week 1 Flashcards
1
Q
name 5 drug properties which affect absorption in CV
A
MW
ionisation
solubility
formulation
liberation
2
Q
name 3 patient related factors which affect absorption
A
route of administration
gastric pH
contents GIT
3
Q
describe how malnutrition can affect drug volume of distribution
A
malnutrient leads to a decrease in albumin which increases the free drug volume and thus the volume of distribution of the drug increases
4
Q
name 5 routes of elimination relating to CVD
A
pulmonary (expired in air)
bile (excreted in faeces)
renal- glomerular filtration, tubular reabsorption, tubular secretion
5
Q
digoxin indication
A
heart failure
arterial fibrillation/ flutter
- doses should be reduced in the elderly
6
Q
describe digoxins half life and VoD
A
T1/2= 26-45 hr
large VoD- it is extensively distributed in tissues
7
Q
what does digoxin inhibit
A
Na/K ATPase enzyme
8
Q
renin-angiotensin- aldosterone axis- what does it do
A
regulates BP
9
Q
how does RAAS regulate BP (5)
A
modulates
- blood volume
- sodium reabsorption
- potassium secretion
- water reabsorption
- vascular tone
10
Q
what is atherogenesis
A
Atherogenesis is the process of forming plaques in the intima layer of arteries.
11
Q
how do we reduce atherogenesis
A
- reduce platelet adhesion
– we do this by using either aspirin (an irreversible cycloxygenase inhibitor) or clopidogrel (adenosine diphosphate receptor inhibitor)
these work by blocking thromboxane A2- which is essential in platelet aggregation
12
Q
how does aspirin reduce platelet aggregation
A
aspirin works by blocking thromboxane A2- which is essential in platelet aggregation
13
Q
how does clopidogrel reduce platelet aggregation
A
block the ADP (adenosine diphosphate) pathway and suppress its amplifying effect on platelet response
ADP- responsible for platelet aggregation
14
Q
define efficacy
A
the degree to which a drug is able to produce the desired response
15
Q
define potency
A
the amount of drug which is required to produce 50% of the maximal response which the drug is capable of inducing
- used to compare compounds within classes of drugs
16
Q
define effective concentration
A
-ED50
the concentration of the drug which induces a specified clinical effect in 50% of subjects
17
Q
define lethal dose
A
- LD50
the concentration if the drug which induced death in 50% of subjects
18
Q
define therapeutic index
A
- measure of the safety of the drug
calculation - LD50/ED50
19
Q
define margin of safety
A
margin between therapeutic and lethal doses
20
Q
give 3 UV/Vis strengths
A
- easy, cheap, robust
- quantitative measurements of drugs in formulations
- routine methods to assess physio-chemical properties of drugs
21
Q
give 3 UV/Vis limitations
A
- only moderately selective
- drug needs to have chromophore
- not really applicable to analysis of mixtures
22
Q
define the terms in this equation A=abc
A
- beer-lambert law
A= absorption
a= absorptivity constant
b= pathlength = 1cm (just size of cuvette)
c= concentration
23
Q
what are the 2 forms of absorptivity in the beer-lambert law
A
molar E
- absorbance of a 1mol/L solution in 1cm cell
- units= Lmol^-1cm^-1
specific
- absorbance of a 1g/100ml solution in 1cm cell
24
Q
define the terms in this equation A=log10 (I0/I1)
A
where I0= light intensity transmitted
where I1= light intensity we can see
25
state the 2 ways of determining the concentration of an unknown solution
- use of literature A(1%, 1cm) or molar (E) values
-- typically used when a pure standard is not available
-- used in many BP assays
- use of a calibration curve
-- y=mx+c (notes symbols don't mean the same here as they do in the beer-lambert law)
-- for linear regression- rearrange equation for x (ie unknown concentration)
26
what stage is a BP of 120-139/ 80-89
prehypertensive
27
what stage is a BP of 140-159/90-99
stage one hypertensive
28
what stage is a BP of 160-179/ 100-109
stage two hypertensive
29
what stage is a BP of >180/>110
stage 3 hypertensive
30
define fibromuscular dysplasia
renovascular hypertension- happens when renal blood flow is compromised
more common in younger patients- esp female
relatively rare
31
what ethnicities are at higher risk of hypertension/ CVD
Asian
african
caribbean
32
what age do men become more at risk of hypertension/ CVD
55
33
what age do women become more at risk of hypertension/ CVD
65
34
name 3 consequences of left ventricle hypertrophy
(thickening of muscle wall)- caused by hypertension
- increase workload of LV
- increase after load of LV
- major risk factor for ischemic heart disease (myocardial infarction), arrhythmias, heart failure
35
CVS - hypertensive impacts (4)
- ventricular hypertrophy (thickening of muscle wall)
- arrhythmias
- coronary artery disease (acute MI)
- arterial aneurysm, dissection, rupture- fatal
36
kidney- hypertensive effects (3)
- glomerular sclerosis (leads to impaired kidney function and finally end stage kidney disease)
- reduction in GFR
- ischemic kidney disease- esp when renal artery stenosis is cause of hypertension (secondary)
37
long term kidney effects of hypertension (3)
- poor BP control
- reduced renal pressure (infrarenal redistribution of pressure and increase reabsorption of salt and water)
- decreased pressure in renal arterioles and sympathetic activity- renin production- angiotensin 2 production
38
name 2 effects of angiotensin 2 in the kidneys
- causes direct constriction of renal arterioles
- stimulation of aldosterone synthesis- sodium absorption and increase in intravascular blood volume
39
describe the importance of RAAS in blood pressure control
- activated in response to reduced blood flow
- this leads to decrease in GFR- which stimulates more angiotensin 2 and aldosterone- both of which raise BP
40
ARB
what does it stand for
example of drug
where does it work
- angiotensin 2 receptor inhibitors
- end in sartan
- act on AT1 receptors- found in heart, blood vessels, kidneys
41
name 4 effects of hypertension on the nervous system
- stroke
- intracerebral and subarachnoid haemorrhage
- cerebral atrophy
- dementia
42
name 3 effects of hypertension on the eyes
- retinopathy, retinal haemorrhage and impaired vision
- vitreous haemorrhage, retinal detachment
- neuropathy of nerves - leading to extra ocular muscle paralysis and dysfunction
43
effects of hypertension on the heart
sympathetic fibres- noradrenaline, B1 receptors, increasing the permeability of the nodal cell plasma membrane to Na+ and Ca2+
parasympathetic - ACh- M2 receptors, increasing the permeability to K+ and decreasing the Na+ and Ca2+ permeability
increased HR- more parasympathetic
44
name 2 receptors involved in the regulation of arterial BP
baroreceptor reflex
chemoreceptor reflex
45
name the responsible parties for immediate and long term vascular blood pressure control
neural- sympathetic - immediate
hormonal- long term (vasopressin- antidiuretic, angiotensin 2, aldosterone and atrial natriuretic peptide ANP)
46
name the 3 types of diuretics
loop
thiazides
potassium sparing
47
what do all diuretics do
all indirectly prevent reabsorption of water in the kidneys- they do this by preventing the reabsorption of sodium
48
what kind of diuretic is furosemide
where does it act
how good is it
loop
very powerful blocks ~85% of sodium
acts on thick segment- ascending limb of Henle's loop
49
describe loop diuretic MOA
act by inhibiting the Na+/K+/2Cl- co transporter which is responsible for sodium reabsorption- as a result water moves by osmosis- following the higher sodium concentration
(potassium moves out of the cell)
50
name one problem with loop diuretics
hypokalaemia - potassium too low
51
what kind of diuretic is bendroflumethiazide
where does it act
thiazide
acts on early distal convoluted tubule
52
describe bendroflumethiazide MOA
- inhibits the sodium-chloride transporter in the distal tubule
53
which diuretic is most effective
loop
54
name 2 potassium sparing diuretics
amiloride
spironolactone
55
describe the MOA of potassium sparing diuretics
- spironolactone
- amiloride
remember these act differently to achieve a similar effect
amiloride- distal tubule Na+ channel inhibitor- this leads to excretion of water and sodium and also potassium retention
spironolactone- aldosterone receptor antagonist - competitively binds to aldosterone receptor- inhibiting its effects - this enhanced sodium and water excretion whilst retaining potassium
56
where do potassium sparing diuretics work
tubule and collecting duct- distal nephron
57
what do B1 antagonists do
reduce sympathetic input-
reduces renin release
58
ACE inhibitors
pril ending
angiotensin converting enzyme inhibitors
ie blocks conversion of angiotensin 1 to angiotensin 2
59
decreased angiotensin 2 results in... (4)
- vasodilation
- decrease blood volume
- decrease cardiac and vascular remodelling
- potassium retention
60
increased bradykinin results in.. (3)
- vasodilation
- cough
- angiodema (rare)- dilation of blood vessels in the face- puffy face
61
blocking angiotensin 2 action results in.. (3)
- reduced peripheral vascular resistance (after load)- which lowers BP
- dilates efferent glomerular arteriole- reduces glomerular pressure
- reducing aldosterone- promotes sodium+ water secretion- can help with venous return (preload) - beneficial effect in heart failure
62
aldosterone antagonists
spironolactone (potassium sparing diuretics)
eplerenone
have a direct effect in the kidney (block aldosterone)
competitively bind to aldosterone receptor
promotes Na+ and H2O excretion in collecting tubule and duct
63
where does angiotensin keep NA
pre synaptic
64
where do the following drugs act: prazosin, terazosin and labetalol
vascular A1 receptors
65
where do the following drugs act: propranolol and metoprolol
cardiac B1 receptors
66
where do the following drugs act: clonidine and methyldopa
brain stem
67
actions of B adrenergic blockers in hypertension (5)
- Blockade of cardiac beta-1 receptor- decrease HR and contractility- decrease CO
- Improve efficacy
- Suppress reflex tachycardia caused by vasodilators
- Blockade of beta-1 receptors in JG cells in kidney- decrease renin release – decrease RAAS mediated vasoconstriction (angiotensin 2) and volume expansion (aldosterone)
- Long-term use- decreases peripheral vascular resistance
68
where are B1 adrenergic receptors present
cardiac specific
69
why are B adrenergic blockers useful in heart failure
they reduce the oxygen requirement by reducing myocardial workload
70
name 2 calcium channel blockers (dihydropyridines)
nifedipine
amlodipine
71
first line treatment for hypertension in a 57 y/o male of African decent
calcium channel blocker such as amlodipine 5mg once daily initially- can be increased to 10mg daily
72
how do calcium channel blockers work
- block Ca2+ channels in arterioles
dilate peripheral vessels- which lowers BP
dilates coronary arteries which increases coronary perfusion
73
why are calcium channel blockers (dihydropyridines) not indicated in patents with cardiovascular disease
they increase heart rate and heart force
74
name 2 calcium channel blockers (non dihydropyridines)
verapamil
diltiazem
75
calcium channel blockers (non dihydropyridines)
can be used for arrhythmias
cardiac selective
76
Of the many types of adrenergic receptors found throughout the body, which is most likely responsible for the cardiac stimulation that is observed following an intravenous injection of Noradrenaline?
β1-adrenergic receptors
77
From the choices below which ONE drug would have the greatest effect on the adrenoreceptor family?
Isoprenaline
Adrenaline
Noradrenaline
Phenylephrine
adrenaline
78
Actions of angiotensin II include which of the following
Vasodilation
Increased sympathetic nerve release of noradrenaline
Inhibition of the reuptake of noradrenaline
Promotes renal excretion of sodium and water (natriuretic and diuretic effects)
Inhibit cardiac and vascular remodelling associated with chronic hypertension, heart failure, and myocardial infarction.
vasodilation
79
what does L-NOARG do
blocks NO which in turn increases BP
80
do diabetic patients produce more or less natural NO
less
81
first line primary prevention for white male with cardiac risk over 10%
atorvastatin 20mg once daily
82
what should a patient who is type one diabetic and; over 40 OR had diabetes for 10+ years OR has established nephropathy OR has another CV risk factors ie is a smoker, be started on
atorvastatin 20mg
83
what is the dose for atorvastatin secondary prevention
40mg-80mg depending on risk and preveious treatment
84
define rhabdomyolysis
abnormal muscle breakdown, which can lead to kidney problems and be life-threatening- very rare
can be caused by stains
85
cholesterol target range
no more than 5mmol/L
86
HDL target range
should be at least 1mmol/L
87
describe the MOA of ACE (chemistry)
ACE hydrolyses the peptide bond between Phe and His (amino acids) in angiotensin 1 to create angiotensin 2
88
name 2 of the main side effects associated with captopril
rashes
loss of taste
89
why is enalapril active
it is a prodrug- liver esterase enzymes metabolise it into enalaprilat which is active
90
name the three most common hypertension causes
- malfunction of the sympathetic drive (over stimulation of baroreceptors)
- malfunction of the renin-angiotensin-aldosterone system
- inflammatory process in endothelium (causes a thickening of arteriole lumen- causing pressure increase)
91
what is the most likely cause of hypertension in a young white patient
malfunction of renin-angiotensin- aldosterone system
92
name 6 risk factors for cardiovascular complications
- coronary heart disease
- stroke
- heart failure
- renal failure
- retinopathy
- vascular dementia
93
what is ambulatory BP and why is it used
a BP cuff that stays on for a few days to monitor BP
- used to distinguish between the white coat effect and actual hypertension
94
what is the ACD rule
1st line= ACEi / ARB
2nd line= calcium channel blocker
3rd line= diuretic (thializide)
95
what is first line treatment for white male, 45 y/o with high renin and hypertensive
ACE I such as ramipril 2.5mg OD to start
96
what is first line treatment for a 56 year old women of Caribbean descent with hypertension
calcium channel blocker such as amlodipine
97
in what condition is bendroflumethiazide contraindicated
gout
98
why are beta blockers no longer preferred treatment
less effective in preventing cardiac events- esp stroke
99
why is aspirin 75mg daily only used in secondary prevention
unlicensed in primary prevention- no evidence to say it works - higher risk of upper GI damage
100
why should NSAIDs be avoided in hypertension
they exacerbate the condition by increasing sodium reabsorption and therefore water reabsorption
101
what drugs should be avoided in hypertensive patients (5)
- NSAIDs
- oestrogen (oral contraceptives)
- sympathomimetics (decongestants)
- corticosteroids
- antacids with high salt content (gaviscon and peptac)
