CV med toxicities

what is HTN urgency

SBP >/=180 or DBP >/= 120 with no end organ damage

Tx of HTN urgency

intiating/reinitiating/intensifying ORAL antihypertensive meds

do we do aggresive lowering of BP for HTN urgency? why/why not?

no- pt with chronically uncontrolled Htn will have shifts in autoregulation that make intensive BP lowering suboptimal for organ perfusion

therefore, overly aggressive BP lowering places pts at risk of ischemic complications

what is HTN emergency

SBP >/= 180 or DBP >/= 120 + end organ damage (AKI, retinal hemorrhage, hemorrhagic stroke, encephalopathy, HF, rupture of aneurysm)

HTN emergency Tx

require ICU admission for IV antihypertensives - IV meds aimed at vasodilation or adrenergic inhivition

continuous IV infusions allow dose titration- titrate up quickly for rapid control, if Bp decreases too much can decrease infusion to minimize SE’s

hypotension

SBP <90 or MAP <70

BP inadequate to perfuse organs

Tx of hypotension

fluids, vasopressors, specific antidotes

acute HF Tx

stabilization- oxygen, diuretics, fluid restrictions, etc

others: BB, ACEI/ARBs

conduction abnormalities (bradycardia, AV block) Tx

atropine, symptom treatment (hypotension), specific antidotes

tachycardia HR

>100BPM

supraventricular tachycardia characteristics

can progress to hypotension, chest pain, asystole

supraventricular tachycardia Tx

BB, cardioversion

ventricular tachycardia characteristics

sustained can be life threatening

ventricular tachycardia Tx

depends on Sx - BB, cardioversion, implantable device

QRS prolonging Tx

sodium bicarb

QT prolongation Tx

magnesium

non DHP CCB effects

inhibitory effect in SA/AV node- decrease conduction, decrease HR, decrease CO, decrease BP

which non DHP CCB has most profound effect on SA/AV node

verapamil

DHP CCB effects

peripheral vasodilation, greatest affinitiy for peripheral vascular SM therefore decrease SVR, ( may get reflex tachycardia)

absorption of CCB

well absorbed po but undergo extensive first pass metabolism

distribution of CCB

highly protein bound (cant remove thru dialysis)

Vd varies btwn agents

metabolism of CCB

all metabolized thry CYP3A4 to inactive metabolites- except verapamil - active metabolite with 20% activity

saturated in poisining

drug int- caution with non DHP; compete for 3A4: inhibitors can increase levels

excretion of CCB

renally excreted- varies by agent

clinical manifestations of CCB toxicity

hypotension and bradycardia (hallmark)

decrease LOC, decreased blood flow

AV block, ventricular arrythmias

hyperglycemia- suppressed insulin release from pancreas (insulin release is dependant on Ca influx via L type channels)

diagnostic evaluation of CCB toxicity

history

EKG (continues cardiac and hemodynamic monitoring)

blood work- glucose, electrolytes, Cr, BUN, O2 sat

CCB toxicity management (list them)

airways, breathing, circulation

check vitals- BP, HR, LOC

GI decontamination

1. fluids

2. atropine

3. calcium

4. glucagon

5. insulin

6. vasopressors/catecholamines

7. others; PEDi, lipid emulsion Tx

when are fluids used in CCB tox

if hypotensive

when to use caution with fluids in toxicity management

HF, aRDs, CKD

when is atropine DOC in CCB tox

symptomatic bradycardia (increases HR by increases Sa and AV node conduction)

when is atropine NOT effective in ccB Tox

severe CCB poisoning due to peripheral CCB effects

when to avoid using calcium in CCB toxicity

if digoxin tox hasnt been ruled out

what has diminished the need for extensive calcium admin in CCB tox

high dose insulin

types of calcium used in CCB toxicity

10-20mL of 10% CaCL2 OR 30-60mL of Ca2+ gluconate

**need to run CaCl2 thru central line because of concentration

how often to monitor calcium levels when giving calcium for CCB tox

q 30-60min

calcium ae

hypercalcemia, hypophosphatemia, vomiting, flushing, constipation

DOC in BB toxicity

glucagon

if pt has not responded to fluids + Ca2+ what next for CCB tox

try glucagon 3-5mg IV over 3-5min, reassess in 5min then 4-10mg - continue with maintenance infusion (short half life)

adverse effects of glucagon

N/V, hyperglycemia

treatment of choice for severely poisoned CCB patients

high dose insulin

what is given with high dose insulin in CCB tox

dextrose (unneccessary if BG >16mmol/L)

ae of high dose insulin

hypoglycemia

hypokalemia

monitoring of BG when using high dose insulin as CCB tox treatment

BG q 15-30min until fusions are stable then q 1hr

vasopressors examples used in CCB tox

NE, epi, dobutamine, dopamine, vasopressin

what is given after atropine, Ca2+, glucagon and fluids fail

vasopressors

BB moa

competitively antagonize the effects of catecholamines on B receptors and blunt. the chronotropic and intropic response to catecholamines

also help to slow SA and AV node conduction

which BB has most self poisoning and deaths

propranolol

why does propranolol have higher risk of toxicity

highly lipid soluble and can cross BBB

main mechanism of BB tox

effects on cardiac receptors

hallmark manifestation of BB toxicity

hypotension and bradycardia

clinical signs/sx of BB toxicity

arrythmias- agents with MSA inhibits fast Na channels (acebutolol, propranolol)

K channel blockade- prolong QT, torsades, ventricular dysrythmias

vasodilation- more pronounced hypotension (carvedilol)

CNS effects- usually with lipophillic agents (delirium, coma, seizures) - propranolol

respiratory depression- rare unless pt has pre existing asthma or COPD

list order of management of BB tox

1. fluids

2. atropine

3. glucagon

4. calcium

5. insulin (if above fails)

6. vasopressors

digoxin toxicity causes in children

dosing errors, decimal point error (10 times dose)

adult digoxin toxicity causes

acute changes- renal fx, drug int - changes in protein binding, decreased Cl in liver

diseased hearts become digoxin toxic at lower levels compared to healthy hearts (CHF, CAD, arrythmias)

digocin toxicity moa

increases force of contraction of the heart by increeasing cytosolic calcium, decreases rate of conduction thru SA and AV node

kinetics of digoxin

biphasic distribution- levels taken before 6hr post dose will be misleadiningly high

long half life- shortened in toxicity due to increased Cl

narrow therapeutic index drug

what causes predisposition to digoxin toxicity

comorbidities, concomitant meds, low K

when do you develop Sx of digoxin toxicity (what levels)

>2ng/mL (lowe rlevels with diseased heart, drug int, physiologic changes, low K)

acute digoxin toxicity clinical manifestations

early on- may be asympt

GI sx (N/V, ab pain)- if no GI sx after several hours not likely to develop severe tox

CNS- lethargic, weak (bc decreased CO)

chronic digoxin toxicity clinical manifestations

slow developing, non specific Sx - difficult to diagnose

GI sx- loss of appetite, N/V, weight loss

CNS- drowsiness, delirium, confusion, disorientation

visual disturbances- photophobia, yellow green halos

electrolyte abnormalities in digoxin toxicity

hyperkalemia- marker for increased risk of mortality (correction doesnt decrease death tho)

cardiac manifestations of digoxin toxicity

can cause EVERY known arrythmia- typically bradydysrythmias

does acute digoxin tox respond to atropine

yes

does chronic digoxin tox respond to atropine

often not

diagnosis of dig tox

characteristic arrythmias, serum digoxin levels 6hr post ingestion, electrolytes, SCr, EKG

treatment of dig tox

GI decontamination

if hypokalemic give K

if hyperkalemic- >5 give antidote (digibind)

• if cant give digibind try to shift K intracellularly with: insulin/dectrose, Na bicarb, sodium polystyrene (Ca Contraindicated)

if hypomagensia give Mg sulfate

digibind

indications of digibind

severe tox/arrythmias

no response to atropine

K >5

dig conc >12.8nmol/L at steady state

large ingestions

monitoring after dig tox

monitor closely for 24hr after ingestion

efficacy- Sx improving, EKG, vitals

lab work- electrolytes, renal fxn

safety: hypoK, symptoms of CHF