Cardiovascular III - Treatment of Hypertension Flashcards Preview

Pharmacology > Cardiovascular III - Treatment of Hypertension > Flashcards

Flashcards in Cardiovascular III - Treatment of Hypertension Deck (73):

Definition of hypertension?

Hypertension is the key risk factor in ____ and a major risk factor for?

Consistent resting arterial BP in excess of 140/90

Stroke; myocardial ischemia, MI, cardiac arrhythmias, and the progression of atherosclerosis


Two complete clinical consensus?

Goal of physician treating hypertension?

a. Failure to treat will cause harm

b. Sucessful treatment of hypertension is a benefit

Get the pressure down any way you can


First line medical treatment of hypertension?

NOT drugs: employs weight loss, excercise, salt restriction, cessation of smoking and limiting alcohol consumption


First line pharmacological treatment:

What are the 5 first line agents?

Thiazide Diuretics

Beta blockers

Alpha 1 blockers

ACE Inhibitors

Calcium channel blockers


Thiazide Diuretics:

Why are they used so widely? (3 main reasons)

a. They lower blood pressure by themselves

b. They potentiate the actions of other antihypertensive agents

c. ***They reduce the incidence of stroke associated with hypertension


Thiazide Diuretics:

Mechanism of action:

1. Initial effects?

2. What happens after 6 weeks?


1. Effects are initially related to diuresis and natriuresis with resultant decrease in ECVF (extracellular fluid volume) --> decrease in CO

2. Volume and CO return to normal


Thiazide Diuretics:

Mechanism of action:

What are the chronic effects?

Reduction of vascular resistance


Thiazide Diuretics:

Side effects:

What are the three side effects?


Hypokalemia, glucose intolerance, hyperlipidemia


Thiazide Diuretics:

Side effects: Hypokalemia

1. What pathology is associated with hypokalemia?

2. How can this be managed?

1. ventricular ectopy, ventricular tachycardia, and ischemic ventricular fibrillation

2. Lower the dose, K+ supplement, or K+ sparing diuretic


Thiazide Diuretics:

Side effects: Glucose intolerance

How is glucose intolerance generated?

Hypokalemia suppresses insulin secretion


Thiazide Diuretics:

Side effects: Hyperlipidemia

What occurs to the lipid profiles?


INCREASED cholesterol, triglycerides, and LDL


Thiazide Diuretics:

Side effects:

1. May increase mortality in what patients?

2. What serious event is positively correlated with thiazide diuretic dose?

1. Coronary artery disease patients: but more likely in geriatric hypertensive patients and when K+ wasting is associated with diuretic administration

2. Sudden cardiac death


Thiazide Diuretics:

Current recommendations:

1. Low doses of what drugs are beneficial either alone or in combination with other drugs?

2. What is important to note about greater doses?

1. Chlorthalidone or hydrochlorothiazide

2. It will cause greater diuresis but NOT greater antihypertensive effect while at the same time will produce K+ wasting and hypokalemia


Thiazide Diuretics:

1. Why are loop diuretics NOT recommended as first line agents?

2. Why are K+ sparing diuretics NOT recommended as first line agents?

1. Single doses are potent but short acting and increasing the dose to twice a day greatly increases risk of side effects

2. Side effects


Beta Adrenergic Antagonists:

1. What beta-adrenergic antagonists are effective? What grades of hypertension?

2. They reduce what two adverse events associated with hypertension?

1. ALL are effective for ALL grades of hypertension

2. CV disease and death


Beta Adrenergic Antagonists:

1. Examples of antagonists without intrinsic sympathomimetic activity (ISA)?



1. Atenolol, Betaxolol, Bisoprolol, Metoprolol, Nadolol, Propranolol, Timolol



Beta Adrenergic Antagonists:

When are beta adrenergic agonists without ISA recommended? Why?

After MI because of long term cardioprotective effects


Beta Adrenergic Antagonists:

When are beta-adrenergic antagonists the PREFERRED DRUG OF CHOICE?

For hypertensive patients with MI, MYOCARDIAL ISCHEMIA, or HEART FAILURE


Beta Adrenergic Antagonists:

4 proposed mechanisms of action?


2. DECREASED plasma renin activity

3. Central hypotensive activity

4. Presynaptic INHIBITION of sympathetic nerve activity


Beta Adrenergic Antagonists:

Without ISA initially DECREASES ___ and ___ and cause a ____ INCREASE in ___ ___ ___.

Inpatients that see a BP lowering effect with these drugs their resistance eventually?

HR; CO; reflex; periperal vascular resistance


Resistance eventually returns to normal or lower than normal values (it decreases)


Beta Adrenergic Antagonists:

Beta adrenergic antagonists WITH ISA produce ____ DECREASE ___ and ___ compared to those without ISA. Their anti-hypertensive effects are correlated with lowering of ___ ___ below normal through activation of ____ receptors.

less; HR; CO; vascular resistance; beta2


Beta Adrenergic Antagonists:

Side effects:

1. Severe ____ and decreased ___

2. What does extremity vasoconstriction cause?

3. What can specifically occur with patients on non-selective beta blockers?

4. What can specifically occur in beta blockers without ISA?

1. bradycardia; CO

2. cold extremities

3. Epinepherine mediated hypertension and bradycardia during hypoglycemia

4. Increased triglycerides and decreased HDL


Beta Adrenergic Antagonists:


Patients with diabetes, asthma, SA/AV node conduction disorders, or with drugs that reduce AV conduction


Beta Adrenergic Antagonists:

Why are they contraindicated in diabetics?

Why are they contraindicated in asthmatics?

Beta blockers prolong hypoglycemia after an insulin reaction. They exacerbate glucose intolerance


Beta blockers cause bronchoconstriction


Alpha 1 Antagonists:

1. Primarily ____ dilators. How?

2. NOT first choice monotherapy: when are they used?

1. Arterial (but still provide some venodilation) by antagonizing catecholamine receptors

2. Alpha antagonists are used in combination with beta blockers when that agent and a diuretic cannot lower BP OR when beta blockers are contraindicated


Alpha 1 Antagonists:

Initially cause?

What are advantages of alpha 1 blockers?

Alpha 1 blockers initially cause reflex tachycardia and INCREASED plasma renin activity (return to normal over time)


Cause little postural hypotension (except after first dose) and do not adversely affect lipid profiles


Alpha 1 Antagonists:

Side effects?

Alpha 1 Antagonists have infrequent and mild side effects including dizziness, palpitations, headache, and lethargy


ACE Inhibitors:

These are effective even when what is not present?

What do they lower?

ACE Inhibitors are effective even if high renin levels are not present


ACE inhibitors lower TPR (unclear mechanism)


ACE Inhibitors:

They improve prognosis of what patients?

They blunt the rise in ___ and ___ loss following ___ administration and thus potentiate the anti-hypertensive effects of?

ACE Inhibitors improve the pronosis of patients with severe loss of left ventricular bunction

aldosterone; K+; diuretic; diuretics


ACE Inhibitors:

When are they PREFERRED? Why?

ACE Inhibitors are good for patients whose hypertension is complicated by DIABETES because they exert RENAL PROTECTIVE effects


ACE Inhibitors:

Side effects? What could be taken for the side effects? Example?

ACE inhibitors ahve few notable side effects. However, some cases present with cough and angioedema

Can be treated with an AII blocker such as Losartan


Calcium channel blockers:

Which class/drug should be avoided? Why?

Calcium channel blockers like DHPs/nifedipine should be avoided because their rapid onset and short action can cause risk of sudden cardiac death


K+ channel openers:




K+ channel openers:

When is it used? Why?

K+ channel openers are only used for hypertensive emergencies because of their undesireable side effects


K+ channel openers:

Mechanism of action:

How do they reduce BP? 

At the cellular level, action?

K+ channel openers relax vascular smooth muscle directly thus lower vascular resistance


They open ATP activated K+ channels resulting in hyperpolarization and causing inactivation of the Ca++ channels




K+ channel openers:

Side effects that are an extension of pharmacological effects?

Minoxidil can cause hypotension, dizziness, flushing, fluid retention, reflex tachycardia, and decrease renal perfusion


K+ channel openers:

Major unique side effect?

K+ channel openers can cause hypertrichosis (increased hair growth)


K+ channel openers:

What else can Minoxidil be used for?

Male pattern baldness (rogaine) due to hypertrichosis


Direct vasodilator:




Direct vasodilator:

Hydrazaline has been attributed to the stimulation of? or direct production of?


Preferentially dilates?

Hydrazaline stimulates EDRF or direct production of NO from the drug


Arteries over veins


Direct vasodilator:

These can only be used in conjunction with?

Duration of action?

Hydrazaline can only be used in conjunction with drugs that counteract sodium/fluid retention and that counteract reflex tachycardia


Up to 12 hours


Direct vasodilator:

1. Hydrazaline side effects?

2. Biggest drawback?

3. What is seen with long-term administration?

1. headache, hypotension, dizziness, and flushing

2. Hydrazaline has reflex activation of the SNS and fluid retention (is thus bad monotherapy)

3. Lupus syndrome (after more than 6 months)


Nitrodilators - Sodium Nitroprusside:

1. Actions are same as?

2. __ stimulated ___ mediated vasorelaxation

3. When is it used?

1. Nitric oxide

2. NO; cGMP

3. Sodium nitroprusside is used for hypertensive emergencies or to cause purposeful acute hypotension in surgery


Dopamine Receptor Agonists:




Dopamine Receptor Agonists:

1. Fenoldopam acts as ___ vasodilator

2. Duration of action?

3. Given for what?

1. Fenoldopam acts as an arterial vasodilator

2. Short duration

3. Fenoldopam is given for hypertensive emergencies (with poor renal perfusion) and post-operative hypertension.


Dopamine Receptor Agonists:

Fenoldopam side effects?

Contraindications? Why?

Similar to other direct vasodilators: flushing, tachycardia, headache, hypotension, dizziness 


Fenoldopam is contraindicated in patients with glaucoma because it increases IOP.


Catecholamine metabolism modifiers:

Two drugs?

alpha-methyltyrosine and methyldopa


Catecholamine metabolism modifiers:

Alpha-methyltyrosine seves as? and thus inhibits?

Alpha-methyltyrosine is a false substrate for tyrosine hydroxylase and inhibits synthesis of NE


Catecholamine metabolism modifiers:

Alpha-methyltyrosine reduces synaptic __ ____ and reduces effects on ___ end organs.


Clinical application?

Alpha-methyltyrosine reduces synaptic NE concentration and thus reduces effects on autonomic end organs


For severe hypertension associated with phochromocytoma


Catecholamine metabolism modifiers:

Methyldopa is metabolized to what? Where?

What does this metabolite do? What receptor?

Clinical application?

1. Methyldopa is metabolized to alpha-methylnorepinepherine in the brain

2. Alpha-methylnorepinepherine activates the central alpha2 receptors to lower arterial BP

3. Originally it was an antihypertensive but has since been replaced


Inhibitors of catecholamine storage/reuptake:

1. Eventually deplete vesicular stores of ___. 

2. What do these cause initially? Why is this important

1. NE

2. First displace NE from the nerve terminals causing a burst of NE mediated effects (indirect sympathomimetic effects) and this burst can be dangerous


Inhibitors of catecholamine storage/reuptake:

3 drug examples?

Guanethidine, Guanadrel, and Reserpine


Inhibitors of catecholamine storage/reuptake:

Guanethidine and Guanadrel:

What occurs with acute administration?

Guanethidine and Guanadrel when administered acutely acts as an indirect sympathomimetic because it displaces NE stored in the synaptic vesicles and results in a massive efflux of NO through the NET acting in reverse (there is too much NE for the MAO to handle); it thus floods the synapse causing a huge increase in sympathetic stimulation


Inhibitors of catecholamine storage/reuptake:

Guanethidine and Guanadrel:

What occurs when they are administered chronically?

Guanethidine and Guanadrel, when administered chronically, is concentrated in synaptic vessels and replaces NE. In addition the MAO degrades the small pool of NE that remains in the cytoplasm. 


Inhibitors of catecholamine storage/reuptake:

What is Guanadrel specific for?

Why are they no longer first choice agents?

Guanadrel is specific for peripheral adrenergic neurons


Guanethidine and Guanadrel are no longer first choice because of the effects of initial massive NE release


Inhibitors of catecholamine storage/reuptake:


Mecanism of action?

Reserpine irreversibly blocks the vesicular monoamine transporter in the nerve terminal and eventually depletes the terminal of its NE stores because MAO destroys free NE in the terminal. (cant package NE)


Inhibitors of catecholamine storage/reuptake:


What occurs if too much Reserpine is given?

What are the major side effects?

If too much Reserpine is diven the depletion process can be overwhelmed and force the NET to work in revers and essentially dump excessive NE out of the nerve terminal


MAJOR CNS side effects: can mimic paranoid schizophrenia, psychotic depression, and homocidal/suicidal ideation



Alpha-antagonists used for other pathologies:





1. Selectivity for what receptor? Action?

2. Clinical uses?

3. Adverse effects?


1. Tamsulosin has selectivity for alpha one receptors to relax muscles in the bladder neck and prostate

2. Treatment of urinary tract symptoms of enlarged prostate and good for hypertensive patients with BPH

3. dizziness, drowsiness, weakness, diarrhea, nasal congestion


Preferred and least preferred drugs for:

African heritage?


African - give diuretics (with ACEI or angiotensin receptor blocker (ARB)) or CCB. DO NOT give Beta blocker


Pregnancy - give methyldopa, labetalol (beta blocker), or hydrazaline. CONTRAINDICATED: ACEI, ARB, aliskiren


Preferred and least preferred drugs for:

Angina pectoris


Angina: give Beta blocker or CCB CONTRAINDICATED: hydrazaline and minoxidil


Asthma: give CCB, ACEI, or ARB CONTRAINDICATED: Beta blocker


Preferred Drug for:



MI - Beta blocker, ACEI, ARB, aldosterone antagonist


CHF - ACEI, ARB, Beta-blocker, thiazide diuretic


Preferred drugs for:

Stroke prevention?

Kidney disease?


Stroke prevention - Thiazide diuretic + ACEI/ARB


Kidney disease - ACEI or ARB


Preferred drugs for:



Diabetes - ACEI or ARB


BPH - alpha-blocker


Preferred drugs for:



Migraine: Beta-blocker, CCB


Osteoporosis - thiazide diuretic


Type of drug given to hypertensive patients with atrial fibrillation, supraventricular tachycardia, or sinus tachycardia?

non-ISA beta blocker, verapamil, or diltiazem


Type of drug given for hypertensive patients with irritable bowel (with diarrhea)?



Type of drug given for hypertensive patients with recurrent renal calculi?

Thiazide diuretics


Type of drug given for hypertensive patients with senile tremor, cardiac awareness, or glaucoma?



Multiple drug therapy:

Diuretics + ACE inhibitors = 

Diuretics + ACEI = potentiates antihypertensive action and controls excessive reflex AII effect


Multiple drug therapy:

Diuretics + hydralazine =?

Diuretics + hydralazine = diuretic to prevent fluid retention that occurs from hydralazine


Multiple drug therapy:

Diuretic + Beta-blocker =?

Diuretic + Beta-blocker = the diuretic causes reflex activation of CV and RAS that is controlled by the beta-blocker


What is the biggest problem with antihypertensive therapy? Why?


What class of drugs cause a negative effect on K+, total cholesterol, LDL, HDL, and triglycerides?

Noncompliance because the patient cant feel the problem until it is too late.


Thiazide and loop diuretics