ILAs Flashcards
1
Q
How does atherosclerotic plaque form?
A
- endothelial cell injury
caused by toxins eg tobacco, diabetes + at areas of great force eg arterial bifurcation - lipoprotein deposition
increased permeability to lipoprotein due to eci
gain entry + are modified
forms LDL = inflammatory
taken up by macrophages = foam cells
causes fatty streaks in arterial wall = transitional plaque - inflammatory reaction
LDL are antigenic
release of cytokines eg PDGF attracts more macrophages - smooth muscle cell cap formation
cytokines cause smooth muscle migration + proliferation
collagen production keeps increasing
creates fibrous collagen cap = advanced plaque
2
Q
How does stable atherosclerotic plaque form?
A
grows slowly + reduces lumen size
3
Q
How does unstable atherosclerotic plaque form?
A
grows rapidly + becomes unstable
undergoes thrombosis + obstructs vessel or ruptures
= complicated plaque
4
Q
What are the modifiable risk factors for atherosclerosis?
A
smoking sedentary lifestyle obesity high BP raised cholesterol diabetes
5
Q
What are the non-modifiable risk factors for atherosclerosis?
A
family history of angina (under 55 especially)
age (55+)
gender - male
south asian/afro-caribbean descent
6
Q
How does smoking cause atherosclerosis?
A
smoke contains free radicals = oxidative stress + endothelial cell injury
components activate neutrophils + cytokine release = increases adhesion of inflam cells, LDL levels + thrombosis
7
Q
How does a sedentary lifestyle cause atherosclerosis?
A
increases oxidative stress and endothelial dysfunction by increasing vascular ROS
8
Q
How does obesity cause atherosclerosis?
A
increased cholesterol, risk of diabetes + BP
elevated LDL = higher lipoprotein deposition
9
Q
How does a high BP cause atherosclerosis?
A
mechanical shear stress on arterial walls = endothelial cell injury
triggers plaque build-up
10
Q
How does raised cholesterol cause atherosclerosis?
A
elevated LDL = induces inflam reaction + increases plaque
leads to smooth muscle migration + proliferation
increases LDL = increases endothelial cell injury
11
Q
Does HDL contribute to atherosclerosis?
A
no, HDL is protective
12
Q
How does diabetes cause atherosclerosis?
A
increases free radicals = increases apoptosis and reduces NO
increases blood flow + inflammation + high blood sugar + = increased damage to endothelial cells + increased plaque
increased deposition of LDL
13
Q
How does family history put someone at risk of atherosclerosis?
A
genetic alteration may make endothelium more susceptible
history of increased cholesterol
14
Q
How does the male gender put someone at risk of atherosclerosis?
A
men do more risk-taking behaviour
sex hormones contribute
15
Q
What are the non-medicinal primary prevention measures of atherosclerosis?
A
healthy diet with reduced fat intake (<30% total energy) + lower cholesterol
lower saturated fats and replace with unsaturated fats
increase physical activity (>150 mod/intense aerobic/week)
reduce BMI below 25
reduce alcohol intake
smoking cessation
manage diabetes + BP effectively
16
Q
What are the medicinal primary preventions for atherosclerosis?
A
aspirin (or clopidogrel)
statins
17
Q
How does aspirin work as a primary prevention method for atherosclerosis? Side effects?
A
at low doses = anti-thrombotic, prevents STEMI/NSTEMI
SE: stomach ulcers (give PPI)
18
Q
What dose of aspirin should be used for atherosclerosis and why?
A
low dose 75mg: anti-thrombotic = prevents STEMI/NSTEMI
high dose 300mg: PROMOTES THROMBOSIS = for pain relief and inflammation only
19
Q
What medicine is given for primary prevention of atherosclerosis if aspirin is contraindicated?
A
clopidogrel: inhibits platelet aggregation
after an MI give both aspirin and clopidogrel
20
Q
How do statins work as a primary prevention method for atherosclerosis? Side effects?
A
lowers LDL levels = prevents atheroma forming
SE: rhabdomyolisis (muscle aches and pains)
21
Q
What are the secondary prevention measures for atherosclerosis?
A
GTN spray longer acting nitrates beta-blockers ca2+ channel blockers ACE inhibitors surgery - stent or bypass
22
Q
How does GTN spray work as a secondary prevention method for atherosclerosis?
A
nitrate: fast-acting vasodilator
sublingual route
reduces flow, pressure + resistance
23
Q
What does GTN spray stand for?
A
glyceryl trinitrate
24
Q
What are the side effects of GTN spray?
A
fainting
dizziness
headaches
25
How do longer acting nitrates work as a secondary prevention method for atherosclerosis?
vasodilator = prevents thrombus forming
26
How do secondary prevention measures work for preventing atherosclerosis?
vasodilation
27
Give an example of a longer acting nitrate for atherosclerosis?
isosorbide dinitrate
| come oral, skin plasters etc
28
When are blood thinners used for thrombi?
venous thrombosis only - DVT, pulmonary embolisms
29
Give 2 examples of beta-blockers?
end in -lol
atenolol
bisoprolol
30
How do beta-blockers work as a secondary prevention method for atherosclerosis?
block beta receptors and inhibit sympathetic NS
= vasodilation in heart + bronchoconstriction in lungs
= decrease heart rate and BP
31
What are the side effects of beta-blockers?
bradycardia
can worsen lung diseases eg asthma, COPD - contraindicative
sometimes need cario specific ones to avoid bronchoconstriction
32
Give an example of a Ca channel blocker?
end in -pine
| nifedipine
33
How do ca channel blockers work as a secondary prevention method for atherosclerosis?
decrease contractility of heart
| decreases force of LV contraction = more fluid backed up
34
What are the side effects of ca channel blockers?
```
peripheral + pulmonary oedema
postural hypertension (BP drops from lying to standing)
```
35
How do ACE inhibitors work as a secondary prevention method for atherosclerosis?
control of hypertension: stop conversion of angiotensin I to II
increase vasodilation = decreases BP
acts as a diuretic
continued until BP has dropped
36
What are the side effects of ACE inhibitors?
fainting
dizziness
chronic dry cough
K+ diuretics cause galactorrhea in men (breasts enlarge and produce milk)
37
Give 2 examples of ACE inhibitors?
ends in -il
ramipril
lisinopril
38
How does a stent work as a secondary prevention method for atherosclerosis?
angioplasty procedure
| side effects: death, acute MI, restenosed later on
39
When are surgical interventions used for atherosclerosis?
when angina persists with medication
40
How does a bypass work as a secondary prevention method for atherosclerosis?
coronary artery bypass graft
| usually uses mammory artery + connects it to the coronary artery
41
Is stent or bypass surgery more effective for atherosclerosis?
bypass = higher success + less likely to be restenosed
| but is higher risk
42
What are the contents of an atheroma?
lipids (LDL), macrophages, smooth muscle
43
What are the key features of stable angina?
```
crushing chest pain
comes on AFTER exertion
retro-sternal
lasts a few minutes
no sweating, nausea or vomiting
fibrous cap remains
```
44
How does stable angina become unstable?
fibrous cap ruptures = thrombosis
| either embolises and blocks other arteries or leads to unstable angina
45
What are they key features of unstable angina?
comes on AT REST
46
Are ischaemia or infarction associated with angina?
ischaemia associated
| no infarction
47
What do serum cardiac markers look like for stable and unstable angina?
```
stable = normal
unstable = abnormal
```
48
What are the 3 acute coronary syndromes?
1. unstable angina
2. NSTEMI angina
3. STEMI angina
(worsen in this order)
49
What are the signs and symptoms of ACS?
nausea, vomiting, radiating pain
| increased cardiac markers
50
What is an NSTEMI?
non-ST elevated MI
| partially occluded artery
51
What is a STEMI?
ST elevated MI
| full occluded artery
52
What is the difference between an NSTEMI and a STEMI?
ST elevation in STEMI, otherwise present similarly
| NSTEMI may show ST depression
53
What are the cardiac markers tested for?
creatine kinase
| troponin
54
What ECG changes are there in stable angina?
no changes, unless done during an acute attack - rare
| sometimes ST depression or T wave inversion
55
Define anaphylaxis
severe + potentially life-threatening allergic reaction to a trigger with rapid onset
type 1 hypersensitivity reaction, IgE mediated
involves mast cells and basophils
56
Why does anaphylaxis generally occur on the 2nd exposure and not the first?
1st time immune system becomes sensitised to the trigger
| triggers small immune response, sometimes unnoticed
57
What are the common triggers for anaphylaxis?
food - nuts, shellfish, dairy and egg
idiopathic
venoms - wasps, bess, hornets
medication - antibiotics, antisera (tetanus, diptheria), latex, painkillers, opioids, dextran
58
What is the cause of low oxygen in anaphylaxis?
histamine release: vasodilation + increased vascular permeability
more leaky = blood leaks out into interstitium
reduces BP + blood flow = reduces oxygen
anaphylactic shock when multiple organ systems starved of oxygen
59
What is the cause of oedema in anaphylaxis?
histamine release: vasodilation + increased vascular permeability
more leaky = blood leaks out into interstitium
= angio-oedema eg in tongue
60
What is the cause of a high resp rate + expiratory wheeze in anaphylaxis?
histamine release: smooth muscle contraction in airways = wheeze
= reduced airflow to lungs = high resp rate
61
What is the cause of a high heart rate and low BP in anaphylaxis?
histamine release: increases heart rate and vasodilation
| = decreases BP
62
What is the cause of prolonged capillary refill in anaphylaxis?
> 2 seconds abnormal
| due to low BP
63
When does hypertension start?
140/90 mm Hg
64
What is the cause of a widespread urticarial rash in anaphylaxis?
histamine release: vasodilation
65
What is synosis?
symptom of anaphylaxis
severe hypoxia
body goes blue as lungs don't get enough oxygen
(deoxygenated blood is blue)
66
What is stridor?
symptom of anaphylaxis
| abnormal high-pitched sound when airflow passes through an obstructed airway
67
What is the term for hypertension combined with tachycardia?
haemodynamically unstable
68
What are main chemical mediators in anaphylaxis?
histamine
leukotriene
prostaglandins
tryptase
69
What are the main 3 effects of histamine in anaphylaxis?
increased vascular permeability
smooth muscle contraction
vasodilation
70
What to do in an emergency anaphylactic reaction?
ABCDE Adrenaline
A- airway (swelling, hoarseness, stridor)
B- breathing (rapid, wheeze, fatigue, cyanosis, low sats, confusion)
C- circulation (pale, clammy, low BP, faint, drowsy)
D- disability
E- exposure
diagnosis: look for ABC and skin changes
call for help: lie flat and raise their legs
give adrenaline
71
How is adrenaline given for anaphylaxis?
via an EPI pen
or intra-muscularly
IV is only for specialist use
72
What are the contraindications for adrenaline? What is given instead?
allergy or if on beta-blockers
| salbutamol (IV) given instead - doesn't affect the heart, only the lungs (B2 receptor selective)
73
What is the action of adrenaline in anaphylaxis?
eases breathing difficulty + restores cardiac output
reduces release of chemical mediators
alpha 1 adrenoceptor agonist: vasoconstriction = increases vascular resistance, coronary perfusion + BP + decreases oedema
beta 1 adrenceptor activity: positively ionotropic and chronotropic
beta 2 adrenoceptor activity: reduce oedema + bronchodilation
74
Why is high flow oxygen given in anaphylaxis?
to prevent collapse of reservoir on inspiration
| to increase O2 sats
75
What is the recommended treatment for anaphylaxis?
```
adrenaline
high flow oxygen
IV fluids
antihistamines
steroids
```
76
Why are IV fluids given in anaphylaxis?
to increase BP
large volumes will have leaked from circulation
type does not matter
77
Why are antihistamines given as a 2nd line treatment in anaphylaxis?
decreases histamine-mediated vasodilation and bronchoconstriction
not life-saving alone
78
Which antihistamine is given in anaphylaxis?
chlorphenamine
79
Why are steroids given in anaphylaxis?
anti-inflammatory
| strop release of chemical mediators
80
What is a biphasic anaphylactic reaction?
symptoms occur again a few hours later
81
What is a protracted anaphylactic reaction?
symptoms last for hours or days
82
When is a 2nd dose of adrenaline given?
repeated 5 minutes after 1st dose if no improvement is seen
| according to BP, pulse and resp function
83
What is the conformational blood test for anaphylaxis?
mast cell tryptase - shows elevated levels
84
When is the mast cell tryptase done in anaphylaxis?
immediately, 1-2 hours after and 24 hours after
| 24 hrs to see baseline levels
85
When does mast cell tryptase peak during anaphylaxis?
1-2 hours after onset
86
What tests are done during anaphylaxis?
mast cell tryptase
IgE levels
monitor BP, SATs, pulse
continuous ECG
87
What should be done after an anaphylactic reaction?
give patient an EPI-pen and medical information bracelet with details of anaphylaxis
do allergy skin prick test to confirm trigger
88
What type of drug is Ramipril?
ACE inhibitor
89
What type of drug if Furosemide?
loop diuretic
90
How do drugs travel in the blood?
1. some of the drug binds to plasma proteins (albumin, lipoproteins)
2. rest if left unbound
91
Why do some drugs need to be bound to plasma proteins?
they are a reserve for when all the unbound drug has been metabolised
92
What level of protein binding should an anaesthetic drug have for anaesthesia to be induced quickly?
low protein binding
| high levels of unbound drug
93
Why should an anaesthetic drug have low protein binding and high levels of unbound drug?
unbound can diffuse across cell membranes as they are not bound to proteins
able to cross blood-brain barrier = fast onset
only unbound provide substrate for drug metabolising enzymes
94
The volume of distribution of a drug is inversely proportional to what?
protein binding
95
What level of lipid solubility should an anaesthetic drug have for anaesthesia to be induced quickly?
high lipid solubility
96
Why should an anaesthetic drug have a high lipid solubility?
can freely diffuse across cell membranes due to phospholipid bilayer
can cross blood-brain barrier
= rapid brain uptake = high distribution = fast onset
97
Why does an additional volatile gas drug have to be given after the first anaesthetic IV drug and as soon as as a patient is asleep?
otherwise patient would wake up
IV drugs act quickly eg thiopental
distribute very rapidly to highly perfused tissues
have a high lipid solubility = redistribution
drug goes back into blood and into lower perfused tissues eg fat, muscles and away from the brain
98
What happens when the first anaesthetic IV drug in reaches an equilibrium between the blood and tissue?
diffusion slows
lots of drug goes to brain so diffusion favours the blood
= need a second drug to maintain anaesthesia
99
What is an agonist drug?
chemical that binds to a receptor and activates it
| can be full or partial
100
Give 2 examples of agonist drugs?
morphine (u-opioid receptor)
| clonidine (a2-adrenceptor)
101
What is an antagonist?
binds to a receptor in order to decrease the effect of an agonist
doesn't activate the receptor
102
Give 2 examples of antagonist drugs?
naloxone (competitive, opioid receptors)
| ketamine (non-competitive, NMDA-glutamate receptor)
103
What are competitive antagonists?
competes for and binds to the same site as the agonist to block the agonist binding
104
Give an example of a competitive antagonist?
atenolol (b1-adrenergic receptor) for high BP
105
What is a non-competitive antagonist?
binds to an allosteric site to prevent an agonist activating the receptor
106
Give an example of a non-competitive antagonist?
ketamine (NMDA-glutamate receptor)
107
What are the 4 drug targets?
1. receptors
2. enzymes
3. transporters
4. ion channels
108
Give an example of a drug which targets enzymes and how it works?
NSAIDS: ibuprofen
inhibit enzymes cyclooxygenase (COX)
= prevents production of prostaglandin H2 which is involved in inflammation, pain, fever and swelling
109
What is the pathway for how NSAIDS acts on their enzyme target?
membrane phospholipid > (PLA2) > arachidonic acid > (COX) > prostaglandin H2
NSAIDS inhibit enzyme COX
110
Give an example of a drug which targets transporters and how it works?
proton pump inhibitors eg lansoprazole
inhibits acid secretion by irreversibly inactivating the proton pump
= gastro protection to stop ulceration
111
Give an example of a drug which targets ion channels and how it works?
calcium channel blockers eg amlodipine
blocks channel = prevents influx of calcium
less vasoconstriction, stops cardiac action potential = reduces heart rate + BP
treats hypertension
112
What is bioavailability?
proportion of drug which enters the circulation so is able to have an active effect
113
What is 1st pass metabolism?
goes to liver first before it's target by which time most of the drug will have been eliminated
= limited uptake of drug via the oral route
114
Which route is fastest for morphine uptake? IM or oral?
IM
115
What % of oral morphine is metabolised by 1st pass metabolism? What effect does this have on it's bioavailability?
50%
| bioavailability hugely reduced
116
How much more oral morphine is required compared to IM morphine?
give double the amount for oral route
| same efficacy as IM route
117
Why is lower doses + longer intervals of morphine given to patients with renal failure?
patient may not clear drug for up to a week - don't want it to stay in the body
morphine > morphine-6-glucuronide
m-6-g much more potent + renally excreted
builds up in renal failure = respiratory depression + seizures
118
What is the difference between pharmacodynamics and pharmacokinetics?
dynamics: how the drug effects the body eg side effects
kinetics: how the body effects the drug eg how fast it's taken up
119
What are the ideal pharmacokinetic properties of a anaesthetic drug?
```
low protein binding
high lipid solubility
= rapid onset, reaches brain fast
no active metabolites (lengthen onset time)
rapid clearance and metabolism
```
120
What are the ideal physical properties of a anaesthetic drug?
cheap
long shelf life
stable in solution (often given with saline)
not painful on injection
121
What are the ideal pharmacodynamic properties of a anaesthetic drug?
```
no cardio/resp effects
no histamine release (increase risk of anaphylaxis)
no gastro irritation
no sickness
quick recovery
no hypersensitivity reaction
```
