HTN 2 Flashcards
What is typically first line management of HTN?
- Weight loss
- Healthy diet (DASH diet)
- Reduced intake of dietary sodium
- Enhanced intake of dietary potassium
- Physical activity
- Moderation in alcohol intake
What are the 6 different antihypertensive groups?
- RAAS
- ACE
- ARB
- Sympathetic Antagonists/Agonists
- Beta Blockers
- Alpha 1 Blockers
- Central alpha agonists (Alpha 2 Agonists)
- Calcium Channel Blockers
- Diuretics (thiazide)
- Aldosterone antagonists
- Direct vasodilators
What do agents that block production or action of angiotensin do?
Reduce peripheral vascular resistance and (potentially) blood volume
What do sympatholytic (sympathoplegic) agents do?
Lower BP by reducing PVR by inhibiting cardiac function
increasing venous pooling in capacitance vessels.
- The latter two effects reduce cardiac output
What do calcium channel blockers do?
Inhibits calcium influx leading to coronary and peripheral vasodilation
What do diuretics do in regards to lowering blood pressure?
Lower blood pressure by depleting the body of sodium and reducing blood volume and perhaps by other mechanisms.
What do aldosterone antagonists do?
Inhibits aldosterone resulting in inhibition of sodium and water retention and inhibiting vasoconstriction
What do Direct vasodilators do?
Reduce pressure by relaxing vascular smooth muscle thus dilating resistance vessels and increasing capacitance to varying degrees
Oral antihypertensives–> What are the primary agents?
- Thiazides (Chlorthalidone, Hydrocholorthiazide, Indapamide, Metolazone)
- ACE inhibitors (Benazepril, Captopril, etc)
- ARBS (Azilsartan, Candesartan, Eprosartan, Irbesartan, Losartan)
- CCB- Dihydropyridines (Amlodipine, Felodipine, Isradipine, Nicardipine, Nifedipine, etc)
- CCB- nondihydropyridines (Diltiazem, Verapamil)
The following are oral antihypertensive drugs that are _____Agents (primary or secondary?)
- Diuretics- Loop (Bumetanide, Furosemide, Torsemide)
- Diuretics- Potassium sparing (Amiloride, Triamterone)
- Diuretics- Aldosterone antagonists (Eplerenone, Spironolactone)
- Beta Blockers- Cardioselective (Atenolol, Betaxolol, Bisoprolol, Metoprolol,etc)–> POST-MI
5. Beta blockers- Cardioselective and vasodilatory (Nebivolol)
- Beta blockers- noncardioselective (Nadolol, Propanolol)
- Beta Blockers- Intrinsic Sympathomimetic activity (Acebutolol, Penbutolol, Pindolol)
- Combined alpha and beta Beta blockers
- DRI
- Alpha Blockers
- Central alpha agonists
- Direct vasodilators (Hydralizine, Minoxidil)
Secondary
Overview of the site of action of diuretics
RAAS sites of action of antihypertensive drugs
***Make sure to know this!***
Which part of the nephron is:
- the major site for sodium chloride and sodium bicarbonate reabsorption
- Responsible for 60–70% of the total reabsorption of sodium.
Proximal Convoluted Tubule (PCT)
•Conversion of bicarbonate to carbon dioxide via _______permits rapid reabsorption of the carbon dioxide in the PCT of the nephron
Carbonic acid
What is a carbonic anhydrase inhibitor and what is its clinical appications?
Acetazolamide
Clinical applications= Glaucoma, Mountain sickness, edema w/ alkalosis
The following describes the pharmacokinetics of which inhibitor?
Oral, parenteral
Diuresis is self-limiting
Effects in glaucoma and mountain sickness persist
Carbonic anhydrase inhibitors (Acetazolamide)
ADEs of what?
- Metabolic acidosis
- Sedation
- Paresthesias
- Hyperammonemia in cirrhosis
Carbonic anhydrase inhibitors (Acetazolamide)
What are 3 loop diuretics
- Bumetanide
- Furosemide
- Torsemide
What are the 4 Thiazide diuretics?
- Chlorthalidone,
- Hydrochlorothiazide (HCTZ)
- Indapamide
- Metolazone
What are 3 Potassium sparing diuretics?
- Amiloride w/wo HCTZ
- Triamterene
- Triamterene/HCTZ
What are the 2 Aldosterone Antagonists (also potassium sparing)
- Spironolactone w/wo HCTZ
- Eplerenone
The following is the overall mechanism of which meds?
–Blocks the reabsorption of sodium and chloride
–Water follows due to the osmotic pressure w/in the nephron
–Diuresis results in decreased plasma and stroke volume
-Site of action varies along the nephron
Diuretics
The following is describing which part of the nephron?
- Segment pumps sodium, potassium, and chloride out of the lumen into the interstitium
- major site of calcium and magnesium reabsorption
- Reabsorption of 20–30% of the sodium filtered at the glomerulus
Thick Ascenting Limb of the Loop of Henle (TAL)
Reabsorption of sodium, potassium, and chloride are all accomplished by a Na+/K+/2Cl− carrier (NKCC2) in which part of the nephron?
What type of medications target this?
Thick Ascending Limb of the Loop of Henle
Target of loop diuretics
The following in the mechanism of which group of medications?
- Blocks the Na+ K+ Cl- symporter (NKCC2) at the thick ascending Loop of Henle
- More potent diuresis, a smaller decrease in PVR and less vasodilation (HCTZ more effective in lowering BP)
Loop Diuretics (Furosemide, bumetanide, torsemide)
The following describes the efficacy of what group of meds?
–**Diuresis exceeds BP lowering
–Useful when GFR <30ml/min or serum creatinine of 2.5-3.0
–**Preferred in heart failure or severe edema
–**Less likely to cause hyperglycemia, hyperlipidemia
Loop Diuretics (furosemide, bumetanide, torsemide)
The following are drug interactions (similar to HCTZ) of which group of meds?
–May increase level/effect of cardiac glycosides-digoxin and certain antiarrhythmics
–Increases levels of Lithium
–NSAIDS may decrease efficacy
Loop Diuretics (furosemide, bumetanide, torsemide
What are ADH Agonists
Desmopressin
Vasopressin
Mechanism of which meds?
Agonists at V1 and V2 ADH receptors, activate insertion of aquaporin water channels in collecting tubule, reduce water excretion
ADH Agonists (Desmopressin, vasopressin)
What are ADH and Desmopressin useful in tx?
Pituitary Diabetes insipidus
no value in the nephrogenic form of diabetes insipidus
- Salt restriction, water restriction, thiazides, and loop diuretics may be used
- These therapies reduce blood volume, which is a very strong stimulus to proximal tubular reabsorption
- Proximal tubule partially substitutes for the deficient concentrating function of the collecting tubule in nephrogenic diabetes insipidus
What is the P-kinetics of ADH agonists
SQ nasal
What are the 2 ADEs of ADH agonists?
Hyponatremia
HTN
ADH and desmopressin ______urine volume and _____ its concentration
Reduce, increase
How can SIADH be treated?
- Certain tumors produce peptides (eg, small cell carcinoma of the lung) which can cause significant water retention and dangerous hyponatremia
- This syndrome of inappropriate ADH secretion (SIADH) can be treated with demeclocycline and conivaptan (ADH antagonists)-
- also can use lithium but more toxic
_______ and _____inhibit the action of ADH at some point distal to the generation of cAMP and presumably interfere with the insertion of water channels into the membrane.
Demeclocycline and Lithium
- Demeclocycline was previously used for this purpose.
- Lithium also has ADH-antagonist effects but is never used for this purpose.
•What 2 meds are ADH antagonists.
Conivaptan and tolvaptan
Mechanism for what meds?
Antagonist at V1a, V2 receptors
which one is more selective for V2 receptors?
ADH antagonists (conivaptan, tolvaptan)
Tolvaptan is like conivaptan but more selective for V2 receptors
Toxicity of agonists and antagonists:
•In the presence of ______or _______, a large water load may cause dangerous hyponatremia. Large doses of either peptide may cause hypertension in some persons
ADH or desmopressin
Toxicity of agonists and antagonists
•_____ and _______ may cause demyelination with serious neurologic consequences if hyponatremia is corrected too rapidly
Conivaptan and tolvaptan
________may cause infusion site reactions
Conivaptan
•In children younger than 8 years,___________ causes bone and teeth abnormalities
Demeclocycline (like other tetracyclines)
_______ causes nephrogenic diabetes insipidus as a toxic effect; because of its other toxicities, the drug is never used to treat SIADH
Lithium
