331

Which diuretic is first line of therapy for reducing blood pressure

- thiazides - work well at reducing BP, cheap, least risk

How can thiazides be administered?

- PO only (onset- 2 hours)

Which diuretic needs good renal blood flow and GFR to be effective?

- thiazides (loop diuretics work well, even with renal insufficiency)

Types of diuretics

- High-ceiling (loop) diuretics - Thiazide diuretics - potassium sparing diuretics

peripheral resistance is determined by...

- arteriolar constriction

What class: warfarin (Coumadin)

Anticoagulants oral

Which is the "OLOL" group?

Beta Blockers

Cardiac output = _____ x _____

stroke volume x heart rate

All beta blocker drugs have what name ending?

"olol"

ACE inhibitor drugs end in what

"pril"

Uses for ACEI- hypertension

(1) Arterial vasodilation (2) Reduced blood volume (3) Better than adrenergic agents (a) no effect on cardiac contractility or exercise ability (b) no orthostasis, no bronchial effects, CNS (c) reduce the risk of CV mortality due to HTN (4) Better than diuretics - no fluid and electrolyte effects

Alpha1 adrenergic blockers- Doxazosin does what?

(1) Blocks α1 receptors on arterioles and veins (2) dilation of arterioles - direct ↓ BP (3) dilation of veins decreases venous return to heart decreases CO - which ↓ BP (4) used primarily for HTN (5) also for benign prostatic hypertrophy (BPH) - reduced contraction of smooth muscles in neck of bladder and prostate capsule

Adverse effects of non-selective beta-blockers

(1) Bradycardia - decreased HR (2) AV heart block (3) Heart failure - decreased force of contraction (4) Rebound cardiac excitation - from abrupt drug withdrawal (5) Bronchoconstriction --(a) Block Beta- 2 receptors in the lung -- (b) Block normal bronchodilation when needed →bronchospasm (6) Inhibition of glycogenolysis --(a) Decreases breakdown of glycogen to glucose --(b) Dangerous for diabetics ---(i) who may need glucose if insulin dose is too much ---(ii) suppresses early sx of hypoglycemia (7) CNS - depression, insomnia

pharmokinetics of non-selective beta-blockers

(1) Highly lipid soluble (2) Well absorbed PO (3) Extensive first pass - 30% available (4) Hepatic metabolism - renal excretion

Uses for ACEI- MI

(1) Reduce mortality and heart failure after MI (2) Start right after MI

Uses of ACEI- In patients with high CV risk

(1) Those with stroke, CAD, DM, PVD and one CV risk factor (2) To reduce CV event - Keeps BP down - Stops negative effects of aldosterone and angiotensin 2

Uses for ACEI- heart failure

(1) lowers arterial resistance -(a) reduces afterload -(b) increases CO -(b) reduces pulmonary congestion (2) renal vessel dilation -(a) increased renal blood flow -(b) Na/water excretion -(c) and therefore reduced edema and blood volume (3) Reduce pathologic wall thickening

Adverse effects of cardio-selective beta blockers

(a) Bradycardia - decreased HR (b) AV heart block (c) Heart failure (d) Rebound cardiac excitation

Adverse effects of alpha1 blockers

(a) Orthostatic hypotension --Advise- dizziness, change position slowly --increase fluids (b) Reflex tachycardia ---Baroreceptors notice that volume has decreased, and tell heart to beat faster (c) Nasal congestion (Vessels in nares dilate) (d) Inhibition of ejaculation

Adverse drug reactions to thiazides?

(similar to loop, but no ototoxicity) - hyponatremia - hypochloremia - dehydration - hypokalemia

Beta-1 blockade does what?

- reduces HR - decreased force of heart contraction - Suppressed conduction through AV node; ---reduces CO and BP - suppress renin secretion (Block β1 receptors at the JG apparatus)

ACE inhibitors reduce BP by ___

- reducing vascular resistance and increasing urine output

Where do adrenergic receptors fall within the nervous system?

- Adrenergic receptors are a part of the Sympathetic nervous system; which is a part of the autonomic nervous system; which are motor neurons within the peripheral nervous system

Besides affecting Na reabsorption in the collecting duct, how else do K+ sparing diuretics work?

- Aldosterone antagonist (diuretic) -block aldosterone

Sympathetic baroreceptor reflex

- Baroreceptors- are in aortic arch and carotid sinuses - they are pressure receptors - (when pressure changes, activated) - When pressure low- activate SNS to increase squeeze - When pressure high- decrease- vasodilation to reduce pressure

Action of ARB drugs

- Block angiotensin II action (not production) - Receptor antagonists --(1) on blood vessels - causing vasodilation (arterioles and veins) (2) in the heart - reduce cardiac remodeling (3) in adrenal glands - decrease release of aldosterone - promotes excretion of Na and water (4) Does not increase bradykinin which causes the ACEI cough - angiotensin II is still produced, but the action is blocked at the receptors

Cardio-selective beta blocker do what? (Basic)

- Blocks β-1 receptors only - at normal doses - ALL actions results from beta blockade of cardiac beta-1 receptors (Metoprolol)

Beta-2 blockage does what?

- Bronchoconstriction - Inhibition of glycogenolysis -skeletal muscle & liver - do not want this

Alpha2 agonists do what? (basic)

- Decrease sympathetic impulses from the CNS to the heart and arterioles, causes vasodilation (blocks norepinephrine)

Uses for non-selective beta blockers

- HTN- reduced CO, RAA - angina- decreased workload - dysrhythmias (tachy) - MI- reduces pain, infarct size, reduces mortality and risk of reinfaction, migraine, stage fright

How are loop diuretics administered? (plus onset times)

- PO, IM, IV (a) Onset in 60 min (PO), 5 min (IV) (b) Works well with poor renal blood flow or reduced GFR

Alpha 2 agonists do what?

- Suppresses sympathetic outflow from the CNS - ↓ α and β adrenergic receptor peripheral activation ---Dilation of arterioles ---Slowing of the HR conduction velocity - Decrease/prevent release of norepinephrine - less of a squeeze - vasodilation

Systems that regulate blood pressure

- Sympathetic baroreceptor reflex - Renin-angiotensin-aldosterone system - Renal regulation of blood pressure (Through ADH and naturetic peptides)

Where are beta2 receptors located?

- arterioles- heart, lungs, skeletal muscle - lungs- bronchi - liver - heart - skeletal muscle

What does alpha2 do?

- deactivates alpha1 - Inhibits release of norepinephrine from CNS - Blocks constriction - Opposite on alpha1

How do thiazides reduce blood pressure?

- decrease blood fluid volume - Inhibit NaCl reabsorption in DCT - Na, Cl, and K stay in tubule- excreted - water follows - decreased stroke volume

What does beta1 do?

- decreased heart contraction - decreased HR - decrease AV conduction - Kidney- stimulates release of renin

Adverse drug reactions of diuretics

- dehydration (hypovolemia) - hypokalemia (loose K+ with NaCl) - hyperuricemia - glucose intolerance (do not excrete uric acid and glucose as well) - hypercholesterolemia

What does beta2 do?

- dilation of heart, lung, skeletal muscle arterioles- more blood flow - dilation of bronchi- more air - liver- glycogenolysis- make sugar for energy - Skeletal muscle- contraction enhanced - Energy, strength, blood flow increased - Fight or flight

MONA-B

- drugs used during an MI Morphine (pain), Oxygen, Nitrates (vasodilation), Aspirin (anti-platelet), Beta blocker (reduce cardiac workload)

Where are beta1 receptors located?

- heart and kidneys

cardiac output is determined by...

- heart rate - contractility - blood volume - venous return

Adverse drug reactions to Potassium sparing diuretics

- hyperkalemia ---if reabsorb too much K+ ---especially when used alone ---Caution when using other drugs that increase K (ACE Inhibitors)

Adverse drug reactions of the loop diuretics

- hyponatremia, hypochloremia - hypokalemia - ↑ excretion in distal tubule - dehydration - hypotension (orthostatic) - ototoxicity ---with high doses (especially lasix) ---tinnitus

What do diuretics do? (basic)

- increase fluid output and decrease fluid volume to decrease blood pressure --reducing SV which reduces CO - Reduce reabsorption of Na actively (Na excretion) which passively increases excretion of water

If a medication stimulates the sympathetic nervous system, what are a few effects that can be expected?

- increased heart rate - blood pressure increase - bronchial dilation - increase glucose production fight or flight

What do alpha1 receptors cause?

- increased pupil size - constriction of arterioles ---skin, viscera, mucus membrane ---Constrict non-vital organs to get blood to vital organs (heart and lungs) ---Veins (peripheral) are also constricted in the same areas

Alpha 1 blockers do what? (basic)

- inhibit sympathetic activation in arterioles, causing vasodilation

Why are K sparing diuretics weak diuretics?

- most Na has already been absorbed - Decrease in K excretion; used to balance K loss from diuretics ---K is reabsorbed into body - Used in conjunction with loop diuretics - Helps prevent hypokalemia from loop diuretics (slow onset- 1-2 days)

The 2 types of beta blockers

- non-selective (both beta1 and beta2 blockade) - cardio- selective (only beta1 blockade)

Which drugs work on the collecting duct?

- potassium sparing diuretics - weak diuretic - Na stays in tubule, collecting duct, and excreted ---water follows - K is reabsorbed in body (can get hyperkalemia)

Uses of cardio-selective beta blocker

- primarily for HTN - Also for angina, - MI (MONAB), - heart failure; helps to balance oxygen supply and demand by reducing demand - tachydysrhythmias - surgery patient- want BP around 60-70 bpm, will give metoprolol if a little over)

Where are alpha 1 receptors located?

- the eye - peripheral arterioles - veins

Normal K range

3.5-5 mg/dL

Goal K value for cardiac patient

4.0 Narrow margin, because problems with electrical conduction system, prevent dysrhythmia

What class: captopril (Capoten)

ACE inhibitors

What is the "pril" group?

ACE inhibitors

Classes of antihypertensive drugs

ACEI, ARBs, Beta Blockers, Calcium Channel Blockers, Diuretics

Drugs used for MI prevention

ASA Clopidogrel (Plavix) Cholesterol-lowering drugs ACE inhibitors

What class: losartan (Cozaar)

Angiotensin II receptor blockers

What is the "sartan" group?

Angiotensin II receptor blockers

What class: heparin, enoxaparin

Anticoagulants parenteral

What class: clopidogrel (Plavix)

Antiplatelet aggregates

Which HTN drugs decrease the force of contraction?

Beta blockers Alpha/beta blockers

Which HTN drugs decrease heart rate?

Beta blockers Alpha/beta blockers Alpha 2 agonists

What class: Propranolol (Inderal)

Beta blockers (non selective)

What class: Metoprolol (Lopressor, Toprol)

Beta blockers (selective)

What class: Cholestyramine (Questran)

Bile-Acid Sequestrants

Angiotensin receptor blockers (ARB) do what? (basic)

prevent angiotensin II from reaching receptors, causing vasodilation anti-hypertensive

Which is the "pine" group?

Calcium channel blockers

What class: Ezetimibe (Zetia)

Cholesterol absorption inhibitor

What drugs are used for dysrhythmias?

Class IB: Sodium channel blockers (Lidocaine) Class II: Beta blockers (Propanolol, acebutolol) Class III: Potassium channel blockers (Sotalol and amiodarone) Class IV: Calcium channel blockers (verapamil, diltiazem) Other: Adenosine

Uses of ACEI- Diabetic nephropathy

Diabetic (I and II) and non-DM nephropathy (1) Increases renal blood flow (2) Decreases glomerular filtration pressure (3) Slows progression of renal disease

Drug classes for heart failure

Diuretics ACE inhibitors ARB's (less favorable) Aldosterone antagonists (spirolactone) Betablockers Alpha/beta blocker (Coreg) Cardiac glycosides (Digoxin)

Which HTN drugs decrease preload?

Diuretics Angiotensin II Receptor Blockers Aldosterone Antagonists

Drug classes that treat HTN

Diuretics Beta blockers Alpha1 blockers Alpha/Beta blockers Centrally Acting Alpha2 Agonists Adrenergic Neuron Blockers Calcium Channel blockers (CCBs) ACE Inhibitors (ACE) Angiotensin II Receptor blockers (ARBs) Aldosterone Antagonists

Which HTN drugs decrease peripheral resistance?

Diuretics Calcium channel blockers Angiotensin II Receptor Blockers ACE inhibitors Aldosterone Antagonists Alpha/beta blockers Alpha 2 agonists

What class: Gemfibrozil (Lopid)

Fibric acid derivatives

What class: Lovastatin (Mecavor)

HMG-CoA Reductase Inhibitors

Examples of loop diuretics

Furosemide (Lasix), Ethacrynic acid (Edecrin), Bumetanide (Bumex)

What is the "statin" group?

HMG-CoA Reductase Inhibitors

Examples of thiazides

Hydrochlorothiazide (HCTZ), metolazone, others ending in "thiazide"

Angiotensin Converting Enzyme Inhibitors (ACEI) do what?

Inhibit conversion of angiotensin I to angiotensin II: - therefore, no vasoconstriction a) Arteriole vasodilation, less effect on veins b) Reduction of blood volume - reduction in aldosterone ---(b/c angiotensin 2 causes release of aldosterone) ---Without aldosterone, Na is not reabsorbed, water does not follow c) Reduction of cardiac and vascular hypertrophy and remodeling (redistribution of mass)

Which is the strongest category of diuretic?

Loop diuretic Inhibit transport of Na / K in loop of henle -decrease SV; reduces reabsorption of Na - causing Na and water loss in urine.

Will a patient with HTN and asthma be given metoprolol (cardio-selective beta blocker)?

No, because of bradycardia adverse affect

Prototype non-selective beta blockers

Propranolol/Inderal

In addition to affecting the loop of henle, what other action do loop diuretics do?

Relaxation of venous smooth muscles - decreases preload - reduces BP

Examples of potassium sparing diuretics

Spironolactone (Aldactone) (Also used to reduce aldosterone release in Heart failure - improves mortality)

Which drug affects the distal convoluted tubule (DCT)?

Thiazides - moderate diuresis - Na, Cl, and K stay in tubule- excreted - water follows

What class: alteplase recombinant (TPA)

Thrombolytics

Drugs that dilate the venous system results in what?

a reduced stroke volume which reduces the cardiac output allows more blood to be within the venous system

Adverse drug reactions of ACEI

a) first dose hypotension - most often with high BP and dehydrated b) cough; 5-10% ---Affects epithial cells of lung, put on ARB instead c) hyperkalemia - esp combined with K sparing drugs or K supplements d) angioedema - rare 1% ---Face, larynx, etc. swells and have difficulty breathing - Want to take drug at night

Pharmacokinetics of ACE inhibitors

a) good oral absorption - most all PO b) most are prodrugs - converted to active form in intestine or liver c) most OK with food d) most have long half-life; given qd or bid (except captopril) e) significant drug accumulation in renal disease --Excreted by kidney

Adverse affects of beta-1 and beta-2 blockades

beta-1: - bradycardia - reduced CO - heart failure (if give too much, relaxes too much) - AV heart block (slow so much, blocked) beta-2: - Bronchoconstriction - Inhibition of glycogenolysis

Are beta blockers positive or negative inotropes?

negative inotropes - reduce contractility - reduces workload, heart doesn't have to work as hard

where do loop diuretics work?

on the ascending loop of henle - Na, Cl, and K stay in the tubule and are excreted - water follows

Adverse drug reaction for alpha 2 agonists

orthostatic hypotension

Beta blockers reduce BP by ____

reducing heart rate (and therefore reducing cardiac output) - also reduce myocardial contractility

BP= cardiac output x ______

systemic vascular resistance

Why are loop diuretics called "high ceiling"?

the more drug given, the greater the effect