Involuntary Nervous System

Autonomic

SYMPATHETIC

Involuntary Nervous System

Autonomic

PARASYMPATHETIC

Fine discrete control; homeostatic reflexes

Voluntary Nervous System

SOMATIC MOTOR NERVES

Control the movement of skeletal muscles.

Controls movement respiration and posture

Neurotransmitter

What do ADRENERGIC fibers release and where are they found?

The release norepinephrine

The are found only in the sympathetic nervous system

Neurotransmitter

What do CHOLINERGIC fibers relaease and where are the found?

PREGANLIONIC FIBERS

Where do they orginate?

What nervous systems have them?

Fibers originate in the CNS and innervate at the ganglion.

Both sympathetic and parasympathetic nervous systems have pregangliotic fibers.

POSTGANGLIONIC FIBERS

Where do they orginate?

Which nervous systems have them?

They originate in the ganglion and innervate at the end organ.

Both sympathetic and parasympathetic nervous systems have postganglionic fibers.

What kind of fibers are used in the parasympathetic nervous system?

What do the preganglionic and postganglionic fibers release?

Wave of depolarization down the fiber--ACh is released info the synaptic cleft--> ACh diffuses in the synaptic cleft--->Ach binds to a cholinergic receptor on the postganglionic fiber---> A sequence of events occur

A wave of polarizaiton comes down the preganglion---> NE released into the synaptic cleft---> NE difuse--> a few attach the to post synaptic receptor-->Stimulates the receptor (which is either an alpha-1, beta 1, beta- 2) which leads to an effect

What is Sequence of events of Adrenergic Fiber?

How do you TURN IT OFF?

Adrenergic Stimulation

Fight or Flight Response

How does your body get ready for action?

MASS SYMPATHETIC STIMULATION

Increase delivery of fuels (oxygen and glucose) to skeletal muscles: 1. Bronchodilation 2. Increased glucose into blood ( glycogenolysis which breaks down glucogen and gluconeogenesis which makes glucose) O2 and glucose to large muscles. 3. Increased HR 4. Dilate blood vessels in skeletal muscles. 5. Constrict blood vessels in viscera: Decrease GI motility (shunt blood away from stomach to pump more fuel into the blood)

Specific Receptors

ADRENERGIC

What happens with

ALPHA1 stimulation?

1. Blood Vessels: arteriolar constriction in skin, mucous membrane and viscera causing and increase in peripheral resistance (BP=PRxCO , BP=peripheral resistance x Cardiac output)

2. Eye: pupillary dilation (mydriasis-dilation, longer word)

3. Bladder: sphincter contraction

4. Prostate: Increases tension of smooth muscle surrounding the prostate gland, becomes tense

Specific Receptors

ADRENERGIC

What happens with

Alpha 2 stimulation?

SHUTS THE NE SYSTEM OFF

1. CNS: reduced sympathetic outflow resulting in peripheral vasodilation; can cause orthostatic hypotension by decreaseing peripheral sympathetic stimulation.

Specific Receptors

ADRENERGIC

What happens with

BETA 1 Stimulation?

What organ does it effect and what are the ways it is stimulated?

HEART: Stimulates the heart in three different ways

1. Increases the heart rate--->+chromotropic effect (timing/its speed, its rate)

2.Increases the force of contraction-->+inotropic effect (more forcefully)

3. increases the speed of conduction speed-->+ dromotropic effect (

Specific Receptors

ADRENERGIC

What happens with

BETA 2 Stimulation?

What organ does it effect and what are the ways it is stimulated?

1. LUNG- Dilates smooth muscle of the bronchial tree

2. Blood vessels: dilates arterioles of skeletal muscles causing peripheral resistance to decrease (Note: the NET effect of ALPHA1 and BETA2
3. Liver: releases glucose from liver by glycogenolysis and gluconeogenesis stimulation is an increase in peripheral resistance).
4. Potassium: Serum potassium may be decreased by shifting potassium into cells.
5. Bladder: Relaxes detrusor muscle
6. GI:  slows intestinal peristalsis
7. Uterus: Inhibits contractions (relaxed)
8. Tremor (toxicity of beta2 stimulation)

Alpha 1 causes what?

Beta 2 causes what?

When they both are stimulated what happens?

1. increases peripheral resistance

2. decreases peripheral resistance

3. Net effect is it goes up, but not as much as it would of if beta 2 wasn't acting

Adrenergic Blockade

When adrenergic receptors are blocked...?

Muscarinic Cholinergic Stimulation

Parasympathetic Nervous System

Heart

a. Rate is decreased (negative chronotropic effect) by decreasing slop of phase 4 depolarization.
b. Speed of conduction is decreased (negative dromotropic effect).
c. Decreases force of contraction (negative inotropic effect) of atrium only.

They do the opposite

-So if someone had an increased HR, you could take away NE to decrease the HR

-If someone had a decreased HR you could block ACe to decrease the HR

Muscarinic Cholinergic Stimulation

Parasympathetic Nervous System

Eye

What happens to the eye?

a. Pupil is constricted (miosis)
b. Lens becomes rounder allowing the eye to focus on a nearby object (accommodation).
c. Lowers intraocular pressure in patients with glaucoma

Muscarinic Cholinergic Stimulation

Parasympathetic Nervous System

Bladder

What happens to the bladder?

Causes contraction of the detrusor muscle and relaxation of sphincter

Muscarinic Cholinergic Stimulation

Parasympathetic Nervous System

Gastrointestinal system

What happens to the GI?

a. Increases GI motility
b. Increases gastric acid secretion
c. Increases pancreatic enzyme secretion
d. Increases bile release
e. Increase lower esophageal sphincter tone

(Everything is stimulated)

Muscarinic Cholinergic Stimulation

Parasympathetic Nervous System

Lung

What happens to the lungs?

Blockade of the Muscarinic Receptor

When blocked the result is the opposite of when the receptor is stimulated. What happens?

Mad as a hatter (psychosis and seizures) central excessive blockade in brain, mercury in felt hats
Dry as a bone (secretions are decreased-dry mouth, dry skin, ACe block in secretions)
Blind as a bat (eye cannot accommodate - can't see close, CAN NOT read, same when they dilate eye)
(pupil cannot constrict - photophobia)
Red as a beet (cutaneous blood vessels dilate)
Hot as a hare (skin feels warm)
ALSO:
Can’t See (Duplicate from above)
Can’t Pee (Urinary retention)
Can’t Spit (Dry mucus membranes)
Can’t Shit (It’s OK! It rhymes with spit) GI slowing (constipation, decreased bowel sounds)
Pupillary dilation
Increased heart rate

MUSCARINIC AGONIST

PARASYMPATHETIC

a. Mechanism of action (MOA) - directly stimulates the muscarinic receptor (M1-M3) and is relatively selective for the GI tract and the bladder.
b. Clinical Uses - GI and bladder atony (atrophy, when you use it)
c. Patient Related Variables (NOT CONTRA, way risks and benifits):  asthma (increase bronchial tone) , peptic ulcer disease (release acid in the stomach) , heart conduction defects (Negative donotropic, AVblock, might make worse) .

MUSCARINIC AGONIST

PARASYMPATHETIC

a. MOA - nonspecific direct stimulation of the muscarinic receptor. reduces intraocular pressure, causes miosis.
b. Clinical Uses - applied topically to the eye for glaucoma, Sjogren’s syndrome
c. Patient Related Variables - asthma, peptic ulcer disease, heart conduction defects

(PILLS work fine too, but poison the entire body to get to the eye. * eye drops have system effects, can see systemically, not as much as pill but can happen)

Atropine/Scopolamine/Belladonna

What kinds of drugs are these? How do they work?

What are patient related variables?

MUSCARINIC ANTAGONISTS

MOA competitively blocks muscarinic receptors.
Small doses (<0.5mg in an adult) causes bradycardia!

"Belladona" pretty lady, dilates pupils to become prettier

-PRV: benign prosthetic hypertrophy (relax anymore, wont be able to urinate), exposure to high enviromental temperatures(can't sweat, can't cool off) , esophageal reflux esophagitis (relax tone, make reflux worse)

Atropine

What are the clinical uses?

What happens if you give too little of this drug?

- pre-operatively to decrease salivation
- block vagal effects on the heart
- dilate pupil for eye exam (homatropine – not atropine) homatropine falls apart 5 hours later, atropine hangs around for a week
- treatment of bradycardia (ACLS) CAN CAUSE BRADYCARDIA IF TOO LITTLE
- reverse toxicity of an agent that is
causing too much muscarinic stimulation.

patch used to prevent motion sickness

Single fixed pupil, scope patch, got it on their finger and poisened the eye, blown pupil.

ANTICHOLINERGIC

quaternary amine, has a permanent charge, forced drug to have a charge to can't cross the brain blood barrier, engineer molecules to decrease adverse effects

a. MOA – nonselectively blocks muscarinic receptors
b. Clinical Uses - Used in COPD to cause bronchodilation or prevent bronchoconstriction/bronchospasm

Dicyclomine (Bentyl)

What are the clinical uses?

a. MOA – blocks M3 receptors
b. clinical use – decrease movement and secretion of the gut, used for irritable bowel syndrome
c. Patient related variables – tachycardia, confusion, urinary retention, increased intraocular pressure

a. MOA – nonselective blocker of muscarinic receptor
b. Clinical use – urinary incontinence due to detrusor smooth muscle spasms
c. Patient related variables – tachycardia, confusion, increased intraocular pressure

Nicotinic Receptors

Where are they found?

What do they control?

What happens when you block them?

Neuromuscular Receptors

Skeletal muscle movement

Paralysis

Atracurium and Pancuronium

What is the pharmacology of these drugs? How do they work?

How are there affects reversed?

They competitively block the action of ACh at the neuromuscular junction. Effects are reversed by AChase inhibitors.

( They are competing for a spot on the receptor, when ACHase is inhibited, there are more ACh so there is a better chance it will win the spot for the receptor)

Atracurium and Pancurium

What are the clinical use? What are there toxicity?

How is it reversed?

NICTINIC ANTAGONSITS (Neuromuscular Blockers)

NON-DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS

b. Clinical use - adjunct to general anesthesia, mechanically ventilated patients.

c. Toxicity - respiratory paralysis. Tubocurarine, more so than pancuronium, blocks the nicotinic receptor of the ganglion which may lead to hypotension.

Reversed by AChase inhibitors (i.e., neostigmine)

Succinylcholine

What is the pharmacology?

Depolarizing Neuromuscular Blocking Agents

(Depolarizes by moving closer to 0, keeps them depolarized)

Pharmacology - Produces a persistent depolarization resulting in a transient muscular stimulation (fasciculation) followed by neuromuscular blockade.

Muscle fibers are stimulating for one time, patients bounce around, intubation, relaxes well and rapid.

*The blockade CANNOT be reversed by AChase inhibitors (i.e., neostigmine).

Succinylcholine

What are the clinical uses?

What are the patient related variables? *

-anesthesia, emergency tracheal intubation

-Patient Related Variables - genetic deficiency of pseudocholinesterase which leads to a marked prolongation in the activity of succinylcholine.

(warning on the package label, don't use with these people, associated with fatal hypokalemia; rock and hard place, people end up just giving it)
Avoid in: Acute phase following major burn
Multiple trauma
History of skeletal muscle myopathy
History of malignant hyperthermia

Neostigmine, Pyridostigmine, Physostigmine, Edrophonium

KNOW

What is the pharmacology?

What are drugs called that can't enter the CNS?

What are drugs called that can?

Nicotinic & Muscarinic Agonists - Acetylcholinesterase (AChase) Inhibitors.

-Reversibly block the action of AChase which allows more ACh to reach the receptor. Neither neostigmine nor pyridostigmine enter the CNS because they are charged compounds (quaternary amines). Physostigmine is able to penetrate into the CNS because it is not charged (tertiary amine). Edrophonium has a rapid onset and short duration of action.

MUSCARINIC EFFECTS          NICOTINIC EFFECTS
nausea                                   muscle cramps
vomiting                               muscle fasciculation
diarrhea
increased salivation
increased bronchial secretions
bronchoconstriction
bradycardia

Organophosphate Insecticides / nerve gas

What is the pharmacology?

What is the antidote for toxicity?

Nicotinic & Muscarinic Agonists - Acetylcholinesterase (AChase) Inhibitors

a. Pharmacology - irreversibly block the action of AChase allowing more ACh to reach the receptor. (Too much ACh
b. Toxicity - antidote is Pralidoxime(pulls poison off the ACh) and atropine

Cholinergic

Nicotinic & Muscarinic Agonists - Acetylcholinesterase (AChase) Inhibitors

What are the also used in

Nicotinic & Muscarinic Agonists - Acetylcholinesterase (AChase) Inhibitors

blocks AChase work centrally and are used for Alzheimers disease

Isoproternol (Isoprel)

What receptors does it stimulate?

Is it used often?

adrenergic agonist

Stimulates beta 1 and beta 2, Equal stimulation of both

-Don't use a lot, Killed asthmatics, ACLS: didn't work well

-Seen in heart transplant patient, but in short supply.Transplanted heart not connected by nerves, so why atropine won't work.

Isoproterenol used primarily for testing purposes only (e.g., chemical stress test, electro physiologic studies). In the old ACLS guidelines, isoproterenol was suggested for patients with denervated hearts to support cardiac function prior to pacing – dobutamine is now suggested for this use.

Sympathetic nervous system is turned off.

Peripheral dialtion can cause orthostatic hypotension by decreasing peripheral sympathetic stimulation

Metaproterenol

Used as a bronchodilator in asthmatics and is preferred over isoproterenol for this purpose because of metaproterenol's relative selectivity.

"Renal Dose"excrete urine

big dose is similar to Norepinephrine

Confuse with something else, increase errors

Not a lot of evidence that it works

Adrenergic Agonist

adrenergic agonist

Used to support cardiac function, potent vasoconstriction

Epinephrine

ADRENERGIC AGONIST

Ist drug you would use in ACLS

-Primary drug used in cardiac arrest (vasopressin also used as first line)
-Used to treat anaphylaxis. *(Failure Modes: make sure patient knows how to use Epi pen, looks like top of ball point pen, so people his it, fumble around and inject your foot, needs to hold it there for a count of 10)
-Used to produce local vasoconstriction to prolong the effect of locally administered anesthetics.

Phenylephrine (NeoSynephrine)

What does receptor does it stimulate?

What is it used for?

ADRENERGIC AGONIST

alpha 1 agonist, peripheral resistance

Used as a topical decongestant.agonist, capilary permeability, decrease stuffiness
IV used to support blood pressure

ADRENERGIC AGONIST

Used to inhibit uterine contractions in preterm labor

ADRENERGIC AGONIST

-Central stimulation of the alpha2
-Stimulation of the alpha receptor decreases CNS sympathetic outflow, decreases sympathetic stimulation (hypertension, narcotic withdrawal)
2 receptor in the spinal cord causes analgesia.

WITHDRAWING FROM AN OPIOD, ALOT OF DEPENDANCE

ADRENERGIC AGONIST

What occurs when you have toxicity from these drugs?

BETA1

ADRENERGIC AGONIST

What occurs when you have toxicity from these drugs?

BETA2

ADRENERGIC AGONIST

What occurs when you have toxicity from these drugs?

Alpha 1

Hypertension, decreased organ perfusion

DON'T GIVE AN ALPHA AGONIST WHO IS HYPOVOLEMIC, GIVE THEM FLUIDS, ALPHA 1 AGONIST WILL CLAMP DOWN ON ORGAN PERFUSION

ADRENERGIC AGONIST

What occurs when you have toxicity from these drugs?

Alpha 2

ADRENERGIC AGONIST

What are the patient related variables for BETA1?

ADRENERGIC AGONIST

What are the patient related variables for BETA1?

Hypertension, hypovolemia

ADRENERGIC BLOCKERS: ALPHA BLOCKERS

**Used to save infiltrated drugs (epinephrine) into the tissue then you have a bad situation, need to rescue out of tissue very quickle

-Blocks ALPHA1 and ALPHA 2
-Used to reverse the local vasocontricting effect of extravasated alpha agonist such as norepinephrine (levarterenol) and dopamine.
-Blocking ALPHA2 causes an increase release of NE (NE release is not turned off) resulting in tachycardia.

Prazosin (Minipress), Terazosin (Hytrin), Doxazosin (Cardura)

What is the action? Clinical Uses? and Toxicities?

ADRENERGIC BLOCKERS: ALPHA BLOCKERS

Action: Block ALPHA1
Clinical Uses: receptor, Hypertension, Benign Prostatic Hypertrophy (alpha 1 receptors around prostate, if increased then becomes tense, if we block this then it relaxes and able to urinate)
Toxicities:Orthostatic hypotension, nasal stuffiness, peripheral edema

Tamsulosin (Flomax)

 What is the action? Clinical Uses? and Toxicities?

ADRENERGIC BLOCKERS: ALPHA BLOCKERS

Action: blocks alpha1 receptors
Clinical use: benign prostatic hypertrophy
Adverse drug effects: orthostatic hypotension (may be less than with prazosin, terazosin, doxazosin)

BETA Blockers (Propranolol-BETA 1&2)

What is the clinical uses?

adrenergic blockers

HTN, angina pectoris, antarrythythmic

BETA Blockers (Propranolol-BETA 1&2)

What is the toxicity?

adrenergic blockers

Heart Failure (in acute decompensated HF may decrease cardiac output)
Bradycardia
Bronchospasm

BETA Blockers (Propranolol-BETA 1&2)

Patient related Variables

1. Decrease the signs and symptoms of congestion
2. Maintain, as much as possible, a normal life style
3. Prolong life

SYSTOLIC DYSFUNCTION

(more common and what we are going to talk more about)

Reduced contractility (EF [<40%] & LVEDV-Left Ventricle 100 ml)

a. Reduced muscle mass (ischemia)
b. Dilated cardiomyopathy
c. Ventricular hypertrophy
i. Pressure overload (systemic/pulmonary HTN; aortic/pulmonic valve stenosis)
ii. Volume overload (valve regurgitation)

Reduced ventricular filling - (normal EF & normal or LVEDV)

Things that cause this:

a. Ventricular hypertrophy (long-standing HTN)
b. Increased stiffness of ventricles
c. Restrictive process (amyloid, sarcoid)
d. Valvular stenosis (mitral/tricuspid)
e. Pericardial disease
f. Ischemia

The amount of the blood comming into the heart, pressure coming back to the hear after systemic circulation

What the heart has to work with

force at which the heart has to pump out against. After ig goes through the hear and is pumped out, the force at which it pumps out against

H.F

See page 2 of notes

H.F.

Frank- Starling Mechanism

(Increased SV)

• RAAS(renin angiotension aldosterone system)activation = Increase in H2O/ Na retention
• Normally, as preload increases, cardiac output increases. In HF, increased preload does not result in a comparable increase in cardiac output and may actually cause a decrease in cardiac output. O/Na retention
o Volume overload, increased myocardial oxygen demand

H.F.

Increased HR

• SNS activation (epinephrine/norepinephrine)
          -Increase myocardial oxygen demand, ischemia, arrhythmias; decrease filling time

H.F.

Vasoconstriction

H.F.

Ventricular hypertrophy and remodeling

DIURETICS

ACEINHIBITOR

BETA-BLOCKER

These are the core treatment, really start at Stage C

Reduce the force against which the heart has to pump allowing an increase cardiac output (AL - is estimated by mean arterial pressure)

NSAID causes you told hold onto sodium and water

Would want to remove it from therapy or not add it

NOT contraindicated but may cause increased edema

a. Beta Blockers (only metoprolol, carvedilol, and bisoprolol) block the beta2 stimulation
b. Angiotensin Converting Enzyme Inhibitor (ACEI) block formation of angiotensin 2
c. ARBs (Aldosterone Receptor Blockers)
d. Aldosterone antagonists (i.e., spironolactone, eplerenone)

MONIROTING THERAPY

What are the signs and symptoms of L sided HF?

a. Dyspnea on Exertion (DOE)
b. Orthopnea

c. Paroxysmal Nocturnal Dyspnea (PND)
d. Rales

MONIROTING THERAPY

What are the signs and symptoms of R sided HF?

a. Peripheral Edema (Weight, I&O's)
b. Jugular venous distention (JVD)
c. Hepatojugular reflux
e. S3
f. Decreased exercise tolerance gallop
g. Fatigue

MONIROTING THERAPY

What are the signs and symptoms of excess fluid loss?

1. Orthostatic hypotension
2. Dizziness
3. Decrease urinary output

Pulmonary Capillary Wedge Pressure

The amount of blood coming into the heart from the systemic circulation

NORMAL = 18 mmHg

Low CO (cool) and Low PCWP

Hypoperfusion: give fluids and positive isotropes after giving the fluids

 Fluids ae backing up into the systems and cause PULMONARY CONGESTION

-Treat with loop diuretics and vasodilators

PULMONARY CONGESTION: Give Diuretics

HYPOERFUSION: vasodilators and inotropes

Nitroglycerine

Vasodilator

induces smooth muscle relaxation in the venous and arterial system. (decreases preload and afterload)Mainly venodilator although become arterial dilator at doses greater than 100 mcg/min. Common side effects include headache, hypotension, tachycardia. Tachyphylaxis can occur within 12 hours.

Nitroprusside

*What Do you want to measure when a patient has been on for a few days?

Vasodilator

VERY POTENT/ Used in ICU/*prolonged period of time, would want to meausure for thiocyanate when blood levels are >10mg/dl (esp in renal dysfunction)

-nausea, vomiting, and fatigue. Can also cause cyanide toxicity(kills people by not allowing people to use oxygen, doesn't deliver o2 to the capillaries)  especially if high doses (>3mcg/kg/min) are given for >3 days. - trembling, respiratory distress, convulsions.

Nesiritide

*What is the main toxicity of this drug?

Vasodilators

MAIN TOXICITY IS HYPOTENSION

SHOULD NOT USE IN THE SETTING OF CARDIOGENIC SHOCK WITH A SYSTOLIC BP < mm H, Drug is not used a lot, should only be used for 72 hours.

-This drug antagonizes both the renin-angiotensin-aldosterone system and the sympathetic nervous system

Inotropic agents

*This drug inhibits the production of Phosphodiesterase III which normally inhibits cyclic-AMP. When more cyclic-AMP is hanging around there is increased cardiac contrctility.

Dobutamine and Dopamine

What class of drugs are they in?

What do they each cause and how are they different?

1. Inotropic agents

2. Dobutamine causes increased HR and increased contractility and has MINIMAL effect on MAP

3. Dopamine causes INCREASED MAP

What is the drug selection for diastolic HF?

*What is a drug that is used in Diastolic HF but NOT in Systolic HF?

1. Low sodium diet (2g/day)
2. Diuretics (very important in both HF's, more for symptom management)
3. ACEI
4. B-blockers or nondihydropyridine CCBs (calcium channel blockers) *** Main nondihydropyridine is NEPHEDIPINE (negative inotrope, avoid in systolic HF)

Systolic Heart Failure

What would be a good drug to add when ACE1, Digoxin, beta blocker and loop diuretic are already on board?

In a study of HF patients (NYHA III-IV), adding spironolactone (12.5mg-25mg once daily) to conventional therapy (ACEI, Digoxin, beta blocker, and a loop diuretic) was associated with a significant reduction in mortality.

NOTE: monitor closely for hyperkalemia when spironolactone is administered concurrently with an ACEI. Another drug similar to spironolactone is eplerenone (Inspra), its advantage over spironolactone is that it does not cause gynecomastia. Eplerenone is significantly more expensive than spironolactone.

ACE inhibtiors PROLONG LIFE

*Beneficial in mild to severe heart failure. These drugs significantly reduce mortality rate and should be used in patients with CHF (Stage B and above) unless contraindicated

*increase K

* Only if cant use ACE do you use ARBs (not as much research

*TOXICITY: ACE cough, back on the dose, and then come back in, Need to educate the patient to hang in there and it ususally gets better over a few weeks. Really want to try and get patient to use it. MAKE SURE YOU USE THE RIGHT DOSE THAT WILL IMPROVE MORTALITY.

Hydralazine plus nitrates

When do you want to use this for therapy?

*this was the first drug to show prolonged life in the setting of heart failure. not as well tolerated as the ACE inhibitor.

-This combination is reserved for patients who cannot tolerate ACEI or ARBs or as add-on therapy in African Americans. (showed pg 94, did well)

Heart Failure

Beta Blockers

How do they help the heart?

What are the three drugs that have been shown to work in clinicical trials?

In heart failure the heart is being excessively stimulated by beta cells. So much so that is hurting the heart. Beta-blockers decrease the stimulation just enough that contractility is possible because only a small amount of the beta cells are blocked.

3 Drugs that have been shown to work in clinical trials:

1. carvedilol (Coreg)

2. metetprolol (toprol XL)

3. bisoprolol

ususally an initial dose, a target dose and a maximal dose. Creep it in, may need to back off if HR gets worse. ONLY IN STABLE HF

Aldosterone agonists

Spironolactone and eplerenone

What do you want to watch for

hyperkalemia

DRUGS TO AVOID

Not contraindicated but cautiously

1. NSAIDS and COX2 inhibitor: hold onto Na and water

2. Any drug that causes adrenergic stiumulation: decongestants

3. TZDs antitiabetic drugs

4. Antiarrythmiscs with negative inotropic activity

5. Antiarrythmics that prolong QT interval

***6. Calcium Channel Blockers (CCB): good in diastolic, relax more and pump out more drug. AVOID IN SYSTOLIC HEART FAILURE***

cardiax glycosides

Pharmacology:Positive inotropic effect (direct effect) - Inhibits Na-K pump leading to an increase in intracellular sodium. Increase intracellular sodium decreases activity of the Na-Ca exchanger leading to increase intracellular calcium, which in turn increases activation of contractile elements.

Vagotonic effect -stimulates the effect of the vagal nerve...decreased heart rate, decreased conduction through AV node (accounts for its ability to protect the ventricles in the setting of atrial fibrillation or atrial flutter)

3. Increased cardiac automaticity - formation of abnormal pacemakers

Digoxin

ADMINISTRATION

1. Obtain a baseline EKG prior to initiation of therapy.
2. Avoid IM administration - it's very painful and is erratically absorbed.
3. IV administration should be given slowly (over 5min).
4. In obese patients, dose should be based on lean body weight and NOT on TBW
5. Observe for signs of toxicity BEFORE giving dose
a. Apical pulse <60/min (adult) - monitor for full minute or PR interval >0.2 sec
b. Sudden anorexia, GI upset or fatigue
6. Therapeutic Level is 0.5 – 0.8 ng/ml - Blood levels should not be drawn until a given dose of digoxin has had a chance to equilibrate into the myocardial tissue (8-12 hrs). This is true whether digoxin is given orally or parenterally.

Digoxin

Cardiac Toxicities

a. Bradycardia
b. Atrial or Ventricular arrhythmias
c. AV block

Digoxin

Non-Cardiac Toxicities

The Holland Experience

a. Fatigue 95%
b. Visual disturbances 95%
blurred vision
problems with green-yellow color perception
c. Muscular weakness 82%
d. Anorexia, Nausea 80%
e. Hallucinations, confusion, insomnia 65%

Digoxin

Patient Related Variables

1. Factors Increasing Digoxin Effect without Increasing Levels

a. Hypokalemia
- a common problem when diuretics are used
- use only KCl as a potassium replacement, almost have to use potassium chloride
- consider a potassium sparing diuretic (spironolactone, triamterene, amiloride)
b. Hypomagnesemia
- particularly a problem in alcoholics or in malnutrition
- "potassium sparing" diuretics also spare magnesium
c. Vagal stimulation (shower massage, vlsalva, rectal exams/enemas) plunge arm into cold water, HR goes down, stimulates vagal nerve. NEVER DIGITALIZED SOMEONE WHO HAS BEEN DIGITALIZED.
d. Hypercalcemia (IV calcium administration)

Digoxin

Patient Related Variables**

2. Factors leading to High Digoxin Concentrations

a. Renal failure
b. Amiodarone, Verapamil*** causes dig level to go up
c. Using the same dose IV that was used for oral tablets
d. Basing a dose in an obese patient on total body weight
e. Erythromycin - Will increase digoxin concentration in pts who normally metabolize digoxin in their intestinal tract (this will affect about 10% of the population)

Digoxin

Patient Related Variables

3. Factors Leading to Low Digoxin Concentrations

a. Antacids (along with, it will bind and decrease amount in the system)

b. Rifampin

NEEDS TO MATCH; THE AMOUNT OF NEED OF O2 AND THE AMOUNT OF SUPPLIED O2

decreased supply of oxygen to the heart muscle. IHD includes chronic stable angina and the acute coronary syndromes (ACS). Unstable angina, non-ST elevated myocardial infarction (NSTEMI) and ST elevated myocardial infarction (STEMI) make up the ACSs.

is a syndrome characterized by chest pain resulting from myocardial ischemia or an imbalance in myocardial oxygen supply and demand. If myocardial ischemia persists too long or becomes sufficiently severe, myocardial cell death occurs which is myocardial infarction (MI). Angina and MI may be difficult to distinguish early during an acute event.

MEDICAL EMERGENCY

(UA) is either new onset angina, angina at rest, or onset of angina with less exertion than before and may be a transition stage between stable angina and myocardial infarction. Unstable angina is a medical emergency. Common EKG changes: transient ST-segment depression > 1 mm and/or T-wave inversions in two or more contiguous leads, which partially or completely resolves with symptom relief, with or without medical intervention.

reproducible pattern of pain following a given amount of exertion. Atheroclerotic plaques cause a narrowing in of the coronary artery but a fibrous cap decreases the risk of plaque rupture compared to ACS. (Reproducible amount of exercise)

STEMI results from plaque rupture that leads to myocardial cell death that extends the thickness of the myocardial wall. After a STEMI, Q waves are commonly seen on an EKG

Caused by coronary artery vasospasm resulting in ischemia. May evolve to an MI but generally does not. Typical anginal pain usually occurs at rest. When mucscle wall dries enzymes are released.

refers to a spectrum of symptoms resulting from myocardial oxygen deprivation and includes UA, NSTEMI and STEMI.

an imbalance between oxygen supply to the myocardium muscle and oxygen demand of the myocardium.

Ischemic Heart Disease

Determinants of oxygen supply:

a. Oxygen in inspired air
b. Lung function
c. Hemoglobin (carrier, anemia is getting worse)
d. Blood flow through coronary arteries
e. Oxygen extraction
f. diastolic filling time

(plenty of oxygen but dont deliver it to their capilaries, not the time to start smoking, Co2 binds to oxygen spots)

Ischemic Heart Disease

What are the three determinants of oxygen demand?

KNOW the three and that oxygen demand goes up, thats it

a. Heart rate (as goes up, needs more oxygen)
b. Inotropic state of the heart (Contractility, doing more work, need more oxygen)
c. Myocardial wall tension -(Demand for oxygen goes up) As the pressure inside the heart increases the tension (pressure) in the wall of the myocardium increases. (more pressure more work, need more oxygen) The heart requires more oxygen when it has to push against a high pressure. Decreasing the amount of blood going into the heart from the venous side (PRELOAD) can reduce the pressure inside the heart. Another way to decrease pressure inside the heart is to allow more blood to escape from the heart into the arterial side. This can be done by reducing the force against which the heart has to pump (reducing AFTERLOAD). Decreasing peripheral vascular resistance reduces afterload.

1. atherosclerosis (fixed obstruction)

2. variant angina

3. platelet aggregation

Morphine: not immediatly, help with pain, venodilator which decreases pre-load, decrease wall tension

Oxygen: increase the amount of O2

Nitro: under the tongue.

ASA (Chew and swallow 3, 81 mg asa)

STEMI--> CATH LAB RIGHT AWAY

ASA

inhibits COX-1

Will reduce risk of MI and save lives

ANTIPLATELET THERAPY

Thienopyridines

TICLOPIDINE (TICLID)

Do not use much anymore because it causes neutropenia in 3% of patients, Clopidogel (plavix) works just as well and doesn't have that side effect

ANTIPLATELET THERAPY

Thienopyridines

CLOPIDOGEL (PLAVIX)

PRODRUG: IT IS INACTIVE AND MUST BE ACTIVATED BY AN ENZYME IN YOUR LIVER, OMIPRAZOLE PPI TO DECREASE ACID, IT BLOCKS THE ENZYME THAT ACTIVATE CLOPIDOGEL PLAVIX, clinical significance is debates

i. Used as primary therapy for NSTEMI and STEMI. Should be used in combination with ASA in patients receiving a stent. Used in combination with fibrinolytics in STEMI. Used for at least 12 months in patients undergoing drug eluting stents.
ii. Can be used in patients you require antiplatelet therapy but do not tolerate ASA.
iii. In patients undergoing PCI, loading dose is 300-600 mg followed by 75 mg daily.

GLYCOPROTEIN IIb/IIIa RECEPTOR INHIBITORS

(the platelet has this receptor on it, if you block it, platelets don't work)

Abciximab (reopro); Eptifibatide (Integrilin); Tirofiban (Aggrastat)

What is the main toxicity?**

a. Mechanism – Abciximab is an antibody directed against the glycoprotein IIb/IIIa receptor and eptifibatide and tirofiban block the glycoprotein IIb/IIIa receptor. Fibrinogen bridges from between glycoprotein IIb/IIIa receptors of the surface of platelets forming a thrombus.

b. given in combination with ASA, clopidogrel, and UFH or LMWH
c. Used in angioplasties to prevent re-stenosis.
a. Bleeding is the main toxicity. Serious bleeding is increased 2x compared to the use of heparin plus aspirin alone.

ANTICOAGULANTS

HEPARIN (unfractional heparin)

a) Initiate therapy in the ED for patients with suspected ACS. Load 80 units/kg and start continuous infusion of 18 units/kg/hour). Draw aPTT/anti-Xa level in 4-6 hours.
b) Monitor: aPTT, Hgb/Hct, Platelet count (ALSO AN ANTIPLATLET)

(STUDY THAT ENOXAPARIN IS MORE EFFECTIVE THAN HEPARIN, NOT BY MUCH BUT A LITTLE BIT)

Low Molecular Weight Heparin (fractionated heparin)
a) Has been shown to decrease mortality, MI, and recurrent angina in the setting of acute coronary ischemic syndrome. Bleeding is the main complication.
b) In patients with STEMI, combination enoxaparin for up to 8 days vs UFH for 48 hours in patients receiving fibrinolytics showed a decrease in death or MI by 17% but an increased risk of bleeding.
c) AHA/ACC guidelines recommend patients undergoing fibrinolytic therapy receive treatment with enoxaparin over UFH for up to 8 days

ANTICOAGULANTS

Fondaparinux

a. Considered first line therapy for patients with STEMI receiving thrombolytics
b. Should not be used in patients with renal dysfunction

ANTICOAGULANTS

Bivalirudin

a. Direct thrombin inhibitor
b. May be used in patients undergoing primary PCI
c. Bind to and prevent thrombin that is bound in the clot as well as circulating thrombin

NITRATES (nitroglycerin (NTG), isosorbide dinitrate, isorbide mononitrate)

PHARMACOLOGY

(IT IS USED TO BLOW UP MOUNTAINS)

a. In vascular smooth muscle, nitrates are converted to nitric oxide (NO) NO causes venous and arterial dilation which results in a decrease in preload and afterload.
b. The MAJOR antianginal effect of nitrates is to cause venodilation, which will reduce the amount of blood returning to the heart (PRELOAD IS REDUCED). Preload reduction reduces the pressure of blood in the heart which is pushing against the wall of the heart (REDUCED WALL TENSION). Reducing wall tension will decrease the amount of oxygen needed by the heart to function (DECREASED OXYGEN DEMAND).
c. A MINOR effect is to decrease wall tension by decreasing afterload. Another MINOR effect is to increase oxygen supply by dilating coronary arteries.

NITRATES (nitroglycerin (NTG), isosorbide dinitrate, isorbide mononitrate)

*ADMINISTRATION*

High first past effect* PO dose is much larger than SL dose, vasculature in mouth bypasses the liver.*

a. ORAL used prophylactically to decrease number of anginal attacks. Nitrates undergo a large FIRST PASS EFFECT. The dose given orally is therefore much larger than the dose given sublingually, topically or parenterally.

**MUST HAVE A NITRATE FREE PERIOD DURING THE DAY, 8-12 HOURS, if have 24 hours a day, patient will become "tachyphylaxisis" which means they become tolerant and it it doesn't work anymore.

used to treat an acute attack. To avoid the nitroglycerin from evaporating out of the tablet, keep tablets in a tightly closed dark colored glass container.
-Sublingual NTG is also available in a spray (long shelf life- clear red pump action spray bottle needed to be primed before first use and again if not used for over 6 weeks – point spray away from yourself when priming – hold bottle upright when spraying)
-Sublingual NTG can be used 5 to 10 minutes before strenuous exercise to prevent ischemia.
Following ischemic pain:
Sit
Place tablet under tongue (don't swallow)
If pain persists after 5 min, dial 911 (q5min while waiting for EMT)

This tablet is placed between the upper teeth and the inner lip. Once in place the tablet will continue to release NTG for 4 to 5 hours. This form can be used for both acute angina and prophylaxis. Tablets should be removed at night to limit tolerance and to prevent the tablets from being aspirated.

used prophylactically to decrease number of anginal attacks. The amount of nitroglycerin absorbed through the skin is dependent on the body surface area covered by the preparation. The dose of ointment should be expressed as surface area covered by ointment and not by "inches" of ointment dispensed from tube.

should be removed for 10-12 hours/day (usually overnight) to limit development of nitrate tolerance – (NOTE: during acute therapy, nitrates may not be removed, instead does may be increased to counteract building tolerance to the drug.)

a. Burning under tongue from sublingual tablets - this is not a reliable marker of potency.
b. Postural hypotension (syncope) - This mandates a reduction in dose.
c. Throbbing headache
d. Reflex tachycardia
*e. Drug interaction with sildenafil citrate (Viagra, Revatio) (wait 24hours) or tadalafil (Cialis) (wait 48 hours) - causing decreased myocardial blood flow and ischemia. – (PDE Type 5) Phosphodiesterase 5

cGMP(increases nitric oxide, potent vasolilator, broken downs by PDE type 5, and is inhibited by Viagra, so you will have more nitric oxide than normal and BP will plummit)

BETA BLOCKERS (propranolol, atenolol, metoprolol, esmolol)

PHARMACOLOGY

a. Beta blockers decrease myocardial oxygen demand by decreasing heart rate, contractility, blood pressure and myocardial oxygen demand. Beta-blockers also decrease the risk of arrhythmias and infarct size. A toxic effect of a drug in one setting may be a therapeutic effect in another setting. (“One patient's poison is another patient's cure”.) – Do not use beta blockers in patients on cocaine (can use labetolol).
b. Aerobic threshold is attained at a given Rate Pressure Product (MAP x HR). When hits this RPR, they will have ischemic ekg changes. Beta-blockers minimize increases in HR thereby helping to avoid a patient’s individual aerobic threshold. Normally, CO increases during exercise more than necessary. This is why decreasing exercise induced increases in heart rate will allow the patient to exercise while helping to avoid aerobic threshold. IMPROVES EXERCISE TOLERANCE

BETA BLOCKERS

ADMINISTRATION

what should you not do when a patient is on a beta-blocker?**

b. In the setting of post-MI, will improve survival and reduce risk of reinfarction
c. Target resting heart rate is 50-60 beats per minute. Maximum exercise HR < 100.
d. Abrupt discontinuation of therapy in patients with ischemic heart disease may be associated with increased frequency, duration, and severity of anginal attacks. Sudden death has also been reported. The dosage should be tapered over a two-week period when discontinuing therapy. MAKE SURE DO NOT RUN OUT OF THEIR MEDICINE

BETA BLOCKERS

PATIENT RELATED VARIABLES

a. Raynaud's Disease (vasospastic disease, beta 2 stimulation keeps veins open, block beta 2 receptor and vasospasm worsens, may make vasospastic heart worse
b. Variant Angina (vasospastic angina)
c. Diabetes Mellitus (monitor glucose) (beta 2 stimulation causes glucose to be relaeased into blood, time it takes to return to normal glucose level)
d. Severe unstable HF
e. Asthma (monitor for wheezing)
f. Heart block (PR seg >0.24, 2° or 3° AV block)
g. Heat rate <50 without beta blockers ( can get worse)

CALCIUM CHANNEL BLOCKERS

verapamil, diltiazem, nifedipine.

PHARMACOLOGY

a. Calcium channel blockers decrease oxygen demand by causing arteriolar dilation (DECREASE AFTERLOAD) and by decreasing the INOTROPIC state of the heart (nondihydropiridines).

b. Variant Angina - These drugs prevent and reverse coronary artery spasm making them particularly useful in variant angina.
c. Because of significant reflex tachycardia, do not use immediate release calcium channel blockers (nifedipine causes the most reflex tachycardia).

Calcium channel blockers

NIFEDIPINE

(Dihydropyradimes)

causes the most relex tachycardia and significant vasodilation/ Does not have a direct effect on the heart/ Beacause causes so much vasodilation it stimulates the sympathetic nervous system/ DO NOT USE NIFEDIPINE IN ANGINA

Vasodilation: greatly increases

Sympathetic/ Renin Activation: greatly increases

Heart Rate: increases

Decreased AV & SA node conduction: None

Ventricular Contractility: None

Constipation: none

Diltalizem/ Verapramil

(Non-hydropyridines)

*Does have a direct effect on the heart

Vasodilation: increases

Sympathetic/ Renin Activation: ?

Heart Rate: decreases (direct suppressing effect on the heart

Decreased AV & SA node conduction: decreases

Ventricular Contractility:decreases

Constipation: increases

CCB

Toxicities

a. See comparative chart
b. Reflex tachycardia (especially with nifedipine) can worsen anginal symptoms.
c. Constipation – verapamil; use a stool softener to prevent
d. Ankle edema unrelated to heart failure; diuretics or ACEIs can be helpful

3 of drugs we would consider using in someone who has had their first heart attack

1. ASA
2. Clopidogrel (1 -12 months depending on stents)
3. Beta-blockers
4. ACEI/ARB (Prevent remodeling/increase mortality)
5. Aldosterone antagonists (EF<40% already on ACEI or ARB)
6. Statins (high cholesterol)

Chronic stable angina

1. ASA
2. Statins
3. ACEI or ARB
4. NTG/long-acting nitrates
5. B-blockers
6. Calcium channel blockers

Hypertension

Definition

-is a syndrome characterized by a sustained elevation in arterial blood pressure.
- The diagnosis is based on the average of at least two blood pressure readings (separated by at least 2 min) at each of two or more visits after the initial screening visit.

-Treatment JNC 7

a. Cerebrovascular accidents
b. Heart disease
-myocardial infarction
-sudden death
-heart failure
c. Kidney failure
4. Angina
5. Retinopathy
6. Peripheral arterial disease

Mortality increases with increasing blood pressure

HTN

EPIDEMIOLOGY

1. Approximately 1 billion people in the world have hypertension. One in three adults in the US is estimated to have hypertension. Hypertension is more common in African Americans compared to whites and Hispanics. (data from 2002).

CLASSIFICATION OF HYPERTENSION

What is the goal for diabetic and chronic kidney disease?

Normal

Prehypertension: Life systyle changes unless:

**Goal for diabetic and chronic kidney disease <130/80; ACE or ARB preferred

HTN

ETIOLOGY

1. Primary (Essential) Hypertension – unknown cause
2. Secondary: a. Pheochromocytoma (adrenal tumor)
b. Renal artery stenosis c. Drug induced
- Oral contraceptives
- NSAIDs, sympathomimetics
- Other
d. Chronic Kidney Disease (CKD)
e. other
3. Resistant – failure to achieve BP goal despite max doses of 3 antihypertensives
a. secondary hypertension
b. Drug induced
c. Comorbidities – obesity, pain, vasoconstriction

HTN

PATHOPHYSIOLOGY

a. BP = cardiac output (CO) x peripheral resistance (PR) all effective therapies of high blood pressure decrease the product of cardiac out put and PR
b. Genetic polymorphisms: populations of patients may have geneticly different enzymes. increase or decrease ability of certain drugs to work
c. Sodium regulation
d. Alterations in RAAS
e. Overactivation of sympathetic nervous system
f. Increase peripheral arterial resistance
g. Other – see above

HTN

Therapeutic Goals

1. To eliminate the excess cardiovascular risk and end organ damage associated with high blood pressure. Achieve a normal blood pressure.
2 Institute life style changes in patients who are prehypertensive. In diabetics and patients with chronic kidney disease – use medications to achieve a blood pressure <130/80.
3. If drugs are needed, a regimen should be selected which is simple, affordable and produces minimal side effects. Most patients with hypertension will require 2 or more drugs.
4. Satisfy patient and family: really important, good bedside manner

FACTORS THAT INCREASE MORBIDITY AND MORTALITY OF HYPERTENSION

(So if have these with HTN)

Smoking, Dyslipidemia, Diabetes mellitus, Age >60yo, Male, Postmenopausal women, Family history of cardiovascular disease (in mother <65yo or in father <55yo), chronic kidney disease.

HTN

PATIENT EDUCATION ISSUES

1. Patient should understand the importance of treatment.
2. Although therapy may be life long, some patients successful at life-style changes can be removed from drug therapy with continued monitoring. A good rapport between the patient and the health care provider is essential for long term success.
3. Drugs and drug dosages may have to be changed.(Set up: no one knows the best therapy for you, with your help we are going to find the best therapy for you, set the expectation, don't assume that they know that changes may need to be made)
4. Refill prescriptions BEFORE running out of medications.
5. Side effects from the drugs may be more bothersome to patient than the disease.
6. Help the patient develop methods for remembering to take medication. (tell me about your day, daily routine)
7. Involve the entire family.
8. When talking with the patient, avoid describing their hypertension as mild or moderate because these terms do not imply that therapy is not really necessary. Also use the term "high blood pressure" instead of "hypertension." The patient may mistakenly infer from this latter term that their problem is too much "tension" or stress.

HTN

THERAPY

All effective therapies will decrease blood pressure by reducing the product of CO x PR. anthypertensive drugs muck around with this equation and relationship of these factors
Consider the following relationship:

BP = CO x PR

CO=SV x HR

Decreased BP -->reflex increases HR

Increased BP --> reflex decreases HR

HTN

DIURETICS

Thiazides**

hydrochlorothiazide (Hydrodiuril)
metolazone (Zaroxolyn)
Pharmocology

MORE EFFECTIVE IN DECREASING BP THAN LOOP DIURETICS. Normal renal function.

-**Thiazides decrease peripheral resistance through an unknown mechanism. Their diuretic effect is caused by blocking sodium reabsorption from the proximal part of the distal renal tubule. This, in turn, causes increased renal loss of sodium and water.

-Thiazides are more effective antihypertensive drugs than loop diuretics in patients with normal renal function. In patients with renal dysfunction (CCr < 30 ml/min), thiazide diuretics (except metolazone) lose their effectiveness. In this situation, use metolazone or loop diuretics. HOLD ONTO CALCIUM

HTN

LOOP DIURETICS

furosemide (Lasix)

PHARMOCOLOGY

good to use in impaire renal function. PEE OUT CALCIUM

-The mode of action of loop diuretics in hypertension is also unclear. Their diuretic action results from blocking sodium and chloride reabsorption from the ascending loop of Henle. This, in turn, causes increased renal loss of sodium and water (this will be covered in more detail during the lecture on diuretics).

-Renal elimination of Ca - Loop diuretics increase renal elimination of Ca and the thiazide diuretics decrease Ca elimination. Decreased renal elimination of Ca may be a desired effect in a patient with a calcium renal stone. In a patient with hypercalcemia, a loop diuretic would be preferred. MORE EFFECTIVE IN MAKING PEOPLE PEE

If somone has asthma?

I would prefer to order?

And what would I avoid?

-Diuretic, CCB (brochodilators)

-Beta blockers

Diuretics

BOTH THIAZIDE AND LOOP DIURETICS

ADMINISTRATION

a. To avoid nocturia, give as a single daily dose in the morning.
b. To see full hypotensive effect, 2 to 4 weeks of therapy should be allowed. NOT SEEN BEFORE YOU GET TO STEADY STATE. Some drugs take much longer after steady state
c. Use low daily dose: HCTZ 12.5 - 25 mg or chlorthalidone 6.25-25mg

HTN

Diuretics

BOTH THIAZIDE AND LOOP DIURETICS

Toxicity

***

**a. Hypokalemia - Low sodium diet will decrease renal loss of potassium.
Hypokalemia is treated or prevented by giving potassium CHLORIDE supplementation or by adding another diuretic that decreases the renal loss of potassium (i.e., spironolactone, triamterene or amiloride) or an ACEI. Potassium bicarbonate tastes good and doesn't work. Kidneys can't hold onto potassium unless chloride is pressent
b. Hyperuricemia - renal elimination of uric acid is decreased. Generally not a problem unless the patient has a high baseline uric acid or has recurrent gout.
c. Hyperglycemia - Insulin effect is antagonized by thiazide diuretics and is usually only an issue in diabetics. In diabetes, the mild hyperglycemic effect

drug. For insulin to work you need potassium, so before you add more insulin, make sure K is normal.

d. Increased Serum Lipids – High doses of diuretics increase serum cholesterol and triglycerides and should be avoided in patients with already high serum lipid levels.
e. Hypomagnesemia - This may be a problem particularly in malnourished patients or alcoholics. Potassium sparing diuretics will also decrease the elimination of Mg.

HTN

Diuretics

BOTH THIAZIDE AND LOOP DIURETICS

PATIENT RELATED VARIABLES

a. Gout or hyperuricemia
b. Cardiac glycoside therapy (e.g., digoxin) - hypokalemia will increase the toxicity of cardiac glycosides.(THIAZIDES, INCREASED DIG TOXICITIES, can be managed if K doesnt go down)
c. Diabetes Mellitus (decreased K leads to insulin resistance)
e. Renal dysfunction – patients with renal dysfunction should be treated with a loop diuretic (e.g., furosemide) instead of a thiazide diuretic (exception is metolazone).
f. Drug interaction: NSAIDS (including COX-2 inhibitors) antagonize antihypertensive effect (not a contraindication) Increased Na and water reabsorption and can inhibit the effect of your diuretic therapy

HTN

Beta Blockers

PHARMACOLOGY

a. Patients with uncomplicated hypertension will benefit more with other antihypertensive drugs.
Beta-blockers decrease BP through decreasing CO and decreasing the release of renin from the kidneys. Blockade of the BETA2 receptor will cause an INCREASE in peripheral resistance and blockade of the BETA1 receptor leads to a decrease in cardiac output. Cardiac output is reduced more than peripheral resistance thus the net effect of CO x PR is a reduction in blood pressure. Peripheral resistance will decrease back to baseline with continued therapy.

HTN

BETA BLOCKERS

ADMINISTRATIONS

*What will an abrubt discontiuation of this drug cause?

a. Abrupt discontinuation of therapy in patients with ischemic heart disease is associated with an increased frequency, duration and severity of anginal attacks. Sudden death has also been reported. (Bump in BP so don't want to run out!) Although a cause and effect relationship between abrupt discontinuation of beta blockers and these deleterious effects has not been proven, it is suggested that the dosage be tapered over a two week period when discontinuing therapy.
b. The antihypertensive effect is long lasting compared with the relatively short half-lives of these drugs. Once daily dosage is effective for extended release products.

HTN

BETA BLOCKERS

TOXICITY

a. Bronchoconstriction in asthmatics - All beta-blockers can cause this toxicity. If a beta-blocker must be used, relatively selective beta1 blockers are preferred.
b Heart Failure - secondary to negative inotropic effect. (Except Carvedilol- Coreg) (large dose can cause harm, the right dose is good)
c. Exacerbation of peripheral vascular insufficiency (e.g., Raynaud's disease or intermittent claudication). Relatively selective beta1 blockers cause the least problem.
d. Beta blockers cause a delayed return of blood glucose concentration after a hypoglycemic episode. This is secondary to blockade of glycogenolysis and gluconeogenesis. ALSO, the adrenergic response associated with hypoglycemia can result in a marked elevation of blood pressure because the vasodilator caused by beta2 stimulation is blocked. Again, relatively selective beta1 blockers cause these effects less than nonselective beta blockers. (beta causes liver to dump glucose, will take longer for you to return to normal)
e. Tachycardia, as a sign of hypoglycemia, is blocked.
f. Beta Blocker Blues - depression, fatigue, somnolence.
g. Vivid dreams

HTN

BETA BLOCKERS

PATIENT RELATED VARIABLES

*What is a major drug interaction?

a. Asthma
b. Heart Failure (HF)
c. Peripheral vascular insufficiency
d. Diabetes Mellitus
e. Variant angina
f. Drug interaction with Clonidine withdrawal:
g. Drug Interaction with NSAIDS
h. Pregnancy (OK after first trimester; during 1st trimester-associated with decreased growth rate)

HTN

ALPHA-1 BLOCKERS

(Prozosin, Terazosin, Doxazosin)

PHARMACOLOGY

a. Blocks alpha-1 receptors in arterioles resulting in a decrease in peripheral resistance.

HTN

ALPHA-1 BLOCKERS

ADMINISTRATION

*What can this drug cause?

a. This drug will occasionally cause "first dose syncope" (orthostatic hypotension) which may occur within two hours of the initial dose. To minimize this effect, start with a dose no larger than 1 mg and give the first dose at bedtime. Hypovolemic patients are at most risk. (initiate in the evening, lieing down for bedtime)

HTN

ALPHA-2 AGONISTS

(methyldopa, clonidine)

PHARMACOLOGY

(DIMINISH SYMPATHETIC STIMULATION) Used in Opiod withdrawal

a. These agents work by stimulating centrally (mid-brain) located alpha2 receptors. Stimulation of these receptors results in decreased sympathetic outflow from the central nervous system.
c. Methyldopa is the drug of choice in pregnancy because it has been evaluated most extensively in this setting. ( kind to child)
d. Clonidine - Analgesic when given via epidural injection
e. Can be used as adjunct therapy in children to help them sleep. (used in ADHD)

HTN

ALPHA-2 AGONISTS

(methyldopa, clonidine)

Administration and Toxicity.

a. Rebound hypertension can occur from abrupt discontinuation of these drugs. This phenomenon occurs more frequently with clonidine than with methyldopa.

b. Orthostatic hypotension (not as severe as with the adrenergic neuron blocking agents - see below)
c. Sedation/Confusion especially in elderly
d. Impotence

HTN

DIRECT ACTING VASODILATORS

(hydralazine, minoxidil, nitroprusside, diazoxide)

PHARMACOLOGY

a. These agents reduce peripheral resistance by directly dilating arterioles. Reflex tachycardia is common and aldosterone secretion is stimulated leading to sodium and fluid accumulation. (almost always on 2 other drugs, beta blocker and a diuretitc)

HTN

DIRECT ACTING VASODILATORS

(hydralazine, minoxidil, nitroprusside, diazoxide)

ADMINISTRATION

What two drugs are usually given with this drug?

a. A beta blocker is often added to lessen the reflex tachycardia and a diuretic is often used to lessen the sodium and fluid accumulation.
b. Nitroprusside and diazoxide are given parenterally and are used to treat hypertension emergencies.
c. To minimize day to day variations, hydralazine should be given the same time each day with a meal.

AND A DIURETIC GIVEN

HTN

DIRECT ACTING VASODILATORS

(hydralazine, minoxidil, nitroprusside, diazoxide)

a. Excessive reflex tachycardia leading to cardiac ischemia
b. Excessive fluid which may cause edema or exacerbate HF
c. Minoxidil - Hypertrichosis (topically, grow hair loaccally, go as bald as you would of had you never started it)
d. Hydralazine - Reversible Systemic Lupus Erythematosus like syndrome (fever, arthritis, pleuritis, arthralgias, rarely involves the skin). More common with doses greater than 200 mg/day.

HTN

ANGIOTENSIN COVERTING ENZYME INHIBITORS (ACE) & ANGIOTENSIN II BLOCKERS

ADMINISTRATION

***

a. Precipitous reduction in blood pressure can sometimes occur within 3 hours of the initial dose. Patients most at risk are those who are hypovolemic generally caused by severe sodium restriction or over treatment with diuretics.
b. Captopril requires BID or TID dosage. All other ACEI can generally be given QD.
c. **ALDOSTERON HELPS EXCRETE POTASSIUM, ACE INHIBITOR BLOCKS THE RELEASE OF ALDOSTERONE ..Avoid ACEI if serum potassium is > 5mEq/L or if serum creatinine is >3 mg/dL.

GENETIC POLYMORPHISM

ASIAN

-CONVERT ANGIOTENSIN I TO ANGIOTENSIN II WITH ANOTHER ENZYME THAN ACE... SO WE USE ARBS

-AFRICAN AMERICANS ALSO DOESN'T WORK AS WELL, DON'T HAVE THE ACE ENZYME EITHER, THATS WHY WE ADDED THE DIURETIC IN HF.

brochochonstriction and the "ACE COUGH"

Really important to get patient through the cough

HTN

ANGIOTENSIN COVERTING ENZYME INHIBITORS (ACE) & ANGIOTENSIN II BLOCKERS

TOXICITY

a. Precipitous blood pressure reduction following first dose (see above). Can also occur in patients with bilateral renal artery stenosis.
b. Dry/hacking/nonproductive cough (try reducing dose then increase later; can resolve after several weeks)
c. Neutropenia
d. Rash
e. Angioedema: secondary to increased levels of bradykinin
f. Decreased ability to taste

HTN

ANGIOTENSIN COVERTING ENZYME INHIBITORS (ACE) & ANGIOTENSIN II BLOCKERS

PATIENT RELATED VARIABLES

a. Contraindications
- Pregnancy (pregnancy category C/D) (DECREASED AMNIOTIC FLUID
- Bilateral renal artery stenosis (Highly dependent on RENIN to maintain BP, their BP will drop)
- History of angioedema
b. Diabetes Mellitus – ACEI/ARB are renal protective. GOOD

SL NIFEDIPINE

Should you use this anymore for a HTN emergency?

SHOULD NOT BE USING THIS ANYMORE

Not actually absorbed sublingually. May cause uncontrolled drop of blood pressure and should not be used in the treatment of hypertensive urgency or emergency. Gel capsule and squirt under the tongue, when swallow, massive and unpredictable drop in BP, many studies where patients had a stroke.

NO

DIURTETIC

DEFINITION

is a drug that decreased renal reabsorption of sodium either directly or indirectly. This action causes a secondary increase in urine formation. Because diuretics work at different sites in the nephron, their specific effects on electrolyte excretion vary.

TERMS/DIURETICS

DIURESIS

TERMS/DIURETICS

FILTRATION

TERMS/DIURETICS

SECRETION

TERM/DEFINITON

DIURETICS

REABSORPTION

TERM/DEFINITON

DIURETICS

EXCRETION

TERM/DEFINITON

DIURETICS

NATRIURETIC

1. To increase or maintain urine output (e.g., Renal Failure)
2. To alter solute concentration of body fluids (e.g., Hypercalcemia, Hyponatremia-remove free water)
3. To remove excess fluid (e.g., CHF, Chronic Liver Disease)
4. Reduce blood pressure (e.g., Hypertension)
5. Increased venous capacity (e.g., Acute pulmonary edema)
6. Other

OSMOTIC DIURETICS

MANNITOL

PHARMACOLOGY

How does it work?

What do you want to watch for when administering?

1. These agents are freely filtered by the glomerulus and are not reabsorbed. Once in the renal tubules, these osmotically active particles will "hold onto water" and retard its reabsorption thus leading to an increase in urine production. Another action is to decrease reabsorption from the collecting tubule by reducing the medullary concentration gradient.
2. Prior to renal elimination, these agents will expand plasma volume just as they "expand" urine volume. In patients unable to excrete the osmotic diuretic, this may lead to signs and symptoms of fluid overload. (i.e., pulmonary edema, worsening CHF). Administration of mannitol should, therefore, not be continued in a patient with persistent oliguria.
3. GLUCOSE IN URINE: Although mannitol is used clinically as an osmotic diuretic, glucose is also capable of causing osmotic diuresis if the concentration of glucose in the blood exceeds the renal threshold of 180 mg/dL.

OSMOTIC DIURETICS

MANNITOL

CLINICAL USES

1. Oliguria acute renal failure
2. Reduction of intraocular pressure
3. cerebral edema

DONT GIVE PO

OSMOTIC DIURETICS

MANNITOL

ADMINISTRATION

1. Mannitol is very poorly absorbed by the GI tract and must be given intravenously to obtain a diuretic effect.(USE AN INLINE FILTER, CRYSTALS)

2. Observe for crystals in the vial prior to use. If crystals are present, the ampule will need to be heated to redissolve the mannitol.
3. When an IV solution containing > 20% mannitol is infused, an in-line filter should be used.

OSMOTIC DIURETICS

MANNITOL

TOXICITY

1. Electrolyte imbalance - If mannitol accumulates in the patient, both because of excessive administration rate or because of poor renal elimination, plasma volume will be expanded and serum K and Na concentrations may be diluted. Conversely, if excess diuresis has occurred, renal loss of water may exceed that of solute loss leading to increased serum K and Na concentrations.
2. Fluid overload (SEE PHARMACOLOGY) - Pulmonary edema, worsening congestive heart failure.
3. Dehydration - tachycardia; decreased urinary output, increase urine specific gravity, hypotension, coma.

CARBONIC ADHYDRASE INHIBITOR

(Azetazolamide, Diamox)

PHARMACOLOGY

1. Carbonic anhydrase is an enzyme which causes Na+ ion to be reabsorbed in exchange for an H+ ion in the proximal tubule. The net effect is the reabsorption of sodium bicarbonate (HOLD ONTO AN ACID AND GET RID OF A BASE). Blocking this enzyme reduces bicarbonate and Na reabsorption. Carbonic anhydrase is also located in other tissues such as the eye; blockade of this enzyme at this site results in a reduction of intraocular pressure. (carbonic anhydrase, if we inhibit, we don't kick out a hydrogen, alkonises the urine and cause a mild METABOLIC ACIDOSIS)

CARBONIC ADHYDRASE INHIBITOR

(Azetazolamide, Diamox)

CLINICAL USE

1. Diuresis - This effect is small and self-limited.
2. Glaucoma
3. Seizures (METABOLIC ACIDOSIS, increases seizure threshold)
4. Altitude sickness (treat and prevent altitude sickness)
5. Metabolic alkalosis

CARBONIC ADHYDRASE INHIBITOR

(Azetazolamide, Diamox)

TOXCITY AND PATIENT RELATED VARIABLES

1. GI distress, paresthesias, anorexia, and metabolic acidosis.

1. Sulfonamide sensitivity (has sulfa in it)

LOOP DIURETICS

PHARMACOLOGY

***What electrolyte will it cause loss in?

1. These potent diuretics block the reabsorption of NaCl from the ascending loop of Henle where 20 to 25% of the filtered sodium is reabsorbed, thus the name "loop" diuretics. This refers to their high maximum efficacy when compared to other classes of diuretics.
2. Will increase the renal loss of Na, K, Mg, Cl, and water
3. UNLIKE thiazides, will INCREASE renal loss of Ca.
4. Furosemide will acutely increase venous capacitance when given intravenously. This action leads to a decreased cardiac preload which in turn decreases pulmonary congestion in the setting of pulmonary edema.

LOOP DIURETICS

CLINICAL USES

1. Hypertension in patients with poor renal function.
2. Edema (heart failure)
3. Hypercalcemia
4. Hyponatremia - when administered with NaCl infusions, loop diuretics increase free water loss (urine that is hypotonic).(PEE OUT NA BUT PEE OUT MORE WATER THAN NA, SO THERE IS MORE NA LEFT OVER)

LOOP DIURETICS

ADMINISTRATION

1. IV administration should be given slowly to avoid transient hearing impairment and or tinnitus.
2. If you get an order for one ampule of furosemide, how much should you give?

LOOP DIURETICS

TOXICITY

1. Hypokalemia - Increased dietary sodium intake will increase potassium loss. Hypokalemia is treated or prevented by giving potassium supplementation or by adding another diuretic that decreases the renal loss of potassium (i.e. spironolactone, triamterene or amiloride).
When using POTASSIUM SUPPLEMENTS, potassium as the chloride salt should generally be used. Diuretic induced hypokalemia is usually accompanied by hypochloremia and potassium will not be effectively retained by the kidneys unless chloride is also replaced.
2. Hyperuricemia - renal elimination of uric acid is decreased. Generally not a problem unless the patient has a high baseline uric acid or has a history of gout.
3. Hyperglycemia - Insulin effect is antagonized by hypokalemia induced by diuretics. Hyperglycemia may only be a problem in diabetics.

4. Ototoxicity - Tinnitus, reversible and irreversible hearing loss.
5. Hypovolemia - hypotension
6. Hypomagnesemia

LOOP DIURETICS

PATIENT RELATED VARIABLES

1. Gout or hyperuricemia
2. Diabetes Mellitus
3. Allergy to any diuretic (most diuretics are sulfa derivatives)
4. Severe Liver Disease (hypokalemia may precipitate hepatic coma)
5. DRUG INTERACTIONS
a. Cardiac glycosides (digoxin)

THIAZIDE DIURETICS

PHARMACOLOGY

1. Thiazide diuretics work on the early distal tubule to block sodium reabsorption.
2. Will increase the renal loss of Na, K, Mg, Cl and water.
3. UNLIKE loop diuretics, will DECREASE renal loss of Ca.
4. All thiazides have equal efficacy and vary only in their duration of activity, potency, and cost.
5. UNLIKE the loop diuretics, the thiazides tend to decrease GFR and may lose their antihypertensive activity in patients with renal disease. For this reason, thiazides are avoided in patients with preexisting renal dysfunction. (Metolazone and Indapamide are thiazide like drugs that are exceptions to this rule.)

THIAZIDE DIURETICS

TOXICITY

1. Hypokalemia
2. Hyperuricemia
3. Hyperglycemia
4. Dehydration
5. Hyponatremia
6. Hypomagnesemia
7. Hypercalcemia
8. Increased total and LDL cholesterol. LDL increases 5-15% in first 12 weeks of therapy then returns to baseline after one year.
9. Constipation in elderly.

THIAZIDE DIURETICS

PATIENT RELATED VARIABLES

What are major drug interactions?

***

1. Gout or hyperuricemia
2. Diabetes Mellitus
3. Allergy to any diuretic (most diuretics are sulfa derivatives)
4. Renal dysfunction - patients with renal dysfunction should be treated with a loop diuretic (e.g. furosemide) instead of a thiazide diuretic.
5. Drug Interactions
a. Cardiac glycosides (digoxin)
b. Lithium (Loop diuretics have a minimal interaction compared to thiazides – thiazides increase Li levels) Looks like Na to the diuretics, will increase LITHIUM LEVELS

DIURETICS

What are the four ways to increase serum potassium levels?

1. K supplementation

2. Renal dysfunction

3. ACE inhibitor

4. K-sparring diuretic

POTASSIUM SPARING DIURETICS

PHARMACOLOGY

1. These agents work by blocking the exchange of sodium for a potassium or hydrogen ion in the late distal tubule. Spironolactone works by antagonizing the effect of aldosterone. Triamterene and amiloride work directly on the distal tubule to block Na reabsorption.
2. Renal loss of potassium and magnesium are decreased.
3. Minimal increased renal loss of Na.

POTASSIUM SPARING DIURETICS

CLINICAL USE

1. Block the potassium wasting action of other diuretics.
2. In states of hyperaldosteronism, those products are used to maintain sodium-potassium balance.
3. Spironolactone improves outcome in the setting of CHF

POTASSIUM SPARING DIURETICS

TOXICITY

1. Hyperkalemia
2. Gynecomastia (spironolactone)

POTASSIUM SPARING DIURETICS

PATIENT RELATED VARAIBLES

1. Drug interactions - May lead to increased serum potassium
a. Potassium supplement
b. Angiotensin Converting Enzyme Inhibitors (ACE, the inhibit the release of Aldosterone which excretes K)
2. Renal Failure - May lead to increased serum potassium

ANTIARRHYMIC DRUGS

CARIAC CONDUCTION TIME

is the time that a propagating impulse takes to go from point A to point B. When conduction time is INCREASED this means that conduction velocity is DECREASED. (inverse relationship)

ANTIARRHYMIC DRUGS

ACTION POTENTIAL

AUTOMATICITY

refers to the ability of a cardiac cell to automatically fire. In PHASE 0, fast sodium channels open allowing the cell to become positively charged (depolarization). When a particular threshold is reached, the cell will fire. All myocardial cells have the ability to automatically fire, but in the normal situation, the SA node is the first to fire.

ANTIARRHYMIC DRUGS

ACTION POTENTIAL

ABSOLUTE REFRACTORY PERIOD

ANTIARRHYMIC DRUGS

ACTION POTENTIAL

PROBLEMS WITH IMPULSE FORMATION

1. Sinus Bradycardia or Sinus Tachycardia. Automaticity of the SA node is either too slow or too fast. (problem when inappropraitly)
2. Abnormal Pace Maker (cell starts firing)
An abnormal pacemaker will develop when a cell in a location other than the SA node is the first to fire. This is caused when the automaticity of that abnormal site is too fast or when the rate of SA node is firing to slow.

ANTIARRHYMIC DRUGS

THERAPY

general principles

A. A particular type of arrhythmia can generally be caused by multiple mechanisms and it is often not possible to know which mechanism is causing an arrhythmia in a given patient.
B. Diagnosis is a matter of probability and a drug is selected which is believed to have the best chance of working.
C. All drugs capable of stopping an arrhythmia are also capable of CAUSING an arrhythmia or making an existing arrhythmia worse. (Mucking around with the heart)

ANTIARRHYMIC DRUGS

GOAL OF THERAPY

What are the 3 goals of therapy?

1. The goal of therapy will be different for every patient.
2. The goal should be established prior to the beginning of therapy.
3. Examples: 3 goals of therapy
a. Remove cause of arrhythmia (e.g., treat thyrotoxicosis treat hyperthyroidism, treat anemia, and correct electrolyte abnormalities: potassium, calcium, magnesium)
b. Prevent recurrence of arrhythmia
c. Control ventricular rate in the presence of Atrial Fibrillation or Atrial Flutter. (protect the ventricle, partial block at AV node)

antiarrythmics

Vaughn-William Classification

ANTIARRHYMIC DRUGS

CLASS 1A DRUGS

(quinidine, procainamide, disopyramide)

PHARMACOLOGY

(THESE DRUGS ARE NOT USED A LOT)

DIRECT AFFECT ON THE HEART

- Conduction speed slowed (monitor for excessive lengthening of the Q-T interval or the QRS complex) get a baseline
- refractory period is prolonged (re-entry arrhythmias suppressed)
- Automaticity is reduced (suppress abnormal pacemaker) get rid of ectopic
- Negative inotropic effect (especially Disopyramide)

INDIRECT EFFECT ON THE HEART

-Vagolytic effect: blocks the effect of the vagus on the hear(Disopyramide)

ANTIARRHYMIC DRUGS

CLASS 1A DRUGS

(quinidine, procainamide, disopyramide)

TOXICITY

What is the main adverse reaction?

a. GI* :Nausea, vomiting and diarrhea (may be minimized by giving with food or by use of the polygalacturonate salt of quinidine
b. Antivagal Effect: dry mouth(antimuscarinic) (esp. disopyramide); Urinary retention; Dry mouth; Blurred vision
c. Proarrhythmic Effect (R on T) - Excessive delay in conduction through ventricle
Torsades de pointes (twisting of the points) Monitor Q-T interval or QRS complex (keep increase ≤25-50% of baseline: example if baseline QRS is 0.08 msec, when is there a 50% increase?).
d. Negative inotropic effect (esp. disopyramide)
May cause or worsen systolic heart failure
e. Procainamide
Hypotension; Reversible Systemic Lupus Erythematosus like syndrome (fever, arthritis, pericardial and pleural effusions, and skin rash) .
f. Quinidine: Quinidine syncope - secondary to quinidine induced torsades de pointes and subsequent hypotension leading to syncope. Patients with hypokalemia, prior prolonged QT interval are at highest risk. Spontaneuously converts.

ANTIARRHYMIC DRUGS

CLASS 1A DRUGS

(quinidine, procainamide, disopyramide)

PATIENT RELATED VARIABLES

a. Systolic heart failure; NEGATIVE INOTROPES, decrease force of contraction
b. Pre-existing AV block
c. Drug interactions: Quinidine will increase blood concentrations of digoxin (2-5x); reduce dose of digoxin by half when adding quinidine.
Quinidine will increase the effect of warfarin.

ANTIARRHYMIC DRUGS

CLASS 1B Drugs

(lidocaine)

PHARMACOLOGY

a. Main effect is on ISCHEMIC ventricular muscle fibers.
b. RP (Refractory period) is prolonged in ischemic tissues and shortened in non-ischemic tissue. Both of these actions may lead to suppression of re-entry arrhythmia.

ANTIARRHYMIC DRUGS

CLASS 1B Drugs

(lidocaine)

CLINICAL USE

a. Ventricular arrhythmias
c. Therapeutic level
Lidocaine 2-5 mcg/ml - antifibrillatory action
6 mcg/ml - control of ventricular ectopy
d. Emphasis in ACLS is on defibrillation and then if needed to use only one antiarrhythmic drug if possible.

ANTIARRHYMIC DRUGS

CLASS 1B Drugs

(lidocaine)

TOXICITY

Neurological - paresthesias, agitation, slurred speech, somnolence, confusion, psychosis, seizures.

ANTIARRHYMIC DRUGS

CLASS 1B Drugs

(lidocaine)

PATIENT RELATED VARIABLES

***

a. Allergy to lidocaine (patients allergic to procaine are not necessarily allergic to lidocaine).
b. Pre-existing AV block
c. Lidocaine - patients with heart failure will need a reduction in loading dose AND maintenance doses; patients with cirrhosis need a reduction in maintenance dose.

d. Drug interactions
Cimetidine (decreased lidocaine metabolism) available other counter**

ANTIARRHYMIC DRUGS

CLASS 1C Drugs

PHARMACOLOGY

Very effective for suppressing ventricular ectopy. SA node automaticity is depressed and conduction is slowed through the atria, AV node, HIS, and ventricles.

ANTIARRHYMIC DRUGS

CLASS 1C Drugs

(flecainide, moricizine, propafenone)

CLINICAL USES

*****

***a. Treatment of ventricular arrhythmias and supraventricular arrhythmias (artrial fibrillation). Used only in patients without evidence of structural heart disease (especially coronary disease) or left ventricular dysfunction.**** There was study when used in one of these patients the probability of death was significantly higher.
b. Used in non-ischemic patients to maintain NSR following cardioversion of AF.

ANTIARRHYMIC DRUGS

CLASS 1C Drugs

(flecainide, moricizine, propafenone)

DRUG INTERACTION

Cimetidine significantly increases level of flecainide
Beta blockers have an additive negative inotropic effect

ANTIARRHYMIC DRUGS

CLASS 1C Drugs

(flecainide, moricizine, propafenone)

TOXICITY
What TOXICITY can flecainide cause?

a. Proarrhythmic effect (especially in ischemic patients)
b. Negative inotropic effect - heart failure
c. Blurred vision and dizziness
d. flecainide - SLE like syndrome, (also hydralzine)

ANTIARRHYMIC DRUGS

CLASS II Drugs

(beta-blockers, e.g. propranolol, esmolol, metetoprolol)

PHARMACOLOGY

a. Decreases the effect of catecholamines on the heart
b. Will slow the rate of firing of the SA node in the setting of increased circulating catecholamines (general: epinephrine, norepinephrine) or increased sympathetic stimulation.
c. Increased circulating catecholamines will increase automatically at sites other than the SA node and may cause an abnormal pacemaker to form. Beta blockers will suppress the automaticity of these abnormal pacemakers.
d. Will slow conduction through the AV node
e. Negative inotropic effect

WILL block the AV conducntion to protect the ventricles in the setting of A.fib

ANTIARRHYMIC DRUGS

CLASS II Drugs

(beta-blockers, e.g. propranolol, esmolol, metetoprolol)

CLINICAL USES

a. Control of ventricular rate in the setting of Atrial Fibrillation or Atrial Flutter (other drugs used to control ventricular rate in AF – digoxin, verapamil, diltiazem)
b. Supraventricular tachycardia secondary to increased sympathetic activity
c. Reduces mortality when used in: post MI, CHF & Congenital long QT syndrome

ANTIARRHYMIC DRUGS

CLASS II Drugs

(beta-blockers, e.g. propranolol, esmolol, metetoprolol)

ADMINISTRATION

****

a. Metoprolol is sometimes used parenterally to treat arrhythmias. The IV dose is MUCH SMALLER than the oral dose. high first pass effect!***
b. Esmolol is an injectable beta blocker with a very fast onset of action and a short duration of action. In situations where it is not certain that beta blockade will do more good than harm, esmolol has an advantage by virtue of its short half-life (9 min). VERY SHORT ACTING, LEAVES VERY QUICKLY, good drug to trial if not sure will work

ANTIARRHYMIC DRUGS

CLASS III Drugs

(amiodarone, sotolol, dofetilide, ibutilide)

PHARMACOLOGY

a. Increases RP in ventricular muscle without altering conduction time.
b. The chemical structure of amiodarone is similar to thyroxine and possesses both calcium blocking as well as antiadrenergic properties. The half life is about 20-50 days (older patients have longer half-lives). Has become drug of choice post code.
c. Amiodarone possesses activity consistent with each of the other classes of antiarrhythmics.
d Sotolol also has beta blocking action

ANTIARRHYMIC DRUGS

CLASS III Drugs

(amiodarone, sotolol, dofetilide, ibutilide)

CLINICAL USES

What is the drug of choice after cardiac arrect?

What Drug does FDA have in the REMS program?

a. Amiodarone has become the antiarrhythmic of choice in the setting of cardiac arrest.
c. Amiodarone is more effective than either sotolol or propafenone in the maintenance of NSR following cardioversion from AF.
d. Dofetilide and Ibutilide are effective for chemical cardioversion in the setting of atrial fibrillation or atrial flutter. Both drugs can cause Torsade de pointes so patients should be monitored closely for 4 hours following a drug administration.
e. Dofetilide must be used according to a strict protocol and physicians, nurses and pharmacist must have special training to use the drug. FDA developed a program to put special rules in place. Risk Evaluation Mitigation Strategu (REMS Programs) Can use with prolonged QT interval. Must be started in the hospital

ANTIARRHYMIC DRUGS

CLASS III Drugs

(amiodarone, sotolol, dofetilide, ibutilide)

TOXICITY

AMIODARONE

Long term oral therapy especially HIGH DOSE ≥400mg/day -GI (give with food to minimize problem)
- Hypo or hyper thyroidism (5%)
- Asymptomatic corneal deposits (all patients)
- Photosensitivity (25%)
- Blue-gray skin discoloration (5%)

- Pulmonary Fibrosis (10-15%)
Spontaneous optic neuritis (decreased peripheral vision and acuity) - Regular eye exams are necessary
Short term IV therapy
- hypotension (minimize by slow infusion)
- bradycardia

ANTIARRHYMIC DRUGS

CLASS III Drugs

(amiodarone, sotolol, dofetilide, ibutilide)

PATIENT RELATED VARIABLES

AMIODARONE

***

Amiodarone - Increased digoxin and warfarin blood levels

****

ANTIARRHYMIC DRUGS

CLASS IV Drugs CCB

(verapamil, diltiazem)

PHARMACOLOGY

*These are CCB that directly effect the heart

a. These drugs decrease the flow of calcium ions into cells and are often referred to as calcium channel blockers. The SA and AV nodes in the heart are particularly dependent on calcium ion influx. Calcium ion influx causes the nodes to depolarize and thus to initiate (SA node), or propagate (AV node), an impulse. Blocking this calcium channel will slow SA node firing and will slow conduction through the AV node. Verapamil has a greater effect on AV node than does diltiazem.
b. Verapamil and diltiazem also produce a negative inotropic effect on the heart.
c. These drugs cause arteriolar vasodilation resulting in a decrease in peripheral resistance and may cause a reflex tachycardia.
d. Like metoprolol, these drugs undergo an extensive first pass effect when given orally.

ANTIARRHYMIC DRUGS

CLASS IV Drugs CCB

(verapamil, diltiazem)

CLINICAL USES

a. Control ventricular rate in the setting of Atrial Fibrillation or Atrial Flutter. (verapamil or diltiazem but NOT dihydropyridines)
b. Effective in Paroxysmal Supraventricular Tachycardia (PSVT) (verapamil or diltiazem but NOT dihydropyridines). Use if adenosine is ineffective or contraindicated.
c. Not used to treat ventricular tachycardia.

ANTIARRHYMIC DRUGS

CLASS IV Drugs CCB

(verapamil, diltiazem)

TOXICITY

a. Bradycardia
b. Excessive AV blockade
c. Heart failure secondary to negative inotropic effect.
d. Hypotension
e. Verapamil – constipation

ANTIARRHYMIC DRUGS

CLASS IV Drugs CCB

(verapamil, diltiazem)

PATIENT RELATED VARIABLES

a. Pre-existing AV block
b. CHF
c. Drug interactions
- Digoxin blood concentrations are increased
- Other negative inotropic drugs such as CLASS Ia and II

ANTIARRHYMIC DRUGS

CLASS IV Drugs

ATROPINE

1. PHARMACOLOGY
a. Block muscarinic receptors
b. Increases heart rate and improves conduction through the AV node
c. Paradoxical bradycardia if dose is too small (<0.5mg adult)
2. CLINICAL USE
a. Heart block, sinus bradycardia, asystole

HEART IS CONNECTED TO NERVES, BLOCKS PARASYMPATHETIC NERVOUS SYSTEM, WON'T WORK IN HEART TRANSPLANT

ANTIARRHYMIC DRUGS

CLASS IV Drugs

ADENOSINE

PHARMACOLOGY

a. Adenosine is a naturally occurring substance found in the body. It slows conduction through the AV node and reduces AV automaticity.
b. Half life is 10 sec. FAST HALF LIFE

ANTIARRHYMIC DRUGS

CLASS IV Drugs

ADENOSINE

What is it the drug of choice for?

***

a. Drug of choice for Paroxysmal Supraventricular Tachycardia (PSVT)
b. Used in the setting of an EKG that looks like ventricular tachycardia to distinguish supraventricular (narrow QRS) from ventricular (wide QRS) origin. If narrow, treat rhythm with calcium channel blocker, if wide consider electric cardioversion. Note: sedate patient before electric cardioversion.

ANTIARRHYMIC DRUGS

CLASS IV Drugs

ADENOSINE

ADMINISTRATION

How do you administer this drug?

And What may occur after you administer it?

****

ANTIARRHYMIC DRUGS

CLASS IV Drugs

MAGNESIUM SULFATE

What is this the drug of choice in?