Module 3.1: ANTI-HYPERTENSIVE (ANTI-HPN) Flashcards by He LP

Normal bp

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Prehypertension

120–135/80–89

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Hypertension

≥ 140/90

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Stage 1

140–159/90–99

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Stage 2

≥ 160/100

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No specific cause can be determined
investigation of autonomic nervous system function, baroreceptor reflexes, the RAAS, and the kidney has failed to identify a single abnormality as the cause of increased peripheral vascular resistance

ESSENTIAL/ PRIMARY HTN

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Specific cause identified
Possible causes: renal artery constriction, coarctation of the aorta, pheochromocytoma, Cushing’s disease, and primary aldosteronism.

SECONDARY HTN

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BP is maintained by three anatomic sites:

o Arterioles
o postcapillary venules (capacitance vessels)
o heart

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…contributes to maintenance of blood pressure by regulating the volume of intravascular fluid (triggering the juxtaglomerular aparatus)

kidneys

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…mediated by autonomic nerves, act in combination with humoral mechanisms, including RAAS, to coordinate those anatomical sites’ functions and to maintain normal blood pressure

Baroreflexes

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responsible for rapid, moment-to-moment adjustments in blood pressure: transition from a reclining to an upright posture
Central sympathetic neurons arising from the vasomotor area of the medulla are tonically active

Postural Baroreflex

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stretch of the vessel walls brought about by the internal pressure (arterial blood pressure).

Carotid baroreceptors:

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…causes (1) direct constriction of resistance vessels and (2) stimulation of aldosterone synthesis in the adrenal cortex ->increases renal sodium absorption and intra- vascular blood volume

Angiotensin II

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…regulate water reabsorption by the kidney

Vasopressin (posterior pituitary gland)

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Prehypertension

120–135/80–89

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Hypertension

≥ 140/90

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Stage 1

140–159/90–99

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Stage 2

≥ 160/100

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No specific cause can be determined
investigation of autonomic nervous system function, baroreceptor reflexes, the RAAS, and the kidney has failed to identify a single abnormality as the cause of increased peripheral vascular resistance

ESSENTIAL/ PRIMARY HTN

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Specific cause identified
Possible causes: renal artery constriction, coarctation of the aorta, pheochromocytoma, Cushing’s disease, and primary aldosteronism.

SECONDARY HTN

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BP is maintained by three anatomic sites:

o Arterioles
o postcapillary venules (capacitance vessels)
o heart

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…contributes to maintenance of blood pressure by regulating the volume of intravascular fluid (triggering the juxtaglomerular aparatus)

kidneys

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…mediated by autonomic nerves, act in combination with humoral mechanisms, including RAAS, to coordinate those anatomical sites’ functions and to maintain normal blood pressure

Baroreflexes

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responsible for rapid, moment-to-moment adjustments in blood pressure: transition from a reclining to an upright posture
Central sympathetic neurons arising from the vasomotor area of the medulla are tonically active

Postural Baroreflex

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MECHANISM OF ACTION:  Reduction of HR and CO  CNS effect  Inhibition of renin release  Reduction in venous return and plasma volume  Reduction in peripheral vascular resistance  Reduction in vasomotor tone  Improvement in vascular compliance  Resetting of baroreceptor levels  Effects on prejunctional B receptors, reduction in NE release  Attenuation of pressor response to catecholamines with exercise and stress (newer generation decrease in ADRS due to B1 selectivity; B1 is the adrenergic receptor in the heart)

BETA BLOCKERS {-OLOL}

...causes (1) direct constriction of resistance vessels and (2) stimulation of aldosterone synthesis in the adrenal cortex ->increases renal sodium absorption and intra- vascular blood volume

Angiotensin II

...regulate water reabsorption by the kidney

Vasopressin (posterior pituitary gland)

Normal bp

Goal of Anti-HTN: | 1. REGULATE CO

Tachycardia -> Dec filling time -> Dec stroke volume -> Dec cardiac output

Goal of Anti-HTN: | 2. PERIPHERAL RESISTANCE

muscle relaxation -> arteries dilatation, fall in Peripheral Resistance [PR], then BP goes down

right part of the heart; blood returning to the heart; aka degree of distention particularly your right atrium

Preload

anything that decrease venous return

preload unloaders

decrease vasoconstriction in arterioles and arteries

Afterload unloaders

lower blood pressure by depleting the body of sodium and reducing blood volume

Diuretics

ower blood pressure by reducing peripheral vascular resistance, inhibiting cardiac function, and increasing venous pooling in capacitance vessels.

Sympathoplegic agents

reduce pressure by relaxing vascular smooth muscle, thus dilating resistance vessels and—to varying degrees—increasing capacitance as well

Direct vasodilators

 Appropriate for the treatment of arterial HTN, esp in patients who have concomitant ischemic heart disease, HF or arrhythmias

BETA BLOCKERS {-OLOL}

 They are highly heterogenous with respect to various properties  They reduce mortality, nonfatal re-infarction rates and improve clinical outcomes in patients with stable ventricular dysfunction who are receiving conventional HF treatment

BETA BLOCKERS {-OLOL}

INDICATION: - Treatment for arterial hypertension; especially in concomitant ischemic heart failure and arrhythmia  would not only control pressure, also decrease ischemia by decreasing O2 demand;  arrhythmia: block electric conduction>reduction in heart rate

BETA BLOCKERS {-OLOL}

improve survival after MI

METOPROLOL, CARVEDILOL

 MOA: reduce arterial pressure by dilating both resistance and capacitance vessels  DOC for Pt with HTN due to BPH

ALPHA BLOCKERS

...lower BP by blocking postsynaptic vasoconstrictor effects of Norepinephrine

Selective Alpha1 adrenergic antagonists

...cause balanced arterial and venous dilation, with no increase in CO

Hemodynamically, selec a1 receptor inihibitors

[ALPHA BLOCKERS] ADVERSE DRUG REACTION: | Tend to cause greater BP lowering in the upright compared to supine position

ORTHOSTATIC HYPOTENSION]

Non-selective alpha blockers given for patients diagnosed with pheochromocytoma

PRAZOCIN, TAMSULOSIN]

...reduce BP by decreasing SNS outflow, systemic vascular resistance and HR

Central alpha 2 sympathetic agonists

...is an agonist for both central a2 and II-imidazoline receptors

CLONIDINE

...deplete nerve terminal with NE, decrease reflex peripheral arterial and venous constriction, and predispose to orthostatic hypotension

Peripheral sympatholytics

ADR: orthostatic hypotension; rebound hypertension especially when you suddenly stopped using the drug IND: acute hypertension

CLONIDINE

ADR: x’ss tachycardia causing increase in myocardial o2 demand

Nifedipine

IND: pregnancy induced hypertension

Alpha methyldopa [aldomet]

[ACE-Inhibitors] | ADVERSE DRUG RESPONSE

- in pt with hypovolemia leads to severe hypotension; - acute renal failure (particularly in patients with bilateral renal artery stenosis or stenosis of the renal artery of a solitary kidney), - dry cough sometimes accompanied by wheezing, and - angioedema

ADR: orthostatic hyptension, sedation, increase prolactin production (M and F)

METHYLDOPA

 Effective work primarily by selective blockade of AT-I receptors; leading to the same effect as ACE-I  Effective as monotherapy but when combined with other antihypertensive agents, are effective in virtually all populations

ANGIOTENSIN (AT) RECEPTOR BLOCKERS [ARB] {-SARTAN}

Contraindication: depressive pt; TCA may block antiHTN effect of...

CLONIDINE

inhibits the release of norepinephrine from sympathetic nerve endings

ADRENERGIC NEURON-BLOCKING AGENT

ADR: HYPOTENSION, delayed or retrograde ejaculation (returns back into the bladder), diarrhea, HTN crisis among pt with pherochromocytoma

ADRENERGIC NEURON-BLOCKING AGENT

CI:TCA, may lead to severe HTN crisis

ADRENERGIC NEURON-BLOCKING AGENT

for treatment of patients with HF and Chronic kidney diseases

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM [RAAS] BLOCKERS

- increases BK [bradykinin] concentration – leading to cough [remember patho: bradykinin is one of the chemicals release by neutrophils during asthmatic attacks; this causes irritation to the bronchial airways causing cough as ADR] - Long term use may lead to angiotensin escape

ACE INHIBITORS [ACE-I] {- PRIL}

With the exception of_____ & _____, ACE-I are prodrugs, which improves their absorption before hydrolysis to active diacids in the liver or intestines [EX. ENALAPRIL  ENALAPRILAT the active metabolite]

LISINOPRIL and CAPTOPRIL

ACE-I drug whose action could be cancelled by ICATIBANT

CAPTOPRIL

ACE-I drug which is also a lysine derivative of enalaprilat

LISINOPRIL

ACE-Inhibitors are distinguished by...

sulfhydryl (captopril), phosphinyl (fosinopril), or carboxyl side groups

chronic kidney disease patients taking ACE-Inhibitors would lead to...

HYPERkalemia

[ACE-Inhibitors] | ADVERSE DRUG EFFECT

[ACE-Inhibitors] | CONTRAINDICATION

pregnancy

ANGIOTENSIN (AT) RECEPTOR BLOCKERS [ARB] {-SARTAN}

...act by binding selectively to the AT-I receptor

ANGIOTENSIN (AT) RECEPTOR BLOCKERS [ARB] | - competitive (IRBESARTAN, VALSARTAN) or - insurmountable (CANDESARTAN or LOSARTAN)

[ARB] | ADVERSE DRUG RESPONSE

ERECTILE DYSFUNCTION

Renin converts angiotensinogen to angiotensin I. Block by _____ blocks the sequence at its start.

aliskiren

ACE is responsible for activating angiotensin I to angiotensin II and for inactivating bradykinin, a vasodilator normally present in very low concentrations. ______ block this enzyme thus decreases the concentration of a vasoconstrictor and increases the concentration of a vasodilator.

ACE-I

The ___________ lack the effect on bradykinin levels, which may explain the lower incidence of cough observed with these agents.

AT1 receptor antagonists

MOA: Block Na/K/2Cl transporter in renal loop of Henle EFFECT: Reduce blood volume and poorly understood vascular effects + greater efficacy INDICATION: Severe hypertension, heart failure

Loop diuretics: | Furosemide

These CCBs are more CARDIOSELECTIVE

VERAPAMIL AND DILTIAZEM

These CCBs are more VASOSELECTIVE

DIHYDROPYRIDINE

- opening of potassium channels in smooth muscle membranes by minoxidil sulfate, the active metabolite - arteriolar dilation - PO drug/orally active - ADR: Headache, sweating, hypertrichosis

MINOXIDIL

- arterial dilation; given with nitrates for HF and HTN patients - in Pt with IHD, may lead to reflex tachycardia and sympathetic stimulation may provoke angina or ischemic arrhythmias - PO drug/orally active - ADR: nausea, anorexia, palpitations, sweating, and flushing

HYDRALAZINE

- treating hypertensive emergencies as well as severe heart failure - BOTH arteries and vein dilatation - activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme resulting to an increase in cGMP leading to smooth muscle relaxation

NITROPRUSSIDE

- rapid fall in systemic vascular resistance and mean arterial blood pressure - MOA: opening potassium channels and stabilizing the membrane potential at the resting level - arteriolar dilatation

DIAZOXIDE

ADR: excessive hypotension, resulting from the recommendation to use a fixed dose of 300 mg in all patients

DIAZOXIDE

ADR: accumulation of cyanide; metabolic acidosis, arrhythmias, excessive hypotension, and death

NITROPRUSSIDE

- peripheral arteriolar dilator used for hypertensive | - emergencies and postoperative hypertension

FENOLDOPAM

- ADR: reflex tachycardia, headache, and flushing | - CI: glaucoma Pt – increases IOP more

FENOLDOPAM

Direct Renin Inhibitors

ALISKIREN

Dopamine agonists

FENOLDOPAM

MOA: Block Na/Cl transporter in renal distal convoluted tubule EFFECT: Reduce blood volume and poorly understood vascular effects INDICATION: Hypertension, mild heart failure

Thiazides: | Hydrochlorothiazide

MOA: Block Na/K/2Cl transporter in renal loop of Henle EFFECT: Reduce blood volume and poorly understood vascular effects + greater efficacy INDICATION: Severe hypertension, heart failure

Loop diuretics: | Furosemide

MOA: Releases nitric oxide EFFECT: Powerful vasodilation INDICATION: Hypertensive emergencies ROA: Parenteral • short duration TOXICITY: Excessive hypotension, shock

Nitroprusside

SYMPATHOPLEGICS, CENTRALLY ACTING Toxicity: | hemolytic anemia

methyldopa

also used in withdrawal | from abused drugs

Clonidine

MOA: Blocks vesicular amine transporter in noradrenergic nerves and depletes transmitter stores EFFECTS: Reduce all sympathetic effects, especially cardiovascular, and reduce blood pressure INIDICATION: Hypertension but rarely used TOXICITY: psychiatric depression, gastrointestinal disturbances

Reserpine

MOA: Interferes with amine release and replaces norepinephrine in vesicles EFFECTS: Reduce all sympathetic effects, especially cardiovascular, and reduce blood pressure INIDICATION: Hypertension but rarely used TOXICITY: Severe orthostatic hypotension; sexual dysfunction

Guanethidine

MOA: Selectively block α1 adrenoceptors EFFECTS: Prevent sympathetic vasoconstriction • reduce prostatic smooth muscle tone INDICATION: Hypertension • benign prostatic hyperplasia TOXICITY: Orthostatic hypotension

ALPHA BLOCKERS • Prazosin • Terazosin • Doxazosin

Nonselective prototype BETA blocker

Propranolol

Very widely used b1-selective blocker

Atenolol

MOA: Block β1 receptors EFFECTS: Prevent sympathetic cardiac stimulation • reduce renin secretion INDICATION: Hypertension • heart failure

BETA BLOCKERS • Metoprolol, others • Carvedilol

also blocks α receptors

carvedilol

MOA: Nonselective block of L-type calcium channels EFFECTS: Reduce cardiac rate and output • reduce vascular resistance INDICATION: Hypertension, angina, arrhythmias

* Verapamil | * Diltiazem

MOA: Block vascular calcium channels > cardiac calcium channels EFFECTS: Reduce vascular resistance INDICATION: Hypertension, angina

Nifedipine, amlodipine, other dihydropyridines

MOA: Causes nitric oxide release EFFECTS: Vasodilation • reduce vascular resistance • arterioles more sensitive than veins • reflex tachycardia INDICATION: Hypertension TOXICITY: Angina, tachycardia • Lupus-like syndrome

Hydralazine

MOA: Metabolite opens K channels in vascular smooth muscle INDICATION: Hypertension • also used to treat hair loss TOXICITY: Angina, tachycardia • Hypertrichosis

Minoxidil

MOA: Releases nitric oxide EFFECT: Powerful vasodilation INDICAtion

Nitroprusside

MOA: Activates D1 receptors EFFECT: Powerful vasodilation INDICATION: Hypertensive emergencies ROA: Parenteral • short duration TOXICITY: Excessive hypotension, shock

Fenoldopam

MOA: Opens K channels EFFECT: Powerful vasodilation INDICATION: Hypertensive emergencies ROA: Parenteral • short duration TOXICITY: Excessive hypotension, shock

Diazoxide

MOA: α, β blocker EFFECT: Powerful vasodilation INDICATION: Hypertensive emergencies ROA: Parenteral • short duration TOXICITY: Excessive hypotension, shock

Labetalol

MOA: Inhibit angiotensin converting enzyme EFFECTS: Reduce angiotensin II levels • reduce vasoconstriction and aldosterone secretion • increase bradykinin INDICATION: Hypertension • heart failure, diabetes ROA: Oral TOXICITY: Cough, angioedema • hyperkalemia • renal impairment • teratogenic

(ACE-I) Captopril

MOA: Block AT1 angiotensin receptors EFFECTS: Reduce angiotensin II levels • reduce vasoconstriction and aldosterone secretion INDICATION: Hypertension • heart failure ROA: Oral TOXICITY: less Cough, angioedema • hyperkalemia • renal impairment • teratogenic

(ARBs) Losartan

MOA: Inhibits enzyme activity of renin EFFECT: Reduces angiotensin I and II and aldosterone INDICATION: Hypertension ROA: Oral TOXICITY: Hyperkalemia, renal impairment • potential teratogen

RENIN INHIBITOR | • Aliskiren