Antihypertensives & Diuretics Flashcards
BP =
CO x SVR
List the factors that contribute to blood pressure:
- contraction of heart ventricles
- SVR
- elasticity of arterial wall
- blood volume
Secondary causes of HTN:
- CKD
- Cushing’s
- Untreated OSA
- Obesity
- Pheochromocytoma
Drugs that can cause HTN:
- Na+ and H2O retention
- steroids
- NSAIDs
- sympathomimetics
- MAOIs
- acute withdrawal from Clonidine
Where are baroreceptors located and where do they form the vagus nerve?
- located in carotid sinus (off the ICA just above split from common carotid)
- located in aortic arch (where they join up to form the vagus nerve)
Describe the cascade of events when BP drops:
- baroreceptors send signals to adrenal medulla
- catecholamines released
- sympathetic activity increased/activate A & B receptors
- B1: increase HR and SV –> increase CO and BP
- A1: vasoconstriction
Sympatholytics =
adrenergic antagonists
Describe the actions of sympatholytics:
- inhibit activity of SNS (mediated by Epi and NE)
- bind to adrenergic receptors of smooth muscle - vasodilation and decreased SVR
- alpha-blockers and beta-blockers
MOA of Phenoxybenzamine:
- irreversible
- non-competitive
- non-selective adrenergic antagonist
- changes shape of receptor so it cannot bind to catecholamines
- takes 24 hours to synthesize new receptors
What condition is Phenoxybenzamine used to treat? When should it be started?
- Pheochromocytoma
- started 7-10 days before operation d/t slow onset
SE of Phenoxybenzamine:
- HTN
- tachycardia
- arrhythmias
MOA of Phentolamine:
- reversible
- competitive adrenergic antagonist
- lasts 4 hours (fast)
What conditions is Phentolamine used to treat?
- Pheochromocytoma
- Extravasation of an A-receptor agonist (NE)
- ED
- HTN crisis
Non-selective adrenergic antagonists block A1 receptors (good), but also A2. What happens when A2 receptors are blocked?
- NE acts on A2 receptors to inhibit its own release
- blocking A2 causes an increase in NE
- NE can stimulate B1 receptors
- HTN and tachycardia
MOA of selective A1 antagonists:
- selectively and reversibly block A1 receptors in vascular smooth muscle
- reduced PVR & BP
SE of A1 antagonists:
hypotension
tachycardia
(baroreceptor reflex)
Name the selective A1 antagonists:
“-osin”
Prazosin
Terazosin
Doxazosin
Alfuzosin
Silodosin
Tamsulosin
Alfuzosin/Silodosin/Tamsulosin used to treat:
Side effects:
- treat: enlarged prostate
- SE = orthostatic hypotension, HA, nasal congestion
(reflex tachycardia less likely)
Name a selective A2 antagonist:
What is it used for?
Yohimbine
- dietary supps for ED
- reverse sedation in vet med
Where are B1 receptors located and what does stimulation of them do?
- heart: increase HR and contractility
- kidney: stimulate juxtaglomerular cells to release renin
Where are B2 receptors located and what does simulation of them do?
- smooth muscle
- lungs: bronchodilation
- GI: decreases motility
- eye: maintains shape
- liver: promotes glucagon release
Describe the first generation BB MOA and effects:
- non-selective
- mostly act on B1 receptors in heart
- decrease HR, delay AV node conduction, reduce contractility
- decrease CO and O2 demand of the heart
What are the first gen BB?
Propranolol
Pindolol
Nodolol
Timolol
Sotalol
Which BB is lipid soluble? What is it used for?
- Propranolol
- can penetrate the CNS and is used for migraine prophylaxis
What BB is used to treat glaucoma?
- Timolol
- when applied topically, decreases intraocular pressure
First gen/non-selective BB should be avoided in which patient populations?
COPD & asthma d/t chance for bronchoconstriction
What makes 2nd gen BB different?
- selective for B1 receptors
- more suitable for chronic lung patients
- “cardio-selective” BB
List the 2nd gen BB:
Atenolol
Acebutolol
Bisoprolol
Esmolol
Metoprolol
What makes 3rd gen BB different?
- includes both non-selective & selective BB
- non-selective: block both B1, B2 and A1
- produce peripheral vasodilation
Carvedilol and Labetalol fall under which generation of BB?
3rd gen
non-selective/selective BB
What effect do 3rd gen BB have on the kidneys?
- inhibit B1 receptors on kidneys
- suppress renin release
- suppress formation of angiotensin II
- suppress secretion of aldosterone
- cause decrease in SVR & BP
What is the 3rd gen selective BB? What does it do?
- Nebivolol
- produces vasodilation by introducing NO from endothelial cells to relax smooth muscle
Two BB have intrinsic sympathomimetic activity. What are they and how does this occur?
- Pindolol & Acebutolol
- block but also weakly stimulate B1 and B2 receptors
- diminished effect on HR and CO
- nice for pts with preexisting heart block/bradycardia
Which BB depends on kidneys as primary route of elimination?
Atenolol
Which BB is metabolized by RBC esterase?
Esmolol
SE of BB:
- bradycardia
- hypotension
- fatigue
- cold hands and feet
- dry mouth/skin/eyes
- HA
- GI upset
- diarrhea or constipation
MOA of CCB:
work on voltage-gated ion channels to block inward movement of Ca2+ across myocardial and vascular smooth muscle to cause arterial vasodilation
Effects of CCB:
- decrease myocardial contractility
- decrease myocardial O2 requirements
- decrease arteriole tone and SCR
- decrease LV stress
- reduce or block impulse generation in the SA node & conduction in the AV node
Clinical uses of CCB:
- HTN
- SVT
- prevent cerebral vasospasm
- decrease CP
MOA of dihydropyridines:
- selectively inhibit L-type Ca2+ channels in vascular smooth muscle
- cause vasodilation & decreased SVR
List the dihydropyridines:
Nifedipine
Nicardipine
Nimodipine
Clevidipine
Nifedipine is used for…
- tx of angina
- no direct depression of SA or AV node
- SE: flushing, vertigo, HA
Nicardipine is used for…
- tx of angina and HTN
- no direct depression of SA or AV node
Which drug has the greatest vasodilating effect of all CCB?
Nicardipine
Which CCB crosses the BBB?
Nimodipine
How is Clevidipine metabolized?
plasma esterase
(elimination half-time = 1 min)
What 3 drugs is Clevidipine incompatible with?
Hydromorphone
Epi
Milrinone
MOA of nondihydropyridines:
- non-selective inhibitors of L-type Ca2+ channels
Name the 2 dihydropyridines:
Diltiazem
Verapamil
SE of nondihydropyridines:
excessive bradycardia
cardiac conduction abnormalities
Which nondihydropyridine is more effective at decreasing contractility?
Verapamil > Diltiazem
SE of nondihydropyridines:
- hypotension
- bradycardia
- AV block
- HA
- abdominal discomfort
- peripheral edema
MOA and effects of ACE inhibitors:
- inhibit conversion of angiotensin I to angiotensin II in the lungs
- cause relaxation of BV, decrease in blood volume, decrease BP, and decrease heart O2 demand
Brief overview of the RAAS:
- renin released from juxtaglomerular cells of afferent arteriole
- renin converts angiotensinogen to angiotensin I
- angiotensin I is converted to angiotensin II by angio converting enzymes in the lung
- angio II promotes vasoconstriction and aldosterone release
Which ACE inhibitor should not be used in renal patients?
Captopril
(all ACE inhibitors are eliminated by kidneys)
What is important to note about Lisinopril?
limit salt substitutes or K+ supps d/t r/f hyperkalemia
SE of ACE inhibitors:
- hypotension
- COUGH
- hyperkalemia
- HA/dizziness
- renal impairment
ACE inhibitors are contraindicated in which patient populations?
- renal artery stenosis
- insulin-dependent DM
- hyperkalemia
- pregnancy
MOA of ARBs:
interfere with binding of ATII with its receptor –> inhibition of ATII mediated vasoconstriction by inhibiting aldosterone
Important SE of Losartan:
- hyperkalemia (d/t increasing aldosterone)
- increases lithium reabsorption by kidneys
What are the centrally acting adrenergic drugs?
Clonidine
Methyldopa
MOA of centrally acting adrenergic drugs:
selective stimulate pre-synaptic A2 receptors –> provide negative feedback to reduce catecholamine production/release
What is Clonidine used to treat?
- HTN
- ADHD
- anxiety
- ETOH withdrawal
Why should you not abruptly stop Clonidine?
withdrawal after long term use can be associated with HTN crisis d/t increased sympathetic activity
Methyldopa needs WHAT to be effective?
converted to its active metabolite (methylnorepinephrine)
What is the site of action of carbonic anhydrase inhibitors?
proximal tubule
MOA of carbonic anhydrase inhbitors:
- block sodium bicarbonate reabsorption
- cause sodium bicarb diuresis
SE of carbonic anhydrase inhibitors:
- hyperchloremic metabolic acidosis
- renal stones
- renal K+ wasting
Clinical indications for carbonic anhydrase inhibitor use:
- urinary alkalization
- metabolic alkalosis
- glaucoma
Clinical indications for osmotic diuresis use:
- increase urine volume
- reduce ICP or IOP
Classification and effects of Mannitol:
- osmotic diuretic
- extracts water from intracellular compartment
SE of Mannitol:
- CHF complications
- pulmonary edema
- HA
- N/V
- dehydration
- hypernatremia
Where do osmotic diuretics work in the kidney?
proximal tubule and descending loop of Henle
Loop diuretic site of action:
ascending loop of Henle
Loop diuretic MOA:
selectively inhibits Na+, K+, and Cl- reabsorption through competition for the Cl- binding site
Clinical indications for loop diuretic use:
- pulmonary edema/edema in general
- acute hypercalcemia
- enhance K+ excretion in renal failure
Toxicity effects of loop diuretics:
- hypokalemic metabolic alkalosis
- ototoxicity
- hyperuricemia
What drug class is Bumtanide?
loop diuretic
(40x more potent than Lasix)
MOA of thiazide diuretics:
- inhibit reabsorption of Na+ and Cl- from distal tubule
- enhance Ca2+ reabsorption in distal convoluted tubule
Site of action of thiazide diuretics:
distal tubule and distal convoluted tubule
Clinical indications for thiazide diuretics:
- HTN
- CHF
- nephrolithiasis
- nephrogenic diabetes insipidus
Adverse effects of thiazide diuretics:
*hyponatremia
- hypokalemia metabolic alkalosis
- impaired carb tolerance (hyperglycemia, hyperlipidemia)
Contraindications to thiazide diuretic use:
- hepatic cirrhosis
- borderline renal failure
- CHF
Thiazide diuretics share cross sensitivity with which drug class?
sulfonamides
2 examples of thiazide diuretics:
- hydrocholorothiazide
- cholorothiazide
Where is the only site in the nephron that membrane water permeability can be regulated?
collecting tubule
*site of mineral corticoid effects
Site of action of K+ sparing diuretics:
cortical collecting tubule and late distal tubule
MOA of K+ sparing diuretics:
- antagonize effects of aldosterone
- reduce Na+ in collecting ducts and tubules
Which class of diuretics is used for mineral corticoid management?
K+ sparing
Toxicity risks of K+ sparing diuretics:
- hyperkalemia
- hyperchloremic metabolic acidosis
- acute renal failure
- kidney stones
Describe Spirinolactone:
(K+ sparing diuretic)
synthetic steroid that acts as a single diuresis for ascites & liver failure
