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MPharm Semester 2 > Hypertension > Flashcards

Hypertension Flashcards

1
Q

What is hypertension?

A

A condition where the blood pressure is elevated to an extent where clinical benefit is obtained by lowering it

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2
Q

What is the text book value for normal blood pressure and what is it measured in?

A

120/80 mmmercury

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3
Q

What is systolic and diastolic pressure?

A 
S= pressure when heart contracts
D= pressure when ventricles relax
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4
Q

Give four consequences of high BP:

A

Myocardial infarction (heart attack)
Cerebral vascular accident (stroke)
Heart failure
Renal disease

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5
Q

Give four high risk patients for high blood pressure:

A

Patients with evidence of cardiovascular disease
Elderly
Diabetic
Renal failure

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6
Q

What type of ethnicity experiences more commonly experiences a high BP?

A

Black Africans + Black Caribbeans

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7
Q

What is primary hypertension caused by and how much hypertension is due to primary?

A

90-95%- unknown cause however there are risk factors e.g. smoking, gender, age, stress

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8
Q

What is seconday hypertension caused by and how much hypertension is due to secondary?

A

5-10%- underlying causes e.g. combined oral contraceptives, NSAIDs, steroids, pseudoephedrine

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9
Q

What are the symptoms of high BP?

A

No symtoms, that’s why screening is important

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10
Q

What is the only type of symptomatic high BP and how high is it?

A

Malignant hypertension

180/120

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11
Q

What are the symptoms of malignant hypertension?

A

Confusion, visual loss, headache, coma

Evidence of small vessel damage e.g in eyes/ kidneys/ brain

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12
Q

What are two ways of measuring blood pressure?

A

Auscultatory detection of Korotkoff sounds with stethoscope (manual)
Oscillometrially (automatic)

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13
Q

What are the two types of sphygmomanometers?

A 
Mercury sphygmomanometer
Aneroid sphygmomanometer (the one we used in blood pressure practical)
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14
Q

What are the sounds of systolic and diastolic sounds when measuring blood pressure manually?

A 
S= First repetitive appearance, faint 
D= When sound disappears completely
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15
Q

Why is it best to measure blood pressure when the patient is standing up AND sitting down?

A

The BP may drop when standing, postural hypertension

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16
Q

What should be the consequence if the blood pressure of a patient is more than 140/90 but less than 180/120?

A

Offer ambulatory bp monitoring or home monitoring or come back three separate times

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17
Q

Give two additional investigations assessments when to do when a patient has higher BP:

A

Assess 10 year cardiovascular risk

End organ damage

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18
Q

What is the value for severe hypertension and what is the consequence:

A

180/120
Refer/ admit and treat
Medical emergency

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19
Q

What is the value for stage 2 hypertension and what should be the consequence?

A

160/100

Treatment required

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20
Q

What is the value for stage 1 hypertension and what should be the consequence of this?

A

140/90
Offer ambulatory (home) BP monitoring
Lifestyle interventions
Assess CV risk and end organ damage

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21
Q

What is the value of normal BP for under 80’s and what is the consequence of this?

A

Less than 140/90

Reassess every 5 years

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22
Q

What is the value of normal BP for over 80’s?

A

150/90

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23
Q

What is the target BP value for type 1 diabetics? If evident complications, what should be the alternative value?

A

140/80- no complications

130/80- with complications

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24
Q

What should be the target BP value for type 2 diabetics?

A

The same for non diabetics e.g. for under 80’s 140/90

for over 80’s 150/90

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25
Q

What side of the heart pumps deoxygenated blood?

A

Right

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26
Q

What is the difference between pulmonary circulation and systemic circulation?

A

Systemic is to the rest of the body, pulmonary is to the heart

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27
Q

Why are arteries elastic?

A

Allows for stretch and recoil

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28
Q

What are the three layers of the artery and vein and describe each of their composition:

A
  1. Tunica Intima- innermost, includes the endothelium and squamous cells
  2. Tunica Media- middle, many circular smooth muscle and elastin
  3. Tunica Aventitia- outermost, fibrous connective tissue rich in collagen and elastin
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29
Q

What is the function of the arteries and explain its properties for this:

A

Rapid transit for blood from heart to organs

  • Have a large radius for low resistance to blood flow
  • Elastic nature which contains elastin and collagen fibres for elasticity and tensile strength
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30
Q

What is vascular compliance in the arteries?

A

Act as a pressure reservoir to provide driving force for blood when heart is relaxing

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31
Q

What are the factors that affect the force exerted by blood against a vessel wall?

A
  1. volume of blood contained within the vessel

2. compliance of vessel walls

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32
Q

Define is systolic pressure:

A

Peak pressure exerted by ejected blood against vessel walls during cardiac systole

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33
Q

Define diastolic pressure:

A

Minimum pressure in arteries when blood is draining off in the vessels down stream

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34
Q

Why is there a higher pressure in systemic circulation compared to pulmonary circulation?

A

Blood has to go further and also lungs are delicate so less pressure is used.

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35
Q

What are the sounds when measuring blood pressure?

A

KorotKoff sounds

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36
Q

What is the pulse pressure and how do you calculate it?

A

Difference between systolic and diastolic pressure

e.g if bp is 120/80, pulse pressure would be 40mmHg

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37
Q

What is mean arterial pressure and how is it calculate?

A

Average pressure driving blood forward into tissues throughout cardiac cycle
MAP= diastolic pressure + 1/3pulse pressure
e.g. at bp of 120/80 MAP= 80+13=93

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38
Q

What do capillaries do and how do their properties relate to their function?

A

Site of exchange between blood and surrounding tissue
One cell thick, maximise SA and minimise diffusion distance
Small radius so velocity of blood flow is slow so provides good exchange time

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39
Q

How do molecules move in and out of the capillaries?

A

Diffusion

Bulk flow- through pores and intracellular clefts

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40
Q

What happens when capillaries lose fluid?

A

Lymph nodes collect them

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41
Q

What are capillaries surrounded by to aid then when resting and how do they work?

A

Precapillary sphincters
Contraction of sphincters reduces blood flow
Relaxation of sphincters increases blood flow

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42
Q

What are the functions of the veins and what are its properties related to their function?

A

Transports blood back to the heart
Large radius so low pressure therefore little resistance to blood
Most of the blood is in the vein
Have valves to maintain a one way flow
Skeletal muscle pump, contraction of muscle squeezes the veins and pushes the blood up

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43
Q

Give five factors that enhance venous return:

A
  • Driving pressure from cardiac contraction
  • Sympathetically induced venous vasoconstriction
  • Skeletal muscle activity
  • Effect on venous valves
  • Respiratory activity
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44
Q

What are lymph vessels made of and what is their properties?

A

Formed by conversion of initial lymphatics
Empty into venous system, where blood enters the right atrium
One way valves at spaced intervals to direct flow to veins

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45
Q

What are the function of lymph vessels?

A

Return excess filtered fluid that is lost
Defence against disease, have phagocytes
Return of filtered protein

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46
Q

What problems occur is the lymph vessels go wrong?

A

Oedema, swelling of the tissues when too much interstitial fluid accumulates

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47
Q

What is smooth muscle contraction due to and how does this work?

A

Increase in Ca2+ ions in the cytoplasm
Ca2+ binds to calmodulin which activates myosin light chain kinase which phosphorylates myosin leading to myosin power-stroke, leading to smooth muscle contraction

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48
Q

What is shear stress and what is it detected by?

A

The frictional force parallel to the wall at the surface of the endothelium directly related to blood flow velocity
It is detected by receptors on the endothelial cell which activates nitric oxide synthase and therefore stimulates NO production

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49
Q

How does nitric oxide (NO) cause smooth muscle relaxation?

A

NO diffuses through the inter membrane space and activates soluble guanylyl cyclase
This increases GMP so protein kinases causes smooth muscle relaxation

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50
Q

How is Mean Arterial Pressure calculated?

A

Cardiac output x peripheral resistance

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51
Q

What hormones can influence arterial radius?

A 
Adrenal medullary hormones:
-Adrenaline and Noradrenaline 
-Adrenoreceptors
  Alpha 1= contraction
  Beta 2= relaxation
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52
Q

What are two potent vasoconstrictors and what do they control?

A

Vasopressin and angiotensin 2

Important in controlling fluid balance

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53
Q

What are two factors that can have an affect on total peripheral resistance?

A

Arterial radius

Blood viscosity- not in this module

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54
Q

What are the functions of the arterioles and how does its structure help carry out its function?

A

Determines the relative blood flow to organs
Small enough radius to offer considerable resistance but large enough to carry blood
Major factor in mean arterial pressure

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55
Q

What is the part of the body where the blood supply always remains constant?

A

Brain

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56
Q

What are two local chemical influences on arterial radius?

A

Local metabolic changes

Histamine release

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57
Q

What are two local physical influences on arterial radius?

A

Local application to hot or cold

Myogenic response to stretch

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58
Q

What are the four types of muscle tissue?

A

Striated
Cardiac
Skeletal
Smooth

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59
Q

What are the steps in the actin-myosin force generation?

A
  1. Myosin cross bridge attaches to actin myofilament
  2. Powerstroke, myosin head pivots and bends as it pulls one. the actin filament, pulling towards the M- line
  3. New ATP attaches to the myosin head, the cross bridge detaches
  4. As ATP-> ADP+Pi, cocking of the myosin head occurs
60
Q

What is the mechanism of action using Ca2+ ions to create muscle tension?

A

When Ca2+ enters the cell the intracellular concentration increases and Ca2+ is released from the sarcoplasmic reticulum
Ca2+ binds to calmodulin (CaM) x4
Ca2+ - calmodulin activates myosin light chain kinase (MLCK)
MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity
Active myosin cross bridges slide along actin and create muscle tension

61
Q

What is the name for pressure sensors?

A

Baroreceptors

62
Q

How is Cardiac Output (CO) calculated?

A

CO=HR x SV

63
Q

What is stroke volume and how is it controlled by?

A

Volume of blood in one heart beat

It is controlled by the venous return

64
Q

What are the short term control adjustments of baroreceptors?

A

Occur within seconds
Mediated by autonomic NS
Influences on heart, veins and arterioles

65
Q

What are the long term control adjustments of baroreceptors?

A

Require minutes to days

Involve adjusting total blood volume by restoring normal salt and water balance, by urine output and thirst

66
Q

What are chemoreceptors sensitive to?

A

Low O2 and high acidity levels in the blood

67
Q

What is the blood pressure value for hypotension?

A

Below 100/60 mmHg

68
Q

When does hypotension occur?

A

When there is too little blood to fill the vessels

Heart is too weak to drive the blood

69
Q

What is orthostatic (postural) hypotension?

A

Insufficient compensatory responses to gravitational shifts in blood when person moves from horizontal to vertical position

70
Q

Name the two atrioventricular valves and what are they composed of?

A

Bicuspid(mitral) valves
Tricuspid valves
Supported by chordae tendineae, papillary muscles contract with ventricles to prevent back flow

71
Q

What are the pulmonary and aortic valves and describe how they work:

A

Semilunar, half moon
Three cusps
Evertion prevented by upturned nature and positioning of cusps
Close under back pressure

72
Q

What is diastole and describe it?

A

Heart relaxing and filling, isovolumetric relaxation
AV valves closed and pulmonary aortic valves closed
As diastole proceeds the weight of the blood will open the AV valves and aortic and pulmonary valves still closed
Blood moves from atria to ventricles

73
Q

What is systole and describe it?

A

Contraction and emptying of the heart
AV valves and aortic and pulmonary valves are closed
Ventricles contract
AV valves still closed to prevent back flow but aortic and pulmonary valves open as blood is pushed from ventricles to aortic and pulmonary arteries

74
Q

What is the equation to calculate stroke volume?

A

End diastolic volume- end systolic volume

75
Q

What sac is the heart surrounded by and give its structures and functions?

A

Pericardial sac
Double walled, tough covering
Anchors the heart
Has pericardial fluid which lubricates the heart and stops it from rubbing at ribcage and other tissues

76
Q

What is pericarditis?

A

When the pericardial fluid becomes infected, virally or bacterially, and there is painful rubbing

77
Q

State and describe the three layers of the heart wall:

A

Endothelium and endocardium- inner layer which lines the entire circulatory system, barrier between blood and underlying tissue
Myocardium- forms sheets which wraps around the heart, which drives contraction
Epicardium- outer layer, made up of connective tissue

78
Q

What is the blood supply to the heart called?

A

Coronary arteries

79
Q

What type of muscle is the heart made of?

A

Striated, in branches

80
Q

What are cardiac muscle fibres interconnected by, describe these connections:

A

Intercalated discs
Desmosomes- mechanical
Gap junctions- electrical

81
Q

What is the sarcomere?

A

A functional contractile unit made up by myosin and actin filament

82
Q

What is the strength of a sarcomere contraction, and what is it called?

A

Small force but many of them

End of sarcomere has a Z line, when contracts the Z lines moves closer together

83
Q

Describe the process for using Ca2+ for contractile function of the cardiomyosite:

A

Ca2+ binds to uranium receptor on sarcoplasmic reticulum
Ca2+ enters the cytoplasm and binds to troponin, this activates myosin contraction by changing conformation of actin
Ca2+ reabsorbed by sarcoplasmic reticulum by ion channel pump SERCA

84
Q

What is cardiac output and what is the average CO?

A

Volume of blood pumped per ventricle per minute

4900 ml/ min

85
Q

How is heart rate controlled and how does it work?

A

By the sinoatrial (SA) node (pacemaker)
This SA node reaches a threshold resulting in action potential which spreads through the heart which induces the heart to contract ( have a heart beat)

86
Q

What type of hormones act on the SA node and consequently do what to the heart rate?

A

Increase in plasma adrenaline, noradrenaline and epinephrine increase HR

87
Q

What is preload?

A

Volume of blood in the ventricles at the end of diastole ( end diastolic pressure)

88
Q

What is afterload?

A

Resistance left ventricle must overcome to circulate blood

89
Q

What are the three things that can affect stroke volume?

A

Changes in venous return (intrinsic control)
Changes in sympathetic stimulation (extrinsic control)
changes in after load ( disease)

90
Q

What happens to the stroke volume if end diastolic volume is increased and why?

A

Increases as stretch of cardiomyocytes stretch more

91
Q

What is intrinsic activity?

A

Purely due to the makeup of the heart, more blood in= more blood out

92
Q

What is the Frank Starling curve?

A

More blood in in diastolic, more blood out in stroke

93
Q

How can sympathetic stimulation increase stroke volume?

A

Activates B1 adrenoreceptors in cardiomyocytes which increases cardiomyocytes contractility so increases strength in contraction. This increases Ca2+ so greater actin-myosin cross-bridge
This is independent of end diastolic volume and only changes sv

94
Q

How would you calculate the ejection fraction and what is the normal percentage and the failing %?

A

SV/EDV
Normal= 50-70% or fit people 90%
Failing heart= 30%

95
Q

How does after load have an affect on stroke volume?

A

Afterload is arterial blood pressure, so if arterial BP increases, the workload increases due to the elevated BP because of the narrowing arteries which becomes blocked (stenoticexit valve)
conpensation by enlarging cardiac muscles to oppose this but in older weaker hearts this can lead to heart failure

96
Q

What are two things Angiotensin II can regulate?

A

Cardiac output

Total peripheral resistance

97
Q

Where is Angiotensinogen released from and what does it do?

A

Realeased from the liver

Can be cleaved to form Angiotensin I

98
Q

Where and when is Renin released, and what does it do?

A

Renin is released from the kidney (maculadensa) when there is a drop in blood pressure/ fluid volume
It cleaves angiotensingoen to form angiotensin I

99
Q

What does ACE stand for and where is it released from?

A

Angiotensin- converting enzyme, released from the lungs

100
Q

What does ACE do and how does it do this?

A

Membrane bound protein on the endothelial cells, so as angiotensin I passes across the endothelial membrane it cleaves the inactive angiotensin I to the active angiotensin II

101
Q

What are two things angiotensin II can do to increase BP?

A
  1. Act directly on the blood vessels (smooth muscles), stimulating vasoconstriction
  2. Act on adrenal glands to stimulate the release of aldosterone
102
Q

What does aldosterone do?

A

Acts on the nephron to stimulate the increase reabsorption of salt (NACl) and water from the urine to the blood.

103
Q

How does noradrenaline increase BP?

A

Vasoconstriction

104
Q

How does Angiotensin II cause vasoconstriction?

A

When Angiotensin II binds to an AT1 receptor, vasoconstriction occurs due to contraction of the smooth muscle cells which causes vasoconstriction and increase in blood volume
AT1 receptor increases Ca2+ conc

105
Q

How does angiotensin II cause vasodilation?

A

Angiotensin II binds to an AT2 receptor found on smooth muscles

106
Q

Give one pathway of the AT1 receptor GPCR reaction to cause vasoconstriction:

A

AT1 receptor is coupled with Gaq G-protein
When angiotensin II binds, Gaq activates phospholipase C which cleaves PIP2 into DAG AND IP3
IP3 binds to the sarcoplasmic reticulum and this opens Ca2+ channels so ions out of store
Ca2+ in the cytoplasm binds to calmodulin which activates myosin light chain kinase and therefore phosphorylates it
This activates a myosin power stroke which increases smooth muscle contraction and there for increases vasoconstriction and BP

107
Q

Give the second pathway of the AT1 receptor GPCR reaction to cause vasoconstriction:

A

After angiotensin II binds to the AT1 receptor, Gaq activates phospholipase C, which cleaves PIP to IP3 and DAG
IP3 binds to the sarcoplasmic reticulum and opens Ca2+ channels so the ions are out of the store into the cytoplasm
These Ca2+ ions activate JAK2 and so a G protein RhoA is activated
Another signalling pathway Rho Kinase ROK 1 and 2 so this leads to phosphorylation and inactivation of myosin light chain phosphatase, which inhibits the dephosphorylate of myosin light chain which increases phosphorylation levels
This increases smooth muscle contraction and vasoconstriction

108
Q

What is the process for how aldosterone increases BP?

A

Aldosterone binds with a cytoplasm receptor
Hormone- receptor complex initiates transcription in the nucleus
New protein channels and pumps (that are responsible for Na+ reabsorption and K+ secretion) are made
Aldosterone induced proteins modify existing proteins and this increases the movement of ions and increases the movement of H2O from urine into blood as water flows with the Na+ ions

109
Q

Why is using aldosterone to increase BP a slower process than angiotensin pathways?

A

Has to go through transcription

110
Q

Which channels are used for the aldosterone Na+ reabsorption?

A

ENaC channels

111
Q

Which channels are used for the aldosterone K+ secretion?

A

ROMK channels

112
Q

What are three pharmacological interventions that can oppose increasing BP?

A
  1. Direct renin inhibitor
  2. ACE inhibitors
  3. Angiotensin II type 1 receptor blockers (antagonists)
113
Q

Why is ACE a metal-protease?

A

Needs a co ordination bond with zinc as it has zinc in its A/S

114
Q

How do renin inhibitors work and give an example:

A

Not often used alone
Reduce plasma renin activity
Aliskiren- indicated for hypertension alone or in combination

115
Q

What is Bradykinin and what does it do?

A

A potent vasodilator when bradykinin is broken down
ACE inhibits the break down of bradykinin as it induces vasodilation on BK1 receptors on the endothelial cells which stimulate NO

116
Q

Where is ACE placed to suit its function?

A

Faces out into the blood

117
Q

Give an example of an ACE inhibitor and how does it work?

A

Lisinopril, prevents the conversion of Angiotensin I to II so II is reduced and the rest of the pathway is inhibited
Bradykinin is also able to be stabilised and increase vasodilation

118
Q

What are other ways in how ACE inhibitors work?

A

Reduce cardiac load so the heart won’t have to pump so hard
Reduce salt retention and vascular growth so preload is reduced
Preferentially acts on kidney, heart, brain and vascular bends

119
Q

How do Angiotensin II type 1 receptor blockers (ARB’s) work?

A

Inhibit AT1 receptors and decrease BP as prevent angiotensin from activating vascular smooth muscle cells to constrict
AT2 receptors are still active is affects vasodilation via NO and bradykinin pathways

120
Q

Give two examples of ARB’s:

A

Losartan

Valsartan

121
Q

What are the benefits of ARB’s compared to ACE inhibitors?

A

More effective as don’t inhibit the breakdown of bradykinin and other kinins fewer side effects then an ACE inhibitor such as a dry cough

122
Q

How does Renin cleave angiotensinogen to angiotensin I?

A

Recognises the amide bond between 10 (leucine) and 11 (valine) and cleaves between them

123
Q

How does ACE cleave angiotensin I to angiotensin II?

A

Recognises the amide bond between 8 (phenylalanine) and 9 (histidine) and cleaves between them

124
Q

What converts Angiotensin II to Angiotensin III and how?

A

Amino-peptidases- recognises amide bond between 1 (aspartic acid) and 2 (arginine) and cleaves bond between them

125
Q

How would the inhibition of amino peptidases increase blood pressure?

A

Stop converting angiotensin II to III. Angiotensin II increases BP more as it’s more active so less would be converted to III and activity of II would increase.

126
Q

What type of protease is Renin?

A

Aspartyl protease

127
Q

What are the three main types of ACE inhibitors and give an example of each:

A
  1. Sulfahydryl inhibitors- Captopril (not used anymore)
  2. Dicarboxylate inhibitors- Enalapril
  3. Phosphonate inhibitors- Fosinopril
128
Q

What three factors do you need to consider when designing an inhibitor?

A
  • Structure of the enzyme
  • Structure of the natural substrate
  • Structure of the inhibitor
129
Q

Give information about initial inhibitors to lower blood pressure:

A

Venom boy South American pit viper lowered BP
Does this by potentiates the action of Bradykinin
e.g. Teprotide- effective in IV but not orally, lots of prolene’s, suggests its important

130
Q

What are mettaloproteases?

A

e. g carboxypeptidase, three main binding interactions:
- negative charge of peptide sub binds to a + charge in protein (arg)
- hydrophobic pocket
- a zinc atom close to the labile bond which stabilises the intermediate

131
Q

What does carboxypeptidase A do to work as ACE?

A

Removes final a.a from carboxyl terminus

132
Q

What is the difference between ACE and an inhibitor?

A

ACE removes the last two a.a from the carboxyl terminus, the inhibitor doesn’t do this

133
Q

Give three sulfahydryl ACE inhibitors?

A

Succinyl Proline- changing a.a from proline reduces activity
2-methyl succinyl proline
Catopril

134
Q

What type of drug is Enalapril and what does this mean?

A

Pro-drug of an ester, no activity outside the body, must be hydrolysed in body to activate drug
Have N containing ring

135
Q

Name four -Pril drugs:

A

Quinapril
Lisinopril
Perindopril
Ramipril

136
Q

What are dual action enzyme inhibitors?

A

Atrial natriuretic peptide, leads to increases Na+ excretion and a decrease in BP

137
Q

What are the problems with ACE inhibitors?

A

Dry cough

Caused by inhibition of break down of Bradykinin, where high levels of it are found in the lung

138
Q

Why would it be good to use peptide mimics rather than peptides?

A

Peptides have low bioavailability orally

139
Q

What are two advantages of using angiotensin antagonists?

A

No effect on bradykinin degradation

AT1 selective

140
Q

Give the first Angiotensin antagonist and its features:

A

Losartan- not a pro drug so readily metabolised
Add a bioisostere, tetrazole group for +ve charge on a.a means an ionic interaction
More lipophilic and good bioavailability
Hydrophobic pocket for lipophilic halogen and alkyl chain

141
Q

Name two other Angiotensin antagonists:

A

Valsartan and Irbesartan

142
Q

Name five types of CaV channels:

A 
L- Type (1) 
P/Q- Type (2.2)
N- Type (2.1)
R- Type (2.3)
T- Type (3)
143
Q

What are the three types of calcium channel blockers that act on L- type?
What do they bind to?

A
  1. Phenylakylamines- verapamil (heart)
  2. Dihydropryidines- Nifedipine (hypertension)
  3. Benzothiazepines- Diltiazem
    All binding to the a1 subunit
144
Q

What are some side effects of calcium channel blockers and why?

A

Flushing, headaches, ankle swelling, constipation

Due to the blocking of CaV channels in other places

145
Q

Where do different calcium channel blockers bind?

A
  1. Verapamil (heart) - IVS6
  2. Dihydropryidines- domains IIIS5, IIIS6, IV
  3. Diltiazem - Cytoplasmic loops joining III to IV segments controlling sensitivity to drugs
146
Q

Why should you not give a black African Caribbean or a person aged over 55 an ACE inhibitor or ARB as a first line treatment for hypertension?

A

Due to them not producing enough renin, so its better not to involve the renin- angiotensin system

MPharm Semester 2 (9 decks)

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