Anti-Hypertensives part 2 Flashcards
What are the first choice agent for hypertension and congestive heart failure and the most commonly prescribed diuretic?
Thiazides
Describe the 2 main action and location of action of Thiazides
- Inhibition of active Na+ reabsorption in the proximal and distal tubules
- Inhibition of carbonic anhydrase = decreased availability for H+ exchange with Na+
What are the desired effects or outcomes of Thiazide diuretics?
- Lower BP
- Decreased cardiac output
- Decreased peripheral resistance
- Normalization of cardiac output after several days
Thiazide diuretics lower BP by lowering what specific fluid volumes?
- Decrease plasma volume
2. Decrease extracellular fluid
What cardiac principle explains a decreased cardiac output by Thiazide diuretics?
Starling’s Law = if decrease amount of blood returning to the heart (preload), heart doesn’t have to work as hard to eject blood back into the systemic circulation
Name the main brand name and generic name drug that is classified as a thiazide diuretic?
○ HCTZ (Microzide)
- Hydrochlorothiazide
3 uses of HCTZ
- Hypertension
- Edema from congestive heart failure
- Nephrotic syndrome
A patient presents in your office with hypertension and is currently taking microzide. What oral complications might you suspect?
- Xerostomia
- Lichenoid drug reaction
- Photosensitivity
If a patient is on a thiazide diuretic, what adverse effects may occur at a physiological level?
○ As Na+ accumulates in distal proximal tubule, more K+ is lost. This may result in hypokalemia.
○ Hypokalemia has toxic effects in heart and muscles
○ **If sodium intake increases, potassium loss is exacerbated
Name the 10 adverse effects of Thiazide Diuretics
- Hypokalemia
- Loss of carbonate (HCO3-)
- Hypomagnesaemia
- Hyponatremia
- Hyperuricemia
- Hyperglycemia
- Elevated cholesterol
- Elevated triglycerides
- Weakness/fatigue
- Sexual dysfunction
What type of hypertensive patients would not be considered good candidates for a Thiazide diuretic?
- Diabetic patients (Increased glucose)
- High cholesterol or lipids
What are the two preparations of thiazide drugs?
- Hydrochlorothiazide
- Chlorothiazide
What is the diuretic of choice for serious edema?
- Loop diuretic
- Cause a major loss of volume
Name the indications that would warrant a prescription of a loop diuretic?
- Acute HTN
- Pulmonary edema
- Congestive heart failure
Method of action for a loop diuretic
- Potent inhibition of active Na+ reabsorption in the ascending loop of henle by blocking reabsorption of Cl-
- Inhibits the Na+ K+ Cl- symporter
Why are loop diuretics considered toxic?
- They can be toxic due to such rapid loss of electrolytes
What does it mean that all loop diuretics are ototoxic to some degree?
- They cause hearing loss/deafness
Name the classic example of a loop diuretic
- Lasix
Generic: furosemide
Use of Lasix
- HTN
- Edema from congestive heart failure
- Hepatic/renal disease
If a patient presents in your office and is taking Lasix, what oral complications might you suspect?
- Vomiting
- Oral irritation
- Xerostomia
- Lichenoid drug reaction
Adverse effects of loop diuretics
- Hyponatremia
- Hypokalemia (risk for arrhythmias)
- Hyperglycemia
- Hypocalcemia (heart toxicity from Ca+ loss)
- Hyperuricemia
- Nephrotoxicity (inc. risk if used with Keflex)
- Ototoxicity
- GI distress
- CNS effects
Name the common loop diuretics
- ethacrynic acid (Edecrin)
- furosemide (Lasix)
- bumetanide (Bumex)
- torsemide (Demadex)
What is the cellular mode of action for Potassium-sparing diuretics?
○ Competes with aldosterone for receptor sites in the distal renal tubules
○ This increases Na+, Cl- and water excretion while conserving K+ and H+
○ **More simply stated:
- Blocks affect of aldosterone
- Prevents usual loss of K+
Name the preparations of Potassium-sparing diuretics
- Spironolactone (Aldactone)
- Triamterene (Dyrenium)
- Eplerenone (Inspra)
Potassium-Sparing diuretics are commonly used together with what other diuretic?
Thiazides
Helps prevent thiazide induced hypokalemia
Adverse effects of Potassium- sparing diurects
- Hyperkalemia
- Gynecomastia
- Tenderness of breasts in young women
- Menstrual irregularities
- Decreased libido in males
Cellular mode of action for Carbonic Anhydrase Inhibitors
- Inhibits carbonic anhydrase
- Exchange of H+ is decreased and more Na+ is excreted with an accompanying volume of water.
Renal target of action for a carbonic anhydrase inhibitor?
- Proximal convoluted tubule
- Distal convoluted tubule
Primary use for a Carbonic Anhydrase Inhibitor?
- Used primarily for glaucoma
- Decreases production of aqueous humor
- Adjunctive therapy for congestive heart failure
- … Also works in CNS to retard abnormal/excessive discharge from CNS neurons
Name the different carbonic anhydrase inhibitors
- Acetazolamide (Diamox)
- Methazolamide (Neptazane)
When are Osmotic diuretics used?
- Used in emergency situations when need to decrease blood volume
- If patient’s kidneys shut down, use this to get flow started again
Renal target for osmotic diuretics
Bowman’s capsule in proximal tubule
- Name the preparations of osmotic diuretics
Urea (Ureaphil)
When are Acidifying agents used?
- Rarely
- In treatment of hypochloremic states or metabolic alkalosis
- Used in Emergency room to produce a large amount of chloride
Chemical action of Acidifying agents
- Increases amount of Cl- in urine and Na+ stays with it
- This = diuresis
Name the preparations of Acidifying agents
Ammonium chloride
What are Xanthines used for?
- Respiratory drugs (theopylline) for asthma and COPD
2. Stimulants (like caffeine which is a xanthine)
Why would Xanthines be used in a similar way as diuretics?
Because like caffeine, they make you pee!!!
Describe the mode of action of Xanthines
- Stimulates cardiac function to increase renal blood flow and glomerular filtration rate
- Inhibits tubular reabsorption of Na+
- Inhibit ADH
Site of action for Xanthines
Afferent arteriole to Bowman’s capsule
Rank the potency of diuretics from Most potent to Least potent
- Loop
- Thiazides
- Carbonic anhydrase inhibitors (very mild)
- Potassium-sparing
Name the general dental considerations to keep in mind when a patient presents to your office while taking a diuretic
- Xerostomia from water loss
- Aphthous stomatitis (mouth ulcers)
- Lichenoid drug reaction
i. Fake lichen planus from thiazides and loops
- **Delayed drug hypersensitivity reaction
Use of what other drug can decrease effectiveness of diuretics?
Use of NSAIDS for >3 weeks
Because of the severe potassium loss from diuretics, can you recommend a patient to supplement with potassium supplements?
Yes
What contraindications exist before suggesting a potassium supplement?
- Contraindicated if severe renal impairment or if taking potassium-sparing diuretics
- Contraindicated with ACEIs (hyperkalemia)
What is the major adverse effect with potassium supplements in patients that it is contraindicated?
GI distress
Other than diuretics, what other classes of drugs can be used to lower BP?
- Drugs that impair sympathetic nervous system functioning
- ACE inhibitors (ACEIs)
- Angiotensin II receptor blockers (ARBs)
- Calcium channel blockers (CCBs)
Mechanisms of action for a Beta Receptor blocker
- Decrease cardiac output
i. Decrease work of heart - Decrease renin secretion
- Reduce plasma volume and venous return
- Decrease sympathetic outflow from CNS
- Reduce peripheral resistance
Name the two classes of beta blocker drugs
- Cardioselective
- Non-cardioselective
Describe the naming system that is in place to differentiate between cardioselective and non-cardioselective beta blockers
- Cardioselective
i. Starts with letter A-M
ii. Block beta1 only - Non-cardioselective
i. Starts with letter N-Z
ii. Block beta1 and beta2
Name the exception to the naming rule of beta blocker drugs
- Mostly opthalmic preparations for glaucoma
2. New drug nebivolol (Bystolic) is a cardioselective drug
Name the cardioselective Beta blockers
- atenolol (Tenormin)
- betaxolol (Betoptic)
- bisprolol (Zebeta)
- esmolol (Breviblock)
- metoprolol (Lopressor, Toprol)
- nebivolol (Bystolic)
Cardioselective beta blockers block what beta receptor?
Beta-1
Non-cardioselective beta blockers block what beta receptor?
Beta-1 and Beta-2
Name the non-cardioselective beta blockers?
- nadolol (Corgard)
- propranolol (Inderal)
- sotalol (Betapace)
The side effects of beta blockers are associated with what?
They are consistent with over-activity of the parasympathetic nervous system.
You are deciding whether or not to prescribe to one of your patients a beta blocker for antihypertensive purposes, what contraindications must you consider?
○ Congestive heart failure
- Already have decreased cardiac output
○ Asthma
- Don’t want to block B2 in case of bronchoconstriction
- Use cardioselective beta blocker
○ Heart block
- These drugs decrease heart rate and force of contraction
○ Diabetes
- Beta blockers decrease glycogenolysis and glucagon secretion
- Use cardioselective beta blocker
In what two specific cases would you choose a cardioselective beta blocker over a non-cardioselective beta blocker?
- Asthma patients
- Diabetic patients
Where are Alpha-1 receptors located?
On postsynaptic receptor tissues
Action of Alpha-1 receptors
Produce vasoconstriction and increase peripheral resistance if stimulated
What is the action of an Alpha-1 BLOCKER?
Produce peripheral vasodilation in arterioles and venules, decreasing peripheral vascular resistance
T or F, Alpha-1 blockers work on the peripheral vessels rather than on cardiac output and renal blood flow
True
How can you increase the efficacy of Alpha-1 blockers?
More effective when used with diuretics and/or beta blockers
Other than the vascular effects of Alpha-1 blockers, what other effects can be seen?
The blockage of these receptors blocks certain smooth muscle contractions leading to decreased resistance to urinary outflow.
Other than Hypertension, what type of patients could be prescribed an Alpha-1 blocker?
○ Used to improve urination in men with enlarged prostate and those with bladder problems
- Men with enlarged prostate
- Bladder problems
- Benign Prostatic hypertrophy
Describe the patients who may be using Alpha-1 receptor blockers
- Old Men
- Hypertension + improve urinary flow due to prostatic hypertrophy
Name the 3 adverse effects of Alpha-1 blockers
- Orthostatic hypotension
i. Worse if patient exercises or drinks alcohol
ii. More likely if volume or sodium depleted (diuretic?) - CNS effects
i. Varies, headache, drowsiness or excitation - Cardiovascular effects
- Name the different Alpha-1 Receptor blocker drugs
- Doxazosin (Cardura)
- Prazosin (Minipress)
- Tamsulosin (Flomax)
Which Alpha-1 receptor blocker is used to facilitate urination in men with enlarged prostate?
Tamsulosin (Flomax)
What is the side effect of Flomax?
Severe orthostatic hypotension
