Question | Answer |
Diuretics | Decrease renal Na reabsorption which reduces water reabsorption |
Thiazide Diuretics
Prototype | Hydrochlorothiazide |
Thiazide Diuretic: HCTZ Site of Action | Site of action: Distal Tubule |
Thiazide Diuretic: HCTZ Mode of Action | MOA- Competitive antagonism of Na/Cl cotransporter to decrease intravascular volume and direct vasodilatory effect |
Thiazide Diuretic: HCTZ AE | AE: LOW HYPOkalemia, hyperuricemia, hyperglycemia, dehydration. Less effective if CrCL |
Potassium-Sparing Diuretics Prototypes | Triamterene, Amiloride (Combo HCTZ/TMT- Maxide) |
Potassium-Sparing Diuretics: Triamterene, Amiloride Site of Action | Site of Action: Collecting Duct |
Potassium-Sparing Diuretics: Triamterene, Amiloride MOA | MOA: Na channel blockade; increase reabsorption of K |
Potassium-Sparing Diuretics: Triamterene, Amiloride AE | HYPERkalemia (HIGH K) |
Beta Blockers do what? | antagonism of catecholamines at Beta receptors
Decrease CO by Decreasing HR and contractility
(initial compensatory increase in PVR)
decrease PVR longterm = decrease renin
produces resting bradycardia and reduction in exercise-induced tachycardia |
Beta Blockers AE | Acute asthma, wheezing
symptomatic bradycardia, fatigue, depression, HYPOglycemia, sexual dysfunction, detrimentally affects lipid profile
Avoid sudden withdrawl |
Non-selective Beta Blocker Prototype | Prototype: Propranolol (Inderal) |
Non-selective Beta Blocker
Prototype: Propranolol (Inderal)
MOA | MOA: antagonizes catecholamines at B1 and B2 receptors, inhibition of sympathetically induced renin secretion |
Non-selective Beta Blocker
Prototype: Propranolol (Inderal)
Contraindications | CI in pt with asthma |
Non-selective Beta Blocker
Prototype: Propranolol (Inderal)
Hepatically metabolized by: | Hepatically metabolized by CYP2D6, 2C19 |
Beta 1 Selective Beta Blockers Prototypes | Metoprolol (Lopressor, Toprol XL), atenolol, bisoprolol, esmolol
Dose-dependent cardioselectivity
Atenolol less lipid-soluble and Renally excreted unchanged
Dose-dependent cardioselectivity
Metoprolol
Hepatically metabolized by CYP2D6 |
Partial B-Blockers (mixed agonist/antagonist) | Acebutolol, carteolol, penbutolol, pindolol |
Partial B-Blockers
Acebutolol, carteolol, penbutolol, pindolol
MOA: | MOA: ISA (intrensic sympathemiminic Activity)
-Less decrease in HR and CO
-Agonist when Sympathetic tone is low (less resing bradycardia
-antagonist when SNS is high; still blocks exercise-induced tachycardia |
Mixed α1/β1/2 Blockers Prototypes | Prototypes: Labetalol and Carvedilol |
Mixed α1/β1/2 Blockers Carvedilol (Coreg) | S(-) isomer - non-selective β-blockade
R(+) isomer - α-blockade
Primary use is in heart failure |
Mixed α1/β1/2 Blockers Labetalol (Normodyne, Trandate) | 3:1 β to α antagonism (orally)
Used IV to treat hypertensive emergencies |
α1- Blockers Protype | Prototype Prazosin |
α1- Blockers Protype Prototype Prazosin
MOA | MOA: Inhibitor Peripherial vasomotor tone, reducing VC and decreaseing SVR |
α1- Blockers Protype Prototype Prazosin
Precautions | Precaution: “first dose effect” – postural hypotension |
Can cause Na+/H2O retention when given without diuretic | Prazosin-
Alpha 1 Blocker |
Prazosin-
Alpha 1 Blocker Used to treat | BPH |
Prazosin-
Alpha 1 Blocker hepatically metabolized by | hepatically metabolized by non-cyp |
Centrally Acting Agents MOA | MOA Reduce sympathetic outflow from vasopressor centers in the brain stem |
Centrally Acting Agents AE | AE: Sedation
Impaired concentration
Nightmares
Depression
Vertigo
EPS
Lactation in men |
Centrally Acting Agents Prototypes | Protypes: Methyldopa (Aldomet)and Clonidine |
Converted to alpha-methyldopamine and alpha-methylnorepinephrine in CNS | Centrally Acting Agents
Methyldopa (Aldomet) |
Stimulates central α2 leading to a reduction in the activity of the vasomotor center | Centrally Acting Agents
Methyldopa (Aldomet) |
Renal blood flow maintained – good in renal insufficiency
Recommended for pregnant women | Centrally Acting Agents
Methyldopa (Aldomet) |
Centrally Acting Agents Clonidine
Site of Action | Site of action: CNS non-adenergic binding sites and α2 receptor agonism |
Centrally Acting Agents Clonidine | BP reduction from decreased CO due to decreased HR and peripheral resistance
Use with TCAs block effect
Rebound hypertension with abrupt cessation
PO or transdermal patch available
50/50 hepatic metabolism and renal excretion |
Mixed α1/β1/2 Blockers Carvedilol (Coreg) is primarly used when the pt has what disease? | Primarily used in heart failure |
Mixed α1/β1/2 Blockers Labetalol is used IV to treat what? | Used IV to treat hypertensive emergencies |
beneficial for patients with renal insufficiency? | Centrally Acting Agent Methyldopa (Aldomet)is beneficial for a pt with HTN and what disease |
What HTN drug/class is recommended for pregnant women | Centrally Acting Agent Methyldopa (Aldomet) |
ACE Inhibitors Site of action: | Site of action: ACE in endothelium |
ACE Inhibitors | Lisinopril, captopril, ramipril, enalapril, fosinopril, quinapril, benazepril |
ACE Inhibitors MOA | MOA: blocks ACE conversion of angiotensin I to angiotensin II; blocks inactivation of bradykinin |
Ramipril, enalapril, benazepril, fosinopril are prodrugs. What class and what does prodrug mean? | ACE Inhibitors; prodrugs mean that they have to be activated in their active form to produce an affect. |
ACE Inhibitors
Beneficial for | Beneficial for diabetics with proteinuria (and or HTN) |
ACE Inhibitors Adverse effects | Adverse effects
Hyperkalemia, angioedema, cough (bradykinin) |
inhibiting Bradykinin and substance P will result in the side effect know as what? | dry cough
(caused why) |
ACE Inhibitors
Contraindications | Contraindications
Pregnancy, renal artery stenosis |
ACE Inhibitors | Comment: NSAIDs may impair effects by blocking bradykinin-mediated vasodilation |
Angiotensin Receptor Blockers (ARBs) | Losartan, valsartan, candesartan, irbesartan, telmisartan, eprosartan |
Angiotensin Receptor Blockers (ARBs)
Site of action: | Site of action: angiotensin II receptors |
Angiotensin Receptor Blockers (ARBs)
MOA | MOA: Competitive binding results in decreased peripheral vasoconstriction |
No effect on ACE or bradykinin
Can cause hyperkalemia
Contraindication: pregnancy | Angiotensin Receptor Blockers (ARBs)
Losartan, valsartan, candesartan, irbesartan, telmisartan, eprosartan |
Direct Renin Inhibitors
Site of action: | Site of action: renin binding pocket |
Direct Renin Inhibitors
MOA | Mechanism of action: prevents conversion of angiotensinogen to angiotensin I by renin |
Direct Renin Inhibitors
Okay in Pregnancy??? | Contraindication: pregnancy |
2 classes of CCB | Dihydropyridines and Non-Dihydropyridines |
CCB Calcium Channel Blockers prototypes | Amlodipine, felodipine, nifedipine ER, nicardipine, nimodipine |
Calcium Channel Blockers
Dihydropyridines
MOA: | MOA: Block entry of extracellular calcium which is necessary for contraction
Selectivity for smooth muscle over cardiac muscle
Skeletal muscle unaffected since contraction not dependent on extracellular Ca |
Calcium Channel Blockers
Dihydropyridines
AE: | Adverse effects - peripheral edema, dizziness, headache, flushing, reflex tachycardia |
Calcium Channel Blockers
Dihydropyridines
Metabolized by | CYP3A4 |
Calcium Channel Blockers
Non-Dihydropyridines | Verapamil, diltiazem |
Calcium Channel Blockers
Non-Dihydropyridines
MOA | MOA: Blocks extracellular calcium entry
SA and AV nodal tissue, other cardiac and arterial smooth muscle |
Calcium Channel Blockers
Non-Dihydropyridines
Adverse effects: | Adverse effects: conduction disturbances
Diltiazem: ha, bradycardia, edema, heart failure
Verapamil: constipation, dizziness, heart failure |
Calcium Channel Blockers
Non-Dihydropyridines | Substrates and inhibitors of CYP3A4 |
NO formation
K+ channel openers
D1 stimulation | Vasodilators |
Hydralazine
Vasodilators
MOA | MOA
Stimulates NO synthesis from endogenous sources in endothelial cells
Dilates arterioles only |
Well-absorbed but rapidly metabolism by first-pass
Variable effect due to variable acetylation | Hydralazine
Vasodilators |
Hydralazine
Vasodilators
AE | Adverse effects
SLE-like syndrome with higher doses |
Nitroprusside
Vasodilators
MOA | MOA
Gives off NO itself which then enters smooth muscle
Arterial AND venous dilation |
Nitroprusside
Vasodilators
Duration of action | IV only
Hypertensive emergency
Short duration of action |
Nitroprusside
Vasodilators
AE | Adverse effects - cyanide toxicity |
Nitroprusside
Vasodilators AE CAN BE ENHANCED IF PT HAS WHAT INSUFFICIENCY? WHAT AE? | AE: Cyanide toxicity
Insufficiency: liver and kidney |
Fenoldopam
Vasodilators
MOA | MOA:
D1-dopamine receptor agonism
Decreased PVR and increased renal blood flow, diuresis, natriuresis
Minimal adrenergic effects |
Fenoldopam
Vasodilators
is used at what times | Use: hypertensive emergency |
Minoxidil
Vasodilators
MOA | K+ channel opener
Produce hyperpolarization of smooth muscle membrane reducing excitation and contraction = vasodilation |
Minoxidil
Vasodilators
Half-life | Half-life of 4 hours but active metabolite can cause persistence of hypotensive effect for 24 hours |
Minoxidil
Vasodilators
AE | Adverse effects: hypertrichosis |
What is the first-line therapy in tx HTN? | First-line therapy is thiazide diuretic unless there is a “compelling indication.” |
T/F: In many cases, it is more effective to add a second agent from a different drug class than to increase the dose of the first agent. | True |
First-line therapy is thiazide diuretic unless there is a “compelling indication.”
What are the Complling Indications | Heart failure
MI
High CVD risk
DM
Chronic Kidney Disease
Recurrent stroke prevention
Isolated Systolic HTN |
Rx's Heart Failure | Thiazide diuretic, β-blocker, ACEI, ARB, aldosterone antagonist |
Rx's MI | β-blocker, ACEI, aldosterone antagonist |
Rx's High CVD Risk | Thiazide, β-blocker, ACEI, CCB |
Rx's DM | Thiazide diuretic, β-blocker, ACEI, ARB, CCB |
Rx's Chronic kidney disease | ACEI or ARB |
Rx's Recurrent stroke prevention: | Thiazide diuretic, ACEI |
Rx's Isolated systolic hypertension: | Thiazide diuretic, CCB |
HTN Urgency | Diastolic pressure >120 with evidence of progressive end organ damage
Goal: decrease DBP to 100-105 within 24 hrs
Clonidine |
Hypertensive Crisis | Diastolic pressure >120 with evidence of end organ failure
Goal: decrease DBP 100-105 asap
Nitroprusside, NTG, Labetalol, Fenoldopam |
Diuretics
Indications | Heart Failure
Systolic HTN |
Diuretics
CI | Gout |
BB
Indications | Migraines
tachyarrhythmias |
BB
CI | asthma
heart block |
A-blockers
Indications | BPH |
A-Blockers
CI | Heart Failure |
CCBs
Indications | Systollic HTN |
CCBs
CI | Heart Block |
ACEIs
Indications | Heart Failure
Previous MI
Diabetic Nephropathy |
ACEIs
CI | RAS
Pregnancy
HYPERkalemia |
ARBs
Indications | ACEI-associated cough
Diabetic nephropathy
Heart Failure |
ARBs
CI | RAS
Pregnancy
HYPERkalemia |
Down-regulation of sympathetic tone | β1-blockers
α1-blockers
α2-agonists |
Modulation of vascular smooth tone | Calcium-channel blocker
Potassium-channel openers |
Reduction of intravascular volume | Diuretics |
Modulation of renin-angiotensin-aldosterone system | ACE Inhibitors
ARBs |