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Flashcards in Drugs and Vasculature Deck (24)
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1
Q

Give 3 things that sympathetic nerves release

A
  1. NA
  2. NPY (neuropeptide Y)
  3. ATP
2
Q

What is the equation connecting resistance in blood vessels to their radii?

A
  • R = 1 / r^4
3
Q

What is the equation for blood pressure?

A

BP = CO x TPR

4
Q

1) What is normal BP?
2) What is an acceptable BP boundary, above which you get HTN?

A

1)

  • 120 / 80 mmHg

2)

  • 140 / 90 mmHg
5
Q

True or false, beta-blockers are the first line of therapy in treating HTN?

A

False, both alpha and beta-blockers are now the last line of treatment

6
Q

Label the blocked parts in regards treatment of HTN

A
7
Q

Describe the various lines of treatments of HTN, in people 55 yrs or younger and those over 55 yrs or of afro-carribean descent

A

1a. 55 years and under - ACEi or ARB
1b. > 55yrs / afro-carribean - CCB or thiazide type diuretic
2. ACEi + CCB or ACEi + thiazide type diuretic
3. ACEi + CCB + thiazide type diuretic
4. Add either further diuretic therapy or alpha / beta-blockers

8
Q

Why do elderly individuals and afro-caribbeans not respond as well to ACE inhibitors to control HTN?

A
  • They have low renin hypertension (renin doesn’t contribute to it much) so ACE inhibitors which target the RAAS system have little effect
9
Q

What are 3 major stimuli that stimulate renin production?

A
  1. ↓ Renal Na+ reabsorption - macula densa cells respond to [Na+] in the filtrate
  2. ↓ Renal perfusion pressure
  3. ↑ Sympathetic NS activation - SNS nerves innervate JGA cells
10
Q

Outline the whole RAAS pathway, and include the effects on bradykinin and the ultimate effects of ATII

A
  1. Angiotensinogen is secreted by the liver
  2. Renin secreted from the JGA in the kidneys converts angiotensinogen into ATI
  3. ATI is converted into ATII by ACE
  4. ACE also cleaves bradykinin (a vasodilator) so destroys the vasodilatory effect of bradykinin
  5. ATII also stimulates aldosterone secretion
  6. ATII acts on ATI receptors in the brain, in the arterioles and in the kidneys to cause thirst, vasoconstriction and salt and water retention in the kidneys both directly and by aldosterone’s effect
11
Q

What effects does ATII have and by what receptor?

A

ATII acts on ATI receptors in the brain, arterioles and kidneys

  • SNS activation / thirst
  • Vasoconstriction
  • Salt and water retention
12
Q

How do ACE inhibitors treat HTN?

A
  • They prevent ATI conversion into ATII
  • So ATII cannot act on ATI receptors on arterioles which would otherwise cause vasoconstriction - thereby lowers the TPR
  • ATII can also not now act on ATI receptors on the kidneys which would otherwise directly and indirectly (via aldosterone) cause salt and water retention and thus increase CO. So it lowers CO
  • Remember BP = CO x TPR. So ACEi reduce both CO and TPR to reduce blood pressure and thus combat hypertension
13
Q

How does ACEi treat HF?

A
  • Note in HF - your heart can’t keep up with the amount of work it needs to put in
  • They prevent ATI conversion into ATII
  • ATII cannot now act on ATI receptors on arterioles to cause vasoconstriction which would otherwise increase afterload and thus require greater myocardial work to overcome
  • ATII can also not now act on ATI receptors on the kidneys which would otherwise directly and indirectly (via aldosterone) cause salt and water retention and thus increase CO and thus greater venous return and thus preload and finally therefore cause greater myocardial work
14
Q

How do ARBs work + name an example drug?

A
  • Block the ATI receptors that ATII acts on
  • E.g. Losartan
15
Q

1) What side effects can both ACE inhibitors and ARBs have and how?
2) What is one characteristic side effect of ACE inhibitors?

A

1)

  • HOTN - if given too much - obvious reasons
  • Hyperkalaemia - by blocking ATII, you downregulate aldosterone secretion. Aldosterone normally causes Na+ retention (reabsorbed into blood) and K+ excretion into the urine. So by downregulating aldosterone, you get less K+ excretion so you get hyperkalaemia
  • Renal failure in patients with renal artery stenosis - renal perfusion pressure is low in RAS, ATII normally increases renal perfusion pressure by vasoconstriction in the kidneys

2)

  • Cough due to bradykinin cleavage for some reason
16
Q

Outline the process of smooth muscle contraction

A
  1. Membrane depolarisation opens VGCCs
  2. Ca2+ enters and causes Ca2+-induced-Ca2+ release and also
  3. Ca2+ binds to calmodulin (CaM)
  4. Ca2+-CaM complex binds to MLCK
  5. MLCK mediated phosphorylation → smooth muscle contraction
17
Q

Give a class of drugs that are non-rate limiting calcium channel blockers

Give an example drug name belonging to this class

A
  • Dihydropyridines
  • E.g. Amlodipine
18
Q

What do non-rate limiting calcium channel blockers do?

A
  • They block calcium channels in smooth muscle only
  • So they do not have negative inotropic or chronotropic effects
19
Q

1) Give a class of drugs that are rate limiting calcium channel blockers
2) Give an example drug name belonging to this class

A

1)

  • Non-DHP (non-dihydropyridines)

2)

  • Verapamil
20
Q

What do rate limiting calcium channel blockers do?

A
  • They block calcium channels in cardiac and smooth muscle
  • So they also have negative inotropic and chronotropic effects
21
Q

Compare the efficacy of RAS inhibitors and CCBs in heart failure and stroke

A
  • ACE inhibitors seem to be more effective for heart failure patients
  • CCBs seem to be more effective if you are likely to develop stroke
22
Q

Compare RAS inhibitors and thiazides for their effects on HF, stroke and systolic BP

A
  • Thiazides seem more effective for BOTH heart failure AND stroke
  • Thiazides also have a more profound effect on systolic BP
23
Q

How do alpha receptor blockers treat hypertension - basic principle of their mechanism

A
  • They block alpha adrenergic receptors
  • Alpha-1 adrenoreceptors mediate vasoconstriction
  • Or they block alpha-2 adrenoreceptors thereby preventing the prejunctional negative feedback of NA release (i.e. ultimately there is greater [Na] as a result) - this causes vasoconstriction
24
Q

Name 2 hypertensive medications that are alpha-adrenoreceptor antagonist drugs and their targets and hence mechanisms of actions

A
  1. Prazosin - alpha-1 receptor selective antagonist - thereby preventing alpha-1 mediated vasoconstriction
  2. Phentolamine - unselective alpha antagonist - so prevents both alpha-1 mediated vasoconstriction and also prevents the noradrenaline negative feedback mechanism mediated by the prejunctional alpha-2 adrenoreceptors