3/26/2015

Cardiovascular Pharmacology

Robert C. Bosack, DDS

Last update 3/2015

Relevance
• Renew / gain familiarity with CV drugs
• Appreciate nuances in medical management
of CV diseases which will affect your patients
• Gain insight into the health / disease of your
patients

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To be discussed
with a “mini-pathophysiology” review
• HTN, CAD, HF, arrhythmias
• RAAS - ANS
• Drugs (anti-hypertensive + other indications)
– Diuretics
– ACEI – angiotensin converting enzyme inhibitors
– ARBS – angiotensin receptor blockers
– CCB – calcium channel blockers
– β blockers
• Nitrates
• Inotropes
• Anti-arrhythmics
• CIED – cardiac implantable electronic devices
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The CV system is the 1st to go

• 50% + deaths due to CV disease
• Treatment
– Lifestyle changes
– Drugs
– Devices
– Surgery

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General Considerations
• These are “life-long” treatments
– Asymptomaticdisease
• Earlier intervention
– “milddisease”
• Aggressive intervention
– “seriousdisease”
• New therapies may be adopted too quickly
– “study errors”
• Long term side effects
• Polypharmacy / drug interactions
• Medication errors
• Pill burden and dosing complexity
• Non-compliance *****
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Side effects are huge

• Dry, non-productive cough
– ACEI – 5 – 20%, (not dose related)
• Hypotension…syncope
– β blockers
– Diuretics
– All vasodilators – nitrates, CCB, α blocker
– α blockers
• FloMax (tamulosin)
• Hytrin(terazosin)
• Minipres(prazosin)
• Cardura (doxazosin)
• Thyroid trouble – hyper / hypo
– Amiodarone
• Fatigue, lethargy
– β blockers
• Masked signs and Sx of hypoglycemia
– β blockers
• Erectile dysfunction
– β blockers

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Common Drug Interactions.

• Bradycardia
– Digoxin ± β blocker ± non dihydropyridine CCB
(diltiazem, verapamil) ± amiodarone
• Postural hypotension
– Nitrates ± diuretic ± vasodilator ± α blocker ± CCB
• Hyperkalemia
– ACEI ± spironolactone ± NSAID
• Masked hypoglycemic reaction
– Insulin ± oral hypoglycemic ± β blocker
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• 5 major classes of
antihypertensive agents
• Also used to tx
– Myocardial dysfunction
– LVH
– HF
– Renal disease
– Many, many more……..

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Which drugs should you discontinue prior to

dental treatment ?

• None
• You did not prescribe it, you are not
authorized to stop it

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Hypertension
• Powerful risk factor for
– CAD (atherosclerosis), Acute MI, HF, renal failure, AA
• 1/3 of adults, AA preponderance, underDx, underTx
– Primary Hypertension
• No identifiable cause, gradual onset
• Environment – Obese, EtOH, smoke, DM, sedentary, hyperlipidemia
• Heredity
• Secondary Hypertension
• Identifiable cause, usually rapid onset/discovery
• Renal insuff, pheos, renal artery stenosis, Cushing’s, NSAIDs, OSA, Coarc.
• Work up
– Search for target organ damage
– CAD, PVD, LVH, CVD, HF, kidney, eye
– UA, creat, echo, bruits, fundoscopic
• Tx – behavior modification, drugs, monitoring
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Hypertension
• Current guidelines target < 150/90mmHg if
> 60 years of age and 140/90 for everybody
else
– To minimize long term risk for CV M and M
• Needless to say, you should check pressures
on all of your patients, especially before local
anesthetic injection.
• 180 / 110 mmHg is maximum, and consider
referral if this patient is not being treated for
HTN
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Drug Regimen
• Any of the following are good choices
– Thiazides
– CCB
– ACEI
– ARB
• Special situations for treating HTN
– African American
• Should try thiazides/CCB as first choice
– Chronic Kidney Disease
• Initial or add-on therapy should be ACEI or ARB
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Coronary Artery Disease

• Hardening, narrowing +/or
dysfunction of coronary vessels
• Interrupts the balance of myocardial
O2 supply and O2 demand
• Stenotic – fixed
– Fairly steady course
– Plaque impedes blood flow
– Ischemia of demand
• Thrombotic – acute
– Variable presentation
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Pathophysiology of acute coronary syndromes

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CAD
• Tx
– Lifestyle changes, anti-lipids
– β-blockers
• Slow the heart rate, reduce demand, prolong diastolic coronary perfusion
– ACEI / ARBS
• Reduce adverse ventricular remodeling after MI
• Improve long term post-MI survival
– Calcium Channel Blockers
• Slow the heart rate, etc., reduce afterload
– Nitrates
• Venodilator – reduce preload
• Coronary vasodilation
• NTG – short duration of action
• Isosorbide – prolonged duration of action
– Antiplatelet – ASA, clopidogrel, Glycoprotein IIb/IIIa receptor
antagonists
• Coronary revascularization
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O2 Supply O2 Demand

Anti-anginals

Cardiac
Vasodilators
Depressants

Nitrates CCB CCB β blockers

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Heart Failure
• Progressive, complex clinical syndrome of
inadequate CO
– Systolic Dysfunction – can’t pump
• LV dilatation, impaired contractility
– Diastolic Dysfunction – can’t fill
• Normal to small chamber size
• Left ventricular hypertrophy

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Heart Failure
• Current treatments for HF are aimed at
prolonging survival, not just Sx relief
• Prolong life with
– ACEI
– β blockers
– Aldosterone antagonists
• Improve Sx with
– Diuretics, loop and thiazides
– Digoxin
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Heart failure – NYHA class I – IV

none, mild, moderate or severe Sx

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Heart Failure – 3 symptom classes

• ↓ Cardiac Output
• Low EF (s/b 55-75%)
• Exercise intolerance
• Decreased renal perfusion
• Sympathetic stimulation
• Tachycardia, cold extremities
• Fluid Retention
• Edema, ascites, cough, constipation, dyspnea, weight
gain, orthopnea, PND

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Sympathetic Activation in HF

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Compensatory Mechanisms: RAAS

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Vicious Cycle of HF management

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ANS review

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Sympathetic NS – adrenergic

• α 1 - vasoconstriction
• α 2 – inhibit NE release
• β 1 - ↑ rate and force
– ↑ renin secreon
• A2 and aldosterone – NaCL/H2O
retention
– ↑ cardiac output
– ↑ conducon vel oci ty
• β 2 – vasodilation, bronchiolar
dilation
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β1 receptor blockade
• Decreases O2 demand / consumption
– By ↓ in rate and contracl ity
• Decrease rate prolongs diastolicperfusion
• Decrease Blood Pressure
– Mechanism is not fully elucidated
• ↓ tachyarrhythmia
– By ↓ conducon thr ough AV node
• ↓ automac i ty of an ectopi c pacemaker
• ↓ renin secreon
• Inhibits platelet aggregation
• Blunts the stress response to surgery
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β2 receptors - dilate
• Trachea, bronchioles and arterioles
– Except skin and brain
• β2 blockade
– Leaves α constriction unopposed
– Aggravates
• Coronary artery spasm
• Raynaud’s phenomena
– Bronchiolar constriction

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β blockers
Some
α blocking
activity

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α and non-selective β blockers

direct vasodilator properties

• Labetolol (Trandate, Normodyne)

– Useful for hypertensive emergencies
• Lasts 4 hours
• Bronchospasm, paradoxical HTN
– Preferential β blockade of skeletal muscle vasodilatory
β receptors at low doses
• Carvedilol (Coreg)
– Useful for systolic dysfunction
• Nebivolol (Bystolic)
– β1 + nitric oxide vasodilation
– For HTN 34

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Pindolol (Visken)
• β blocker with “intrinsic” sympathomimetic
activity
– Milder β blocker effects and minimize peripheral
vasoconstriction

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Indications for β blockers

• CAD
– Decrease O2 demand
– Angina, MI (limit infarct size)
• HTN
– Decreases renin and CO
• Tachydysrhythmias
– Increase refractory period, conduction time, ectopic
automaticity, overall decrease of cardiac sympathetic
activity
• Neurocardiogenic syncope
– Blocks intense LV contraction that may ppt paradoxical
vagal reflex
• Migraines, tremor, glaucoma, pheos, thyrotoxicosis
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Potential Side Effects of β blockers

• Symptomatic bradycardia and heart block

• Bronchospasm (asthma)
• Impotence, fatigue, depression, insomnia
• Unopposed α effects
– Exacerbate vasospastic or cocaine induced chest pain
– Peripheral vascular disease –claudication
– Raynaud’s phenomena (un-opposed α)
– Cold extremities
– ↑ BP / ↓ HR with epi
• Mask or exacerbate diabetic hypoglycemia
– Facilitate hypoglycemia
– Blunt catecholamine surge with hypoglycemia
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Adverse Drug Interaction

• Non-specific β blockers and epinephrine
– If you look !!!
– Hypertension and bradycardia
• Hypertension
– Unopposed α vasoconstriction from β blocker
– α vasoconstriction from epinephrine
• Bradycardia
– From the β blocker
– Reflex bradycardia from β blocker
• BP on all patients prior to local anesthetic
injection
• Careful with epi for patients on β Blockers
– In this case, recheck 5 mins after injection
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Discontinuation of β blockers
• Blockade can lead to receptor up-regulation
• Conformational changes in molecular structure
– Abrupt discontinuation can lead to angina,
hypertension, any sympathetic surge

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The α 1 receptor vasoconstricts

• On arterioles and veins
• Blockade – vasodilation
• ↓PVR, without ↓ CO or reflex tachycardia
• Orthostatic hypotension,syncope
• Inhibits NE induced contraction of prostate smooth muscle
– α 1 blockers – HTN, HF, Angina, Pheos, BPH
• Doxazosin (Cardura)
• Prazosin (Minipress)
• Terazosin (Hytrin)
• Amiodarone
• Phenothiazines

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α 2 receptor
• Only in the CNS
–
outflow
• α 2 agonists
– Clonidine (Catapres)
• ↓ CO, HR, SVR, renin
• Hypertensive urgency
• Rebound HTN with abrupt
withdrawal
– Dexmedetomidine

Parasympathetic Nervous System

cholinergic – rest and recovery

• Slows heart rate

– M2 – cardiac
• ↓ frequency of firing of SA node
• ↓ conducon vel oci ty of AV node
• Prolongs refractoryperiod
• Increase GI motility
• Stimulate bladder emptying
• Increase biliary contraction
• Contract smooth muscle
– M3 - bronchioles
• Lowers blood pressure
– M3 – vascular endothelium

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Parasympathetic innervation

• Cranial - 3, 7, 9, 10
• Sacral – bladder, bowel and pelvis
• Vagus accounts for most parasympathetic traffic
• Cholinergic (mediator is AcH)
– Muscarinic – effects blocked by atropine
– Nicotinic – what remains after full ATR blockade

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Atropine – dose related

• 0 – 0.5mg
– Mild paradoxical bradycardia, dry mouth, ↓ sweang
• 0.5-1.0mg
– Cardio-acceleration, very dry mouth, pupillary dilation
• 1.0 – 2.0mg
– Above + blurred vision
• > 3.0mg
– Red, hot skin, agitation, delirium, coma

Glycopyrrolate vs.Atropine
• Glycopyrrolate has
– Slower onset, longer duration
– Quaternary structure – does not X BBB
– Less cardiac effects
– More potent anti-sialogogue

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Anti-muscarinic overdose ↓AcH

• Xerostomia • DRY as a bone

• Blurred vision – No sweating
– No salivation
– Loss of accommodation
– No lacrimation
• Constipation
– Additives with narcotic
• BLIND as a BAT
– pain meds • HOT as HELL
• Tachycardia – No sweating

• Cognitive dysfunction • RED AS A BEET

– Cutaneousvasodilation
• Exacerbate narrow < glaucoma – Atropine flush
• MAD as a HATTER

Anti-cholinergic syndrome
• Usually involves combination of drugs with
anticholinergic properties
– TCAs – esp. amitriptyline
– Phenothiazines
– Anti-histamines
– Anti-parkinson agents
– SSRI
– Thioridazine
– Clozapine
– Various anesthetic agents ???? BZ??

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Diuretics
• Mainstay of Tx of HTN and HF, reduce mortality from HTN
LVH regression
– Eliminate Na+ and H2O
• Improve pulmonary congestion and peripheral edema within days
– inial ↓ int ravascul ar vol ume to lowe r BP
• after 2 months may activate vascular endothelial channels to reduce SVR
– May activate vascular endothelial channels to SVR
• Improves BP control by blocking compensatory Na+
retention from other anti-HTN meds !!!!
• Thiazides, loop and K+ sparing

Diuretics
• Increases rate of urine output
• Most increase rate of solute excretion, esp Na and Cl
– Most ↓ Na resorb from tubules
• Causes natriuresis (increased Na output)
• Causes diuresis (increased water output)
• May indirectly alter urine concentration of other solutes
• Most common use is to reduce ECF volume
– But won’t last forever, as compensatory mechanisms will
be activited
• ↓ ECF volume reduces BP and GFR, increases renin and A2

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Diuretics
• Osmotic diuretics
– Urea, mannitol and sucrose
– Are not reabsorbed, therefore osmotically draw
water into tubules, into urine
– GLUCOSE
• When it reaches transport maximum ~ 200mg/dl
• Lost of water stimulates thirst to replenish

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Diuretics
• Thiazides
• Hydrochlorothiazide (Hydrodiuril)
• Chlorothiazide (Diuril)
• Chlorthalidone (Hygrotin)
• Indapamide (Lozol)
– Inhibit Na+ and Cl- resorption in the early DCT
– Less potent than loop diuretics, but longer
duration of action
– DCT are “fine tuning” excretion, affects only 5 –
10% of filtrate

Diuretics
• Carbonic anhydrase inhibitors
– Acetazolamide inhibits carbonic anhydrase in PCT,
therefore inhibits HCO3- reabsorption.
– Will reduce Na+ reabsorption (which is coupled to the
Na+/H+ counter transport mechanism)
– Decrease HCO3- reabsorption will also decrease Na+
reabsorption.

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Diuretics
• Loop Diuretics
• Furosemide (Lasix)
• Bumetanide (Bumex)
• Torsemide (Demadex)
– Impair Na resorption in the thick ascending loop of Henle
• Block 1Na-2CL-1K cotransporter
• Interfere with countercurrent multiplier
– For advanced degree of HF, and renal insufficiency, where
hyperkalemia may be a risk
– Combo therapy with thiazides with impaired renal function
“sequential nephron block”
– Acute management of pulmonary edema

Diuretics
• K+ sparing Diuretics
– Aldosterone Antagonist
– Compete at aldosterone binding site in cortical collecting tubule – decreasing
Na and K resabsorption (aldo promotes K excretion)
• Spironolactone(Aldactone)
– Aldosterone independent
– Inhibit Na resorp and K secretion in collecting tubules
– Block Na reentry into tubular cells, therefore K cannot be lost
• Triamterene (Dyrenium)
• Amiloride (Midamor)
• Rarely used alone (weak)
– ACEI + loop diuretic ± dig --- improves HF Sx and reduce mortality
• Spironolactone in that mix Inhibits adverse effect of aldosterone on
myocardial remodeling

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Diuretic side effects

• ↓ CO, hypotension
• K+ and Mg++ depletion – arrhythmia, cramps
– Thiazides > loop, consequences for ectopy ?
• Hyperkalemia with K+ sparing diuretics
• Impaired glucose tolerance, insulin resistance
– Esp with low normal K+

Diuretics and sites of action

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Calcium Channel Blockers

• Block inward movement of Ca++ ions across cell

membranes
– ↓ contractility of Ca++ dependent actions
• vascular smooth muscle cells - VASODILATION
• cardiac muscle cells - ↓ contracl ity
• nodal pacemakers - ↓ HR
– Tx HTN, angina, rate control when β blockers
contraindicated, fast heart rhythms

Nodal function is Ca++ dependent

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Calcium Channel Blockers

improve coronary flow, decrease preload and afterload by lowering BP, and slowing
heart rate and decrease contractility

• Dihydropyridines – (more potent vasodilators)

– Nifedipine (Procardia, Adalat)
– Amlodipine (Norvasc) – safe with systolic dysfunction
– Felodipine (Plendil)
–
–
Isradipine (Dynacirc)
Nicardipine (Cardene)
↓ BP
– Clevidipine (Cleviprex)
• Non-dihyropyridines (less potent vasodilators)
– Slow the heart, good for rate control, AFIB, SVT
– Careful if with β blockers
– Verapamil* (Isoptin, Calan, Verelan)
– Diltiazem* (Cardizem, Tiazac, Dilacor)
↓ HR

Side effects CCB

• Peripheral edema (not related to HF)
• Dizziness, headache, gingival hyperplasia
• Bradycardia, AV block
• Flushing
• Constipation (verapamil)

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Renin-Angiotensin-AldosteroneAxis

• Kidney and brain are adept at autoregulation

• Kidney is susceptible to damage at high or low BP
• Kidney controls its own perfusion
– Fast – mediates vasoconstriction ((10-15min)
– Slow – alters blood volume

• RAAS
– modulates fluid and pressure in response to detected
changes in renal blood flow
1. Hypotension leads to RENIN release
2. RENIN cleaves angiotensinogen to angiotensin I
3. Angiotensin I ACE Angiotensin II
4. Angiotensin II stimulates aldosterone release
• Na+, H2O resorption at DCT

ACE
• Converts A I to A II
• Breaks down vasoactive peptides (including bradykinin)
• Other pathways produce angiotensin II also
• “angiotensin escape” - gradual rise of A II with long term ACEI

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Renin-Angiotensin-AldosteroneAxis

• Drugs that interfere with this axis are very important

in the regulation of HTN, CV and CR disease
– ACEI – the “prils”
– ARB – the “sartins”
• Vasodepressor
• Able to slow progression of renal, cardiac and
vascular disease – “tissue protective”

ACEI /ARBS
• “darlings of CV disease Tx”
• Postulated to reduce sympathetic outflow
• Improve endothelial function, facilitate
vascular remodeling and favorable alter the
fibro-elastic properties of blood vessels
• Indications
– First line HTN – esp with DM, renal disease
– Reduce LVH
– First line systolic HF

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ACE Inhibitors – “Prils”

• Mainstay of Tx for HF with LV systolic dysfunction
– ↓ PVR without ↓ in CO or GRF, or ↑ HR!!!!
– “reno-protective” in patients with DM, proteinuria
• Captopril (Capoten)
• Enalapril (Vasotec)
• Lisinopril (Zestril, Prinivil)
• Ramipril (Altace)
• Fosinopril (Monopril)
• Quinapril (Accupril)
• Benazepril(Lotensin)
• Trandolapril (Mavik)

ACE Inhibitors
• Side effects
– Hypotension (esp with concomitant diuretics, volume depletion)
– Hyperkalemia (esp. with renal dysfunction) and K+ sparing
diuretics (may worsen renal dysfunction if pre-existing)
– Dry cough, loss of taste, rash, angioneurotic edema

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Angiotension II Receptor Blockers

ARBs

• Block the Angiotensin II AT1 receptor to block renin-

angiotensin system
• No dry cough, less ?? angioneurotic edema
• Still can have hypotension, hyperkalemia
• More costly than ACEI, less effective?
– For patients who cannot tolerate ACEI or develop resistance to them

Angiotension Receptor Blockers

ARBs – “sartins”

• Losartan (Cozaar)
• Candesartan (Atacand)
• Irbesartan (Avapro)
• Valsartan (Diovan)
• Olmesartan (Benicar)
• Telmisartan (Micardis)
• Eprosartan (Teveten)

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Direct Renin Inhibitors

Dr. Alice Huxley

Direct Renin Inhibitor - aliskerin

• A direct acting renin blocker

• To Tx HTN ± diuretic
• no cough, no angioedema

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Nitrates
• Tx stable and unstable angina
• Convert to NO (endothelium derived relaxing factor)
and stimulates formation of cGMP
– Mediates vascular smooth muscle cell relaxation, relax
coronary vessels
• ↓ preload, therefore heart size, ↓ O2 demand
• Interferes with platelet aggregation

Nitrates

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Nitrates
• Spray or tablet – NTG
– Dilates coronary arteries, reduce preload and
afterload, reduces pain
– BP > 90mmHg systolic
– SubL – onset ~ 3 minutes, duration 30 min
• Isosorbide (Isordil) – long acting tablet
• Topical ointment
• IV preparations - nitroprusside

Nitrates
• Can develop “tolerance” to nitrates
– Space dosing to 10 hours or more
• Avoid with PDE inhibitors
– Also a vasodilator – sudden drops in pressure
• 10% of patients are non-responders

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Inotropes
• Indications
– Bridge to transplantation
– Acute compensation with low CO
– “maximal medical therapy”
• The life expectancy of HF patients is shortened
(or at best unchanged) by long term exposure to
inotropes
– ↑ Ca++, enhance contractility, but promote after depolarization
potentials as well - arrhythmogenesis
• Digitalis Glycosides
• Sympathomimetic amines
• Phosphodiesterase Inhibitors

Inotropes
• Digitalis Glycosides
– Inhibit Na+ - K+ ATPase pump in myocardial cell
membranes
• ↑ intracellular Na+ ---- exchanges with Ca++
– ↑ force of contracon (+’ ve inotrope)
• Slows nodal conduction (vagal + sympatholytic effect)
– Good for afib with LV systolic dysfunction
• Part of HF “triple therapy” – Dig – ACEI – diuretic
• Dig toxicity (exaggerates parasymp)
– N, V, anorexia, blurred vision, HA, fatigue, confusion
– PVCs, PAT, block
– Worse with hypoxemia, ↓K+ or Mg++, advancing age, diuretic use

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Inotropes
• Sympathomimetic amines (IV infusion)
– Dopamine (Intropin)
• Low dose 2 - 5μg/kg/min – improve renal flow
• Moderate dose 5 - 10μg/kg/min – inotropy
• High doses - vasoconstriction
– Dobutamine (Dobutrex)
• β1 agonist, less chronotropy vs dopamine
• No vasoconstriction
• Tachyphylaxis possible – switch to ……

Inotropes
• Phosphodiesterase inhibitors
• Milrinone (Primacor)
• Amrinone (Inocor)
– Net effect of ↑ cAMP
– “inodilator” effect
» Positive inotropy with peripheral vasodilation
– Side effects
• Thrombocytopenia
• Hypotension, tachycardia

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Anti-arrhythmic agents

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Anti-arrhythmics
• Caution s/b used when Rx antiarrhythmic
– All can be pro-arrhythmic
– Initial therapeutic response may not be sustained
– Non-cardiac adverse events possible
• Amiodarone has enjoyed recent popularity in critical care
because of its broad range of effects for both ventricular and
supraventricular arrhythmias
• Managing electrolyte abnormalities and treating underlying
disease processes (hypovolemia, ischemia) are critical steps
before the administration of any anti-arrhythmic drug

Anti-arrhythmic agents
• Action
– Improve conduction
– Slow conduction, increase refractoriness
– Restore synchrony
• Choices based on
– Efficacy, therapeutic index, side effects
– LV, kidney, renal status
– REAL possibility of “pro-arrhythmia”
– All will depress LV function
– Empiricism
– These drugs have low TI, and can be toxic

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Rhythm disorders
• Atrial (supra-ventricular)
– Atrial fibrillation
• Worry about thromboembolism
• Tx
– Rate control, then rhythm control
– Ablation, pacemaker are possibilities
– Supraventricular tachycardia
• Defect in electricalsystem
• Spontaneous and inappropriate bouts of tachycardia
• Tx
– Vagalmaneuvers
– Adenosine, CCBG, BB, amiodarone
– Ablation
• Ventricular
– Tachycardias – v-tach, v-fib, PVCs
– ACLS algorithms
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Antiarrhythmic agents
(generalizations)

• Vaughan-Williams classification
– Class IA, B and C
• Na+ channel blockers
– Class II
• non-competitive α and β blockers
– Class III
• predominant K+ channel blockers – prolong repolarization
– Class IV – CCB
• slows the nodes
– Indeterminant (other)
• Adenosine (Adenocard)
• Digoxin(Lanoxin)

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III prolongs this

I slows this

II inhibits this

IV inhibit Ca++ influx

Some class I antiarrhythmic drugs

preventative, in patients without structural heart disease

• Quinidine
• Procainamide
• Disopyramide
• Lidocaine – fallen out of favor for ACLS
• Flecainide (Tambocor)
• Propanfenone (Rythmol)

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Some Class III drugs

• Amiodarone (Cordarone)
– Broad range of effects for ventricular and
supraventricular arrhythmias
• Sotalol (Betapace)
• Ibutilide (Corvert)

Amiodarone
a novel therapy and new mainstay in cardiac care

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Amiodarone: Antiarrhythmic has all 4

Vaughan Williams’ Class Effects
Class I effect Class II effect
Sodium channel blockade Noncompetitive alpha- and
beta-adrenergic inhibition

Na+
Na+ Na+
Na+
Na+
Na+

Na+ Na+

Ca++
++
Ca++ Ca Ca++ Ca++

Ca++
Ca++
Ca++

Class III effect Class IV effect

Prolongation of repolarization Calcium channel blockade
and refractoriness by increased
action potentialduration

Amiodarone
• Wide spectrum of effectiveness
– Class I, II, III and IV effects
– Ventricular and/or supraventricular rhythms
– First line drug in ACLS
• Chronic administration
– increase refractory period

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Amiodarone
• Electrophysiologic effects mimic thyroid ablation
– Perhaps it blocks cardiac effect of T3
– Accounts for slow onset of activity
• Adverse effects
– Photosensitivity
– Slate gray pigmentation
– Pulmonary – dyspnea, cough, fibrosis
– Thyroid abnormalities

Selected Amiodarone Toxicities

Optic Neuropathy

Subcapsular Opacity (Cataract)

Skin Discoloration

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Some Class IV drugs

• Verapamil (Calan, Isoptin)
• Diltiazem (Cardizem)
• Indications
– Rate control for atrial fibrillation
– Blood pressure control
• Side effects
– Bradycardia
– Edema
– Hypotension
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Other agents
• Digoxin
– Action: Inhibits Na/K ATPase
• ↓conducon vel oci ty and pr ol ong ref rac tor y per i od
• Slows ventricular response to a-fib
• Enhance parasympathetic tone to AV node
– Indication
• Rate control in A-fib
– Side effects – narrow therapuetic window
• Toxicity
– Heart Block, GI disturbance, confusion, visual disturbance,
dysrhythmias (slow)
– Can be associated with ↓K+, if chronic.
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Other agents
• Adenosine
– Action
• Intermediate metabolite of AMP, regulate vasomotor
tone
• Mimics acetylcholine + potent vasodilator
• Affects tissues north of the ventricles
– Indication
• Acute management of supraventricular tachycardia
– Side effects
• Flushing, cardiac standstill, hypotension, angina, SOB
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CIED
Cardiac Implantable Electronic Devices

Contents:
1. Pulse generator
2. Battery
3. Sensing and pacing electrodes (usually
bipolar)
• Detect low amplitude cardiac
events
• Data accumulation
• Rate adaptive
4. Capacitor

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CIED –
treat enduring conditions not readily amenable to drug therapy

• Pacemaker
– Stimulate the heart when the intrinsic pacemakers fail
• Bradydysrhythmias
– Sick sinus syndrome, symptomatic bradycardia, AV block
• ICD – implantable cardio-defibrillators
– All pacemaker indications
– EF < 30%, postMI
– Survivors of previous cardiacarrest
– Tachydysrhythmias - SVT, VT – overdrive pacing
– Cardiovert 1 – 30j (unstable supraventricular tachycardias)
– Defibrillate 10 – 30j (lethal ventricularrhythms)
– Data accumulation, telemetry
• CRT – cardiac resynchronization therapy
• Make both ventricles contract simultaneously
• Unhealthy hearts with ejection Fx < 30%

Identifying code system

(5 letters)

• 1st letter – chamber being paced – V, A, D (both)

• 2nd letter - chamber being sensed – V, A, D (both)
• 3rd letter – response to sensed activity
• T – a sensed event triggers pacing
• I – a sensed event inhibits pacing
• D – dual

• e.g., VVI – demand ventricular pacing

• inhibited when ventricle beats on its own
• e.g., DDD – paces and senses both atrial and
ventricles, maintains synchrony, allows for natural
rate increases with exercise

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Atrial Pacing

Ventricular Pacing

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AV sequential pacing
DDD

Defibrillators
• ~ 50% of patients with ICD will have an
adverse event related to the device within the
first year after implantation
• Lead related trouble
– Failure to sense or pace
– dislodgement
• Inappropriate shocks

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Telemetry

Issues
• What type of device it is ?
• What is the underlying?
• Is the device functioning properly?
• Is the patient doing well ?
• Will you introduce EMI ? - NO !!

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Focused patient history

• Why? – underlying pathology
• How do you feel?
– Syncope, near syncope, palpitations
– Weakness, malaise
• Compliance with f/u visits
• Battery status – recent interrogation
• Recent shock?
• Inappropriate shock?
• Patient status optimized?

Cautery
can be interpreted as intrinsic events to inhibit pacing or trigger a
shock

• Bipolar
• Short , intermittent bursts • Safe dental devices
• Lowest setting – Ultrasonic scalers
– EPT
• Unipolar cautery
– Root apex locators
– Pure cut better than blend or coag
– Curing lights
– At least 6 inches away
– Harmonic scalpels
– Grounding plate distant
– Current flow should not cross the lead system
• Battery “burners”OK

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Perioperative management
• Consult with cardiologist – what, why, when
– Underlying dysrhythmia?
– Type of device – recent interrogation – battery status
– Pacemakers
• Is patient hemodynamically dependent on the device
• What is the underlying problem
– ICD
• Shock history

What if it shocks when I’m present

• Device may take up to 30 seconds to detect

and shock a potentially fatal dysrhythmia
– Usually, will deliver up to 5 shocks if needed
• One shock – OK, device is doing what is expected, see in
office within a week, if you feel OK
• 3-5 shocks, something is wrong → ER

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Thank you for your kind attention

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