Cardiac glycosides Flashcards by Iseoluwa Ojo

Cardio-tonic drugs

Cardio_________ drugs (also called “cardiotonic drugs”)

stimulatory

How well did you know this?

Not at all

Perfectly

Cardio-tonic drugs

Enhance cardiac function by
– increasing heart rate (_____tropy)
– myocardial contractility (___tropy),
– May increase electrical conduction (_______tropy) within the heart and
– augment relaxation (_____tropy).

chrono

ino

dromo

lusi

How well did you know this?

Not at all

Perfectly

Cardio-tonic drugs

The cardiac effects of these drugs make them suitable for
–____ failure
–________ shock
– ______tension.

Heart

Cardiogenic

hypo

How well did you know this?

Not at all

Perfectly

Classes of Cardiostimulatory Drugs

________
____________
________________
____________

Beta-agonists
Digitalis compounds
Phosphodiesterase inhibitors PDEI
Calcium sensitizers

How well did you know this?

Not at all

Perfectly

Cardiac glycosides are _____ compounds containing a _______(_____) that act on the ____________ of the cardiac muscle.

organic

glycoside (sugar)

contractile force

How well did you know this?

Not at all

Perfectly

Cardiac glycosides

Important class of (naturally or artificially ?) occurring drugs whose actions include both ______ and ________ effects on the heart.

naturally

beneficial and toxic

How well did you know this?

Not at all

Perfectly

Cardiac glycosides

Found as (primary or secondary?) metabolites in several plants , but also in some _____, such as the __________ ————

secondary

insects

milkweed butterflies.

How well did you know this?

Not at all

Perfectly

Chemistry of cardiac glycosides

All of the glycosides of which digoxin is the prototype combine a

–_____ nucleus linked to an unsaturated ____ membered _______ ring at the ____ position

– and a series of _____ at ______ of the nucleus.

steroid; 5 ; lactone; 17

sugars; carbon 3

How well did you know this?

Not at all

Perfectly

Chemistry of cardiac glycosides

Because they lack an easily ionizable group, their _____________________________________.

_______ nucleus with ———- ring is essential for myocardial action.

solubility is not pH dependent

Steroid; lactone

How well did you know this?

Not at all

Perfectly

CVS effect of Cardiac Glycosides in Heart Failure

Mechanical and Electrical effect

(+ve) ____tropic.
(-ve) _____tropic

→Binding to ———- in the plasma membrane of central & peripheral nervous system → (-) of symp.

ino; chrono

Na pumps

How well did you know this?

Not at all

Perfectly

CVS effect of Cardiac Glycosides

its positive inotropic action results in,

– a. increased _______
– b. decreased _________
– c. decreased ____________
– d. decreased ___________________________
– e. _______ and relief of oedema

cardiac output

heart size

venous pressure

circulating blood volume

diuresis

How well did you know this?

Not at all

Perfectly

Electrical activity of Cardiac Glycosides

——-eased automaticity of SA node indirectly

_____eased Refractory period of the AV node

____eased Condution Velocity at the AV nodal Tissue

(Stimulate or Depress?) vagal Nerve

Decr

Incr

Decr

Stimulate

How well did you know this?

Not at all

Perfectly

Therapeutic uses of Digitalis Compounds

During Heart Failure, to cause:
– ____eased inotropy
– ____eased ejection fraction
– ____eased preload
– ____eased pulmonary congestion/edema

Incr
Incr
Decr
Decr

How well did you know this?

Not at all

Perfectly

Therapeutic uses of Digitalis Compounds

Arrhythmias

– ______ease AV nodal conduction (parasympathomimetic effect)
– ____ease ventricular rate in atrial flutter and fibrillation

decr

How well did you know this?

Not at all

Perfectly

Contraindications of Digitalis Compounds

•Ventricular Tachycardia - because digitalis _____________ especially at high doses

•——————.

increase automaticity

Heart block

How well did you know this?

Not at all

Perfectly

Mechanism of action of Digitalis Compounds

Inhibits the ________, which is responsible for —————- across the muscle cell membrane

Leads to ____eased force of myocardial contraction.

Na+/K+-ATPase

Na+/K+ exchange

Incr

How well did you know this?

Not at all

Perfectly

Digoxin and _____ ions compete for a “receptor” (Na+/K+-ATPase) on the (internal or external?) membrane.

So, the effects of digoxin may be dengerously increaseed by ________, produced, for example, by diuretics.

K+

External

hypokalemia

How well did you know this?

Not at all

Perfectly

Cardiac glycosides : mechanism of action.

Inhibits _______ pump
Increase intracellular ____ conc.

Inhibits ______ exchangers
Decrease ______ efflux from the cell
Increase intracellular _____

____ease cardiac contractility

Na/K atpase; sodium

Na/Ca2+; calcium; calcium

Incr

How well did you know this?

Not at all

Perfectly

Pharmacokinetics of Digoxin

absorption of digoxin after ___ administration ranging from ____-___%.
absorption can be retarded by,

– a. the ______ in the GIT
– b. delayed ________
– c. ______ syndromes
– d. antibiotics, such as ____________
– e. steroid binding _____

oral; 40-90

presence of food

gastric emptying

neomycin

resins

How well did you know this?

Not at all

Perfectly

Digoxin:

Oral availability =
Half life =
Elimination is by??

40 Hours

Kidneys

How well did you know this?

Not at all

Perfectly

Adverse effect of Digoxin

1.Extracardiac

On GIT→ Anorexia, nausea,vomiting Fatigue ,weakness, diarrhoea

Neurological problems ————-,———-

Due to steroid nucleus -_________ in male

blurring of vision, confusion

gynaecomastia

How well did you know this?

Not at all

Perfectly

Adverse effect of Digoxin

Cardiac effect:

i)All type of arrythmia (increased ________ in high dose)

ii) Slowing A-V nodal Conduction- _________ ________

Automaticity

Bradycardia Heart block

How well did you know this?

Not at all

Perfectly

Drug interaction Pharmacodynamic interaction

_________ + digoxin= ↓ AV Conduction - Heart Block

_________+ digoxin= ↓ AV Conduction –Heart Block

Digitalis+ ____________________ = cause K+ loss

B –blocker

Verapamil

Diuretics(Thiazide/Frusemide)

How well did you know this?

Not at all

Perfectly

Drug interaction Pharmacokinetic interaction

Verapamil+ digoxin→_____eased plasma digitalis concentration by ________________________ leading to increased conc. of digoxin →toxicity

incr

competing with digoxin for renal excretion

How well did you know this?

Not at all

Perfectly

Drug interaction Pharmacokinetic interaction Digitalis+Quinidine= ______ digitalis from ___________ , leading to \___eased concentration of digitalis →↑toxicity

displace tissue binding site incr

Digoxin Toxicity ________ is earliest symptom __________ is earliest sign ( if <—— b/min, digitalis not given) Low Therapeutic Index of ____nmol/L

Anorexia Bradycardia; 60 1-2.6

Toxicity of digoxin Treatment: treatment is different in 2 different condition (i) ________ ii) Monitor ____ level( if ________ administer K+, IV KCL)

Stop the drug K+ ; hypokalemia

Hypokalemia K+ and digitalis, interact in two ways- First – hypokaelamia causes ______eases the myocardial localization of digoxin. (Increase or reduction?) in extracellular K+, Cause increased _________ of _______. Digoxin has (lower or higher?) affinity for the phosphorylated form of Na pump. Second – ___________________ is inhibited by hyperkalemia.

incr reduction phosphorylation of Na pump Higher abnormal cardiac automaticity

Digoxin Toxicity Effect of other electrolytes imbalance on digoxin use – Causing toxicity – _______calcaemia Ca++, – _____magnesaemia Mg++

Hyper Hypo

Ca++ facilitates the toxic actions of cardiac glycosides by _____________________________ that appears to be responsible for digitalis-induced ______________

accelerating the overloading of intracellular Ca++ stores abnormal automaticity.

______calcemia therefore increases the risk of digitalis induced arrhythmia.

Hyper

Hypomagnesemia Decreased Mg++ concentration _______________ of cardiac glycosides.

enhances toxicities

Digitalis Toxicity – Use of Antidote If patient still refractory to treatment – Antidotes to digoxin –_________________ (Fab fraction) – digoxin binding specific antibody ( _________ ) given to _________________

monoclonal antibody digibind remove excess digoxin from the body.

HEART FAILURE DRUGS DRUGS FOR _____________ DRUG FOR —————— DRUG FOR _____________________

PREVENTING CARDIAC REMODELLING TREATING SYMPTOM IMPROVING CONTRACTILITY

Drugs for PREVENTING CARDIAC REMODELLING LIST !!!!

ACE INHIBITORS ANGIOTENSIN RECEPTOR BLOCKERS BETA BLOCKERS VASODILATORS

Mechanisms of ACE inhibitors Inhibits ANGIOTENSIN CONVERTING ENZYME Alters the __________ and _______ Thus prevents cardiac remodeling

Pre-load and Afterload

MECHANISM OF ACTION of ANGIOTENSIN RECEPTOR BLOCKERS Inhibits Angiotensin II receptor Alters the __________________ Thus prevents cardiac remodeling

Pre-load and After load

MECHANISM OF ACTION of beta blockers Inhibits Beta adrenergic receptors Reduces ________ and ___________ Thus prevents cardiac remodeling

Heart rate and Force of Contraction

MECHANISM OF ACTION of vasodilators Lead to vasodilation Alter the _________________ Thus prevents cardiac remodeling

Pre-load and Afterload

CARDIOTONICS Are ____________,_________, and ______

CARDIAC GLYCOSIDES BETA 1 AGONIST PDE INHIBITORS

CARDIAC GLYCOSIDES _________ type _______ type

CARDENOLIDE BUFADINOLIDE

EXAMPLES of cardiac glycosides • Cardenolide –_________ –_________ Bufadenolide – Drimia maritima – Kalanchoe daigremontianin – Daigremontianin

Digitalis lanata Digitalis purpura

CARDIAC GLYCOSIDES • Made up of a combination of – _______ – _______ – _______

– Steroid nucleus – Lactone ring – Sugar

CARDIAC GLYCOSIDES Causes _____eased inotropy and ____eased chronotropy

incr decr

CARDIAC GLYCOSIDES PHARMACODYNAMICS : Drug Effect Usually leads to two types of Drug effect ________ effect _________ effect

Mechanical Electrical

Cardiac glycosides Electrical effect Decreased ___________ indirectly Increased _________ of the AV node Decreased _________ at the AV nodal Tissue Stimulate _______ Nerve

Automaticity of SA node Refractory period Conduction Velocity vagal

CARDIAC GLYCOSIDES are highly toxic T/F

Factors affecting toxicity of cardiac glycosides __________mia __________emia ___________emia

Hypercalcemia Hypomagnesaemia Hypokalemia

CARDIAC GLYCOSIDES Extracardiac –_____ like syndrome – ______tension – Headache – Nausea – Diarrhea – Flushing – Tachycardia

Lupus Hypo

CARDIAC GLYCOSIDES ADVERSE EFFECT Cardiac – Arrhythmia •__________ lock •_______ arrhythmia • ___________ arrhythmia

Conduction Atrial Ventricular

CARDIAC GLYCOSIDES Treatment TOXICITY – Treat arrhythmia Atrial arrhythmia –_______ Ventricular arrhythmia – _________ Heart block - ___________

Phenytoin Lignocaine Atropine

BETA AGONIST EXAMPLES Dobutamine Supplied in ______ mixtures Increases ____tropy without increasing ______tropy

racemic Ino Chrono

BETA AGONIST EXAMPLES Dopamine Given _____ Dose is between 1 to 5 μgm/kg/min Has a (short or long?) half life of _____________ Metabolized in the _____ by _____

IV Short 2 to 3 mins Liver COMT

BETA AGONIST MECHANISM OF ACTION Stimulate to Beta 1 adrenergic receptors in the Heart Causes increased ______________________ This leads to improvement in the myocardial contractility

INOTROPY

PDE INHIBITOR Give 3 examples EXAMPLES

Amrinone Milrinone Enoximone

MECHANISM OF ACTION of PDE INHIBITOR Inhibit Phosphodiesterase enzyme This causes an •Increase in _____ •Activation of __________ •Activation of _____________channel •Increase in _____tropy

cAMP protein kinase sarcolemma calcium ino

__________ represent the newest class of cardiostimulatory drugs.

Calcium sensitizing drugs

Calcium sensitizing drugs These drugs increase the _________________ so that more calcium becomes bound to troponin-C, which enhances contractility. At present, these drugs are ___________________________, and therefore not yet approved.

sensitivity of troponin-C for calcium under clinical investigation for heart failure

With dobutamine, there is increase in cardiac workload T/F

F Decrease

Dobutamine does not activate dopaminergic receptors. T/F

__________ is the preferred beta agonist for the management of patients with end-stage systolic dysfunction and CHF.

Dobutamine

Dobutamine is supplied as a racemic mixturethat stimulates ___________ receptor subtypes.

both b1 and b2

Dobutamine In addition, the (–) enantiomer is ______ for a adrenergic receptors, whereas the (+) enantiomer is a ___________

an agonist very weak partial agonist.

DA has limited utility in the treatment of most patients with cardiogenic circulatory failure. T/F

Dopamine At low doses (≤—— μg/kg lean body mass per minute) DA causes vaso_____ by stimulating _______ receptors on smooth muscle Also by stimulating presynaptic ____ receptors on sympathetic nerves in the peripheral circulation(___________ and reducing __________ stimulation of vascular smooth muscle); thesereceptors are prominent in ______ and _________ arterial beds

2 dilation; dopaminergic D2 inhibiting NE release ; a adrenergic splanchnic and renal

Dopamine At intermediate infusion rates (_____ μg/kg/min), DA directly stimulates _____ receptors on the _____ and vascular sympathetic neurons, enhancing cardiac contractility and neural NE release.

2–5 Beta; heart

Dopamine At higher infusion rates (_____ μg/kg/min), peripheral arterial and venous _______ occur, mediated by _______ receptor stimulation.

5–15 constriction a adrenergic

Tachycardia is more pronounced with dobutamine than with dopamine T/F

F Tachycardia, which is more pronounced with DA than with dobutamine, may provoke ischemia in patients with coronary artery disease.

Dopamine it is a drug of choice.(T/F) Very (short or long?) half life ( _______)

T Short 2- 3minutes