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Heme/Cardio Ass 4 Drugs > Vasodilators 2 > Flashcards

Vasodilators 2 Flashcards

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1
Q

Vascular Relaxation Mechanisms

A 
Cyclic GMP (nitrates/nitrites)
-increasing cGMP facilitates dephosphorylation of myosin light chain proteins, prevents myosin-actin interactions
Intracellular Ca (Ca channel blockers and Na channel blockers)
-reduction of Intracellular Ca reduces MLC kinase efficacy; reduces myosin-actin interactions
Cell Membrane Potential (direct vasodilators)
-increases K permeability; hyperpolarization
Cyclic AMP (Beta2 Agonists)
-increasing cAMP increases rate of MLC kinase inactivation reduces myosin-actin interactions
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2
Q

CV Responses of Ca Channel Blockers

A
  • arterial dilation
  • depressed myocardial contraction
  • reduction in SA node pacemaker rate and slowing of intra-cardiac electrical conduction
  • intrinsic natriuretic/diuretic effect
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3
Q

Major CV Effects of Ca Channel Blockers

A

Coronary Vasodilation: Verapamil, Diltiazem, Nifedipine
Cardiac Contractility Suppression: Verapamil, somewhat diltiazem
SA Node automaticity Suppression: Verapamil and diltiazem
AV Node Conduction Suppression: verapamil and diltiazem

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4
Q

Clinical Uses of Ca Channel Blockers

A
  • HTN
  • Angina Pectoris
  • Peripheral Vasospasm
  • Supraventricular Cardiac Arrhythmias
  • Raynaud’s Phenomenon
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5
Q

Side Effects of Ca Channel Blockers

A

Flushing
HA
Peripheral Dependent Edema (nifedipine)
Myocardial Depression (Verapamil, Diltiazem)
Constipation (Verapamil)
Reflex Tachycardia (Nifedipine)
Gingival Hyperplasia (Nifedipine>Verapamil)

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6
Q

Ca Channel Blocker Precautionary Uses and Contraindications

A

Pregnancy: dihydropyridines shouldn’t be used in early pregnancy (limb bud defects) and may prolong labor

Ischemic Heart Disease (angina, MI): dihydropyridines cause reflex Tachycardia

Imparied Myocardial Function: Verapamil, Diltiazem

Impaired Cardiac Conductance (heart block): V, D

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7
Q

Verapamil

A
  1. Arterial Vasodilation, Negative Inotropic and Chronotropic Effects, Natriuretic Effect
  2. Tx for HTN
  3. Management of Suprventricular Arrhythmias
  4. Prevention and Termination of Paroxysmal Supraventricular Tachycardia
  5. Monotherapy for Angina Pectoris
  6. Combination with B-blockers NOT RECOMMENDED
  7. Caution: greater hypotension in elderly
  8. Limiting Factors for use are myocardial depression and constipation
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8
Q

Diltiazem

A
  1. Arterial Vasodilation, Less Cardio-depressant effects than verapamil, natriuretic effect
  2. Treatment for HTN
  3. Tx of Atrial Flutter and Fibrillation
  4. Treatment for Paroxysmal Supraventricular Tachycardia
  5. Monotherapy for Angina Pectoris
  6. May be used in combo with B-blockers
  7. Limiting Factors for use are myocardial depression, acute MI and CHF
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9
Q

Nifedipine

A
  1. Arteriolar Vasodilation, Minimal Cardio-depressant effect, natriuretic effect
  2. Reflex Tachycardia and increase in contractility
    - attenuated with slow-release formulations
  3. Treatment for HTN
  4. not well-tolerated as monotherapy
  5. Used in combo with B-blocker, ACE inhibitors, Diuretics
  6. Limiting Factors for use are precipitation/worsening of angina pectoris, MI, Pregnancy
  7. Caution: greater hypotension in elderly
  8. Peripheral Edema
  9. Don’t use in early pregnancy (limb bud defects)
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10
Q

Summary of Ca Channel Blockers (Major Clinical uses and KEY adverse effects)

A

MAJOR Clinical uses:

  • HTN (D,V,N)
  • Angina Pectoris (D,V,N)
  • Vasospasm (N)
  • Atrial Arrhythmias (D,V)

Adverse Effects

  • HA (D,N,V)
  • Flushing (D,N,V)
  • Dizziness (N)
  • Nausea (N)
  • Dependent Edema (N)
  • Constipation (V)
  • Bradycardia (D,V)
  • Heart Block (D,V)
  • Reflex Tachycardia (N)
  • Limb Bud Defects (N)
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11
Q

Hydralazine

A

Class: Direct Acting Vasodilator (MOA unknown)
-effective orally

Combo Tx with isosorbide dinitrate for HF in African Americans

Side effects and Precautions:

  • presentation of lupus-like Syndrome in some patients (slow-acetylators)
  • Reflex Tachycardia
  • Contraindicated in CAD and Rheumatic Valve Disease
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12
Q

Minoxidil

A

Class: Activates Vascular ATP-Sensitive K channels
-dilates arterioles (prodrug)
Uses: severe refractory HTN, Hair Growth

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13
Q

Diazoxide

A

Class: Activates Vascular ATP-Sensitive K channels
-dilates arterioles (given IV, highly bound to plasma proteins)

Uses: HTN emergencies

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14
Q

Side Effects of K Channel Openers

A
  1. Hypertrichosis (minoxidil)
  2. Reflex Tachycardia
  3. Salt and Water Retention
  4. Hyperglycemia (diazoxide)
  5. Subendocardial Necrosis (by reflex released catecholamines) (diazoxide)
  6. Left Ventricular Hypertrophy and Pericardial Effusion (minoxidil)
  7. Gynecomastia (minoxidil)
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15
Q

Contraindications and Precautions of K Channel Openers

A
  1. HTN caused by pheochromocytoma
  2. Ischemic Heart or Cerebral Disease
  3. Treatment of compensatory hypertension (as with aortic coarctation or AV shunt)
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16
Q

Summary of “Direct” Vasodilators (clinical uses and Key adverse effects)

A

Major Clinical Uses:

  • refractory HTN (M)
  • HTN Crisis (diazoxide)
  • HTN: Pregnancy (H, D)

Adverse Effects

  • Reflex Tachycardia (M,D,H)
  • hypotension (D)
  • Edema (D, H)
  • Hyperglycemia (D)
  • Hypertrichosis (M)
  • Gynecomastia (M)
  • Lupus Syndrome (H)
17
Q

Ranolazine

A

Class: Na Channel Blockers
Use: chronic Angina
-for patients symptomatic on other anti-anginal therapy: 4th line Tc)
-Doesn’t lower BP or HR
-For diabetic patients (Small reductions in HbA1c)
MOA: blocks Na coming into cell during ischemia, regulate the amount of Na coming into the cell, reducing amount of Ca coming in

Side Effects:
-potential for QTc Prolongation

Contraindications:

  • Hepatic Impairment
  • QTc Prolongation
  • Patients takings drugs known to prolong QTc or inhibit P450 (CYP3A)

Drug-Drug Interactions:

  • Drugs that inhibit CYP3A
  • Verapamil
  • Digoxin
18
Q

Mechanism of Nitrovasodilators

A
  • forms NO directly
  • NO activates guanylyl cyclase to promote cGMP formation in VSM
  • Activation of MLC phosphatase which dephosphorylates MLC leading to VSM relaxation
19
Q

Pharmacokinetics and Dynamics of Nitrovasodilators

A
  • low oral availability (exception is isosorbide mononitrate)
  • Nitroglycerin has several routes of administration (sublingual preferred, rapid onset of action)
  • polymorphism is mitochondria aldehyde dehydrogenase contributes to efficacy variability to nitroglycerin; loss of nitro efficacy evident with the Lyse504 allele
20
Q

Nitroglycerin

A

Actions:

  • rapid NO donor
  • stimulates intracellular cGMP production
  • dilates veins at lower concentration and arteries at slightly higher concentrations
  • decrease preload and afterload variables
  • decreases myocardial oxygen demand and increases coronary blood supply

indications/uses:

  • acute angina
  • angina prophylaxis
  • IV for CV surgery to lower BP

Contraindications:

  • hypersensitivity
  • hypotension (IV use)

Adverse Effects:

  • HA
  • postural Hypotension
  • syncope
  • Reflex tachycardia
  • various GI disturbances
  • methemoglobinemia
21
Q

Nitroprusside

A

Actions:

  • NO donor
  • non-selective vasodilator
  • decrease preload
  • decreases afterload
  • rapid onset and reversal

Indications/Uses:
-HTN crisis

Contraindications:

  • HTN Associated with aortic coarctation or AV shunt
  • cerebral ischemia
  • certain genetic disorders

Adverse Effects

  • excessive hypotension
  • rebound HTN upon withdrawal
  • Reflex Tachycardia
  • methemoglobinemia
  • cyanide toxicity
22
Q

Nitrovasodilators (clinical uses and contraindications)

A

***Rarely used alone: add on therapy with Ca channel blockers and/or Beta blockers is better (timolol, propranolol, metoprolol)

Clinical Uses:

  • Angina
  • HTN crisis

Contraindications:
-Hypotension

Adverse Effects:

  • hypotension (NG,NP)
  • HA (NG)
  • Methemoglobinemia (NG, NP)
  • Cyanid Toxicity (NP)

Heme/Cardio Ass 4 Drugs (5 decks)

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