Hypertension

Question 1

arterioles function

Answer 1

Arterioles control blood flow into capillaries and regulate blood pressure by changing their diameter. remeber that arteries branch into arterioles

Question 2

do veins serve as a blood resevoir

Answer 2

yes
Veins store a large volume of blood and are often called the “capacitance vessels” of the circulatory system.

Question 3

at any given time , approximately 70% of blood is found in the veins, true or false

Answer 3

true

when not exercising, blood is mainly contained in the veins as well

Question 4

pulse pressure formula

Answer 4

Systolic bp – Diastolic bp

Question 5

Do blood vessels with higher resistance have lower blood pressure?

Answer 5

A: No — higher resistance raises pressure upstream and lowers pressure downstream of the resistance site.

Question 6

some factors that increase blood pressure

Answer 6

increased stroke volume
increased heart rate
increased stroke volume
increased peripheral resistance
increased blood viscosity

Question 7

what is the cardiovascular centre

Answer 7

a region in the medulla oblongata of the brainstem that regulates heart rate and blood vessel tone

The CV centre receives input from:

o higher brain centres (cerebral cortex, limbic system and
hypothalamus)
o baro-receptors
o chemoreceptors

Question 8

Baroreceptors are stretch receptors located in the aortic arch and carotid sinus that are activated by changes in blood pressure.

Answer 8

Stimulus: Blood pressure changes (↑ or ↓).

Detection: Baroreceptors in the carotid sinus and aortic arch detect the change.

Signal to Brain: Afferent signals sent to the medulla oblongata (cardiovascular center).

response to stimulus occurs

Question 9

descrine the auscultatory method of measuring blood pressure

Answer 9

also known as the Korotkoff method, is the standard technique for measuring blood pressure using a stethoscope and a sphygmomanometer. It involves listening for specific sounds (Korotkoff sounds) as the cuff is inflated and deflated. The appearance and disappearance of these sounds correspond to systolic and diastolic blood pressures, respectively.

Question 10

list some class of drugs used in the treatment of hypertension

Answer 10

• ACE inhibitors
• Calcium channel blockers
• Diuretics
• Drugs which inhibit the sympathetic activity of the ANS:
  o α-adrenoceptor antagonists – prazosin, doxazosin
  o β -adrenoceptor antagonists – propranolol, bisoprolol, metoprolol, carvedilol

o Centrally acting drugs – methyl dopa, clonidine
monoxidil

• Vasodilators

Question 11

a brief description of what happens in RAAS ((Renin-Angiotensin-Aldosterone System))

Answer 11

Trigger: ↓ Blood pressure / ↓ Na⁺ / Sympathetic activation

Steps:
Renin release from kidneys (juxtaglomerular cells)

Renin converts angiotensinogen (from liver) → angiotensin I

ACE (Angiotensin-Converting Enzyme) (mainly in lungs) converts angiotensin I → angiotensin II

Angiotensin II: Vasoconstriction → ↑ BP
Stimulates aldosterone release (from adrenal cortex)

Aldosterone: ↑ Na⁺ & water reabsorption
↑ K⁺ excretion

Overall: ↑ blood volume & pressure

Question 12

does SNS activation stimulate the RAAS system ?

Answer 12

yes

Question 13

does water automatically follow sodium reabsorption in the distal nephron ?

Answer 13

no

ADH/vasopressin must be present for the distal nephron to be permeable to H2O

ADH released from the posterior pituitary gland

Question 14

in the absence of vasopressin the collecting ducts are largely impermeable to water, true or false

Answer 14

true

Question 15

factors affecting the release of vasopressin

Answer 15

osmolarity greater than 250milliosmoles per liter

decreased arterial stretch due to low blood volume

decreased blood pressure

Question 16

What happens to potassium levels during RAAS activation?

Answer 16

Potassium levels decrease due to aldosterone-driven secretion into the urine

Question 17

some of the main side effects of ACE inhibitors

Answer 17

cough
angioedema
hyperkalaemia

Question 18

what is recommendation for females planning pregnancy or pregnant females on the use of ACE inhibitors

Answer 18

Females planning pregnancy should be switched to alternative treatments that have an established safety profile for use in pregnancy, unless continued treatment with an angiotensin-converting enzyme inhibitor is considered essential

avoid if pregnant due to risk of fetotoxicity

Question 19

MoA of angiotension II receptor antagonists

ARBs

Answer 19

the act on AT1 receptors, allowing for more complete inhibition on ATII’s actions

ARBs has no effects on bradykinin metabolism but ACE inhibitors have an affect on it(blocking bradykinin breakdown), leading to cough as a side effect

Question 20

ARBs have severe coughing and angioedema as side effects, true or false

Answer 20

false, because they have no effect on bradykinin metabolism or substance P metabolism

Question 21

describe calcium’s involvement in vascular smooth muscle contraction

Answer 21

Ca2+ enters and binds to calmodulin(CM)

Once active CM activates myosin light-chain kinase
(MLCK)

Activated MLCK phosphorylates the light chains within the head of the myosin molecule

• The activated head cross-bridges with actin
• Results in contraction

Question 22

CCBs MoA

Answer 22

block the entry of calcium through surface L-type channels to relax smooth muscle cells

Question 23

CCB categories ?

Answer 23

dihydropyridines(DHPs) and non-DHP

DHPs are selective for peripheral vascular SMCs while non-DHPs are cardioselective

Question 24

the role of ANP in managing blood pressure

Answer 24

Released by atrial myocardial cells in response to stretch (from increased blood volume).

thereby it Increases sodium and water excretion by:

Inhibiting sodium reabsorption in the nephron.

Increasing glomerular filtration rate (GFR).

Inhibiting renin and aldosterone secretion.

Question 25

the generalm function of diuretics

Answer 25

to decrease extracellular fluid volume(including blood volume)

Question 26

name some classes of diuretics

Answer 26

thiazide diuretics like bendroflumethiazide thiazide-like diuretics like indapimide loop like furosemide collecting duct diuretics like spironolactone

Question 27

which classes of diuretics are used to exert; mild diuretic effects strong diuretic effects

Answer 27

thiazides loop

Question 28

thiazide MoA

Answer 28

they act primarily on the DCT. since 90% of Na+ reabsorption, i.e H20 reabsoprtion, has already taken place before the DCT , the cause a mild or modest reduction in intravascular volume

Question 29

are thiazide-like diuretics the same as thiazides?

Answer 29

no **These have the same mechanism of action as thiazides, but are not structurally the same.**

Question 30

what is the specific protein that is inhibited by thiazide like diuretics in the DCT

Answer 30

the NaCl symporter

Question 31

the more sodium is reabsorbed in the nephron, the less potassium is lost to the filtrate, yes or no

Answer 31

no, The more sodium is reabsorbed in the nephron, ➡️ the more potassium is secreted into the urine, especially in the DCT ## Footnote this happens through the Na/K pumps

Question 32

main site of action for loop diuretics in the nephron

Answer 32

Acts on the thick ascending limb of the Loop of Henle

Question 33

another loop diuretic with a similar mechanism of action to furosemide but a different structure

Answer 33

ethacrynic acid ## Footnote used as a front line therapy for **the relief of pulmonary oedema in the treatment of heart failure**

Question 34

loop diuretics MoA

Answer 34

Reversibly and competitively inhibits the Na+-K+-2Cl- cotransporter on the luminal surface of the LOH ## Footnote note they have a higher affinity for the transporter than Cl- ions note that with the inhibition, sodium ions remain in the filtrate, travelling down the nephron to the DCT, where some of them are exchanged for potassium ions. the more sodium there is to reabsorb, esp in this case, the more potassium will be lost

Question 35

what are some effects of furosemide and other loop diuretics considering their MoA

Answer 35

Decrease NaCl reabsorption Decrease Mg2+ and Ca 2+ absorption Prevents the effective generation of the; *counter current multiplier * hyperosmotic region within the medulla

Question 36

what happens to the urine produced when there is a highly hypertonic medulla(of the nephron) ## Footnote hypertonic=high osmotic pressure

Answer 36

it is more concentrated it is less concentrated in the medulla is less hypertonic

Question 37

how can hypokalemia arise w the use of loop diuretics

Answer 37

Loop diuretics inhibit the Na⁺/K⁺/2Cl⁻ transporter in the thick ascending limb of the Loop of Henle, reducing sodium reabsorption at that site. More sodium reaches the distal nephron, where it is reabsorbed in exchange for potassium. This increased sodium delivery to the DCT stimulates potassium secretion into the urine, leading to hypokalemia ## Footnote this reiterates the fact that loop diureticsc work primarily on the LOH

Question 38

examples of collecting duct diuretics

Answer 38

spironolactone and eplerenone

Question 39

MoA collecting duct diuretics ## Footnote remember that aldosterone acts on mineralcorticoid receptors in the DCT and CD

Answer 39

they supress sodium reabsorption by either antagonising aldosterone(blocking aldosterone receptors) or by directly blocking the epithelial sodium channels(ENaC channels) ## Footnote drugs like amioloride and triamterene are ENac channel blockers while spironolactone and eplerenone antagonise aldosterone

Question 40

why are collecting duct diuretics aka potassium sparring diuretics

Answer 40

Reducing sodium reabsorption in the kidneys (**through direct inhibition of sodium channels or by blocking aldosterone). ** Preventing the excessive secretion of potassium into the urine, thus preserving potassium levels in the blood. ## Footnote think abt the na/k pump

Question 41

what happens to smooth muscle cells when alpha-adrenoceptors(1and 2) are stimulated and what happens if we prevent the action of adrenaline or noradrenaline on these receptors

Answer 41

they cause contraction of the vascular smooth muscles contraction is prevented , so there is vascular SMC relaxation

Question 42

examples of alpha 1 adrenoceptor antagonists

Answer 42

prazosin, tetrazosin, doxazosin, trimozosin ## Footnote examples of alpha 2 antagonists include atipamezole and yohimbine alpha 1 selective for vascular SMCs while 2 primarily found presynaptically in CNS and PNS

Question 43

beta blockers inhibit renin release, true or false ?

Answer 43

true This action contributes to their effectiveness in lowering blood pressure by reducing the production of angiotensin II, a potent vasoconstrictor.

Question 44

which secondary messanger system is initiated when noradrenaline release is stimulated by the SNS

Answer 44

the cAMP system This results in actin and myosin interacting so causing the contraction of the heart.

Question 45

effects of cathecolamines on SA node cells ## Footnote Catecholamines are a group of hormones and neurotransmitters, including **dopamine, norepinephrine, and epinephrine (adrenaline**), that are produced by the adrenal glands and certain nerve cells

Answer 45

they have a positive ionotropic effect, thus increase heart rate and also pacemaker(SA node) potential

Question 46

carvidelol antagonises alpha-1 receptors alongside being a non-selective beta blocker, true or false

Answer 46

true

Question 47

nebivilol MoA

Answer 47

stimulates nitric oxide synthase, essentially leading to vasodilation it is a selective **beta 1 antagonist** so cardioselective, even though it is 3rd generation beta blocker

Question 48

all 3rd generation B blockers are non selective, true or false

Answer 48

false nebivilol is cardioselective

Question 49

alpha 2 receptor blockers may lead to **increased blood pressure,** why is this the case?

Answer 49

Alpha-2 receptors are presynaptic receptors. When stimulated, **they inhibit norepinephrine (NE) release, which reduces sympathetic outflow.** This leads to vasodilation and lower blood pressure. so if they are blocked , Norepinephrine release is not suppressed ➜ increased sympathetic tone This causes vasoconstriction and increased heart rate ➜ Blood pressure increases

Question 50

methyldopa is a prodrug, true or false

Answer 50

true Methyldopa is a prodrug that is converted in the brain to **alpha-methylnoradrenaline,** a false neurotransmitter.

Question 51

MoA methyldopa

Answer 51

Acts as a** false neurotransmitter** and Stimulates central **α2-adrenergic receptors** → ↓ Sympathetic outflow → ↓ Heart rate & peripheral resistance → ↓ Blood pressure ## Footnote It reduces renal vascular resistance and can be used in patients with renal insufficiency.

Question 52

monoxidine MoA

Answer 52

Binds to imidazoline I1 receptors Located in rostral ventrolateral medulla (RVLM) of the brain Leads to; reduced sympathetic outflow, so Less noradrenaline released to act on blood vessels, therefore Reduced vasoconstriction Leading to lowering of blood pressure

Question 53

some drugs with direct vasodilatory effects ## Footnote these drugs are effective in controlling hypertension

Answer 53

**hydralazine, minoxidil,** diazoxide, sodium nitroprusside **hydralazine, minoxidil,** diazoxide, also stabilise resting membrane potential by opening potassium channels ## Footnote outpatient use of these drugs restricted due to side effects