Pharmacology-HTN Flashcards
What is the major determinant of SBP?
Cardiac Output
What largely determines DBP?
Total Peripheral Resistance
How do you calculate BP?
HR x SV x TPR
What is the major site for sodium chloride and sodium bicarbonate reabsorption?
Proximal Convoluted Tubule (PCT)
List potassium sparing drugs
- Amiloride
- Triamterene
Where in the nephron is sodium, potassium and chloride pumped out of the lumen into the interstitial of the kidney?
Thick Ascending Limb of the Loop of Henle (TAL)
Where is a major site of calcium and magnesium reabsorption?
Thick Ascending Limb of the Loop of Henle (TAL)
Where in the nephron is it responsible for 20-30% of sodium reabsorption
Thick Ascending Limb of the Loop of Henle (TAL)
What is the mechanism of loop diuretics?
Blocks the Na+ K+ Cl- symporter (NKCC2) at the thick ascending Loop of Henle
When do we prefer to use Loop diuretics (i.e. furosemide)
Heart failure
Severe edema (fluid retention pt’s)
Kidney dz pt’s
What are the contraindications to TAL loop diuretics
Hypokalemia Hypomagnesemia Hypocalcemia Hypovolemia Hyperuricemia Ototoxicity
What is a rare allergy to TAL loop diuretics
Sulfonamide allergy
What is a poor antihypertensive?
Furosemide
When do we use Furosemide
Kidney disease
Fluid retention
What do we use to treat hypercalcemia?
Furosemide
Torsemide
What is the mechanism @ the distal convoluted tubule
actively pumps sodium and chloride out of the lumen of the nephron via the Na+/Cl− carrier (NCC)
What is the target of the thiazide diuretics?
Na+/Cl− carrier (NCC)
How much sodium is reabsorbed at the distal convoluted tubule?
5-8%
How much sodium is reabsorbed at the proximal convoluted tubule?
60-70%
What is the mechanism of Thiazide Diuretics?
Blocks the reabsorption of sodium and chloride in the distal convoluted tubule via NCC
How does Thiazide diuretics provide chronic anti hypertension?
through sustained decrease in PVR and direct smooth muscle relaxation
Clinical applications for distal convoluted tubule thiazide diuretics
HTN
Mild heart failure
Contraindications to distal convoluted tubule thiazide diuretics
Hypokalemic Hyponatremia Hypercalcemia Hyperglycemia Hyperlipidemia Hyperuricemia
What are the limitations of thiazides?
GFR < 30ml/min for HCTZ
Unrestricted salt intake reduces efficacy
How much does HCTZ lower SBP?
15 to 20 mmHg
How much does HCTZ lower DBP?
8 to 15 mmHg
What do you need to monitor in Thiazides?
BUN
Creatinine
Uric acid level
Electrolytes: K+, Na+, Ca++, Mg+++
What is the cortical collecting tubule controlled by?
Aldosterone
How much sodium reabsorption is the cortical collecting tubule responsible for?
2-5%
How does the sodium reabsorption occur at the cortical collecting tubule with Aldosterone?
Via ENaC–> accompanied by loss of potassium or hydrogen ions
What is the primary site of acidification of the urine and the last site of potassium excretion?
cortical collecting tubule
What is the site of action of the potassium-sparing diuretics?
Aldosterone receptor
Sodium channels
What are the clinical applications of Spironolactone
Excessive K+ loss when using other diuretics
Aldosteronism
What are the contraindications to Spironolactone
Hyperkalemia
Hyponatremia
Gynecomastia
What are the clinical applications of Amiloride
Excessive K+ loss when using other diuretics
Usually in combination with thiazides
What are the contraindications to Amiloride?
Hyperkalemia
What is the mechanism of potassium sparing diuretics?
Blocks the epithelial Na+ channel action proximal to the distal convoluted tubule
What is the side effect of potassium sparing diuretics?
Hyperkalemia
When is potassium sparing diuretics contraindicated?
Renal failure
When do you want to avoid use of potassium sparing diuretics?
in CrCl <10 ml/min
What does potassium sparing drugs decreases the levels/effect of?
Cardiac glycoside
Mechanism of ARB
Angiotensin receptor blocker—net
List an example of an ARB
Lasartan
What are the two main side effects of ACE inhibitors AND ARBs?
- Modest increase in Sr Cr ~35% or absolute increase of less than 1mg/dL do not warrant changes-vasoconstriction of efferent arterioles
- Hyperkalemia
What are the two main side effects of ACE inhibitors?
- Dry cough
2. Angioedema—Lip and tongue swelling most common
What population are ACE1 and ARBs the most effective?
Young, white patients
What population are ACE1 and ARBs the least effective?
Blacks
older persons
Pt’s predominantly systolic HTN
What antihypertensive is the choice for DM?
ACE1 and ARBs
What labs do we want to monitor in ACE1 and ARBs?
Serum creatinine
K+
What antihypertensive is absolutely contraindicated in pregnancy?
ACE1 and ARBs
List a Renin Inhibitor
Aliskiren
What type of patient should ACEI, ARBs and renin inhibitors be avoided?
- Hyperkalemia
- Pregnant
- Pulmonary/Cough
- Significant CKD
Action of α1receptors
Vasoconstriction of arterioles and venules
Action of α2 receptors
regulation of α1
Action of β1 receptors
Increase HR
Increase contractility
Renin release
Action of β2 receptors
Vasodilation of arterioles and venules
Bronchodilation and Vasodilation: lung, liver, pancreas, and arteriolar smooth muscle
Gluconeogenesis
What is the result of sympathoplegic drugs?
A reduction in one or more of the following: Venous tone HR Contractile force CO TPR
List Beta Blockers
Propanolol
Metoprolol
Atenolol
What is the mechanism of Beta Blockers?
Block β1 and β2 receptors of the SNS:
- Negative chronotropic and inotropic= decreased CO
- Inhibits release of Renin
What are the main side effects of Beta Blockers?
Bradycardia,
AV conduction abnormalities
Acute heart failure
Acute exacerbations of asthma or COPD (bronchospasms)
How are beta blockers differentiated?
- Cardioselectivity
- ISA
- Membrane-stabilizing effect
What should you monitor with beta blockers?
Assess for CHF
Monitor BS in DM
List the Alpha 1 blockers
Prazosin
Terazosin
Doxazosin
What is the main side effect of Alpha 1 Blockers?
First Dose Phenomenon and an increased dose effect: Dizziness/faintness
Palpitations
Syncope
What patients would we recommend an Alpha blocker to?
Pt’s with BPH
PTSD related nightmares and sleep disruption
What are the drug interactions of Alpha 1 Blockers?
Decrease levels of:
Dabigatran
Linagliptin
List Central Alpha 2 Agonists
Clonidine
Methyldopa
Side effects of Methyldopa
- Sodium and water retention-Give a diuretic
2. Hepatitis or hemolytic anemia= transient rise in LFT’s
Side effects of Clonidine
Anticholinergic side effects:
- Sedation
- Dry mouth
- Constipation
- Urinary retention
- Blurred vision
Side effects of Central Alpha 2 Agonists (both meds)
Rebound HTN with abrupt cessation
List the Peripheral Adrenergic Antagonist
Reserpine
What are the side effects of Reserpine?
- Significant sodium and water retention- Give with diuretic (Thiazide)
- Reflex Parasympathetic Activity
- Nasal stiffness
- Increased gastric secretion
- Diarrhea
- Bradycardia
What population would we consider treating with Nondihydropyridine CCB?
Elderly with isolated systolic HTN
What is the only CCB safe to use in pt’s with severe heart failure?
Amlodpine
What do you use to treat Raynauds?
Dihydropyridine CCB
What is an effective antihypertensive in African Americans?
CCB
Side effects of ALL calcium channel blockers?
Gingival hyperplasia
Peripheral edema
Dizziness, flushing, HA
Verapamil side effects
Constipation
Calcium channel blocker drug interactions
1. Inhibit metabolism of: Digoxin Lovastatin Simvastain Cyclosporine
What inhibits Nifedipine metabolism
large quantities of grapefruit juice (> 1quart)
List the direct arterial vasodilators
Hydralazine
Minoxidil
What is a side effect of Hydralazine?
Dose dependent lupus-like syndrome and slow acetylators
What is a side effect of Minoxidil
Hypertrichosis
What is an alternative use of minoxidil?
Male pattern baldness
–>both men and women
List an osmotic diuretic
Mannitol
Clinical applications for Osmotic Diuretics (Mannitol)
- Solute overload in rhabdomyolysis, hemolysis
- Brain edema w/ coma
- Acute glaucoma
What medications are useful in pituitary diabetes insidious?
ADH and Desmopressin
Contraindications in ADH agonists (Desmopression, vasopressin)
- Hyponatremia
2. Hypertension
What would you use to treat syndrome of inappropriate ADH secretion (SIADH)
ADH antagonists
- Demeclocycline
- Conivaptan
What ADH antagonists would you use to treat hyponatremia?
Conivaptan