Phcol 402 > 01/22/16 > Flashcards

01/22/16 Flashcards

(47 cards)

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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

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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

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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

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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

23
Q

Phosphodiester type 5 inhibitors

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

PDE5-Inhibitors: MOA

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A
  • Selectively inhibit PDE5
  • Decrease cGMP breakdown
  • Vasodilation
25
PDE5-Inhibitors: Pharmacokinetics
* oral, sublingual * rapid onset of action (minutes) * long duration of action (hours)
26
PDE5-Inhibitors: Clinical Uses
* Erectile dysfunction * Angina
27
PDE5-Inhibitors: Toxicity
* Vision problems * Contraindicated with nitrovasodilators * Excessive vasodilation * Headache * Dizziness * Flushing
28
Beta-adrenergic receptor anatgonists
* **Propranolol (Inderal)** * Atenolol (Tenormin) * **Metoprolol (Lopressor)**
29
Beta-adrenergic receptor anatgonists: MOA
* Decrease cardiac output * Decrease RAAS activity * Decrease myocardial O2 demand
30
Beta-adrenergic receptor anatgonists: Clinical uses
* Angina: * Oral prophylactic * Increase exercise tolerance * duration ~6 hours
31
Beta-adrenergic receptor anatgonists: Toxicity
* Contraindicated with bradycardia, asthma * CNS sedation
32
Cardioselective Ca2+ channel blockers
* **Verapamil (Calan, Isoptin)** * Diltiazem (Cardiazem)
33
Cardioselective Ca2+ channel blockers: MOA
* Inhibit voltage-gated L-type Ca2+ channels in cardiac myocytes * decrease force and rate of cardiomyocyte contraction * decrease cardiac output
34
Cardioselective Ca2+ channel blockers: Toxicity
* Hypotension * Excessive cardiac depression * Constipation
35
Vascular Selective Ca2+ channel blockers
* Dihydropyridines * **Nifedipine (Procardia)** * Amlodipine (Norvasc)
36
Vascular Selective Ca2+ channel blockers: MOA
* Inhibit L-type Ca2+ channels on vascular smooth muscle cells * Decrease arterial and venous contraction * Decrease TPR
37
Vascular Selective Ca2+ channel blockers: Toxicity
* Hypotension * Flushing, dizziness
38
Vascular Selective Ca2+ channel blockers: Clinical Use in Angina
* Oral prophylactic * Effective for stable and unstable angina * DDI at CYP450 3A4
39
Ranolazine (Ranexa): MOA and Toxicity
* 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
Nitroglycerin: Drug card
* 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
Sildenafil: Drug Card
* Brand Name: * Viagra * MOA: * PDE5 inhibitor * Clincal Uses: * Angina * ED * Toxicity: * Tachycardia * Hypotension * Visual disturbances (yellow halos) * Extra Info: * Contraindicated with vasodilators
42
Propranolol: Drug Card
* 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
Metoprolol: Drug Card
* 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
Verapamil: Drug Card
* 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
Nifedipine: Drug Card
* 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
Ranolazine: Drug Card
* 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
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