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Phcol 402 > 01/22/16 > Flashcards

01/22/16 Flashcards

1
Q

What is angina?

A
  • Ankhon “strangling”, pectus “chest”
  • Chest pain experienced as squeezing or pressure
  • Also localized to shoulders, neck, jaw or back
  • A symptom of coronary artery disease (CAD)
  • Secondary artherosclerosis
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2
Q

Types of Angina

A
  • Stable
    • Commons, follows predictable pattern
    • Increase exercise, decrease with rest
  • Unstable
    • No pattern
    • Not relieved by rest
    • Precursor to heart attack, acute coronary syndrome
  • Variant (or Prinzmetal;s)
    • Rare
    • Occurs at rest between midnight and early morning
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3
Q

Coronary Arteries

A
  • Branch off aorta
  • Pass along outside surface of heart
  • Supply myocardium
  • Two main CA’s: left and right
  • Branches penetrate cardiac muscle
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4
Q

Schematic of Coronary Arteries

A
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5
Q

Anatomy of an Artery

A
  • composed of 3 distinct layers
  1. Adventitial
    • Supporting layer
    • Macrophages, monocytes, fibroblasts
  2. Medial
    • Contractile layer
    • Vascular smooth muscle cells
  3. Intima
    • Inner layer adjacent to lumen
    • Endothelium and elastic lamina
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6
Q

Anatomy of an Artery (Figure)

A
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7
Q

Anatomy of an Artery (Figure #2)

A
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8
Q

Contraction of Vascular Smooth Muscle

A
  • Contractile Galphaq-coupled GPCRs on vascular smooth muscle cells
    • alpha1-adrenergic
    • Angiotensin II type I
    • Endothelin A
    • 5-HT2 serotonin
    • Kisspeptin 1R
  • Activate myosin light chain kinase (MLCK)
  • MLCK phosphorylates myosin
  • Myosin binds actin
  • Vessel contraction
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9
Q

Contraction of Vascular Smooth Muscle (Figure)

A
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10
Q

Nitric oxide production in endothelium

A
  • Vasodilatory GPCRs on endothelium
    • Bradykinin
    • Angiotensin II type 2
    • Endothelin B
    • Muscarinic 1/3
  • eNOS converts L-arginine + NADPH + O2→L-cirtulline + NO
  • NO diffuses into adjacent smooth muscle cells
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11
Q

NO production in endothelium (pathway figure)

A
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12
Q

Nitric oxide stimulates vasodilation

A
  • NO activates guanylyl cyclase→ ^cGMP
    • Activates protein kinase G (PKG)
  • PKG activates myosin light chain phosphtase
    • Dephosphorylates myosin light chains
  • PKG phosphorylates K+ channels
    • ^K+ efflux
    • hyperpolarization
  • Vasodilation
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13
Q

MLCP vs MLCK

A
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14
Q

Coronary Artery Disease (CAD)

A
  • Major cause of death world wide: “silent killer”
  • Cummulative atheroma (i.e. plague) formation in CA’s
  • Decrease lumenal diameter in CA’s
    • Decrease O2/nutrient supply to myocardium
    • Ischemia
    • Myocardial infarction (MI)
  • Rupture of atheroma
    • MI and/or restenosis
  • Leads to heart failure, arrthymia
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15
Q

Atherosclerosis

A
  • Thickening of artery wall to form “plaque” or “nodule”
  • Chronic inflammatory response
  • ROS/LpA2→LDL oxidation→monocytes/macrophages/T-Cells
    • foam cells→”fatty streaks”
  • atheroma: soft/yellow central layer, macrophages
  • outer layer can be fibrous or calcified
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16
Q

Virtual history of calcified nodule

A
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17
Q

Treatment of Angina

A
  1. Decrease venous return/afterload:
    • nitrovasodilators
    • vascular selective Ca2+ channel blockers
  2. Decrease myocardial O2 demand:
    • B-adrenergic receptor antagonists
    • cardioselective Ca2+ channel blockers
  3. Treat CAD/atherosclerosis
    • decrease cholesterol: statins
    • prevent thrombi/clots: aspirin
    • surgical procedures: stents/angioplasty
    • lifestyle changes: exercise, diet, stop smoking
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18
Q

Nitrovasodilators

A
  • Amyl nitrate
  • Nitroglycerin (Nitrostat, Trinipatch)
  • Isosorbide mononitrate (Imdur, Ismo)
  • Isosorbide dinitrate (Isordil)
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19
Q

Nitrovasodilators: MOA

A
  • denitrated by glutathione S-transferase in cells
    • Release N2O
    • Converted to nitric oxide
    • Activated guanylyl cyclase
    • Vasodilation
  • Low doses→venodilation
    • decrease venous return
    • decrease cardiac workload/O2 demand
  • High doses→arteriodilation
    • decrease afterload
    • decrease cardiac workload/O2 demand
20
Q

Nitrovasodilators: Clinical Uses

A
  • Symptom relief of angina
  • stable/unstable angina→decrease venous return→decrease cardiac output
  • variant angina→relax coronary arteries→relieve coronary vasospasm
21
Q

Nitrovasodilators: Toxicity

A
  • Severe vasodilation
    • relax tachycardia
    • orthostatic hypotension
    • headache
  • Tolerance with long-term use
    • RAAS activity→aldosterone→Na+/H2O retention
    • discontinued periodically (~8 hrs between doses)
22
Q

Nitrovasodilators: Formulations

A
23
Q

Phosphodiester type 5 inhibitors

A
  • Sildenafil (Viagra)
  • Vardenafil (Levitra)
  • Tadalafil (Cialis)
24
Q

PDE5-Inhibitors: MOA

A
  • Selectively inhibit PDE5
  • Decrease cGMP breakdown
  • Vasodilation
25
Q

PDE5-Inhibitors: Pharmacokinetics

A
  • oral, sublingual
  • rapid onset of action (minutes)
  • long duration of action (hours)
26
Q

PDE5-Inhibitors: Clinical Uses

A
  • Erectile dysfunction
  • Angina
27
Q

PDE5-Inhibitors: Toxicity

A
  • Vision problems
  • Contraindicated with nitrovasodilators
  • Excessive vasodilation
    • Headache
    • Dizziness
    • Flushing
28
Q

Beta-adrenergic receptor anatgonists

A
  • Propranolol (Inderal)
  • Atenolol (Tenormin)
  • Metoprolol (Lopressor)
29
Q

Beta-adrenergic receptor anatgonists: MOA

A
  • Decrease cardiac output
  • Decrease RAAS activity
  • Decrease myocardial O2 demand
30
Q

Beta-adrenergic receptor anatgonists: Clinical uses

A
  • Angina:
    • Oral prophylactic
    • Increase exercise tolerance
    • duration ~6 hours
31
Q

Beta-adrenergic receptor anatgonists: Toxicity

A
  • Contraindicated with bradycardia, asthma
  • CNS sedation
32
Q

Cardioselective Ca2+ channel blockers

A
  • Verapamil (Calan, Isoptin)
  • Diltiazem (Cardiazem)
33
Q

Cardioselective Ca2+ channel blockers: MOA

A
  • Inhibit voltage-gated L-type Ca2+ channels in cardiac myocytes
  • decrease force and rate of cardiomyocyte contraction
    • decrease cardiac output
34
Q

Cardioselective Ca2+ channel blockers: Toxicity

A
  • Hypotension
  • Excessive cardiac depression
  • Constipation
35
Q

Vascular Selective Ca2+ channel blockers

A
  • Dihydropyridines
    • Nifedipine (Procardia)
    • Amlodipine (Norvasc)
36
Q

Vascular Selective Ca2+ channel blockers: MOA

A
  • Inhibit L-type Ca2+ channels on vascular smooth muscle cells
  • Decrease arterial and venous contraction
    • Decrease TPR
37
Q

Vascular Selective Ca2+ channel blockers: Toxicity

A
  • Hypotension
  • Flushing, dizziness
38
Q

Vascular Selective Ca2+ channel blockers: Clinical Use in Angina

A
  • Oral prophylactic
  • Effective for stable and unstable angina
  • DDI at CYP450 3A4
39
Q

Ranolazine (Ranexa): MOA and Toxicity

A
  • MOA
    • late Na+ channel modulator (INa)→decrease Na+ influx in cardiomyocytes
      • Decrease Ca2+ overload during ischemic event
    • MARISA and CARISA clinical trials compared to other agents
    • Decrease myocardial ischemia, time to exercise induced ischemic event
    • Increase exercise tolerance>>beta blockers, vascular CCB or cardiac CCB
  • Toxicity
    • Can prolong QT interval > Contraindicated in patients with long QT interval
    • Constipation
    • Flushing, dizziness
    • CYP3A4, 2D6 substrate
40
Q

Nitroglycerin: Drug card

A
  • Brand Name:
    • Nitrostat
  • MOA:
    • Nitrovasodilator, nitric oxide donor
  • Clinical uses:
    • Angina
    • acute coronary syndrome
  • Toxicity
    • tachycardia
    • orthostatic hypotension
    • headache
  • Extra Info:
    • Sublingual for acute angina: rapid onset (<1 min), short duration(~10-30 min)
    • Oral for prophylactic: slow onset, longer duration (6-8hrs)
41
Q

Sildenafil: Drug Card

A
  • Brand Name:
    • Viagra
  • MOA:
    • PDE5 inhibitor
  • Clincal Uses:
    • Angina
    • ED
  • Toxicity:
    • Tachycardia
    • Hypotension
    • Visual disturbances (yellow halos)
  • Extra Info:
    • Contraindicated with vasodilators
42
Q

Propranolol: Drug Card

A
  • Brand Name:
    • Inderal
  • MOA:
    • non-selective beta-adrenergic receptor antagonist
  • Clinical Uses:
    • Hypertension
    • Congestive heart failure
    • Angina
    • Arrhythmias
  • Toxicities:
    • Bradycardia, atrioventricular block
    • Bronchospasm
    • CNS sedation
  • Extra Info:
    • Contraindicated in asthma
    • Also used for performance anxiety and migraine
    • Crosses blood brain barrier
43
Q

Metoprolol: Drug Card

A
  • Brand Name:
    • Lopressor
  • MOA:
    • selective beta1-adrenergic receptor antagonist
  • Clinical Uses:
    • Congestive heart failure
    • Hypertension
  • Toxicities:
    • Bradycardia, atrioventricular block
    • CNS sedation
  • Extra Information:
    • shown to reduce mortality in heart failure patients
    • widely used for stage I/II HTN
44
Q

Verapamil: Drug Card

A
  • Brand Name:
    • Calan
  • MOA:
    • Cardioselective L-type Ca2+ channel blocker
  • Clinical Uses:
    • Hypertension
    • Angina
    • Arrhythmias
  • Toxicities:
    • Excessive cardiac depression
    • Constipation
  • Extra Information:
    • Strong cardiac blocking effect
    • weak vascular smooth muscle blocking effect
45
Q

Nifedipine: Drug Card

A
  • Brand Name:
    • Procardia
  • MOA:
    • Vascular selective L-type Ca2+ channel blocker
  • Clinical Uses:
    • Hypertension
    • Angina
    • Arrhythmias
  • Toxicities:
    • Hypotension
    • Flushing
    • Dizziness
  • Extra Information:
    • Strong vascular smooth muscle blocking effect
    • Weak cardiac muscle blocking effect
46
Q

Ranolazine: Drug Card

A
  • Brand Name:
    • Ranexa
  • MOA:
    • late Na+ channel current modulator
  • Clinical Uses:
    • Chronic angina
  • Toxicities:
    • Constipation
    • Dizziness
  • Extra information:
    • Avoid use in patients with long QT syndrome
    • Numerous DDI’s due to CYP3A4, 2D6 metabolism
47
Q
A

Phcol 402 (11 decks)

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