Brainscape's Knowledge GenomeTM

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


See full index

Drugs: from molecules to man > Hypertension 2 > Flashcards

Hypertension 2 Flashcards

You may prefer our related Brainscape-certified flashcards:
Organic Chemistry 101 flashcards
1
Q

What system are calcium channels normally classified according to?

A

A system based on their location or functional characteristics. This system uses single letters and defined groups of channels that share similar characteristics

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

What alpha subunits do L type calcium channels have and where are they found?

A
  • subunits Cav 1.1-1.4

- found in heart, smooth muscle and CNS

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

What alpha subunits do P/Q type calcium channels have and where are they found?

A
  • Cav 2.1

- found in Purkinje neurons, cerebellar granule cells

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

What alpha subunits do N type calcium channels have and where are they found?

A
  • Cav 2.2

- found in brain and peripheral nervous system

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

What alpha subunits do R type calcium channels have and where are they found?

A
  • Cav 2.3

- found in cerebellar granule cells

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

alpha subunits do T type calcium channels have and where are they found?

A
  • Cav 3.1-3.3

- found in neurons, pacemaker cells and the thalamus

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

Which calcium channel is an ideal target for modulating blood pressure and why?

A

L type because it is found in both cardiac muscle and vascular smooth muscle

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

Why can we avoid blocking the L type channel in skeletal muscle?

A

There are several different types of L type channel, and the one in skeletal muscle is sufficiently different from that in cardiac and smooth muscle, that we can avoid blocking it

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

What is peripheral resistance determined by?

A

Peripheral resistance determined by diameter of vessels – smooth muscle contraction changes diameter of resistance vessels

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

What is smooth muscle contraction triggered by?

A

stimulation of the sympathetic nervous system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does noradrenaline affect vascular tone?

A
  • Noradrenaline acts on alpha1 adrenoceptors
  • This activates phospholipase C
  • Activation of Phospholipase C triggers release of inositol triphosphate (InsP3) release
  • This triggers the calcium store to open and release intracellular calcium (this doesn’t trigger muscle contraction though)
  • This leads to calcium sensitive chloride channels being activated
  • There is then a Cl- efflux which leads to depolarisation
  • This depolarisation leads to opening of L-type calcium channels
  • Leads to Ca2+ influx
  • And then contraction via Ca-calmodulin Ca2+ release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What stops the opening of L type calcium channels and what does this mean?

A
  • L type calcium blockers

- This stops contraction of smooth muscle and so will dilate resistance vessels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Give examples of Calcium Channel blockers

A
  • Diltiazem (a benzothiazepine – heart L type calcium channels)
  • Verapamil (a phenylalkylamine – heart L type calcium channels)
  • Amlodipine and Nifedipine (a dihydropyridine – vascular L type calcium channels)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Give a summary of what calcium channel blockers do

A
  1. Reduce the opening of L-type calcium channels
  2. Target organs: vasculature (and heart)
  3. Vessels: inhibit Ca2+ entry
  4. Heart: reduced contractility and A-V conduction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the side effects from Calcium Channel blockers?

A

headache, constipation, sometimes hypotension (most pronounced when patient takes first dose: initial dose hypotension, also when patient changes position: postural hypotension) which produces momentary faintness

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

What are some useful drug name hints?

A
  1. ACE inhibitors – pril
  2. ATII antagonists – artan
  3. Ca2+ blockers (DHP) – ipine
  4. B-blockers – olol
  5. A-blockers – zosin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do all diuretics cause?

A

diuresis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is diuresis?

A

Increased urine output

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What do diuretics cause?

A
  • Intravascular salt and water depletion
     Short term effect
     Renal failure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Apart from hypertension what else are diuretics used to treat?

A
  • Also used to treat oedema
     Pulmonary oedema due to heart failure
     Side effects of other therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the general considerations to do with Diuretics?

A
  • Increase excretion of Na+, Cl- and water
  • Pattern of electrolyte excretion and max response varies with class
     The closer to the glomeros the diuretic is acting the larger the maximum effect)
  • Effects can be additive or synergistic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the three main classes of diuretics?

A

 Loop
 Thiazide
 Potassium sparing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does the loop of Henley work?

A

 Descending limb: no active transport, water permeable
 Ascending limb: active transport Na+, active transport K+, Cl-, water impermeable
 Ascending limb pumps salt into surrounding tissues, creates a gradient, water leaves from descending limb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do loop diuretics work?

A

Block ion transport processes in ascending limb:
- If we block salt-sodium chloride transport process we will stop moving salt out of the urine and into the surrounding tissues, therefore water cannot be absorbed from the descending limb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the main examples of loop diuretics?

A

furosemide (frusemide) and bumetanide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What does the loop diuretic inhibit in the loop of Henle?

A

Loop diuretic inhibits Na+/K+/2Cl- co-transporter in ascending limb of the loop of Henle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the clinical uses of loop diuretics?

A 
 Heart failure 
 Pulmonary oedema 
 Renal failure 
 All involve salt and water overload
 Hypertension with renal failure: also get vascular effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Why is the loop diuretic called a high ceiling diuretic?

A

Because it is one of the most powerful diuretics

29
Q

What do thiazide diuretics focus on?

A

They focus on the distal convoluted tube of the nephron. This is where sodium chloride is removed

30
Q

What happens if we block the sodium chloride removal process?

A
  • we can’t dilute urine as much
     Increased NaCl passes to more distal segments
     Less difference in osmolality between urine and plasma
     Lesser ability to reabsorb water in more distal portions
31
Q

What are the main examples of thiazide diuretics?

A

Bendroflumethiazide and Chlortalidone

32
Q

How do thiazide diuretics work?

A

Act by inhibiting Na+/Cl- cotransport in distal convoluted tubule

33
Q

What are the clinical uses of thiazide diuretics?

A

 Oedema due to heart failure
 Hypertension (lower doses)
 Initial effects due to diuresis
 Later, get vascular effect

34
Q

What strength are thiazide diuretics?

A

Mild/moderate

35
Q

What is a major problem with loop diuretics and thiazide and why?

A
  • Hypokalaemia (low potassium levels)
  • principle cells in collecting duct have potassium channels and ENaC and sodium potassium ATP pump on the other side
  • Increased NaCl passed on to collecting duct increases transport across PRINCIPAL cells
  • Increases lumen -ve potential leading to K+ loss
  • Increased volume of urine: increased flushing of K+
36
Q

What is the general mechanism of potassium sparing diuretics?

A

General mechanism: decrease trans-principal cell Na+ movement, decrease -ve lumen potential

37
Q

What are the main examples of potassium sparing diuretics?

A

Spironolactone and amiloride

38
Q

What does Spironolactone do?

A
  • Aldosterone antagonist
  • Aldosterone increases sodium absorption by:
  • Increasing number of Na+/K+ ATPases (genomic)
  • Stimulating ENaC Na+ channels via protein mediator
  • Spironolactone blocks genomic effects of aldosterone (competitive antagonist at hormone receptor - mineralocorticoid) may interfere at eNaC
39
Q

What does Amiloride do?

A

Blocks ENaC sodium channels in the luminal membrane

40
Q

Why are potassium sparing diuretics usually used in combination with other diuretics?

A

Because they have weak action on their own

41
Q

What is Spironolactone used in?

A

hyperaldosteronism
 Cirrhosis (failure to metabolise ALD)
 Conn’s syndrome (adrenal tumour)

42
Q

Give features of the Renin-angiotensin-aldosterone system (RAAS)

A

• Slow ‘compensatory’ control
• Under control of sympathetic nervous system
• Also responds to decrease in blood flow in kidney:
- leads to production of renin (not rennin)
- Leads to angiotensin being produced
- Leads to vasoconstriction and aldosterone being produced
- Aldosterone leads to increase salt and water retention
- This leads to increased blood pressure

43
Q

How are angiotensin hormones generated?

A
  • Renin cleaves angiotensinogen (plasma globulin) to produce angiotensin I (inactive)
  • ACE cleaves angiotensin I to produce angiotensin II (8mer) which is active
  • Aminopeptidase cleaves angiotensin II to produce angiotensin III (partially active)
44
Q

When angiotensin II binds to AT1R what do we see?

A
  • Aldosterone secretion

- Vasoconstriction

45
Q

What is the physiological control of renin secretion?

A
  • Secreted by cells of juxtaglomerular apparatus in kidneys
  • Responds to:
  • adrenaline (B-adrenoceptors)
  • Prostacyclins
  • Decreased Na+ in distal tubule
  • Decreased blood pressure in kidney
  • Actions of other hormones
46
Q

What are the tissue distributions of renin, angiotensin and ACE?

A
  • Renin – discrete (juxtaglomerular apparatus)
     Global control – secreted into circulation
  • Angiotensin – produced in liver – secreted into circulation
  • ACE – found in many tissues
     Several subtypes
     Local production of angiotensin’s
47
Q

What are the drugs acting on the RAA system?

A
  • Spironolactone acting on aldosterone
  • ACE inhibitors
  • Blockers of receptors for angiotensin II
  • Aliskiren (renin inhibitor)
48
Q

What did post market surveillance show about renin inhibitors?

A

They cause:
 Kidney problems
 Stroke
 Hypotension

49
Q

What did lessons learned from studying renin aid?

A

Research on HIV protease inhibitors

50
Q

What are ACE inhibitors and what do they do?

A
  • One of the first line drugs in NICE care pathways
  • If we can block ACE we can stop the forming of active forms of angiotensin
  • Stops aldosterone production
  • Stops vasoconstriction
51
Q

What are some main examples of ACE inhibitors

A

captopril (not widely used anymore), lisinopril

52
Q

What unwanted effects do ACE inhibitors have?

A

initial dose hypotension, cough (caused by build up of bradykinin, a hormone which is broken down by ACE)

53
Q

How was Catopril developed?

A

by studying the venom of a Brazilian pit viper
 Viper kills it’s prey by causing a massive drop in blood pressure
 Compound in venom is a peptide
 Captopril was developed using computer modelling of the venom peptide

54
Q

What angiotensin receptors are there?

A
  • G protein coupled receptors – multiple subtypes
  • Angiotensin II type 1 receptor (AT1 Receptor)
     AT1 – vascular effects/ aldosterone release
  • Angiotensin II type 2 receptor (AT2 receptor)
     AT2 – growth and development
55
Q

What do angiotensin II antagonists (ARBs) do?

A
  • Block angiotensin II type 1 receptors

- Known as angiotensin II antagonist or angiotensin receptor blockers

56
Q

What are some examples of angiotensin II antagonists?

A

losartan and candesartan

57
Q

What are some side effects of ARBs?

A

hypotension but not cough (ACE is still available so it can degrade bradykinin)

58
Q

What are other clinical uses of ACE inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs)?

A
  • Can be used in heart failure
  • Useful in decreasing sodium and salt retention
  • Useful after a heart attack
  • Some studies indicate centrally active ACEIs and ARBs may be useful in Alzheimer’s disease
59
Q

What are adrenoceptor antagonists subdivided into and what are these subdivisions used for?

A
  • Subdivided into alpha blockers and beta blockers
  • The alpha blockers are only really used for hypertension
  • Beta blockers are also valuable in other cardiovascular disorders and even in treating anxiety – not the first line treatment for hypertension
60
Q

What do alpha1 and beta1 adrenoceptors do?

A 
• Alpha1: 
- Vasoconstriction (increase BP) 
• Beta1: 
- Increase heart rate and force of contraction 
- Release of renin 
- In the brain
61
Q

What is Doxazosin and what does it do?

A
  • alpha blocker
  • Dilates arterioles and veins by blocking a1-adrenoceptors
  • Used where other therapy has proved ineffective or unacceptable
62
Q

What are the unwanted effects of Doxazosin?

A
  • postural hypotension (fades with time)

 Urinary incontinence and retrograde ejaculation in males (relaxes bladder)

63
Q

What is propranolol?

A

 Competitive antagonist
 Beta blocker
 Non-selective B-adrenoceptor antagonists
 Blocks B1 and B2 adrenoceptors
 Relatively lipid soluble (good penetration of CNS)

64
Q

What are Atenolol and Bisoprolol?

A

 Competitive antagonists
 Beta blockers
 B1 selectivity: Bisoprolol > atenolol > propranolol)
 Relatively water soluble (poor penetration of CNS)

65
Q

Where are B1 adrenoceptors found in the heart what do they do there and so what will beta blockers do?

A
  • Target B1 adrenoceptors in heart – sympathetic nervous system innervated B1 adrenoceptors in nodes and muscle
     In the SA nodes B1 receptor increase HR when stimulated and increase conduction in AV node – B blockers decrease heart rate
     In muscle produce increase in contractility – B blockers decrease stroke volume
     Both effects lower cardiac output which decreases blood pressure
66
Q

What do Beta blockers do in the kidney?

A

block renin release in the juxtaglomerular apparatus which dampens the angiotensin system and decreases blood pressure

67
Q

What do B1 receptors in the CNS in the vasomotor centre and medulla oblongata do?

A

 Increase sympathetic tone

 So beta blockers decrease sympathetic tone

68
Q

What are the unwanted effects of beta blockers?

A
  • Bronchoconstriction (due to beta2 receptors in lungs)
     Bronchial asthma
     Bronchitis
     Emphysema
  • Precipitation of cardiac failure/ heart block (because they decrease cardiac output)
     Patients with heart disease
     Carvedilol, bisoprolol, nebivolol (UK), (Us: metoprolol) – used to help treat patients with compromised heart function)
  • Glucose control
     Patients with diabetes
     Type 2: reduced insulin sensitivity (can precipitate)
     Type 1 – masks hypoglycaemia warning signs
  • Cold extremities
     Raynaud’s phenomenon and claudication
  • Vivid dreams
     Propranolol (because penetrates CNS), not a problem with atenolol or bisoprolol
69
Q

What happens with beta blockers and hypoglycaemia?

A
  • Too much insulin leads to hypoglycaemia (with people with type 1 diabetes)
  • Glucose release from liver controlled by B-adrenoceptors can help counteract hypoglycaemia
  • Hypoglycaemia leads to sympathetic NS activation -> increased heart rate which provides a warning of hypoglycaemia
  • Non-selective beta blockers will stop the counteraction of hypoglycaemia and stops warning of hypoglycaemia
  • B1 selective beta blockers will stop the warning signs of hypoglycaemia being provided

Drugs: from molecules to man (22 decks)

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