Pharmacology Exam 3: Antihypertensive drugs

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The 2 main factors influencing BP are…
CO x TPR (total peripheral resistance)

CO is influenced by HR, contractibility and filling tone. Filling tone is controlled by blood volume and VENOUS tone.

TPR is controlled by ARTERIAL tone

Goals of tx in PRIMARY HTN include what 3 things?
1. Reduce systemic vascular resistance
2. Reduce CO (cardiac output)
3. Reduce blood volume

Goals of tx in SECONDARY HTN include what 2 things?
1. Treat underlying diseases
2. Anti-hypertensive medications

The 2 major systems which respond to a DECREASE in BP are…
1. ANS: sympathetic activity
2. Renal blood flow (renin-agiotensin system)

How does a sympathetic response to decreased BP proceed?
A. activation of B1 adrenoreceptors on the heart increases CO
B. activation of a1 adrenoreceptors on smooth muscle increase venous return and increase peripheral resistance
C. activation of B1 adrenoreceptors on the kidney increase renin release

**ALL of these INCREASE BP

How does the kidney respond to a decrease in BP?
A decrease in BP decreases renal blood flow, causing renin release. This increased angiotensin II, increasing peripheral resistance.

Less renal blood flow also decreases GFR, causing an increase in sodium and water retention, increasing blood volume. This increases CO. Angiontensin II also promotes sodium and water retention.

A decrease in kidney perfusion causes the kidney to release…

Renin converts…
Angiotensinogen –> Angiotensin I

ACE converts…
Angiotensin I–> Angiotensin II

Where is ACE found?
On the surface of pulmonary and renal endothelium

Angiotensinogen is produced in the…

What are the effects of angiotensin II (and therefore, what ACE inhibitors are trying to prevent)?
-increase in sympathetic activity
-promotes renal tubule reabsorption of Na+ and Cl-, excretion of K+ and retention of water
-promotes aldosterone secretion from the cortex of the adrenal gland
-causes arterial vasoconstriction–> increases BP
-promotes ADH secretion from the posterior lobe of the pituitary gland

The main goals of anti-hypertensive drugs are to…
Suppress excessive sympathetic activity and modify renal function to counteract the mechanisms responsible for hypertension.

What are the 7 main categories of anti-hypertensive drugs?
(1) vasodilators
(2) β-adrenoceptor antagonists (β-blockers)
(3) α-adrenoceptor antagonists (α-blockers)
(4) angiotensin receptor antagonists
(5) centrally acting sympatholytics
(6) ACE inhibitors
(7) diuretics.

What do diuretics do? What are the 3 main types?
Increase the formation and excretion of urine.

1. Thiazide diuretics
2. Loop diuretics
3. Potassium-sparing diuretics

These type of diuretics are the FIRST line of therapy to treat HTN
Thiazide diuretics

One to note: Hydrocholorthiazide (Esidrix)

These diuretics act promptly even in patients with poor renal function or who have not responded to thiazides or other diuretics.
Loop diuretics.

One to note: Furosemide (Lasix)

2 Potassium-sparing diuretics that inhibit sodium transport are…
Amiloride and triamterene

Name a potassium-sparing diuretic which is an aldosterone receptor antagonist

__________ diuretics are contraindicated in renal failure.
Potassium sparing

The main side effect of potassium sparing diuretics is..

What are the 5 main types of SYMPATHOLYTIC drugs used to treat HTN?
1. Beta blockers

2. Alpha blockers

3. Pre-synaptic adrenergic inhibitors

4. Centrally acting agents

5. Ganglionic blockers

These are the first-line drugs when concomitant disease is present (post MI or with previous MI) to treat HTN…

One to note: Atenolol

What are some side effects of B-blockers?

What are some side effects of loop diuretics?

What are some side effects of Thiazide diuretics?

What is the role of alpha blockers in treating HTN?
Block alpha-1 adrenergic receptors in the vascular smooth muscle, which promotes a decrease in vascular resistance.

What are some side effects of alpha blockers?
short-term tachycardia; salt and water retention

These drugs used to treat HTN inhibit sympathetic discharge.
centrally acting agents

Two of note:

Clonidine: Used in patients who have not responded to two or more drugs

Methyldopa: Can be used in hypertensive pregnant women

Side effects of centrally acting agents include…
sodium and water retention (may be combined with diuretic), and rebound hypertension (withdraw slowly)

How do vasodilators treat HTN and name 2 important examples.
Directly vasodilate the peripheral vasculature by inhibiting contraction of the smooth muscle cells; thus, decreasing the peripheral vascular resistance.

1. Minoxidil
2. Nitropusside

What is the chain of reaction for vasodilators?
1. Nitrates are administered (NO3)
2. Nitrite levels rise (NO2)
3. Nitric Oxide levels rise (NO)
4. cGMP rises
5. Myosin light chain is dephosphorylated
6. Vascular muscle relaxes

*They also activate potassium channels in smooth muscle (causing hyperpolarization and inhibition of calcium efflux).

What are some side effects of vasodilators?
-Orthostatic hypotension

When are vasodilators contraindicated?
Phosphodiesterase V inhibitors (sildenafil, tardenafil, and vardenafil) potentiate the actions of nitrates, resulting in dangerous hypotension.

What is a common ending for ACEI drugs?

What is a common ending for angiotensin II receptor blockers?

These are indicated when first-line agents (diuretics or beta-blockers) are contraindicated or ineffective, or if there are compelling reasons to use them (diabetes mellitus)

Decreased angiotensin II (or the effects of ACEI) are…
-decreased output of the sympathetic nervous system
-increases vasodilation of vascular smooth muscle
-lowers sodium and water retention
-increases levels of bradykinin

**bradykinin causes release of prostacyclin and NO

Both ACEI and angiotensin receptor blockers are contraindicated in…
pregnant women

Concomitant use of potassium supplements, high-potassium diets, and use of potassium-sparing diuretics are contraindications for prescribing ACE inhibitors…
ACE inhibitors

What are some side effects of ACE inhibitors
-dry cough
-skin rash

How to calcium channel blockers function to treat HTN?
Inhibit calcium channels opening, thus inhibiting the activation of contractile elements in smooth/cardiac muscles.

What are the 2 main categories of calcium channel blockers?
1. Dihydropyridines (DHPs). These are vascular selective. Examples include: Nifedipine, Amlodopine

2. Non-dihydropyridines (Non-DHPs). These are both cardiac and vascular selective. Examples include: Verapamil, Diltizem

What are some side effects of calcium channel blockers?

There is a strong interaction between DHPs and _______.
grapefruit (grapefruit inhibits CYP3A4)

What is the DASH diet?
Dietary Approaches to Stop Hypertension

A person with newly diagnosed HTN should limit their salt intake to…

The most common reason for failure of anti-hypertensive meds is…
failure to comply

Two or three drugs in the same pill is referred to as…
combination therapy

__________ can decrease libido and induce erectile dysfunction in males, particularly middle-aged and elderly men. This may cause to discontinuation of therapy.

This drug is given in hypertensive emergencies, but is poisonous when administered orally because it produces cyanide.
Sodium nitroprusside IV

Resistant hypertension is defined as..
BP that remains above the goal despite administration of an optimal three-drug regimen that includes a diuretic.

What are some common causes of resistant hypertension?
-poor compliance
-excessive ethanol intake
-concomitant conditions (diabetes, obesity, sleep apnea, high salt intake, and/or metabolic syndrome)
-use of sympathomimetics, NSAIDs, or antidepressants
-insufficient dose and/or drugs

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