Drugs and Vasculature Flashcards
Give 3 things that sympathetic nerves release
- NA
- NPY (neuropeptide Y)
- ATP
What is the equation connecting resistance in blood vessels to their radii?
- R = 1 / r^4
What is the equation for blood pressure?
BP = CO x TPR
1) What is normal BP?
2) What is an acceptable BP boundary, above which you get HTN?
1)
- 120 / 80 mmHg
2)
- 140 / 90 mmHg
True or false, beta-blockers are the first line of therapy in treating HTN?
False, both alpha and beta-blockers are now the last line of treatment
Label the blocked parts in regards treatment of HTN
Describe the various lines of treatments of HTN, in people 55 yrs or younger and those over 55 yrs or of afro-carribean descent
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
Why do elderly individuals and afro-caribbeans not respond as well to ACE inhibitors to control HTN?
- They have low renin hypertension (renin doesn’t contribute to it much) so ACE inhibitors which target the RAAS system have little effect
What are 3 major stimuli that stimulate renin production?
- ↓ Renal Na+ reabsorption - macula densa cells respond to [Na+] in the filtrate
- ↓ Renal perfusion pressure
- ↑ Sympathetic NS activation - SNS nerves innervate JGA cells
Outline the whole RAAS pathway, and include the effects on bradykinin and the ultimate effects of ATII
- Angiotensinogen is secreted by the liver
- Renin secreted from the JGA in the kidneys converts angiotensinogen into ATI
- ATI is converted into ATII by ACE
- ACE also cleaves bradykinin (a vasodilator) so destroys the vasodilatory effect of bradykinin
- ATII also stimulates aldosterone secretion
- 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
What effects does ATII have and by what receptor?
ATII acts on ATI receptors in the brain, arterioles and kidneys
- SNS activation / thirst
- Vasoconstriction
- Salt and water retention
How do ACE inhibitors treat HTN?
- 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
How does ACEi treat HF?
- 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
How do ARBs work + name an example drug?
- Block the ATI receptors that ATII acts on
- E.g. Losartan
1) What side effects can both ACE inhibitors and ARBs have and how?
2) What is one characteristic side effect of ACE inhibitors?
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
