Found in cigarettes and mineral oils
79
What can aromatic amines?
Bladder cancer
From rubber/dye workers
80
What can nitrosamines cause?
Gut cancer
In processed/smoked
81
What can alkylating agents cause?
Leukaemia
Used to kill certain cancers
Small risk in humans
82
What does increased exposure to UV(A & B) light increase the risk of?
Basal cell carcinoma, melanoma, squamous cell carcinoma
Much higher risk of xeroderma pigmentosum
83
Name some biological, hormonal carcinogens?
Oestrogen - increases mammary/endometrial cancer
Steroids- hepatocellular carcinoma
84
Name a biological, mycotoxin carcinogen?
Aflatoxin B - hepatocellular carcinoma
85
Name some biological, parasitic carcinogens?
Clonorchis sinensis - cholangiocarcinoma
Shistosoma - bladder cancer
86
What does asbestos cause?
Malignant mesothelioma, lung cancer, asbestosis
87
What is a neoplasm?
A lesion resulting from the AUTONOMOUS or relatively autonomous ABNORMAL growth of cells which PERSISTS after the irritating stimulus has been removed.
A new growth.
88
What is the epidemiology of neoplasm?
```
25% of population
All ages
Increased risk with age
Mortality rate high
20% all deaths
```
89
What are the two parts of neoplasm?
Neoplastic cells and stroma
90
What are features of neoplastic cells?
- Nucleated cells
- Usually monoclonal
- Growth pattern mirrors parent cell
- Synthetic activity same as parent cell
91
What are features of neoplastic stroma?
- Connective tissue framework
- Mechanical support
- Provides nutrition
- Fibroblasts and blood vessels
92
What are the three behavioural classifications of neoplasms?
- Benign
- Borderline
- Malignant
93
What are features of benign neoplams?
- Localised, non-invasive
- Slow growth rate
- Low mitotic index
- Close resemblance to normal tissue
- Circumscribed/encapsulated
- Nuclear morphometry often normal
- Necrosis and ulceration rare
- Growth on mucosal surfaces often exophytic
94
How does benign neoplasm cause morbidity/mortality?
- Pressure on adjacent structures
- Obstruct flow
- Produce hormones
- Transform to malignant
- Anxiety
95
What are features of malignant neoplasms?
MUST BE INVASIVE
- Metastases
- Rapid growth rate (compared to benign)
- Variable resemblance to normal tissue
- Poorly defined/irregular border
- Increased mitotic activity (metaphase)
- Necrosis and ulceration common
- Endophytic
- Encroach upon/destroy surrounding tissue
96
What is histogenesis?
The specific cell of origin of a tumour
97
What is the suffix for all neoplasms?
-oma
98
What is a papilloma?
Benign tumour of non-glandular, non-secretory epithelium.
99
What is an adenoma?
Benign tumour of glandular/secretory epithelium
100
What is a carcinoma?
Malignant tumour of epithelial cells
101
What is an adenocarcinoma?
Carcinoma of glandular epithelium
102
What is a lipoma?
Benign neoplasm of adipocytes
103
What is a chondroma?
Benign neoplasm of cartilage
104
What is an osteoma?
Benign neoplasm of bone
105
What is an angioma?
Benign neoplasm of vessels
106
What is a rhabdomyoma?
Benign neoplasm of striated muscle
107
What is a leioma?
Benign neoplasm of smooth muscle
108
What is neuroma?
Benign neoplasm of nerves
109
What is a sarcoma?
Fleshy, MALIGNANT
110
What is a liposarcoma?
Malignant neoplasm of adipose tissue
111
What is anaplastic?
Cell-type of origin unknown?
112
Explain the process of invasion?
Carcinoma in situ -> BM -> Extracellilar matrix -> lymph/blood vessels -> Travel (avoiding WBCs) -> Land -> Stick to vessel wall -> Into extracellular matrix
113
What do tumours have to do at 1-2mm?
Angiogenesis
114
Why do lymphoma and other sarcomas spread to bone?
When in blood the first small vessels broken off bits of tumour come across are in the lungs.
115
How does cancer evade immune defence?
- Aggregation with platelets/themselves
| - Shed surface antigens
116
What neoplasias commonly met in the liver?
Anything colorectal, stomach, pancreas. Through the portal vein.
117
What commonly met in bone?
- Lung
- Thyroid
- Breast
- Prostate
- Kidney
118
What is innate immunity?
Instinctive, non-specific, doesn't depend on lymphoctyes, present from birth.
119
What is adaptive immunity?
Specific 'aquired/learned' immunity requires lymphocytes, antibodies.
Made up of cells & soluble factors (humoral)
120
What is the haematocrit?
RBC volume, ~45%
121
What is serum?
Plasma without fibrinogen and other clotting factors.
122
Where do immune system cells originate from?
Multipotent haemopoetic stem cells. Differentiation depends on which cytokines are released.
123
What type of stain do neutrophils stain with?
Neutral
124
What type of stain do Eosinophils stain with?
Acidic
125
What type of stain do basoophils stain with?
Basic
126
What are the early mononuclear leukocytes and what do they really differentiate into?
Monocyte ---> Macrophage
T-Cells ---> T regulators, T Helpers (CD4) (Th1, Th2), Cytotoxic
B-Cells ---> Plasma
127
What are soluble factors?
Tell cells to do things.
Compliment
Antibodies
Cytokines, chemokines
128
What are compliments?
```
Group of ~20 serum proteins secreted by the liver.
Need to be activated.
Action:
-direct lysis
-attract more leukocytes
-coat invading organisms
-lysis, chemotaxis, oponisation
```
129
What are the antibodies and their proportion?
```
IgG - 70-80%
IgM - ~10%
IgA - 15%
IgD ~1%
IgE ~ 0.05% Allergic reactions/parasites
```
130
What are interferons?
A type of cytokine which induce a state of antiviral resistance in uninfected cells & limit spread of infection?
131
What are interleukins?
A type of cytokine
>30 types.
IL1 = pro-inflammatory
IL10 = anti-inflammatory
132
What are colony stimulating factors?
A type of cytokine
| Cause division and differentiation on basement membrane stem cells.
133
What are tumour necrosis factors?
A type of cytokine
| Mediate inflammation & cytotoxic reactions
134
What are chemokines?
They tell cells where to go
~40 types
Certain chemokines attract certain cells
135
What are innate immunity components?
- Physical & chemical barriers
- Phagocytic cells (neutrophils and macrophages)
- Blood proteins (compliment, acute phase)
136
Define inflammation?
A series of reactions that brings cells and molecules of the immune system to sites of infection/damage.
137
What is extravasation?
Attracting other cells
Lymphoctyes releases TNF alpha --> Causes endothelium to become sticky --> other cells go through endothelium
138
What is involved in oxygen dependant microbial killing?
- Reactive oxygen intermediates (ROI)
- Super oxides O2- are converted into H2O2 then OH radicals
- NO = vasodilation (viagra)
139
What is involved in oxygen independant microbial killing?
- Enzymes
- Proteins
- pH
140
What cells kill which microbes in the adaptive immune system?
- T cells = intracellular microbes
| - B cells = extracellular microbes
141
Primary and secondary lymphoid of T-Cells?
Thymus --> Spleen, lymph nodes, MALT
142
Primary and secondary lymphoid of B-Cells?
Bone Marrow --> Spleen, lymph nodes, MALT
143
Primary and secondary lymphoid of APC, dendritic Cells, macrophages, B Cells?
Bone Marrow --> tissue --> Spleen, lymph nodes, MALT
144
What are features of T Lymphoctyes?
- Don't respond to soluble antigens, only intracellular 'presented antigens'
- T Cells that recognise 'self' killed in thymus
- Receptors detect antigens & associated with major histocompatibility complex (MHC)
145
What are the MHCs?
Major histocompatibility complexes
MHC1 - all nucleated cells (8-10aa's)
MHC2 - only antigen presenting cells (13-24aa's)
146
What do all T cells stem from?
Alpha, beta T
147
What do Alpha-beta T cells develop to?
CD4 & CD8
148
What does CD4 develop into?
When IL-12 is high = TH1
| When IL-12 is low = TH2
149
What do CD8 T cells do
Kill intracellular pathogens directly by producing perforin (apoptosis) and granulysin (punch holes in cells - killing)
150
What do CD4 - TH1 cells do?
IFN gamma helps kill intracellular pathogens
151
What do CD4 - TH2 cells do?
Antibody production
152
What is the process of immunisation?
Exposure/vaccination ---> antigen presentation to T Cells ---> IgM produced ---> highly specific IgG produced --> large amounts of IgGs from plasma cells
153
How does the body handle bacteria/fungi?
Phagocytosis & killing
154
How does the body handle viruses?
Cellular shut-down, self-sacrifice, cellular resistance.
155
What are the problems with immunity?
- Take long time
- Highly specific
- Lots of bacteria/pathogens
156
What patterns on pathogens are detected?
- Gram +ve/-ve
- double stranded RNA
- CpG motifs
157
What are TLRs?
Toll like receptors. The most common type of recpetor.
| Endotoxin is present in gram -ve bacteria.
158
What are secreted/circulating PRRs?
Pattern recognition receptors.
- Antimicrobial peptides secreted in lining fluids, from epithelia and phagocytes.
- Lectins and collectings are carbohydrate-containing proteins that bind carbohydrates or lipids in microbe walls. Activate complement. improve phagocytosis.
- Pentracins - proteins like CRP which have some antimicrobial actions. React with C protein of pneumococci, activate compliment.
159
What are cell associated PRRs?
Pattern recognition receptors.
Present on cell membrane/cytosol of cells.
!!!TLRs are main family!!!
160
What are NLRs?
Nod like receptors.
22 human proteins that detect intracellular microbial pathogens.
Known as NOD1, NOd2 NLRP" etc.
161
What do NOD2 receptors do?
- Recognise muramyl dipeptide (MDP), a breakdown product of peptoglycan.
- Activates inflammatory signalling pathways
- Chron's = non-functioning
162
What are RLRs?
Rig like receptors.
Named after first members of the family Rig-I. Rig Like Helicases.
Couple to activate interferon production for antiviral response.
163
What is natural passive immunisation?
The transfer of maternal antibodies across the placenta.
164
What is artificial passive immunisation?
Treatment with pooled normal human IgG or immunoserum against pathogens or toxins.
165
What vaccines are passive?
Botulism, tetanus, diphtheria (anti toxins)
Hepatitis, measles, rabies (prophylactically)
Anti-venins
166
What are the steps of active immunisation?
Engage innate immune system
Elicit danger signals eg. PAMPs
Engage TLR receptors
Activate specialised antigen presenting cells eg. Langerhans cells
Engage adaptive immune systems - generate T & B cells. Activate T cell helper.
167
What antibodies are active at different parts after exposure?
~ 2 days in = IgM starts
~6 days in = IgG starts
Secondary exposure = lots more IgG, about 900 times more than IgM which is less than the first exposure.
See graph.
168
Why does flu require repeated immunisation?
Rapid onset - become infected before immunological memory activated. So high level of antibody must be kept, also requires different types due to annual escape variants.
169
What are the types of antigens for vaccines?
a) Whole organism
- -> Live attenuated
- -> Killed, inactivated
b) Subunit
c) Peptides
d) DNA Vaccines
e) Engineered virus
170
What vaccines are live attenuated pathogens?
TB- BCG
Polio Sabin
Correct preparation is essential
171
Name some advantages to live attenuated pathogen vaccines?
- Activates natural response machanism
- Prolonged contact with immune system
- Memory response
- Single immunisation required
172
Name some disadvantages to live attenuated pathogen vaccines?
- Can't be used in immunocompromised patients
- Complications
- Occationally can become virulent
173
Name some advantages to the whole inactivated pathogen vaccines?
- No infection risk
- Storage not critical
- Wide range of antigens = good immune response
174
Name some disadvantages to live attenuated pathogen vaccines?
- Just activate humoral - lack of T
- Weak immune response
- Boosters needed
- Patient compliance issue
175
Name some advantages to subunit vaccines?
- Safe
- No risk of infection
- Easy to store and preserve
176
Name some disadvantages to subunit vaccines?
- Immune response less powerful
| - Repeated vaccinations and ajuvants
177
What is a toxoid?
Heat/chemically treated toxin modified to eliminate toxicity
178
What vaccines use bacterial exotoxins?
- Diptheria
| - Tetanus
179
Name some advantages to DNA vaccines?
- Safe
- Not complex storage & transportation
- Drug delivery simple and adaptable to widespread vaccination programmes
180
Name some disadvantages to DNA vaccines?
- Mild response
- Subsequent boosting
- No transient infections
- Limited to proteins, could induce tolerance or anti-DNA antibodies
181
How do recombinant vector vaccines work?
Imitate the effect of transient infection with pathogen but using a non-pathogenic organism
182
Name some advantages to recombinant viral vaccines?
- Create ideal stimulus to immune system
- Produce immunological memory
- Flexible - different components can be engineered in
- Safe - relative to live attenuated pathogen
183
Name some disadvantages to recombinant viral vaccines?
Require refrigeration for transport
Can cause illness in compromised individuals
Immune response to virus in subjects can negate effectiveness
184
What should the ideal vaccine be?
-Safe!
-Should induce a suitable immune response
-Generate T and B cell memory
-Stable and easy to transport
for use in remote areas
-Should not require repeated boosting
185
Define physicochemical properties?
The physical and chemical properties of substances..
eg. sticks to paracetamol and is excreted - adsorption
186
Define pharmacodynamics?
Effect of drugs on the body
187
Define summation?
When drugs have additive effects on the body.
1 + 1 = 2
Pharmacodynamics
188
Define synergistic drug effects
When you give two drugs together it amplifies the results of either one.
1 + 1 > 2
Pharmacodynamics
189
Define drug antagonism?
When two drugs act against each other
1 + 1 = 0
eg. counteract opioid/drug overdose
Pharmacodynamics
190
Define drug potentiation?
When competition means drug A works like normal, drug B changes - may prolong the effect of drug B/
191
Define pharmacokinetics?
The effect of the body on the drug?
192
What does ADME stand for?
A - Absorption
D - Distribution
M - Metabolism - changes them so they can be excreted in the kidney. Turns pro-drugs into drugs that work.
E - Excretion
pharmacokinetics
193
How does the type of drug affect absorption?
IV = acts instantly for a short time but very high concentration
Orally = takes a bit of time to be absorbed but longer to excrete
Oral needs a higher dose
pharmacokinetics
194
What is bioavailability?
Comparing drugs using area under the time-concentration graph
pharmacokinetics
195
How is motility important in drugs?
Any drugs that affect motility will affect absorption
pharmacokinetics
196
How does acidity affect absorption?
- Drugs are in ionised and unionised portions
- The portion that crosses the membrane is unionised
- More alkali = more unionised
- Maintains concentration gradients to get drug into nerve cell
Abscess means local anaesthetic - ruins concentration gradients
pharmacokinetics
197
Explain the effect of distribution on drugs?
- Drugs will attach to proteins, other tissues and the effect sites
- Big volume of distribution = going everywhere - less to where you're aiming for/in blood
- If you give two protein bound drugs - more will float around in blood and can make it toxic
pharmacokinetics
198
Explain the effect of metabolism on drugs?
- Liver
- Morphine --> CYP450 --> morphine-6-glucuronide (6 x more potent) in a normal patient excreted quickly so no affect
- Phenytoin (anti epileptic drug) causes CYP450 to be increased so way more M-6-G
- Alcohol induces CYP450 – careful giving morphine to chronic alcoholics = increased M-6-G
- Metronidazole slows down/inhibits CYP450 so morphine sticks around a lot longer
Pharmacokinetics
199
Explain how excretion affects drugs?
- Most drugs renally excreted
- Aspirin (acidic) – give bicarb of soda = alkalinise urine
pharmacokinetics
200
What is an important drug interaction of warfarin?
Warfarin inhibits vit. K factors with coagulation cascade
Highly protein bond - add another protein drug = increased effect.
Enzyme inhibition/induction highly affect it.
201
What drugs is AKI caused by?
NSAIDs, Gentamicin, ACE inhibitors, Furosemide
202
What juice interacts with lots of drugs including warfarin?
Grapefruit juice
203
What is druggability?
The ability of a protein target to bind small molecules with high affinity. 10-15% human genome may be druggable.
204
What is a receptor?
• A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects.
205
What is an exogenous ligand?
Drug
206
What is an endogenous ligand?
Hormone/neurotransmitter
207
What are the main features of G protein coupled receptors?
- Largest & most diverse group
- Targeted by >30% drugs
- When G proteins bound to GDP = on, when G proteins bound to GTP = off
- Most GPCRs interact with PLC or adenylyl cyclase
208
What are kinase-linked receptors?
- Transmembrane
| - Activated by extracellular ligang --> causes enzymatic activity on the intracellular side
209
How do nuclear receptors work?
Modifying gene transcription
210
What is efficacy?
(Emax) = maximum response achievable from a dose
211
What is intrinsic activity (IA)
ability of a drug-receptor complex to produce a maximum functional response
212
What are the two types of cholinergic receptor?
Muscarine mAChR
| Nicotine nAChR
213
What is the antagonist to mAChR?
Atropine
214
What is the antagonist to nAChR?
Curare
215
What sort of reaction is caused by histamine 1 receptors?
Allergic
216
What sort of reaction is caused by histamine 2 receptors?
Gatsric acid secretion
217
What sort of reaction is caused by histamine 3 receptors?
CNS disorders
218
What sort of reaction is caused by histamine 4 receptors?
Immune system/inflammation
219
What is ligand affinity?
How well a ligand binds to a receptor (agonist and antagonist)
220
What is ligand efficacy?
how well a ligand activates the receptor (only agonists)
221
What is a receptor reserve?
Agonists only need to activate a small fraction of receptors to produce maximal system response (spare receptors)
222
What is receptor tolerance?
Reduction in agonist effect over time due to continuous, high concentrations
