142. CV Drugs

Question 1

Digoxin - where does this med come from?

Answer 1

foxglove

Question 2

Digoxin - 2 CV effects

Answer 2

incr force of myocardial contraction to incr CO in HF

decr AV conduction to slow rate in afib

Question 3

How does digoxin work biochemically?

Answer 3

inhibit Na K atpase pumps to incr intracellular na and extracellular K

incr IC na -> extrudes IC ca after systolie so more into SR more powerful contraction

Question 4

At toxic levels what does dig do?

Answer 4

paralyze na k atpase pump so K cannot go into cell and K can rise to concerning levels

block sa node and depress av node, incr sn sa and av node to catechlamines –> slow HR and incr risk av block

Question 5

digoxin effects on purkinje fibres

Answer 5

decr resting potential resulting in slow ph 0 depol and conduction velocity

decr ap duration incr sn of m fibers to electrical stimuli

enhanced automaticity resulting from incr rate ph 4 repol and edealyed after depol

therefore why can get pvc and instability pending toward dysrhytmia

Question 6

half life elimination of dig

Answer 6

36h in urine

Question 7

digoxin has a __ vol of distrubtion

Answer 7

large

Question 8

sx of chronic dig toxicity

Answer 8

nausea, anorexia, and fatigue; but a variety of gastrointestinal, neurologic, and ophthalmic disturbances

Visual disturbances include decreased visual acuity, scotomata, photophobia, and chromatopsia (aberrations of color vision, classically yellow, but may occur in a variety of colors)

Question 9

chronic poisonijng of digoxin level?

Answer 9

6ng/ml (50% mortality level)

Question 10

Peds and dig - can they tolerate large loads?

Answer 10

yes as longb as healthy hearts

Question 11

Name 8 dysthrymias associated with dig toxicity

Answer 11

PVCs, especially bigeminal and multiform AV heart blocks of all degrees
Sinus bradycardia
Sinus tachycardia
SA block or arrest
Atrial fibrillation with slow ventricular response Atrial tachycardia
Junction (escape) rhythm
AV dissociation
Ventricular bigeminy and/or trigeminy Ventricular tachycardia
Ventricular fibrillation

Question 12

More sp but not pathognomonic dysrhymias assoc with dig toxicity

Answer 12

Atrial fibrillation with slow, regular ventricular rate (AV dissociation) Nonparoxysmal junctional tachycardia (rate usually 70–130 beats/min)
Atrial tachycardia with block (atrial rate usually 150–200 beats/min)
Bidirectional ventricular tachycardia

Question 13

Name 8 factors assoc with incr risk of dig toxicity?

Answer 13

Concomitant kidney injury or underlying kidney disease Concomitant or underlying heart disease:
Congenital heart disease Ischemic heart disease Heart failure Myocarditis

Electrolyte disturbances Hyperkalemia Hypokalemia Hypomagnesemia Hypercalcemia

Alkalosis

Hypothyroidism

Sympathomimetic drugs (e.g., cocaine)

Cardiotoxic co-ingestions
Beta-blockers
Calcium channel blockers
Class IA or IC antidysrhythmics (e.g., flecainide) Tricyclic antidepressants

Drug interactions (may increase serum digoxin concentration) Quinidine
Amiodarone Erythromycin Nifedipine

Drug Interactions (may increase serum digoxin concentration and cause synergistic bradycardia)
Verapamil
Diltiazem

Question 14

Noncardiac sx of cardioactive steroid intox

Answer 14

General
Weakness Fatigue Malaise

Gastrointestinal
Nausea and/or vomiting Anorexia
Abdominal pain Diarrhea

Ophthalmologic
Blurred or snowy vision
Photophobia
Chromatopsia (yellow, green, red, brown, blue vision changes) Transient amblyopia, diplopia, scotomata, blindness

Neurologic
Dizziness
Headache
Confusion, disorientation, delirium Visual and/or auditory hallucinations Somnolence
Abnormal dreams
Paresthesias and/or neuralgia Aphasia
Seizure

Question 15

Acute vs chronic dig poisoning

Answer 15

acute: lower mort
brady and avb vs ventr dysrh
typically yo pt
underlying heart dis less common, less morb and mortality

Question 16

ddx for digoxin toxicity

Answer 16

oleaner plant
lily of valey
cerebra odollam
thevetia peruviana
depressajnt drugs
methanol
metformin
ethambutol quinine
antimalaria

Question 17

Age diff in digoxin intoxication: adult vs ped

Answer 17

toxic a lower [] vs asymp at higher
n, fatigue, fisual disturb vs obtundation and emesis
tachydys as common as block and brady vs bradydysrh and blocks more common
allergic rxn fab fragment uncommon vs extremely rare
vd less variable 5-7.5L/kg vs vd more variable 3.5-6l/kg in premie infant, 8-16.3 infants 2-24mo

Question 18

when to test for. dig [] in concern for toxicity

Answer 18

Peak con- centrations after an oral dose of digoxin occur in 1.5 to 2 hours, with a range of 0.5 to 6 hours. Steady-state serum concentrations are not achieved until after alpha distribution, or 6 to 8 hours after a thera- peutic or toxic dose and may be only 20% to 25% of the peak concen- tration.

Question 19

ideal serum dig [] in HF

Answer 19

0.7-1.1ng/ml

Question 20

serum steady state dig concentration toxicity?

Answer 20

concentrations of 1.1 to 3.0 ng/mL are difficult to interpret; that is, concentrations as low as 1.1 ng/mL have been associated with toxicity, and patients with levels up to 3.0 ng/mL can be asymptomatic. The incidence of digoxin-incited dysrhythmia reaches 10% at a con- centration of 1.7 ng/mL and rises to 50% at a concentration of 2.5 ng/ mL.

Question 21

Management of dig toxicity

Answer 21

digifab

Question 22

Digifab antibodies -risk of allergic reaction in who? what does it look like?

Answer 22

asthma

erythema, urticaria, facial edema

Question 23

Digifab reactions other than allergic - list 3

Answer 23

hypokalemia
heart failure exacerbation
increase in VR with afib

Question 24

List 5 indications for digifab

Answer 24

1. Ventricular dysrhythmias more severe than PVCs
2. Progressive and hemodynamically significant bradydysrhythmias unrespon-
   sive to atropine
3. Serum potassium >5.0 mEq/L
4. Rapidly progressive rhythm disturbances or rising potassium
5. Co-ingestion of cardiotoxic drugs (for examples, see Box 142.2)
6. Ingestion of plant known to contain cardioactive steroids plus severe dys-
   rhythmia or potassium >5.0 mEq/L
7. Acute ingestion of >10 mg or 0.1 mg/kg in a child plus any one of factors 1
   through 6
8. Steady-state digoxin concentration > 6 ng/mL plus any one of factors 1
   through 6

Question 25

How to calculate how much digifab you need?

Answer 25

body load is amount ingested in mg (total): total x 0.8 (which is bioavail of dig tablets) then use this number and divide by 0.5mg bound per vial to determine number of vials

Question 26

Ex: A toxic-appearing 40-year-old woman has acutely ingested fifty 0.25-mg digoxin tablets. If she needs digifab, how much does she need?

Answer 26

Body load = amount ingested × 0.8 ( bioavailability of digoxin tablets) = 12.5 mg×0.8=10 mg Dose of digoxin Fab fragments ( in vials) = 10 mg ÷ 0.5 mg bound per vial = 20 vials

Question 27

Fab or TVP for bradydysrhythmia second line tx after nonresponse to atropine?

Answer 27

fab tvp higher risk of ventricular dysrhymia

Question 28

Expected time to response after fab infusion

Answer 28

19 mins can take hours

Question 29

If the patient is in cardiac arrest, how much fab to give?

Answer 29

maximum number of vials of Fab fragments available (up to 10) should be administered undi- luted as an intravenous (IV) bolu

Question 30

If, in acute or chronic toxicity, the patient is in a life-threatening ventricular dysrhythmia or heart block and the serum digoxin concentration is unknown but the amount of digoxin ingested is known, we recommend full reversal. How is that dosed?

Answer 30

one vial of DigiFab contains 40 mg of Fab fragments, which bind 0.5 mg of digoxin (Box 142.5). In the same patient, if the steady-state serum digoxin concentration is known, we recommend full reversal with Fab fragments based upon the digoxin concentration utilizing the formula in Box 142.6. An exception to the above regimens is the case of yellow oleander poisoning, where a high case fatality rate and poor cross-reactivity of Fab fragments with the offending cardioactive steroids necessitates higher dosing. Therefore, with acute yellow oleander poisoning, 20 to 30 vials (if available) are recommended.

Question 31

A toxic-appearing 4-year-old child weighing 20 kg has a digoxin level of 16 ng/mL 8 hours after ingestion of an unknown number of digoxin tablets. How many vials should they get?

Answer 31

Dose ( in number of vials) = ( serum digoxin concentration × weight in kg) ÷ 100 = (16×20) ÷100 = approximately 3 vials

Question 32

Ca in a hyperkalemic dig patient - what to do?

Answer 32

classic teaching = stone heart: fab first then tx per normal hyperkalemia

Question 33

While awaiting fab fragments in dig toxicity if someone is in a tachydysrhytmia, what can you give?

Answer 33

phenytoin 100mg bolus q5 min until dhysrh improves or until 18mg/kg reached lidocaine only if CI to pheny or once at max of same: 1.5mg/kg puhs then infusion 1-4mg/min starting at one and titrate up to response

Question 34

If fab fragments are ineffective, can consider which tx?

Answer 34

ecmo

Question 35

Beta blocker function overall

Answer 35

block catecholamines like epi at beta adr receptors to prevent incr inotropy, conduction and HR beta 2: vascular sm relax, liver glycogenolysis and gluconeo, lung/bronchodilation, adipose tissue release FFA, uterus sm relaxation

Question 36

Symptoms of a beta blocker OD

Answer 36

bradycardia hypotension altered LOC apnea HYPOGLYC rare adults, mc kids propranolol can cause seizure

Question 37

Which beta blockers imapir sa and av node function, as well as ventricular conduction showing qrs widening?

Answer 37

propranolol nadolol betaxolol acebutlolol

Question 38

Labetalol and carvedilol additionally block which receptor, causing which sx?

Answer 38

hypotension distrib shock block alpha 1

Question 39

Beta blocker toxicity time to onset (generally)?

Answer 39

within 30 mins apparent within 6 hours - can last up to 24h

Question 40

Beta blocker special features if OD sotalol?

Answer 40

qt. prolongation torsades

Question 41

Name 5 dialyzable beta blockers?

Answer 41

nadolol timolol sotalol atenolol acetbuolol

Question 42

DDX beta blocker OD?

Answer 42

clonidine and tizanidine or imid- azoline receptor agonists such as tetrahydrozoline and oxymetazoline may also cause this constellation of symptoms. odium channel poisoning with QRS widening can occur, suggesting other antidysrhythmic drugs or cyclic antidepressants. The differential diagnoses also include sedative-hypnotic drug overdose, hypoglycemic drug ingestion, opioid overdose, CNS injury or infec- tion, various endocrine and metabolic disorders, sepsis, and acute myocardial infarction.

Question 43

Diagnostic testing in a beta blocker overdose

Answer 43

ecg bg med hx

Question 44

Management of a beta blocker overdose

Answer 44

abc IVF o2 as needed for hypoxia atropine if HR <50 IV ca glucagon 3-10mg IV bolus or 0.05mg/kg child then infusion if responds well 3-5mg/hour high dose insulin R 1 U/kg/hr titrated up by 2 U/kg/hr every 10 minutes (up to a maximum of 10 U/kg/hr) with 25g glucose unless bg >20 bicarb boluses til qrs narrows then NE itrate to MAP of 60, second line VP intralipid: initial bolus of 1.5 mL/ kg of 20% lipid solution given over 2 to 3 minutes, followed imme- diately by an infusion of 0.25 mL/kg/min. If a response occurs at this infusion rate, the infusion dose may be decreased to 0.025 mL/ kg/min (1/10th the initial rate) to sustain lipemic serum for a lon- ger period of time ecmo

Question 45

sequential approach to bb poisoning

Answer 45

IV bolus andrepeat symptomatic brady with atropine x3 up to total 3mg hypotension ongoin, give cagluc infused over 10 mins glucagon 5mg bolus to bridge to HDI: with one amp d50, then 1u/kg insulin R -start glucose 25g/hour incr insulin by 2 units q10 mins until hypotension resolves or until max 10 still hypotensive NE +/- tvp +/- vasopressin ECMO or intralipid

Question 46

Phase 1 tx of beta blocker

Answer 46

Activated charcoal as indicated Isotonic fluid bolus 20–40 mL/kg Atropine Calcium Glucagon

Question 47

Phase 2 tx beta blocker

Answer 47

Place central & arterial lines HDI infusion Norepinephrine Vasopressin 3rd agent based on type of shock Pacemaker for bradycardia

Question 48

Phase 3 tx beta blocker OD

Answer 48

IFE ECMO Other mechanical devices if ECMO not available

Question 49

Phase 1 CCB toxicity tx

Answer 49

Activated charcoal as indicated Isotonic fluid bolus 20–40 mL/kg Atropine Calcium

Question 50

phase 2 ccb od tx

Answer 50

Place central & arterial lines HDI infusion Norepinephrine Vasopressin 3rd agent based on type of shock Pacemaker for bradycardia

Question 51

phase 3 ccb od tx

Answer 51

IFE Methylene blue ECMO Other mechanical devices if ECMO not available

Question 52

which bb od pt need to be adm?

Answer 52

Patients with sec- ond or third-degree AV heart block, hypotension not responding to IV fluid administration, or who have hemodynamically significant dysrhythmias should be admitted to an intensive care unit.

Question 53

CCB function

Answer 53

block L type ca channels in myocardium and vascular sm so get peripheral vasodilation reduce contractility depres sa nod activity slow av node

Question 54

ccb onset of toxicity vs longest time to onset

Answer 54

Onset of action and toxicity may occur as early as 30 minutes after ingestion. In contrast, the poisoning from sustained-release ver- apamil may not manifest for 12 hours or more. High protein binding and Vd greater than 1 to 2 L/kg make hemodialysis or hemoperfusion ineffective with calcium antagonists.

Question 55

Clinical features of ccb toxicity

Answer 55

hypot bradycardia av block, smus arresrt, av dissoc, junctiona rhythm, asystole qrs widening may not be seen early on edema including pulmonary edema

Question 56

BG - hyperglycemia in bb or ccb toxicity?

Answer 56

ccb! secondary to insulin inhibition

Question 57

What is a hail mary med for ccb toxicity?

Answer 57

methylene blue vasoncstrictor - inhibits enzyme og guanylyl cyclase resulting in cBMP to incr SVR

Question 58

dose methylene blue for ccb od?

Answer 58

1-2mg/kg bolus of 1% methylene blue followed by infusion of 1mg/kg up to 6h

Question 59

Clonidine mech of action

Answer 59

central acting alpha 2 ag and imidazoline agonist binds to presync alpha 2 adr to inhibit neurons causing decr NE releaes

Question 60

what conditions does clonidine tx

Answer 60

hypertension adhd pheo withdrawal from opioids , etoh and nicotine

Question 61

clonidine sx

Answer 61

brady- cardia, hypotension, decreased mental status, miosis, and occasionally hypothermia.

Question 62

ddx clonidine od

Answer 62

antihypertensive medications (e.g., guanabenz, α- methyldopa), ADHD medications (e.g., guanfacine), muscle relaxers (e.g., tizanidine), and topical vasoconstrictors in dermatologic (e.g., brimonidine),62 ocular, and nasal settings (e.g., tetrahydrozoline, oxymetazoline, and naphazoline

Question 63

clonidine od management

Answer 63

bolus IVF for hypotension less concern pulmonary edema than bb or ccb od ne for map >60 ?naloxone? trial 0.2 --> 0.4 --> 10mg bolus

Question 64

clonidine peak effect and half life

Answer 64

2-4 hours half life 5-13h

Question 65

Example of nitrates causing toxicity action

Answer 65

ntg isosorbide mononitrate dinatrate vasodil - typ. veins but higher dose arteries

Question 66

what are poppers

Answer 66

alkyl nitrites (amyl, butyl, isobutyl, or ethyl nitrite) sexual pleasure prolonging

Question 67

how does methemoglobinemia work?

Answer 67

nitrites and nitrates have oxidizing power of fe2+ to fe3+ which incapable of carrying o2 and shifts ox dissoc curve L - functional anemia impairing ability to o2 deliver

Question 68

methemoglobinemia: clinical features

Answer 68

hypotension reflex tachy headache cyanosis venipuncture choc brown blood nonsp sx fatigue, dyspnea, weakness, dizzy, drowsy, syncope, coma, seizure, death

Question 69

DDx methemoglobinemia:

Answer 69

diuretics, angiotensin-converting enzyme (ACE) inhibitors, and dihydropyridine calcium channel blockers, as well as oxidative phosphorylation uncouplers such as cyanide and carbon monoxide. Non-toxicologic conditions capable of mimicking nitrate poisoning include sepsis and anaphylaxis. The differential diagnosis of methemoglobinemia includes hypoxia, as well as other hemoglobinop- athies such as sulfhemoglobinemia.

Question 70

diagnosis methemoglobinemia

Answer 70

o2 challenge cooximetery for percent methemoglobin if confirm get hemoglobin [] if anemic a smaller am of methemoglobin may be sign

Question 71

Pulse ox readings and methemoglobinemia - how does this work?

Answer 71

pulse oximeters function by read- ing the absorbance of light at wavelengths of 660 and 940 nm, which are selected to separate oxy and deoxyhemoglobin. Methemoglobin absorbs light at both these wavelengths more than either oxy or deoxy- hemoglobin. This results in unreliable pulse oximetry that typically reads near 85%, regardless of the patient’s oxygenation status.

Question 72

Management of nitratev posioning

Answer 72

supine pos ivf removal ofending agent

Question 73

nitrate are CI in which concomittent ddrgu use and why?

Answer 73

erectile dysfunction, such as sildenafil (Viagra) or tadalafil (Cialis). These drugs inhibit type 5 phosphodiesterase, relaxing vascular smooth muscle, which can prolong and intensify the vasodilating effects of nitrates causing severe hypotension. If blood pressure does not normalize with IV fluids and cessation of the nitrate infusion, norepinephrine should be cautiously titrated to a MAP of 60 mm Hg, beginning at 0.1 mcg/kg/min.

Question 74

Tx for methemoglobinemia

Answer 74

supplemental o2 ivf iv methyelne blue as oxidizing agent in presence of NADPH methemoglobin reductase, reduced to leukomethylen blue --> reduces methemeoglobin back to hemoglobin IV 1-2mg/kg of 1% metyhlene blue repeat 1hr if cyanosis not resolved if >7mg/kg methylene blue just makes methemoglobin worse so don't do that