Antihypertensives Flashcards
what are some drug classes and prototypes to consider?
Drug Classes and prototype to consider:
1. Thiazide Diuretics: Hydrochlorothiazide
2. ß1-adrenergic Blocker: Atenolol. Metoprolol
3. a1-adrenergic blocker: Prazosin - Postural Hypotension
4. Vasodilators: Hydralazine, Sodium nitroprusside
5. Ca2+ Channel Blocker: Amlodipine,Nifedipine-DHP
6. ACE Inhibitors: Enalapril, Lisinopril, Ramipril
7. Ang II Receptor [AT1] Blocker - ARB: Losartan
8. Direct Renin Inhibitor (DRI): Aliskiren
9. a2-adrenergic agonist (Clonidine) decrease Central Sympathetic Drive.
Limited Use Hypertensive Emergency: Prazosin, SNP, Clonidine
what is the definition of hypertension? what is essential hypertension?
Sustained BP >140/90 mmHg
Symptoms: Nil
Essential Hypertension – Cause unknown - increase SNS, Kidney water and Na+ handling defects - increase Blood Volume.
Secondary HT: eg. Pheochromocytoma, Glomerulonephritis
what is the prevalence of essential hypertension?
20% of adults. 1% @20; 50% @65
For each 10 mmHg in SBP, stroke risk doubles; MI increases 50%: also heart failure; renal failure increases.
Reducing SBP by 7 mmHg reduces Stroke by 40%; MI by 25%.
what are the 5 stages of hypertension?
normal - 120 systolic, 80 diastolic, no treatment
mild, 121-139/81-90, diet salt restrict, exercise
moderate, 140-159/91-99, mono-drug therapy, add more if there are other CV risk factors
severe, 160-179/100-109, multiple drug therapy
crisis/emergency, >180/>110, attention within 24 hours
what is the pathophysiology of essential hypertension?
BP = CO X TPR, initially CO greatly increases as it resets, TPR is greatly increased
In the Early phase of EHT - CO increase is due to increase plasma Volume & increase plasma volume –> increase Venous Return due to defective renal handling of Na+ and H2O. There is increase Renal SNS activity, TPR increases and it stays higher.
Renin and SNS activity are intimately connected with each other and BP keeps going up, caught in this viscious cycle of renal defect.
what is a major risk factor for CV disease? is it usually symptomless?
√ High blood pressure is a major risk factor for CV disease & requires treatment even though it is symptomless for most of its course.
what about knowing the cause of hypertension, do we know in most cases or not?
√ Only a small proportion of the hypertensive population have high blood pressure due to some known cause (secondary hypertension). In most patients, the cause is unknown and these patients are said to have essential hypertension (HT).
what is amenable to non-pharmacological treatment?
√ Mild hypertension may be amenable to non-pharmacological treatment (salt reduction, exercise, reduce stress, breathing exercises) but most hypertensives require drug treatment.
In the labile hypertensive patient, the elevated BP is due to… what is this elevation thought to induce?
√ In the labile hypertensive patient, the elevated BP is due to elevation in CO. This elevation in CO is thought to induce auto-regulatory adjustments in blood flow that lead to increases in TPR in the well established phase of hypertension.
what is the increase in CO likely due to?
√ The increases in CO are likely due to increases in venous return, possibly due to expansion of blood volume by the kidneys or by decreases in capacitance (venoconstriction).
What do the kidneys play a major role in for arterial pressure?
√ The kidneys play a major role in the long term control of arterial pressure through a pressure-natriuresis or pressure-diuresis mechanism. A defect in this mechanism must play at least a “permissive role” if not a causative role.
In a response to a decrease in BP evoked by an antihypertensive medications, the kidney does what?
√ In response to a decrease in BP evoked by an anti-hypertensive medications, the kidney often retains salt and water. Thus, a diuretic will often potentiate other anti-hypertensive drugs.
what do diuretics do and what happens after 4 weeks?
Reduce Na/H2O reabsorption, early DCT
Initially, reduce plasma volume, reduce venous return, reduce CO (decrease BP)
Later (4 weeks) decrease TPR; increase CO (but BP still lower)
Work with all other classes well, Very Cheap
Drawback Compensatory increase in Renin & SNS Activity.
Few subjective AE; low K, low Na, high Ca, high uric acid (hypokalemia, hypovolemia, hyperuricemia, hyperglycemia, hypercalcemia).
Very cheap like broscht – $0.04/day
for diuretics what is the early reduction in the CO due to?
The early reduction in the CO is due to the fluid and electrolyte loss which lowers mean circulatory pressure and therefore venous return and CO.
for diruetics the progression from the early phase to the late phase appears to be due to what?
The progression from the early phase to the late phase appears to be due to “auto-regulatory” changes in resistance to flow in the individual tissues as a result of local control mechanisms.
