Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Unit 12 (Tommy) > 12.1 Pharmacology of hypertension > Flashcards

12.1 Pharmacology of hypertension Flashcards

1
Q

What is hypertension & the stages

A
  • Persistently raised arterial blood pressure (~25% adults)
  • Normal is a range
    • Systolic 90-120 mmHg
    • Diastolic 60-80 mmHg
  • Abnormal is a range
    • Stage 1: 140/90
    • Stage 2: 160/100
    • Stage 3: SBP > 180 or DBP > 120
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the causes of hypertension & types?

A
  • >90%: ESSENTIAL hypertension (primary)
    • Cause unknown
  • <10%: SECONDARY hypertension
    • Renal disorders
    • Endocrine
      • 1° hyperaldosteronism → (fluid regulation)
      • Pheochromocytoma (is a rare, usually noncancerous (benign) tumor that develops in an adrenal gland)
        • ↑ adrenaline → ↑HR, ↑CVP, ↑vasoconstriction
      • Cushing’s syndrome → (INCREASE in cortisol)
    • Drug-induced
      • ​Abuse: e.g., cocaine → (sympathetic NS)
      • Iatrogenic: e.g., combined oral contraceptive
      • Pregnancy = pre-eclampsia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the consequences of hypertension?

A
  • Increased risk of many cardiovascular disorders
    • Coronary artery disease
    • Stroke
    • Heart failure
    • Peripheral arterial disease
    • Vascular dementia
    • Chronic kidney disease
  • Lowering hypertension → ↑↑ health benefits
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the pathophysiological mechanism of hypertension?

A
  1. Cardiac output
  2. Peripheral resistance
  3. Autonomic nervous system
  4. Endothelium
  5. Vasoactive peptides
  6. Renin-angiotensin-aldosterone system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the equation to work out arterial blood pressure? (ABP)

A

Arterial Blood Pressure = Cardiac Output × Total Peripheral Resistance

ABP = CO × TPR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the equation to work out force?

A

Force = Flow × Resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the equation to work out volts?

A

Volts = Current × Resistance (V = IR)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the equation to work out cardiac output?

A

Cardiac output = Stroke volume × Heart Rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is stroke volume proportional to?

A

Central venous pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Explain the role of the autonomic nervous system of hypertension (e.g. receptors & control)

A
  • Heart function
    • β₁ → ↑heart rate, ↑force → CO
  • Vessel function
    • Arteriolar tone regulates TPR
    • Venular tone regulates CVP
    • α₁ → vasoconstriction
    • β₂ → vasodilation
  • Short-term regulation of pressure & flow
    • Baroreceptor reflexes
  • Little evidence to implicate adrenaline and noradrenaline as causes of essential hypertension
  • Sympatholytic drugs lower ABP and have a role in therapy, even if ANS dysfunction is not the cause
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Endothelium effect on hypertension

A
  • Dysfunction implicated in essential hypertension
  • Endothelial cells produce vasoactive agents
  • Nitric oxide (NO) → vasodilator
    • ↑guanylyl cyclase → ↑cGMP → ↑PKG sm. muscle relaxation
    • Atheroma → ↓NO production
    • Sodium nitroprusside (↑NO) used in hypertensive emergencies
    • Sildenafil inhibits phosphodiesterase V (PDEV) → ↑cGMP
  • Prostacyclin (PGI₂) → vasodilator
  • Endothelin → vasoconstrictor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give examples of some vasoactive peptides & what they do

A
  • Bradykinin → vasodilator
    • ACE inhibitors block bradykinin inactivation
  • Natriuretic peptides (A, B & C)
    • ANP = Atrial: secreted by atrium
    • BNP = Brain: secreted by ventricles
    • CNP = C-type
    • What do they do?
      • → ↑Na⁺ & H₂O excretion
      • NPR1 is a guanylyl cyclase → ↑cGMP → smooth muscle relaxation → vasodilation
      • Dysfunction may → fluid retention & hypertension
  • Vasopressin = anti-diuretic hormone (ADH)
    • Vasoconstrictor, ↑BP & ↑H₂O reabsorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the difference between renin & rennin?

A

Renin

  • Produced by juxtaglomerular cells
  • Regulates ECF volume & blood pressure

​​Rennin

  • Found in the stomach of baby ruminants
  • Used to make cheese
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

From the RAAS system what do essential (primary) hypertension patients have low levels of?

A

Low levels of renin & AT-II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Step by step brief what happens in RAAS

A
  1. (LOW) ABP
  2. Renin
  3. Angiotensinogen
  4. Angiotensin I
  5. Angiotensin II (by Angiotensin-converting enzyme)
  6. Aldosterone
  7. Mineralocorticoid receptor e.g.
    • Epithelial sodium channels
    • Na+/K+ ATPase

Where Na⁺ goes, water follows osmotically → ↑ECF → ↑preload → ↑Stroke Volume → ↑Cardiac Output → ↑ABP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Explain renin (RAAS) and mechanism of making it

A
  • Circulates in blood
  • Cleaves angiotensinogen
  • Secreted by granular cells of JGA into blood mechanism:
    1. ↓BP → ↑Symp. activity & ↓GFR
    2. ↑Symp. → β₁ receptors on GC (granular cells)→ ↑renin
    3. MD (macula densa cells) detects Na⁺/Cl⁻ in DCT
      • ↓GFR → ↓Na⁺/Cl⁻ load at MD → dilation of AFF & constriction of EFF → ↑GFR (= autoregulation)
      • ↓Na⁺/Cl⁻ load at MD → ↑renin
17
Q

Explain angiotensinogen

A
  • Produced by liver and secreted into blood
  • Renin substrate → forms angiotensin I
18
Q

Explain angiotensin I

A
  1. Cleaved from N-terminal of angiotensinogen by renin
  2. Converted to Angiotensin II by angiotensin-converting enzyme (ACE)
    • ACE is widely expressed: lung, kidney..
19
Q

Explain angiotensin II

A
  1. Produced by cleavage of C-terminal by ACE (cleaves 2 amino acids)
  2. Full agonist at AT₁ receptors (GPCR) → release of aldosterone (mineralocorticoid) from adrenal cortex → ↑ECF → arteriolar vasoconstrictor → ↑BP → ↑vasopressin (ADH) release from pituitary
20
Q

Explain the role of ACE 2 (angiotensin-converting enzyme 2)

A
  • Cleaves 1 amino acid from AT-II → AT (1-7)
  • AT (1-7)
    • ​Is a physiological antagonist of AT-II
    • LOWERS BP & is a vasodilator
21
Q

Explain Angiotensin 1 receptors (AT₁)

A
  • GPCR (Gᵢ & Gq signalling)
  • Widely expressed, esp. liver, kidney, adrenal, lung
  • Activation by AT-II
    • ​→ smooth muscle contraction → vasoconstriction
    • → central & peripheral sympathetic stimulation
    • → aldosterone release (adrenal: zona glomerulosa)
    • → ADH release (pituitary)
    • → tubular Na⁺ reabsorption (PCT in kidney)
    • → endothelin release (endothelial cells) -> vasoconstrictor
22
Q

Explain aldosterone (in RAAS)

A
  • Steroid > mineralocorticoid
  • Full agonist at intracellular mineralocorticoid receptor in tubular cells of the DCT
23
Q

Explain mineralocorticoid receptors (in RAAS)

A
  • Expressed in epithelia with high electrical resistance
    • ​e.g. distal kidney tubular cells
  • → selectively changes transcription:
    • ↑ ENaCs
    • ↑ Na⁺/K⁺-ATPase
  • Spironolactone = competitive antagonist
24
Q

Explain epithelial sodium channels in RAAS

A
  • Widely expressed
    • in distal kidney tubules, also in lung & resp. tract, reproductive tracts
  • In principal cells of late DCT/early CD:
    • ↑ENaC expression on apical membrane →
    • ↑Na⁺ permeability →
    • ↑Na⁺ reabsorption from tubule lumen into cell
  • This is the rate-limiting step for salt reabsorption in this part of the nephron
  • They are NOT voltage-gated channels
  • Amiloride = channel blocker
25
Q

Explain Na⁺/K⁺-ATPase (Na⁺ pump) in the RAAS system

A
  • Expressed everywhere
  • For each ATP hydrolysed, 3Na⁺ out & 2K⁺ in
  • Preserves Na⁺/K⁺ gradient across membranes
  • In DCT ↑Na⁺/K⁺-ATPase on basolateral side → ↑Na⁺ from cell into interstitial fluid (ECF) → this preserves low [Na⁺]ᵢ and gradient for Na⁺ entry from lumen
  • Cardiac glycosides (e.g., digoxin) = inhibitor
26
Q

What is Liddle syndrome?

A
  • Rare genetic (autosomal dominant) disorder
  • Severe hypertension, manifesting at early age
  • Mutations in β & γ subunits prevent channel internalization and degradation
  • Overexpression of ENaCs → excess Na⁺ reabsorption
  • Treat with ENaC channel blockers e.g., amiloride
27
Q

List some anti-hypertensive drugs

A
  • Diuretics
    • Thiazide
    • Loop
    • K⁺-sparing (acetazolamide)
  • Renin inhibitor (-kiren)
  • ACE inhibitors (-pril)
  • Angiotensin Receptor Blockers (ARB) (-sartan)
  • β blockers (-lol)
  • Calcium channel blockers (-dipine)
  • Centrally acting α₂ agonists (e.g., clonidine)
  • Vasodilators
    • Nitroprusside = nitric oxide (NO) donor
    • Phentolamine = non-selective α-adrenergic antagonist
    • Prazosin = selective α₁-adrenergic antagonist
    • Hydralazine
    • Minoxidil = potassium channel opener (KCO)
28
Q

What is the class, pharmacology, physiology, clinical of aliskiren

A
  • CLASS: renin inhibitor
  • PHARMACOLOGY:
    • Target: renin
    • Activity: competitive inhibitor
  • PHYSIOLOGY: ↓production of AT-I → ↓RAAS activation
  • CLINICAL: Essential Hypertension
29
Q

What is the class, pharmacology, physiology, clinical of enalapril?

A
  • CLASS: ACE inhibitor (ACEI)
    • Pro-drug: converted to active metabolite → enalaprilat
  • PHARMACOLOGY:
    • Target: ACE
    • Activity: competitive inhibitor
  • PHYSIOLOGY:
    1. ↓production of AT-II
    2. ↓breakdown of bradykinin (vasodilator)
  • CLINICAL:
    • Essential hypertension
    • Heart failure
30
Q

What is the class, pharmacology, physiology, clinical of valsartan?

A
  • CLASS: angiotensin receptor blocker (ARB)
  • PHARMACOLOGY:
    • Target: AT₁ (receptor)
    • Activity: competitive antagonist
  • PHYSIOLOGY:
    1. ↓ effects of AT-II
    2. No effect on bradykinin → no cough
  • CLINICAL:
    • Essential hypertension
    • Heart failure
31
Q

What is the class, pharmacology, physiology, clinical of atenolol?

A
  • CLASS: Selective β₁ blocker
  • PHARMACOLOGY:
    • Target: β₁ receptor
    • Activity: competitive antagonist
  • PHYSIOLOGY: (is not understood)
    1. ↓cardiac output
    2. Alter baroreceptor reflexes
    3. ↓renin secretion
    4. ↓sympathetic outflow (central)
  • CLINICAL:
    • Essential hypertension
    • Angina
    • Arrhythmias
32
Q

What class of drugs are atenolol, propranolol, isoprenaline?

A

Atenolol = SELECTIVE β₁ antagonist

Propranolol =NON-SELECTIVE β antagonist

Isoprenaline = β adrenergic agonist (in asthma)

33
Q

In what clinical situations should adrenaline be used in?

A
  • CPR
  • Acute hypotension
  • Anaphylaxis
34
Q

What is the class, pharmacology, physiology, clinical of amlodipine?

A
  • CLASS: Calcium channel blocker
  • PHARMACOLOGY:
    • Target: L-type voltage-gated calcium channels
    • Activity: gating inhibitor
  • PHYSIOLOGY:
    1. smooth muscle > cardiac muscle
    2. ↓Ca²⁺ mobilisation in sm. muscle
    3. →vasodilation
  • CLINICAL:
    • Essential hypertension
    • Angina
35
Q

Explain voltage-gated calcium channels (hypertension)

A
  • Large protein
  • All open in response to depolarisation
  • Types:
    • L-type: once open, remain open for a long time, inactivate slowly
      • In excitable cells, cardiac, smooth & skeletal muscle
      • Phosphorylated by action of adr/NA
    • P/Q-type: Purkinje neurons (brain)
    • N-type: Neural (CNS & PNS)
      • Neurotransmitter release
    • R-type: Resistant to blockers
    • T-type: open transiently (very short period of time), inactivate rapidly
36
Q

What are the treatment steps of someone with hypertension?

A

Unit 12 (Tommy) (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions