1
Q
What is hypertension
A
high blood pressure
leads to heart attacks and leading cause of death
2
Q
what are the impact of cardiovascular disease
A
- heart attacks
- strokes
- heart failure
- chronic kidney disease
- peripheral arterial disease
- vascular dementia
3
Q
what are the risk factors of CVD
A
- obesity
- physical inactivity
- smoking
- drinking
4
Q
what are the treatments of CVD
A
- antihypertensives
- statins
- anticoagulants
5
Q
what can be used to detect CVD
A
- hypertension
- high cholesterol
- atrial fibrillation
6
Q
what is atrial fibrillation
A
- rapid, irregular heartbeat
- heart rhythm irregularity
- can cause blood clot
7
Q
what is high cholesterol
A
- build up of fatty deposits in arteries
- can cause ischaemic heart disease
8
Q
how to lower cholesterol levels
A
- diet
- stop smoking
- reducing weight
- use of statins
9
Q
what is the range of blood pressure for stage 1 hypertension
A
- 140/90 mmHg to 159/99 mmHg and subsequent ABPM daytime average
- HBPM average blood pressure ranging from 135/85 mmHg to 149/94 mmHg
10
Q
what is stage 2 mechanism for diagnosing hypertension
A
- blood pressure of 160/100 mmHg or higher but less than 180/120 mmHg and subsequent ABPM daytime avergae
- HBPM average blood pressure of 150/95 mmHg or higher
11
Q
what mechanism should prevent sustained elevations in arterial blood pressure
A
- baroreceptor reflex
- in hypertension, its reset itself to a higher level. nerve activity reduces with high blood pressures
12
Q
what is essential hypertensions and how does this differ from secondary hypertension
A
- high blood pressure that doesn’t have a known cause is called essential hypertension.
- secondary hypertension has a known cause
13
Q
what is essential hypertension
A
- develops overtime
- haemodynamic characteristics change over time with patients younger than 40 the cause is mainly associated with high cardiac output with normal total peripheral resistance
- older patients tend to have normal/reduced cardiac output but high total peripheral resistance
14
Q
what is linked to secondary hypertensions
A
- sleep apnoea
- kidney disease
- thyroid disease
- diabetes
15
Q
what is secondary hypertension
A
- caused by an underlying condition
- appear suddenly and cause high blood pressure
- linked to kidney problems, adrenal gland tumours, thyroid tumours, medications
- malignant hypertension is a severe, often acute form of hypertension which carries a significant risk of cardiovascular events. this should be managed as a matter of urgency
16
Q
briefly describe the renin-angiotensin-aldosterone system
A
sympathetic nerves switch on renin release from kidney. this converts angiotensinogen I (inactive) ACE enzyme converts angiotensin I to angiotensin II (active)
17
Q
angiotensin II effects
A
- stimulates adrenal cortex to release aldosterone
- causes release of ADH
- stimulates thirst
- causes vasoconstriction
- cardiac and vascular hypertrophy
18
Q
what happens when the adrenal cortex is stimulated
A
- aldosterone released
- promotes sodium and fluid retention in the kidney
- fluid volume increases
- blood volume increases and blood pressure rises
19
Q
implications of ADH release from pituitary
A
- promotes water reabsorption in the kidneys
- fluid volume increase
- blood volume increases and blood pressure increases
20
Q
implications of vasoconstriction
A
- increases blood pressure
21
Q
what are the implications of cardiac vascular hypertrophy
A
- more muscle mass
- in heart increases cardiac output and thus blood pressure
22
Q
what is the biggest risk factor of hypertension
A
left sided heart failure
23
Q
which drug/drug class would you initially prescribe to a 46 year old Caucasian man recently diagnosed with hypertension
A
- too old for beta blocker (under 40 appropriate) - the younger the patient the more likely it is driven by cardiac output
- ACE inhibitor or angiotensin 2 receptor blocker
24
Q
what are the endings for different classes of drugs
A
- ACE inhibitor = end in pril
- beta blockers = end in ol
25
side effects of ACE inhibitors
- alopecia
- angina
- angioedema
- chest pains
- constipation
- dizziness
26
which drug/drug class would you initially prescribe to a 51 year old man of African Caribbean origin recently diagnosed with hypertension and who does not have type 2 diabetes
calcium channel blocker because ACE inhibitors don't work as well
27
which drug/drug class would you initially prescribe to a 65 year old woman of caucasian origin recently diagnosed with hypertension who does not have diabetes
calcium channel blocker
28
what are the side effects if amlodipine
- cariogenic shock
- constipation
- drowsiness
- gastrointestinal disorders
29
side effects of ca blockers
- dizziness
- flushing
- headache
- nausea
- palpitations
30
the 46 year old caucasians origin following use of an ACE inhibitor does not show a significant improvement towards his target blood pressure and it is decided to change his treatment. what would you of next
- check mediation is taken correctly
- keep him on ACE inhibitor but add in either a calcium channel blocker or thiazide like diuretic
31
the 51 year old man of African Caribbean origin following use of calcium channel blocker does not show a significant improvement towards his target blood pressure and it is decided to change his treatment. what would you do next
- check medicine is taken correctly
- keep him on the calcium channel blocker but either add in ARB, or thiazide-like diuretics
32
which patients are more susceptible to problems due to excessive fluid loss due to diuretics (increases loss of urine)
diabetes
elderly
33
what are the effects of thiazides
- hypokalaemia can occur and is dangerous in severe cardiovascular disease and in patients also being treated with cardiac glycosides
- constipation
- electrolyte imbalance
- headache
- postural hypotension
34
what are the effects of indapamide
- hypersensitivity
- skin rashes
35
what drugs could be considered for patients still not responding to step 3 of treatment
- consider low dose spironolactone diuretic, if the serum potassium level is not elevates
- if contraindicated or ineffective, consider alpha or beta blockers
- if still not responding to the combination of drug, see expert advice
36
what is an example of a calcium channel blocker
amlodipine
37
what do calcium channels blockers act on
myocardial muscle
myocardial conducting system
vascular smooth muscle
38
what is the effect of a calcium channel blocker on myocardial muscle
inhibit contractability
39
what is the effect of a calcium channel blocker on mycardial conducting system
inhibit formation and propagation of depolarisation
40
what is the effect of calcium channel blockers on vascular smooth muscle
coronary or systemic vascular tone reduced - vasodilation
41
what are the the pharmacokinetics of amlodipine
- oral route - bioavailability 60%
- half life 30-50hrs
- steady state plasma concentrations 7 to 8 days
- liver CYP450 - slowly metabolised
- poor renal elimination
42
what is an example of an ACE inhibitor
lisinoprile
43
what is the mechanism of ACE inhibitors
inhibits the angiotensin - converting enzyme in the renin angiotensin system
44
what are the pharmacokinetics of lisinopril
- oral administration - 25% bioavailability
- peak plasma concentration 4-8hrs - half life 12 hrs
- water soluble - not metabolised in liver and undergoes renal excretion unchanged
45
what is an example of ARBs
losartan
46
what is the mechanism of action of ARBs
selective competitive blockers of angiotensin II at the AT1 receptors
47
what are the pharmacokinetics of losartan
- oral administration - 32% bioavailability
- first pass metabolism 14% to active metabolite which is more potent, non-competitive and longer acting
- cytochrome p450 metabolism - half life of 2h and 3-9h for metabolite
- extensive plasma protein binding
- excreted in urine and bile
48
what are the contraindication of ARBs
combination with renin inhibitor in patients with reduced eGFR and in patients with diabetes mellitus
49
what are the cautions of ARBs
use in African-carribean patients - particularly those with left ventricular hypertrophy; elderly patients
50
what are the contraindications of losartan
severe cardiac failure, pregnancy, severe hepatic impairment
51
what are the side effects of losartan
anaemia; hypoglycaemia; postural disorders
52
what are the side effects of ARBs
abdominal pain, diarrhoea, dizziness; headache; hyperkalaemia
53
what is an example of thiazide-like diuretics
indapamide
54
what is the mechanism of action of thiazide-like diuretics
inhibition of Na+ and cl- reabsorption from the distal convoluted tubules by blocking the Na+ - Cl- symporter. at lower doses vasodilation is more prominent than diuresis
55
what is the site of action of thiazide-like diuretics
act on the reabsorptive process in the distal convolute tubule
56
when is indapamide useful
- low dose thiazide such as indapamide sufficient for therapeutic effect
- higher doses - marked changes in plasma K+, Na+, uric acid, glucose and lipid
57
what are the pharmacokinetics of indapamide
- oral administration act within 1 to 2hrs
- administered early in the day doe diuresis does not interfere with sleep
- duration of action 12 to 24hrs
- 75% plasma protein bound
58
what are the contraindications of thiazides
Addisons disease
electrolyte imbalance
59
what are the cautions associated with thiazide-like diuretics
- diabetes; gout; hyperaldosteronism; malnourishment; nephrotic syndrome
- history of hypersensivity to sulphonamides
- avoid in severe liver disease
- thiazides are ineffective if renal function is low
- indapamide acute porphyria
60
what are the side effects of indapamide
- hypokalaemia can occur and is dangerous in severe cardiovascular disease and in patients also being treated with cardiac glycoside
- constipation; electrolyte imbalance; headache; postural hypotension
61
what are the side effects of indapamide
hypersensitivity
skin rashes
62
what is spironolactone
- anti-hypertensive in patients with resistance hypertension
- blocks aldosterone-induced Na reabsorption - causes Na+ and H2O loss, K+ retention
63
what is the mechanism of action off spironolactone
K-sparing diuretics inhibit the action of aldosterone on the collecting ducts. by themselves are weak diuretics but are important for the sparing of K . Often used in conjugation with other more potent diuretics
64
what is an example of an alpha blocker
doxazosin
65
what is the job of alpha blockers
- blocker arterial alpha 1 receptors
- postural hypertension
66
when are beta blockers used
- not a preferred initial therapy for hypertension
- may be considered in younger children
- women of child bearing potential
67
what are the cautions of beta blockers
intolerance or contraindication to ACE inhibitors and ARBs
68
what the the types of heart failure
- acute or chronic
- left sided
- right sided
- biventricular failure
69
what is left sided failure
commonest - due to hypertension
70
what is right sided failure
cor pulmonale - chronic lung disease
71
what is biventricular failure
- both chamber often affected
- left ventricular causes pulmonary congestion which can then lead to right sided failure
72
what is class 1 heart failure
no symptoms during normal physical activity
72
what is class 2 heart failure
- comfortable at rest
- normal physical activity triggers symptoms
72
what is class 3 heart failure
- comfortable at rest
- minor physical activity triggers symptoms
72
what are the clinical features of heart failure
- reduced ejection fraction <40% in echocardiogram - stroke volume reduced
- hypotension - tiredness and dizziness
- reduced urine flow
- cold periperpheris
- breathlessness
- oedema
- atrial fibrillation
73
what is class 4 heart failure
- unable to carry out physical activity without discomfort
- many have symptoms even when resting
73
what are the symptoms of systolic left sided heart failure
- increase in volume of blood left in the left ventricle at the end of contraction
- end systolic volume increases
- as more venous return refills the left ventricle during diastole the reduced systolic emptying leads to end diastolic volume increasing
74
what are the symptoms of left sided heart failure
- reduced ventricular compliance may lead to diastolic dysfunction resulting in left sided heart failure
- pressure in the ventricle during diastole is increased because of stiffness of the ventricular wall
- end diastolic volume reduces due to reduced filling of the ventricle
75
how do you initially treat heart failure
HF with reduced cardiac function (ejection fraction <40%)
first line treatment - ACE inhibit plus beta blocker
76
stages of treating heart failure with reduced ejection fraction - spironolactone
- aldosterone antagonist - spironolactone as add-on therapy
- improves survival in chronic heart failure
- contraindicated if hyperkalaemia or renal impairment
76
what is the action of canrenone
- blocks aldosterone-induced production of sodium transport proteins in the DCT
- causes Na+ and H2Oloss
- K+ retention
76
what is the second line of treatment of chronic heart failure
mineralocorticoid receptor antagonist - spironolactone
77
what drugs used to treat chronic heart failure
- ivabradine
- digoxin
- SGLT2 inhibitors - dapagliflozin
- sacubitril valsartant
- hydralazine with nitrate
78
when is ivabradine used to treat heart failure
- used for treatment of angina and mild to severe chronic heart failure
79
what is the action of ivabradine
- inhibit if current reducing cardiac pacemaker activity
- slows heart rate
- alternative to beta blockers
80
what are the contraindications of ivabradine
mi
cariogenic shock
heart block
slow heart rates
81
what are the cautions associated with ivabradine
- ineffective if atrial fibrillation present
- elderly
- angina
82
what are the side effects of ivabradine
arrhythmias
AV block
dizziness
headache
83
how can sacubitril valsartan be used to treat heart failure
- sascubritil inhibits the breakdown of natriuretic peptides increased diuresis, natriuresis and vasodilation
- may be used in patients not currently taking an ACE inhibitor or ARB
84
85
what is the contra-indication of sacubitril valsartan
systolic blood pressure <100 mmHg
86
what are the side effects of sacubitril valsartan
anaemia
cough
diarrhoea
dizziness
electrolyte imbalance
headache
hypoglycaemia
hypotension
nausea
renal impairments
syncope
vertigo
87
when is hydralazine with nitrate used to treat heart failure
patients intolerant of both ACE inhibitors and ARBs
88
what is the use of venodilators
- reduced pre-load
- reduce the risk of pulmonary congestion
89
what is the use of arterial vasodilators
- reduce after load
- increase stroke volume
90
what are the contraindications of hydralazine with nitrate
acute prophyrias
cor pulmonale
dissecting aortic aneurysm
poor cardiac function
tachycardia
91
what are the side effects of hydralazine with nitrate
angina
headaches
tachycardia
diarrhoea
dizziness
flushing
gastrointestinal disorders
92
what are the cautions of hydralazine with nitrate
cerebrovascular or coronary artery disease
93
why is digoxin
- antiarrhythmic drug - increases vagal tone to heart
- positive inotrope - increases intracellular Ca2+
94
what are the indication for use of digoxin
- chronic heart failure - improves symptoms but not mortality rates
- supra ventricular arrhythmias
- chronic atrial fibrillation
95
what are the pharmacokinetics of digoxin
- oral administration bioavailability 75%
- onset of action 30mins
- peak effect - 1-5hrs
- half life 36h
- elimination 70% renal, GFR
- VD 640L/70kg - binds to skeletal muscle
96
what is the contraindication of digoxin
heart block
97
what are the cautions of digoxin
risks of digitalis toxicity with electrolyte imbalances,
98
what are the side effects of digoxin
arrhythmias
cardiac conduction problems
cerebral impairment
diarrhoea
dizziness
skin reactions
vision disorders
99
when are SGLT2 inhibitors such as dapagliflozin used to treat heart failure
treatment for type 2 diabetes and heart failure
100
what is the action of SGLT2 inhibitors
blocks the SGLT2 glucose transporter in the renal PCT glycosuria and fluid loss
101
what are the haemodynamic changes associated with SGLT2 inhibitors
- reduced pre load and after load
- cardiac function improves
102
what is an example of endothelial cell damage
- atherosclerosis
- vasculitis of any cause
- high levels of homocysteine
- turbulent blood flow at arterial bifurcation
- oxidised LDL
- cigarette smoke
- cytokines
102
what is thrombosis
pathological formation of an intravascular blood clot
can occur in a vein or an artery
102
what are the contra-indication of dapagliflozin
diabetic ketoacidosis
102
what are the adverse effects of dapagliflozin
rare severe ketoacidosis
102
what are the cautions associated with dapagliflozin
elderly
hypotension
risk of volume depletion
103
what is a hypercoaguable states
- due to excessive procoagulant factors or defective anticoagulant
- may be inherited (AT3 deficiency)
- classic presentation is recurrent DVTs or DVTs at a young age
103
describe thrombosis
characterised by the lines of Zahn (if large vessel) and attachment to a vessel wall (both features can be used to distinguish thrombus from postpartum)
103
what are the 3 components of Virchows triad
disruption to blood flow
endothelial cell damage
hypercoaguable stress
103
what are the examples of disruption to blood flow
- immobilisation
- cardiac wall dysfunction
- aneurysm
- atrial fibrillation
- left atrial dilation due to mitral stenosis
104
what causes venous thrombosis
stasis of blood most commonly in deep vein of lower limb
105
what are the symptoms of venous thrombosis
red
swollen
painful leg
skin discolouration
106
what are the risks associated with venous thrombosis
can dislodge to the lungs causing a pulmonary embolism
107
what drugs can be used to treat venous thrombosis
warfarin, or other anticoagulants e.g. rivaroxaban, apixaban
these do not dissolve clot they prevent further formation
the fibrinolytic systems break down the clot
108
what is the cause of arterial thrombosis
- most commonly due to endothelial damage related to turbulent blood flow at bifurcation or over atherosclerotic plaques in high velocity vessels
- in some cases they are mixed thrombi composed of platelets and with RBCs held together by fibrin - lines of Zahn
- hyper coagulability and stasis are rare causes of arterial thrombosis
109
what are the signs of arterial thrombosis
grey/white fibrin clot primarily composed of platelets
110
how can arterial thrombosis be inhibited
inhibitors of platelet aggregation prevent their formation e.g. aspirin
111
what are the examples of arterial thrombosis
MI
small bowel infarction
stroke
112
what are the stages of platelet activation
adhesion
release reaction
aggregation
113
how is a platelet plug formed
- platelets undergo shape change and degranulate
- release mediators ADP (from dense core granules)
- thromboxane A2 (TXA2) - a derivative of platelet cyclooxygenase
- calcium
- ADP induces the expression of GP2b/3a (another essential receptor for aggregation of platelets) and fibrinogen which acts as a linker molecules in the developing cloth
114
what are the functions of thrombin
- acts on fibrinogen to produce fibrin molecules
- activates fibrin stabilising factor 13 which converts these monomers to cross linked fibrin and strengthens blood clot
- acts in a feedback loop to activate several other coagulation factors therefore pivotal in the amplification system
- thrombin itself is switched off by the natural anticoagulant antithrombin limits clot formation
115
what are the functions of plasmin
- breaks down clot
- cleaves fibrin and fibrinogen into fibrinogen degradation products form fragment known as D-dimers
- degrades some clotting factors
- blocks platelet aggregation
116
what are the 3 main drug classes than prevent and/or reverse thrombus formation
anticoagulants
anti platelet agents
fibrinolytic agents
117
what are anticoagulants
factor Xa inhibitors
antithrombins
heparin and vit k antagonists - modify blood clotting mechanisms
118
what are anti platelet agents
aspirin - inhibit COX-1 activity to inhibit platelet aggregation
119
what are fibrinolytic agents
alteplase - breaks down fibrin
120
a 78 year old female has a very swollen, red painful left leg and is struggling to catch her breath. what would be the most appropriate immediate drug class to administer
anticoagulant
121
what are the classes of anticoagulant drugs
- selective factor Xa inhibitors - apixaban
- direct thrombin inhibitors - dabigatran
- heparin and low molecular weight heparins
- vitamin K antagonists - warfarin
122
what is the target of anticoagulants
target various factors in the coagulation cascade preventing formation of a stable fibrin framework
123
what is the treatment for venous thromboembolism
apixaban or rivaroxaban
124
how would you treat a venous thromboembolism if apixaban or rivaroxaban are contraindicated
- low molecular weight heparin, followed by dapigatran extexilate or edoxaban
- LMWH given with a vit K antagonism for at least 5 days or target INR achieved followed by a vitamin k antagonist on its own
125
what are the examples of drug which are direct-acting oral anticoagulants
apixaban
dabigatran extexilate
edoxaban
rivaroxaban
126
what is the mechanism of action of dabigatran extexilate
- reversible inhibitor of thrombin
- idarucizumab reversal agent
127
what is the mechanism of action of apixaban, edoxaban and rivaroxaban
- reversible inhibitor of activated X (factor Xa) - andexanet alfa reversal agent
- prevents thrombin generation
- prevents thrombus development
128
what are the indications of apixaban, dabigatran extexilate, edoxaban and rivaroxaban
- prevention of stroke
- secondary prevention of DVT and/or PE
129
what are the indications of apixaban, dabigatran extexilate and rivaroxaban
prevention of venous thromboembolism following surgery
130
what are the indications of rivaroxaban
prevention of atherothrombotic events in patients with coronary or peripheral artery disease following an acute myocardial infarction
131
what are the contra-indications of apixaban
avoid in conditions with significant risk of bleeding such as gastrointestinal ulceration, malignant neoplasms with high risk of bleeding or oesophageal varices
132
what are risks of apixaban with the elderly
prescription can potentially be inappropriate - STOPP criteria
risk of bleeding e.g. severe hypertension
133
what are the side effects of apixaban
anaemia
haemorrhage
134
what are the pharmacodynamics of heparin
- family of sulphates mucopolysaccharides, found in the secretory granules of mast cells
- inhibits coagulation by activation antithrombin III
135
how does heparin inhibit coagulation by activation. antithrombin III
- AT III is a naturally occurring inhibitor of thrombin and clotting factors IX, Xa, XI and XII
- in the presence of heparin, AT III become 1000x more active and inhibition of clotting factors is instantaneous
136
what are the examples of LMWHs
dalteparin sodium
enoxaparin sodium
tinzaparin sodium
137
what are the pharmacodynamics of LMWHs
- more consistent activity - enoxaparin
- inactivate factor Xa (and thrombin)
- have immediate onset
138
what are the pharmacokinetics of heparin and LMWH
- inactive given orally
- administered IV or SC
- eliminated mainly by renal excretion
- overdose treated by IV protamine
139
what is the pharmacokinetic of heparin
- short half lifer (<1hr, 2h large dose)
- given frequently or as continuous infusion)
140
what is the pharmacokinetic of LMWH
- longer duration of actions (half lifer of 4-5hr)
- allows once daily dosing
141
what are the side effects of heparin and LMWH
bleeding and hypersensitivity
142
what are the examples of vitamin k antagonists
warfarin
acenocoumarol
phenindone
143
what is the function of vitamin k antagonists
inhibits the action of vitamin K1 dependent clotting factors II, VII, IX and X
144
how long does it take for vitamin K antagonists to work
at least 48-72hrs for there anticoagulant effect to develop
145
what are the side effects of vitamin k antagonists
haemorrhage and skin necrosis
146
what is warfarin
- warfarin targets INR
- A small population of patients are genetically resistant to warfarin, due to reduced binding to vitamin K reductases
147
what are the pharmacokinetics of warfarin
- absorption - rapidly and almost totally absorbed from the GI tract. levels peak in blood 0.5-4h after administration
- distribution - low volume of distribution as 99% plasma protein bound
- metabolism - action is terminated by metabolism in the liver by CYP450 enzymes
- excretion - metabolites are conjugated to glucuronide and excreted in urine and faeces
- half life of 15-80hrs
- dose is highly variable
148
what are anti platelet drugs
- inhibition of platelet function is useful prophylactic and therapeutic strategy against MI and stroke caused by thrombosis
149
a 82 year old man is found slumped in his kitchen. he is weak on his left side and has a left sided facial droop. he has chronic arterial fibrillation for which he takes warfarin with a target INR of 2-3. he takes no other medication except amlodipine. a CT scan is performed. briefly describe the most likely cause of this mans stroke
history of hypertension (a risk of thromboembolic and haemorrhage stroke)
150
a 76 year old male experiences severe crushing central chest pain going down his left arm. he is taken to hospital where blood tests and an ECG confirm an acute myocardial infarction. what would be the most appropriate immediate treatment
anti platelet drug such as aspirin
151
what is the action of platelets
- activated platelets cover and adhere to exposed sub endothelial surface of damaged endothelium
- activated platelets release chemical mediators
- chemical mediators released by platelets
- thromboxane A2, ADP, serotonin, PAF
- platelets are recruited into the platelet plug
- thromboxane, ADP, serotonin, PAF
152
what is the mechanism of action of aspirin
- aspirin irreversibly inhibits COX1, therefore inhibits the synthesis of TXA2
- because platelets do not contain DNA or RNA they cannot synthesis new COX1
- the inhibition is irreversible and effective for the life of the circulating platelet
153
what is the clinical use of aspirin
- used prophylactically to prevent arterial thrombosis leading to:
- transient ischemic attack
- stroke
- myocardial infarction
154
give two examples of fibrinolytic drugs
streptokinase
alteplase
155
what are thrombolytic drugs
- thrombolytic drugs potentiate the effects of the fibrinolytic system
- they activate conversion of plasminogen to plasmin which breaks down fibrin, thus dissolves clots
156
a 58 year old man collapsed at work 2 hours ago and is taken to AnE. his work colleagues told the paramedic at the scene that he has complained of his face feeling weird and numbness in his hand before he fell to the ground. he is found to have weakness down his left side and a left sided facial dropping. a CT scan shows normal results. he is diagnosed as experiencing an acute ischaemic stroke. which drug is most appropriate
- CT scan rules out bleed
- acute ischaemic stroke cause by thrombus
- alteplase is recommended in the treatment of acute ischaemic stroke if it can be administered within 4.5h of symptom onset; it should be given by medical staff experienced in the administration of thrombolytics and the treatment of acute stroke, preferably within a specialist stroke centre. treatment with aspirin should be initiated 24 hours after thrombolysis
157
what are the pharmacokinetics of thrombolytic drugs
- administered IV; immediate effect
- short half lives
- main hazard is bleeding
158
what are the main uses of fibrinolytic (thrombolytic) drugs
- restoring catheter and shunt function, by lysing clots causing occlusions
- to dissolve clots that result in stroke
159
aspirin is a cox-2 inhibitor and irreversibly blocks conversion of arachidonic acid to prostaglandin endoperoxide H2 in platelets resulting in inhibition of TXA2 synthesis. select the option that best describes an action of TXA2
constricts vascular smooth muscle
160
select the option that is correct regarding the action of aspirin
- TXA2 synthesis is blocked for the lifespan of the platelets exposed to the drug
- aspirin is an irreversible blocker of platelets
161
select the option that is not a contra-indication for use of aspirin
following coronary by-pass surgery
162
clopidogrel inhibits platelet aggregation and used in the prevention of atherothrombotic events. what is its mechanism of action
irreversible blocker of P2Y12 receptors
163
clopidogrel may be administered orally as a prodrug and undergoes CYP2C19 metabolism by the liver to its active form. a patient is prescribed clopidogrel alongside omeprazole, which they were already taking (also metabolised by CYP2C19). select the correct response from the options below
the risk of thrombus formation is increased compared to when clopidogrel is taken alone
164
glycoprotein IIB/IIIA receptor antagonists such as tirofiban or the monoclonal antibody fragment abciximab inhibit platelet GPIIb/IIIa receptors and may be used in high risk patients who require angioplasty. what is most appropriate route of administration
intra-venous
165
vitamin K deficiency may lead to excessive bleeding (e.g. haemorrhage disease of the newborn. which drug, if used excessively may lead to excessive bleeding due to inactivation of vitamin K dependent clotting factors
warfarin
166
which one of the following does not enhance the effect of the vitamin k antagonist warfarin. enhancing the effects of warfarin increases the risk of haemorrhage
vitamin K
167
which one of the following enhances the effects of the vitamin K antagonist warfarin. enhancing the effects of warfarin increases the risk of haemorrhage
liver disease
168
how is atherosclerosis developed
- circulating LDL gains access to sub endothelial space
- where it is oxidised
- cytokines IL-1 and MCP-1 attract circulating monocytes
- that cross intimate to become macrophages
- smooth muscle cells migrate and proliferate under the influence of smooth muscle mitogens
- a primitive plaque is formed of foam cells, smooth muscle, lipid and necrotic cells
- the plaque enlarges, develops a fibrous capsule and protrudes a vessel lumen
169
which is a cause of primary dyslipaemia
familial hypercholesterolaemia
170
what is the prevalence of familial hypercholesterolaemia
1/250
171
select the incorrect statement regarding cholesterol
it is found in low levels in the gall bladder
172
an average male synthesises ~1000mg cholesterol per day. what is the average daily dietary intake of cholesterol
300mg
173
LMWHs are preferred for use clinically to unfarctionated heparin as they may be given subcutaneously and have longer half-lives. all heparins do have a risk of a heparin-induced thrombocytopenia and in some patients this may lead to thrombosis. why may a heparin-induced thrombocytopenia cause a thrombosis?
heparin may induce antibody synthesis targeting platelets and platelet factors
174
a patient receiving warfarin is not maintaining a consistent INR and the decision is made to switch to the DOAC drug rivaroxaban. when the patient stops taking warfarin their INR is too high which means the blood is taking too long to clot. select the most appropriate statement regarding the introduction of the rivaroxaban treatment
there should be a delay in starting the rivaroxaban until the INR value returns to its target value
175
which one of the below is not true for plasminogen
plasminogen is inactivated once inside a formed thrombus
176
select the incorrect response from below
alteplase is more effective against plasma plasminogen compared to fibrin bound plasminogen
177
select the best description for a clinical use of alterplase
thrombotic stroke
178
select the best option for a caution for clinical use of alteplase
atrial fibrillation
179
what is the definition of ischaemia
is a condition in which blood flow is restricted or reduced in a part of the body. cardiac ischaemia is decreased blood flow and oxygen to the heart muscle
180
what is the definition of infarction
infarction is an obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus causing local death
181
list 4 things that can cause a blockage of artery
build up of fat, cholesterol or calcium in the arteries
blood clot
thrombus
plaque
182
list what factors determine myocardial oxygen supply
- oxygen carrying capacity
- coronary artery flow
- coronary perfusion pressure
- coronary vascular resistance
183
list what factors determine myocardial oxygen demand
- heart rate
- contractility
- ventricular wall tension
184
how is stable angina treated with nitrates
- GTN short acting - isosorbide mononitrate longer acting
- nitrates are vasodilators
185
what are the clinical benefits of GTN
- relax vascular smooth muscle - some reduction of after load
- relax veins - reduction in central venous pressure, reduced preloads
186
what is the mechanism of action of GTN
- nitrates are metabolised release NO
- activates guanylyl cyclase - increases cGMP
- dephosphorylation of myosin light chain
- reduced cytoplasmic Ca2+
- relaxation of smooth muscle
187
what are the adverse effects of GTN
- postural effects
- headache
188
what are the pharmacokinetics of GTN
- sublingual administration - effects in minutes
- rapidly inactivated by hepatic metabolism
189
state one named drug to relieve hypoxia in the immediate drug treatment of MI
only given oxygen if oxygen saturation reduced
190
state one named drug and provide ration for pain relief in the immediate drug treatment of MI
- morphine/diamorphine with an antiemetic
- relieves pain and nausea
- ventilation
191
state one named drug and provide rationale for reduced cardiac workload in the immediate drug treatment of MIU
nitrates - GTN
- vasodilator
- reduced cardiac work
192
state one names drug and provide rationale for reduced risk of another infarction in the immediate drug treatment of MI
- anti-platelet
- aspiring, clopidogrel - prevent further clot formation
193
name 4 subsequent drug treatments used to treat MI
- beta blockers - to improve myocardial perfusion and reduce risk of arrhythmias
- captopril (ACE inhibitor) - improves survival and useful is risk of heart failure/left ventricular dysfunction
- heparin (anticoagulants) - protection from thrombus in a risk patient
- other useful drugs - nitrates, antiarrhthmics, statin - lipid lowering
194
what is the primary prevention for statin treatment
offer atorvastatin 20mg for the primary prevention of cardiovascular disease to people who have a 10% greater 10-year risk of developing cardiovascular disease
- for people 85 years or older consider atrovastatin 20mg as statins may be of benefit in reducing the risk of non-fatal myocardial infarction
195
what causes primary dyslipidaemia
combination of dietary and genetic factors
familial hypercholesterolaemia high risk of CHD
196
what are the causes of dyslipidaemia
consequence of other conditions
diabetes mellitus, alcoholism, renal disease
197
what are the non-pharmacological treatments of dyslipideamia
cardioprotective diet
weight loss
physical activity
reduce alcohol consumption
smoking cessation
198
what are the pharmacological treatments of dyslipidaemia
anti-hyperlipideamic drugs
199
what are lipid lowering drugs
HMG-CoA reductase inhibitors
fibrates
cholesterol absorption inhibitors e.g. ezetimibe, bile-acid binding resins
omega fatty acids
200
what are some of the HMG CoA reductase inhibitors
simvastatin, pravastatin, lovastatin, atrovastatin, rosuvastatin, fluvastatin
201
what are the pharmacokinetics of HMG CoA reductase inhibitors
short acting
oral, night
well absorbed
liver cytochrome P450 metabolism - not rosuvastatin
202
what is the importance of blocking HMG CoA reductase enzyme
rate limiting step in cholesterol synthesis
blocks conversion HMG CoA to mevalonic acid
203
which of the statins are short acting, specific, reversible inhibitors
simavastatin
lovastatin
204
which of the statins are longer lasting inhibitors
atorvastatin
205
what is the benefit of blocking cholesterol synthesis
unregulated LDL receptor synthesis
increases LDL clearance by liver
206
what is the clinical use of primary hyperlipidaemia
reduce LDL by 30%
raise HDL by 20%
207
what are the adverse effects of HMG CoA reductase inhibitors
well tolerated but may have muscle pain, GI disturbance, insomnia, rash
rarely myositis and angio-oedema
208
how do HMG CoA reductase inhibitors increase life expectancy
- serum LDL reduced by 35%
- death reduced by 30%
- death by CHD reduced by 42%
209
what are the beneficial physiological effects of HMG CoA reductase inhibitors
- endothelial function improves
- improve vascularisation of ischaemic tissue
- atherosclerotic plaque stabilisation
- reduces vascular inflammatory response
- reduced platelet activation
- enhanced fibrinolysis
- antithrombotic
210
what are the examples of fibrates
gemofibrozil
fenofibrate
bezafibrate
211
what is the mechanism of action of fibrates
- agonist at peroxisomes proliferator-activated receptors (PPAR-alpha) nuclear receptor that regulates lipid metabolism
212
how do fibrates regulate lipid metabolism
increase synthesis of lipoprotein lipase by adipose tissue
stimulated fatty acid oxidation in the liver
increases expression of apia-I and apoA5
increases hepatic LDL uptake
213
what are the causes of increases lipid
marked reduction circulating VLDL and TG
modest reduction in LDL
increase LDL uptake by liver
214
what are the pharmacokinetics of fibrates
well absorbed from the gastrointestinal tract
high degree of binding to albumin
metabolised by the cytochromes P450
primarily excreted via the kidneys
214
what are the clinical uses of fibrates
hypertriclycerideamia
mixed hyperlipidaemia
TG levels reduced by 20-30%
cholesterol reduced by 10-15% associated
rise in HDL
215
what are the adverse effects of fibrates
rash, GI disturbance
rhabdomyolysis causing renal failure
clofibrate may cause gall stones
216
what are the drug examples of cholesterol absorption inhibitors
ezetimibe, colestipol, cholestyramine
217
what is the mechanism of action of ezetimibe
inhibits intestinal absorption of cholesterol by interfering with Neimann-pick C1-like 1 transport protein
decreases LDL and VLDL
218
what are the pharmacokinetics of ezetimibe
administered orally
absorbed into intestinal epithelial
extensively metabolised into active metabolite
enterohepatic recycling slows elimination
219
what is the clinical use of ezetimibe
treatment of hyperlipidaemia in combination with statins
220
what are the adverse effects of ezetimibe
mild - diarrhoea, abdominal pain, headache
rash and angioedema
secreted in breast milk, contraindicated in breastfeeding
221
what is the mechanism of action of colestipol, cholestyramine
binds bile acid in gut
prevent reabsorption
diverting hepatic cholesterol to BA synthesis
upregulates LDL receptors increases LDL removal from the blood
222
what are the pharmacokinetics of colestipol and cholestyramine
administered by mouth (stays in the GIT)
223
what are the clinical uses of colestipol and cholestyramine
primary hypercholesterolemia when statin is contraindicated
pruritus associated with biliary obstruction
bile acid diarrhoea
224
what are the adverse effects of colestipol and cholestyramine
constipation, bloating
malabsorption of vitamin K, folic acid, ascorbic acid
disrupts absorption of digitalis, thiazides, warfarin, iron
225
what is the mechanism of action of niacin in the liver
reduced VLDL synthesis
reduced VLDL and LDL
226
what is the mechanism of action of niacin in the adipose tissue
reduced hormone-sensitive lipase activity
reduced TG
227
what is the general mechanism of action of niacin
reduced catabolic rate for HDL, increases HDL
increased clearance of VLDL by activating lipoprotein lipase
228
what are the pharmacokinetics of niacin
readily absorbed in GIT following oral administration
metabolised in the liver
excreted via kidneys
229
what are the clinical uses of niacin
hypercholesterolemia
hypertriglycerideamia with low levels of HDL
230
what are the adverse effects of niacin
cutaneous flushing
associated with pruritus and palpitations
reduced with pre-treatment of aspiring or other NSAIDs
dose-dependent nausea and abdominal discomfort
moderate elevation of liver enzymes to severe hepatotoxicity
hyperuricemia in 20% of the patients
231
