Cardia Agents Flashcards
Dobutamine
Dopamine analog, B1 agonist
Active only with IV
Short half life
Production of Nitric oxide in body
Produced from
by?
What does the precursor contain?
- From L-arginine
- NOS
- Guanidine H bonding and Ionic
- Stimulates cGMP
AMyl nitrite
Ester, Inhalation
Fastest acting in class
Short duration
Effect of NO
decreases myocardial workload
this is very reactive
Causes reduced O demand
2 types of nonglycoside drugs
PDE- block cAMP –> AMP
B-adrenergic increase cAMP
Classes of Anti arrythmics
- 1 Membrane depressant, act on fast Na+ channels prevent conductance
- B blockers
- Repolarization prolongers blocking K+
- CCBS inward slow Ca2+
CCB structural classes
Dihydropyridine
Benxothiapine
Aralkylamine
CCBS inhibit Ca influx negative inotropic effects, vasodilation, Smooth muscle
Contamination of Quinidine with? Can be?
Dihydroquinidine more potent but toxic
Cardia glycosides inhibit what phase of the cardiac action potential?
- Na+/KATPase Phase 4
- Contain a carbohydrate and a steriodal group
1 A examples
Slows?
Quinidine, Procainamide, Disopyramide
Quinide
Phase 0 depol
DIs with Organic Nitrates
INteraction with other vasodilators, alcohol
Avoid Viagra fall Bp
CCBS dose adjustment for?
dont give with?
High protein binding causes?
DI with?
Chronic liver disease
Grapefruit
Azole fungal and CYp3A4
Displacement of protein binding with other drugs that protein bind
Diltiazem is a?
Active?
deacetylation is?
O and N demethylation?
Benzothiazepine
Somea activity with the weird one
O and N inactive
Nifedipine is a?
Potent?
Highly?
Metabolism to?
Dihydropyridine
Peripheral vasodilation
Protein bound
Inactive metabolites in urine
AEs of organic
My head hurts, I get dizzy when I stand up, my body is all red, I cant tolerate it anymore
Clevidipine is a?
how to take it?
Onset?
Rapid hydrolysis of?
Dihydropyridine
IV
Fast short acting shortest
of ester inactive
3 classes for IHD
Organic nitrates
CCBs
B BLOCKERs
Amlodipine is a?
Greater?
long?
Metabolized?
Dihydropyridine
Selective for vascualr SM vs Myocardial
Long DOA
Inactive metabolites, Urine
Quinidine is a substrate for P-gp and can inhibit?
Tubular excretion of DIgoxin leading to toxic
Substrate for CYP3A4
unchanges urine
Isosorbide Dinitrate
Ring system
Sub, chew, SR
Slowest onset but longest DOA
Metabolite 5-isosorbide mononitrate is active
Verapamil is a?
Ca2+ ____
Liver dysfunction
Grapefruit
Commone SEs
- Phenylalkylamine
- Ca2+ antagonist
- Intry into Myocardial
- CYP3A4 interaction
- increase verapamil
- Brady, Hypo, Edema
Glyceryl Trinitrate
3 ns
Sublingual - most useful
Prophylactic and acute pain
Rapid onset not as fast at Amyl
Disopyramide
Metabolized?
Weak
AEs
Cardiac activity like procainamide
weak Anticholinergic
AE- Anticholinergic SEs
Explaine the phases of Cardia action potential
Procainamide
Bioisosteric drug design
Treats?
analog of?
Dose adjustment in?
Metabolized into?
analog of procain
Ventricular arrythmias
N-acetyl procainamide is active
Unchanges in urine 50%
Leukopenia and agranulocytosis
Inamrinone
Milrinone
MOA
which one is longer acting
Dose adjustments for?
Inamrinone is longer acting - inhibition of PDE
Milrinon- Greater selectivity
Dose adjustment in renal impairment
SAR of Dihydropyridines
1,4?
C4 position ring with?
C3/5 What functional group?
C2 bulkier?
Free __ group at 1 position
Dihydromoeity essential
Aromatic ring with ortho or meta required
Ester functional group
Can increase potency (amlodipine)
Free NH at one position is REQUIRED
Procainamide
- Synthetic drug. An amide analog of the local anesthetic Procaine (example of bioisosteric drug design principle!)
- Orally bioavailable. Parenteral (IV and IM) formulation also available.
- Indicated for the treatment of ventricular arrythmias
- Hepatic metabolism. Metabolites include N-acetyl procainamide (active) and p-aminobenzoic acid. Renal excretion of unchanged drug (~50%) and the metabolites.
- Might require dose adjustment in hepatic and renal impaired patients
- SEs- Drug induced lupus syndrome. Can also cause (0.5%) serious hematological disorders, particularly leukopenia and agranulocytosis.
1 A examples
Slows?
Quinidine, Procainamide, Disopyramide
Phase 0 depol
Quinidine is a substrate for P-gp and can inhibit?
Tubular excretion of DIgoxin leading to toxic
Substrate for CYP3A4
unchanges urine
Disopyramide
- Synthetic drug. Cardiac activity similar to Procainamide, Also exhibit weak anticholinergic activity.
- Good oral availability. T1/2= 5-7 hr.
- Partially metabolized in liver (CYP3A4), mostly to a mono-N-dealkylated product. Renal excretion of unchanged drug (~50%) and metabolites.
- Dose adjustment might be required in patients with liver/renal impairment
- SEs- are primarily related to anticholinergic activities of the drug, and can include dry mouth, blurry vision, constipation, and urinary retention.
Procainamide
Bioisosteric drug design
Treats?
analog of?
Dose adjustment in?
Metabolized into?
analog of procain
Ventricular arrythmias
N-acetyl procainamide is active
Unchanges in urine 50%
Leukopenia and agranulocytosis
Lidocaine
- Original use as a local anesthetic (Procaine-like).
- Drug of choice for emergency treatment of ventricular arrythmia (IV). Also used parenterally for suppression of arrythmias associated with acute myo cardial infraction and cardiac surgery.
- Rapid onset (1-2 min) and short duration of action (T1/2 = < 30 min).
- Liver metabolized (N-Deethylation and amidase hydrolysis). Renal excretion.
- SEs- Dizziness, paresthesis and seizure in severe cases.
Phenytoin
- Structurally analogous to barbiturates, but does not possess sedative properties.
- Long history of use for the treatment of epileptic seizures.
- Useful antiarrythmic agent for the treatment of digitalis induced arrythmias.
- Orally active. Also available for parenteral (IV) use.
- High plasma protein binding (~ 90%). T1/2 = 15 -30 hrs.
- Slow hepatic (CYP450) metabolism to mono-p-hydroxyphenyl derivative, followed by glucuronide conjugation and excretion in urine.
- Prevention of metabolism, or the presence of other plasma protein bound drugs can cause toxicity.
Flecainide
- Potent antiarrythmic drug with local anesthetic activity.
- Orally administered for the treatment of ventricular arrythmias.
- Plasma half-life ~14 hrs.
- Part of the drug (~50%) is metabolized in liver (CYP2D6). Metabolism involves m-O-dealkylation. Urinary excretion of unchanged drug and the metabolites.
- New or worsened arrythmias have been reported with the use of this drug.
- Other adverse effects: Dizziness, blurred vision, nausea, and headache etc.
Propafenone
- Structural resemblance to class 1C antiarryhmics, as well as β-blockers
- Used primarily for ventricular and supraventricular arrythmias
- Oral drug. Metabolized in liver (CYP2D6; CYP3A4; CYP1A2). Dose adjustment might be required with simultaneous use of other drugs interacting with the above metabolic enzymes.
- New or worsened arrythmias have been reported with the use of this drug.
- Other adverse effects: Agranulocytosis, taste disturbance, dizziness, nausea, and constipation etc.
Class II drugs
β-Adneregic blockers. Suppresses sympathomimetic activity. Slows ‘Phase 4’ depolarization.
Propranolol
Class III drugs
- K+-ion channel blockers. Prolongs ‘Phase 3’ repolarization and duration of action potential.
- A quaternary ammonium salt. Originally developed as an antihypertensive.
- Use limited for the treatment of emergency life threatening ventricular arrythmias resistant to other therapy.
- Usually administered iv or im.
- Adverse Effects : Hypotension (most common), nausea, and dizziness etc.
Class III cont..
- Antiarrythmic effects similar to Bretylium. Approved for the treatment of life-threatening ventricular arrythmias refractory to other drugs.
- Oral and parenteral formulations. Long half-life (several weeks)
- Hepatic metabolism involving N-deethylation (active metabolite).
- Severe toxicity limits the use of this drug (used in hospital setting only)
Class III cont..
- Used orally for tachyarrythmias (esp. AF). T1/2 ~ 10 hr.
- Due to the pro-arrhythmic potential of dofetilide, to be prescribe by physicians who have undergone specific training in the risks of treatment with dofetilide.
- Hepatic metabolism (20%). Metabolites and unchanged drug excreted in urine. Dose adjustment in renal impairment.
- Adverse effects: Induced arrythmia, headache, dizziness, nausea, rash, flu-like syndrome etc.
Class IB drugs and what they do?
- Rapid rate of dissociation from Na+-ion channels. Shortens ‘Phase 3’ repolarization and action potential duration. Drug examples include: Lidocaine, and Phenytoin etc.
Summary of Cardiac effects table
Class IC drugs and what they do
- Slows rate of dissociation from Na+-ion channels. Markedly slow ‘Phase 0’ depolarization
- Flecainide, Propafenone
Class IV
Examples
- Ca2+-ion channel blockers. Slows ‘Phase 4’ depolarization and duration.
- Prototypical drug examples are Verapamil, and Diltiazem etc.
