Cardio STUDY (ELSAID) - IE 1

Sympathetic System

ACh —> Nicotinic receptor —> NE —> Adrenergic receptor

Sympathetic Innervation of Adrenal Medulla

ACh —> Adrenal medulla [Nicotinic receptor] —> NE & Epinephrine —> Adrenergic receptor

Parasympathetic System

ACh —> Nicotinic receptor —> ACh —> Muscarinic receptor

Autonomic System

• Sympathetic Innervation

  • ACh

  • Nicotinic receptor & Adrenal medulla

  • NE+Epinephrine

  • Adrenergic receptor

• Sympathetic

  • ACh

  • Nicotinic receptor

  • NE

  • Adrenergic receptor

• Parasympathetic

  • Nicotinic receptor

  • ACh

  • Muscarinic receptor

Neurotransmission in Adrenergic Nerve Endings

Tyrosine —> Dopamine —> [Dopamine-B-hydroxylase] —> NE —> increase Ca+2 —> NE releases —> Post-synaptic adrenergic receptors (alpha and beta) —> NE diffuses or NET

Alpha-1 Adrenergic Receptor

• Excitatory

• Blood vessels

• Vasoconstriction (increase SVR) —> VASOPRESSOR

Alpha-2 Adrenergic Receptor

• Inhibitory

• Autonomic ganglia

• Inhibit NE release —> (neg. feedback)

Beta-1 Adrenergic Receptor

• Excitatory

• Heart

• Ionotropic (increase contraction) || Chronotropic (increase HR, increase CO)

• Increase renin

Beta-2 Adrenergic Receptor

• Blood vessels in skeletal and smooth muscle

• Vasodilates + bronchodilates

• Glyconolysis + Glucagon increase

• Decrease SVR

BP =

CO x PVR

Dopamine Receptor Affinity

D1 > B1 > A1

Alpha Agonists

• Phenylephrine

• Clonidine

• Dexmedetomidine

Mixed Alpha and Beta Agonists

• Norepinephrine

• Epinephrine

Beta Agonists

• Dobutamine

• Isoproterenol

• Albuterol

Alpha Antagonists

• Prazosin, Terazosin, Doxazosin

• Tamsulosin

• Yohimbine

Mixed Alpha and Beta Antagonists

• Labetalol and Carvedilol

  • CI: Asthma

Beta Antagonists

• Metoprolol, Atenolol

• Propranolol (B1=B2)

  • CI: Asthma

Kidney 2 Functions

1. Blood volume —> BP

2. Renin —> RAAS

2 Mechanisms that Control BP

1. Kidney

2. Baroflex Pathway (carotid sinus & aorta)

Angiotensinogen Conversion

Angiotensinogen —> Renin —> Angiotensin I —> [ACE] —> Angiotensin II —> Aldosterone, ADH, Cortisol —> CONSTRICTION

Aldosterone

Na/K Exchange

maybe disregard this..

ADH Function

Kidney reabsorb water

Antihypertensive Drugs: Kidney

• Thiazides

• ACEI

• Beta-Blockers

Antihypertensive Drugs: Blood Vessels

• Alpha-1 Blockers

• ARBs

• CCBs

Antihypertensive Drugs: Heart

Beta-Blockers (-olol)

Antihypertensive Drugs: Vasomotor Center

Alpha 2 Agonists: Methyldopa, Clonidine

Non-protealytic Activation

Reversible: PRR, Prorenin, AGT, Ang1

Protealytic Activation

Irreversible: Renin, AGT, Ang1

3 Ways to Regulate Renin Secretion

Stimulate renin secretion by:

1. Macula Densa —> Low NaCl re-absorption (totally diff from Na/K exchange??)

2. Low pre-glomerular BP

3. B1 activation

High/Low NaCl Reabsorption stimulates renin stimulation?

Low

What enzyme is responsible for the breakdown of bradykinin?

ACE

What class of antihypertensive drugs causes SE of cough and edema? HOW?

ACE-I; ACE breaks down bradykinin, but inhibiting ACE would cause bradykinin buildup in the lungs —> cough & allergic swelling of tissue —> edema

Antihypertensive drug classes that cause hyperkalemia

• ACEI

• ARBs

• Direct Renin Inhibitors

ACEI/ARB/Direct Renin Inhibitor Side Effects

• Hyperkalemia

• Increase SCr

  • CI: acute renal failure, renal artery stenosis, 2nd/3rd trimester pregnancy

ACEI SE

• Hyperkalemia

• Cough

• Angioedema

ARB Members: AT1 Affinity

A, C=O, I=E, T=V, L

• Azilsartan

• Candesartan

• Olmesartan

• Irbesartan

• Eprosartan

• Telmisartan

• Valsartan

• Losartan

Diuretics

Proximal Convoluted Tubule (PCT)

Acetazolamide, osmotic diuretics

Proximal Tubule

Thiazides (minimal)

Thin Descending Limb of Henle

Osmotic diuretics

Thick Ascending Limb of Henle

Loops

Distal Convoluted Tubule (DCT)

Thiazides

Cortical Collecting Tubule (CCT)

Aldosterone Antagonists

Sodium is Reabsorbed at:

• PCT

• DCT

• CCT

High Water Permeability at:

• PCT

• Proximal Straight Tubule

• Thin Descending Loop of Henle

How does increased sodium reabsorption cause hypertension?

More sodium reabsorption = retain more water —> increase blood volume —> increase CO —> increase BP

• If BLOCK sodium reabsorption (diuretics) —> less sodium in blood, more sodium in urine —> less retention of water —> decrease blood volume —> decrease BP

Which diuretic is 1st line?

Thiazide

Carbonic Anhydrase Inhibitor

Carbonic anhydrase leads to bicarbonate release and loss of Na → SO…. inhibit carbonic anhydrase/bicarbonate release causes metabolic acidosis (since losing bicarbonate)

Thiazide & Thiazide-like

• Target: Na/Cl Symporter

• Hypercalcemia (Ca), hyperuricemia, hyperglycemia

• Hypomagenesia (Mg), hypokalemia (K), hyperatremia (Na)

Loop Diuretic

• Target: Na/K/Cl Symporter

• Hyperuricemia, hyperglycemia

• Hypocalcemia (Ca), hypomagenesia (Mg), hypokalemia (K), hyperatremia (Na)

K+ Sparing Diuretics

• MOA: Inhibit Na/K exchange

Aldosterone Antagonist ADE

• Hyperkalemia

• Gynecomastia

Calcium Channel Blockers

DHP vs. Non-DHP CCB

• DHP: affects Ca+2 channels on BLOOD VESSELS

• Non-DHP: affects Ca+2 channels in HEART

DHP CCB: Amlodipine vs. Nifedipine

• Amlodipine: delayed onset, longer duration of effect

• Nifedipine: quick onset (vasodilation), short duration

  • SE: reflex tachycardia —> so use Nifedipine SR to decrease risk!

SA Purpose

Pacemaker of the heart —> increase HR

Beta Blockers, Alpha Blockers, Vasodilators

Non-Selective BB Contraindication?

Asthmatic patients —> non-selective means blocking B2, too! so inhibit vasodilation

Non-Selective Beta-Blockers

• Carvedilol** (has a1 activity too)

• Labetalol** (has a1 actvitiy too) - IV

• Nadolol - PO only, renal adjust

• Propanolol - IV

Caution for BB

Avoid abrupt D/C —> rebound HTN, tachycardia

Caution for Alpha-Blockers

ADE: orthostatic hypotension

Minoxidil MOA

Open K+ channel —> hyperpolarization —> harder to depolarize —> vasodilatory

ADE: Hirsutism, tachycardia, edema

Nitrates MOA

Release NO from drug or endothelium

Hydralazine

• Preferred vasodilator

• Use in severe CKD or renal failure — OK!!!

• ADE:

  • Edema

  • Drug-induced lupus-like syndrome

  • Tachycardia