BB, CCB, digoxin overdose

CCBs MOA

block VG L-type Ca+2 channels

CCBs block VGCa+C where?

• myocardium

• vascular smooth muscle

dihydropyridine CCBs: affinity

primarily for vascular smooth muscle Ca+2 channels

dihydropyridine CCBs: act as _____

vasodilators

dihydropyridine CCBs: used for

• HTN

• migraine

• vasospasms

nondihydropyridine CCBs: affinity

• myocardial Ca+2 channels

• nodal (SA/AV) Ca+2 channels

• vascular Ca+2 channels

nondihydropyridine CCBs: used for

reduced HR, contractility, vascular resistance

CCBs: metabolism

hepatic metabolism by CYP3A4 enzymes & de-acetylation

CCBs: DDIs

CYP3A4 substrates

CCBS: distribution

highly protein bound, large Vd

CCBs: excretion

primarily renal

physiological roles of Ca+2

• intracellular signaling molecule

• excitation-contraction coupling

• Ca+2 induced Ca+2 release from SR

• spontaenous depolarization of nodal pacemaker cells → most concerning effect of CCB

L-type VGCC causes Ca+ ion release from the _____ ____ of the ____

ryanodine receptor; SR

physiological effects of CCBs overdose

• decrease contractility + HR + vascular resistance

• life threatening

  • severe hypotension

  • brady

  • conduction abnormality

  • complete heart block

CCBs overdose mild symptoms (3)

• fatigue

• dizziness

• lightheadedness

CCBs overdose moderate symptoms (2)

• hypotension

• reflex tachycardia

CCBs overdose severe symptoms (6)

• syncope

• AV nodal block

• AMS

• N, V

• ARDS = acute resp. distress syndrome

ARDS stands for

acute respiratory distress syndrome

CCB diagnostic indicators: on ECG

dysrhythmia, heart block

• elongated PR interval

CCB diagnostic indicators: h_____

hyperglycemia

CCB diagnostic indicators: _____ ____

serum electrolytes

CCB diagnostic indicators: consider other causes of ____ ____ and ____

heart block; hypotension

• any congenital heart disease?

• any other meds that may be causing it?

CCB diagnostic indicators: why hyperglycemia?

insulin release from pancreas is VG Ca+2 channel dependent

→ loss of insulin release

CCB diagnostic indicators: other causes of hyperglycemia to rule out?

diabetes, glucagon administration

management of CCB overdose: what kind of monitoring and support

cardiac + hemodynamic

management of CCB overdose: GI _____

decontamination

management of CCB overdose: orogastric lavage _____ _____ post ingestion

1-2 hours

management of CCB overdose: activated charcoal

oral or NG tube

management of CCB overdose: what can be used if absorption is continuous?

multidose activated charcoal = MDAC

management of CCB overdose: what to use for sustained release formulations?

whole bowel irrigation = WBI with polyethylene glycol (Golytely)

management of CCB overdose: a____

atropine

atropine is used for symptomatic __brady___ from BBs/ CCBs

bradycardia

→ to increase HR + CO

management of CCB overdose: IV _Ca___

IV calcium

• can temporarily reverse negative inotropy, loss of conduction, and hypotension

• repeat doses may be needed, but excess IV Ca+2 can cause complications

• IV calcium max repeat dose: 3-4

which has more calcium: calcium chloride or calcium gluconate?

CaCl2 has 3x the calcium as gluconate salt

management of CCB overdose: glucagon is what?

peptide hormone released by the pancreas

• can activate adenylate cyclase via Gs protein in the myocardium

• to increase HR + contractility

management of CCB overdose: glucagon best used in what?

BB toxicity; can be effective in CCB overdose

management of CCB overdose: glucagon ADEs

hypergylcemia, N

management of CCB overdose: insulin- _____ therapy

euglycemia

management of CCB overdose: insulin-euglycemia therapy works how?

use of insulin-glucose therapy improves glucose uptake by the metabolism

management of CCB overdose: insulin-euglycemia therapy monitoring

glucose monitoring required every 30 minutes for 4hrs

management of CCB overdose: IV ____ ____

fat emulsion

management of CCB overdose: IV fat emulsion used to sequester...

lipophilic drugs in serum, improve intracellular metabolism, activate ion channels

management of CCB overdose: IV fat emulsion, what is key in effectiveness?

lipid phase partition coefficient of the drug

management of CCB overdose: other pharmacological treatment options (3)

• digoxin

• vasopressors

• levosimendan

management of CCB overdose: why is digoxin used?

to inc. intracellular Ca+2

management of CCB overdose: why would digoxin not be used?

dont give to someone with AV block

management of CCB overdose: levosimendan is what?

Ca+2 sensitizer

• last option

management of CCB overdose: non-pharmacological approaches

• cardiac pacing

• intra-aortic balloon to improve CO

BBs functions

• reduce cardiac contractility + rate

• vascular dilation

• uterine relaxation

• bronchoconstriction

• mast cell degranulation

• decrease insulin secretion; gluconeogenesis; glycogenolysis; lipolysis = more powerful metabolically then CCBs

• loss of K+ uptake by muscle and potential hyperkalemia

• block renin secretion

BBs: distribution

is drug specific

BBs: distribution of propranolol (non-selective, B1 + B2)

• highly lipophilic

• highly protein bound

• large Vd

BBs: distribution of atenolol

• highly water soluble

• poorly protein bound

• iv (small) Vd

BBs: elimination of water soluble agents?

renal

BBs: elimination of lipid soluble agents

hepatic clearance

BB overdose: B1 selectivity contributes what?

enhanced cardiac effects

BB overdose: membrane stabilizing effects contribute what?

blockade of Na+ channels can prevent depol. + conduction of myocardium and CNS

BB overdose: ISA contributes what?

reduced B1 specific effects safer in OD

• they activate B2

BB overdose: potassium channel blocking drugs contribute what?

QT prolongation

K channel blocking drugs

sotalol, acebutolol

• can cause QT prolongation

• worsened in:

  • hypokalemia

  • hypomagnesemia

  • bradycardia

  • congenital LQT

BB overdose: vasodilating effects

inc. risk of hypotension, but safer in OD

BB overdose: lipid solubility contributes what?

inc. CNS symptoms

which has more life threatening toxicities? CCB OD or DD OD?

BB OD

BB overdose: 5 severe toxicity effects

• bradycardia

• AV block

• dysrhythmia

• seizures

• coma

more CNS effects

BB overdose: mild symptoms (1)

none (asymptomatic)

BB overdose: moderate symptoms (3)

hypotension, bradycardia, hypoglycemia

BB overdose: severe symptoms (7)

AV block, sinus arrest, hypotension, delirium, coma, seizures, resp depression

BB overdose: severe symptoms can involve what intervals being prolonged?

PR, QRS, QT

BB overdose: severe symptoms are worse in what patients?

existing heart disease (CHF, SSS, congenital AV block)

BB overdose: 3 diagnostic monitoring measures?

ECG, glucose, electrolyte

BB overdose initial management: h____ ____

hemodynamic support

BB overdose initial management: ____

atropine

BB overdose initial management: ______ _____

gastric decontamination

BB overdose initial management: treatment of seizures?

with barbiturates and benzos

BB overdose management: why use glucagon?

increase inotropy (increase contractility)

BB overdose management: glucagon bypasses _____ ____ and activates ____

beta receptors; cAMP

BB overdose management: why use calcium gluconate?

can reverse hypotension

BB overdose management: in what patients is insulin and glucose used?

patients do not respond to glucagon and atropine

BB overdose management: lipid emulsion therapy why use?

draw lipophilic drug away from brain/ heart

BB overdose management: phosphodiesterase inhibitors why use?

increase cAMP despite beta blockade

• use glucagon first, if dont work → phosphodiesterase inhi

BB overdose management: phosphodiesterase inhibitors used in who?

patients failed glucagon

examples of phosphodiesterase inhibitors used?

• milrinone

• amrinone

• enoximone

BB overdose management: use of vasopressors?

at high doses may help

• isoproterenol

• epi

BB overdose management: non-pharm management?

mechanical pacing and life support

digoxin: class

cardioactive steroids

digoxin: called a cardiac glycoside due to its ____ ____ ____

hydrophilic sugar moiety

digoxin: uses

• HF

• cardiac arrhythmias

digoxin: MOA

inhibits Na/K ATPase pump in the cardiac muscle

Na/K ATPase

3 Na out, 2 K in

digoxin: inhibition of Na/K ATPase leads to more Na+ where?

intracellularly

bc Na supposed to go out, but get inhibited → have to stay inside

digoxin: more Na+ intracellulary causes what to reverse?

Na/Ca exchanger

Na/Ca exchanger

3Na into the cell for 1Ca out of the cell

digoxin: net effect of reversing Na/Ca exchanger

intracellular Ca+2 and enhanced contraction

digoxin: second MOA

increase PSNS vagal tone by inc. ACh release at nerve fibers

digoxin: at SA/AV nodes inc. vagal tone ____ ____

dec. HR

digoxin: 2 forms

• digoxin

• digitoxin

digitoxin or digoxin: which has more intestinal absorption?

digitoxin

digitoxin or digoxin: which has more plasma protein binding?

digitoxin

digitoxin or digoxin: which has higher/ larger Vd ?

digoxin

digitoxin or digoxin: which has longer half life?

digitoxin

digoxin: has a ____ compartment PK model

2