CV

Question 1

Aliskiren

Answer 1

• Direct renin inhibitor
• contraindicated w/ use w/ ARBs or ACEIs in patients with renal impairment (i.e. GFR < 60 mL/min)
• Black Box warning w/ pregnancy

Question 2

Angiotensin Receptor-Blockers (ARBs)

Answer 2

• as effecacious as ACEIs
• Lower incidence of kinin-mediated side-effects
• less cough and angioedema
• risk of hyperkalemia
• Black box warning for pregnant women (AngII required for normal fetal development)
• Selectively block AT1 receptor

Question 3

ACE inhibitors

Answer 3

• end in ( - pril) [ex. Captopril]
• Side effects
• ACE breaks down bradykinin in the lungs
• dry cough
• angioedema (greater risk in African-Americans)
• Hyperkalemia
• Increased creatinine (< 30% is normal)
• Black box warning for pregnant women (AngII required for normal fetal development)

Question 4

Diuretics

Answer 4

Effects

• increased Na+ excretion, venodilation, decrease intravascular volume
• eventually decrease peripheral resistance
• Subclasses: Thiazides, Loop, and Potassium-sparing

Side Effects

• Hypotension, orthostasis
• Hypokalemia (hyperkalemia w/ K+-sparing)
• Hyponatremia and hypercalcemia (thiazide)
• Ototoxicity (Loop)
• Hyperglycemia, hypercholesterolemia, hyperuricemia
• Erectile dysfunction
• Sulfa-allergy (thiazide)

Question 5

Aldosterone Antagonists

Answer 5

• Beneficial in resistant HTN when combined w/ other diuretics
• Increased risk of hyperkalemia when combined with ACE-I or ARB
• Spironolactone (non-selective)
• Side effects:
• Men: ED and gynecomastia
• Women: menstrual abnormalities
• Eplerenone (selective but costs more)

Question 6

Calcium Channel Blockers

Answer 6

• block influx of Ca2+ and smooth muscle contraction
• Effects
• vasodilate arteriolar smooth muscle
• decreae peripheral vascular resistance

Side Effects

• gingival hyperplasia
• aggravate GERB
• Non-dihydropyridines
• also decrease Ca2+ influx to myocardium causing bradycardia, AV block and constipation
• Dihydropyridines
• edema, headache, flushing, dizziness, palpitations

Question 7

ß-Adrenoceptor Blockers

Answer 7

• Decreased CO, inhibit renin secretion inhibit norepinephrine release
• reductions of HR (negative chronotropic effects)
• reduces ventricular hypertrophy, stroke, heart failure, coronary events and mortality
• ß1 (selective): targets myocardium, less effect on airways
• ß2 (non-selective): myocardium, vascular, bronchial cells
• vasodilatory properties (carvedilol or labetalol) antagonize a-adrenergic receptor and increase NO release
• Not first line HTN treatment

Side Effects

• bradycardia, heart block, dizziness
• bronchospasm, cold extremities (ß2 effect)
• CNS: fatigue, depression, dry mouth
• ED and hyperglycemia
• Lipid abnormalities (TG elevation and HDL reduction)

Question 8

Hydralazine

Answer 8

• Direct vasodilator
• relax smooth muscle and decrease peripheral resistance
• given w/ diuretic and ß-blocker to prevent “pseudotolerance”
• tachycardia and volume retention
• metabolized by N-acetyltransferase (genetic component)

Question 9

Minoxidil

Answer 9

• Opens K+ channels in vascular smooth muscle
• most useful in pts w/ severe hypertension and renal failure
• Given w/ diuretic and ß-blocker to prevent “pseudotolerance”
• Side effects: pericardial effusion (3%), facial hirsutism

Question 10

a-Adrenergic Receptor Blockers

Answer 10

• Selective a1-antagonists (blocks NE site)
• decrease arteriolar resistance
• beneficial for pts w/ prostate symptoms (ex. doxazosin)
• Side effects:
• Postural hypotension
• dizziness, syncope
• reflex tachycardia
• nasal congestion

Question 11

a2 agonists (clonidine, methyldopa)

Answer 11

• reduce sympathetic outflow to the heart and blood vessels
• Side-effects: sedation, severe dry mouth, ED
• Clonidine: rebound HTN, skin hypersensitivity
• Methyldopa: Coombs’ positive hemolytic anemia, elevated LFTs

Question 12

M₁ Receptors

Answer 12

• tissue
  
  • autonomic ganglia
• response
  
  • depolarizes postsynaptic neurons (slow EPSP)

Question 13

M₂ Receptors

Answer 13

• Heart
  
  • decrease heart rate, conduction velocity, contractility
    
    • bradycardia (SA node)
    • decrease AV node conductivity
    • decrease atrial contractility

Question 14

M₃ Receptors

Answer 14

• Smooth muscle (eye, bronchioles, GI tract, urogenital system)
  
  • contraction
    
    • iris circular muscle –> miosis
    • ciliary smooth muscle –> accommodation
    • bronchoconstriction
    • circular and longitudinal muscles in intestinal walls –> increase motility (relaxation of GI sphincters)
    • gall bladder
    • bladder detrusor muscle (relaxation of trigone and sphincter)
    • contracts uterus
• Secretory glands
  
  • increase secretion
    
    • lacrimation
    • mucous bronchial gland secretion
    • acid secretion from parietal cells
    • gastric and intestinal glands
    • watery secretions from salivary, nasopharyngeal, pulmonary, GI and eccrine sweat glands
• Vascular endothelium (w/o innervation)
  
  • dilates blood vessels
    
    • relaxation of endothelial cells
    • decrease BP
    • penile erection

Question 15

N_M Receptors

Answer 15

• Neuromuscular junction
  
  • skeletal muscle contraction

Question 16

N_N Receptors

Answer 16

• Autonomic ganglia
  
  • depolarizes postsynaptic neurons
• Adrenal medulla
  
  • depolarizes medullary cells –> secretion of catecholamines

Question 17

a₁ Receptors

Answer 17

• smooth muscle (eye, vascular, urogenital, hair follicles)
  
  • contracts smooth muscle
    
    • iris radial muscle –> mydriasis
    • erector pili
    • vasocontriction –> increase BP
    • GI sphincters
    • trigone and sphincter –> urinary retention
    • seminal vesicles, prostatic capsule, vas deferens –> ejaculation
    • uterus
    • secretion from aprocine sweat glands
    • viscous salivary secretions
• liver
  
  • increase glycogenolysis and gluconeogenesis

Question 18

a₂ Receptors

Answer 18

• axon terminals (autoreceptors)
  
  • decrease NE release
• pancreatic B cells
  
  • decrease insulin release
• vascular smooth muscle
  
  • contracts smooth muscle (less than a1)
    
    • vasocontriction –> increase BP
• platelets
  
  • aggregation

Question 19

B₁ Receptors

Answer 19

• Heart
  
  • increase HR, conduction velocity, contractility (opposite of M2)
    
    • tachycardia (SA node)
    • increase AV node automaticity and conductivity
    • increase His-Purkinje automaticity and conductivity
    • increase ventricular automaticity and contractility
• Kidney (juxtaglomerular cells)
  
  • increase renin release

Question 20

B₂ Receptors

Answer 20

• Smooth muscle (eye, bronchioles, GI, urogenital, vascular)
  
  • relaxes smooth muscle
    
    • iris circular muscle –> mydriasis
    • bronchodilation
    • watery secretion via CFTR activation in bronchial glands
    • decrease TPR and increase blood flow to liver and skeletal muscles
    • intestinal muscle –> decreased motility
    • decreased gastric acid secretion, relaxes gall bladder, increases amylase secretion
    • relaxes detrusor –> urinary retention
    • relaxes uterus
• Heart
  
  • increase HR, contractility (B1 dominates)
    
    • tachycardia (SA node)
    • increase AV node automaticity and conductivity
    • increase His-Purkinje automaticity and conductivity
    • increase ventricular automaticity and contractility
• Liver and skeletal muscle
  
  • increased glycogenolysis, gluconeogenesis (liver)
  • slight increase in insulin release

Question 21

B₃ Receptors

Answer 21

• Lipocytes
  
  • activates lipolysis

Question 22

D₁ Receptors

Answer 22

• Vascular smooth muscle, especially renal vasculature
  
  • dilates blood vessesls (increased renal perfusion)
    
    • increase GFR

Question 23

D₂ Receptors

Answer 23

• Axon terminals (autoreceptors)
  
  • decrease DA release
• Cholinergic neurons in the gut
  
  • decrease GI motility