Cardio: Vasodilator Drugs

Question 1

• ↓ TPR via dilation of both Arteries and Veins
• onset time in seconds (arterial afterload and venous preload) w/ small cardia reflex stimulation
• Cyanide toxicity can lead to acid-base disturbances, arrhythmias, and SCD → co-administer w/ Nitrites and Thiosulfate to decrease toxicity (24 - 36 hrs max)
• Thiocyanate toxicity seen in pts. with impaired Renal failure –> disorientation, psychosis, spasms, convulsions
• DOC in Hypertensive Emergencies and **Severe cardiac failure **in conjuction with **Furosemide **(prevent overload)

Answer 1

Sodium nitrorusside

Question 2

• Dihydropyridine calcium channel blockers with onset time in 1 - 5 or 2 - 4 minutes
• One of these two has a long terminal half-life

Answer 2

Nicardipine or Clevidipine (long half-life)

Question 3

• A Dopamine receptor-1 agonist (DA₁) with onset time in 4-5 minutes
• Maintains or increases Renal Perfusion and may be good choice for patients with Renal dysfunction
• Reduces Blood pressure
• Used in Emergency Hypertension

Answer 3

Fenoldopam

Question 4

• A venous arteriolar dilator with onset time in 2-5 minutes is more effective as a Venous rather than as a Arteriolar dilator
• Has been used for treatment of HTN crisis in pts. with Cardiac Ischemia or after Coronary bypass surgery

Answer 4

Nitroglycerin

Question 5

• A non-selective α-blocker with onset time in 1-2 minutes
• Used to treat pts. w/ Catecholamine-related emergencies

Answer 5

Phentolamine

Question 6

• A β-blocker with onset time in < 5 minutes
• Used to treat Aortic Dissection or Postoperative HTN

Answer 6

Esmolol

Question 7

• A α- and β-adrenergic blocker with onset time in 5-10 minutes
• May be safe in pts. with active Coronary disease

Answer 7

Labetalol

Question 8

• Arteriolar dilator with onset time in 10-30 minutes
• Increasing K⁺ efflux, decreasing Ca²⁺ influx, NO release
• Direct relaxation of the Arteriolar smooth muscle
  
  • ​→ ↓↓ TPR via arteriolar dilation (afterload) and BP
  • reflex ↑ in HR, Contractility, Plasma renin, and fluid retention → use w/ Diuretics
• Tx: Mod- to Hypertensive emergencies in pregnancy related to eclampsia, Chronic hypertension
• Contraindicated in pts. with HTN and CAD, may produce SLE like symptoms in slow acetylators (high protein binding w/ free faction), Edema, and reflex Tacycardia

Answer 8

Hydralazine (Apresoline)

Question 9

• Block adrenergic neuron function
• Exogenous false neurotransmitter (replaces norepinephrine in storage vesicles) → NorEpi release
• Inhibits the function of peripheral postganglionic adrenergic neurons
• Effector cells become supersensitive to Norepinephrine

Answer 9

Guanadrel (Hylorel)

Question 10

• Blocks adrenergic neuron function
• Depletes amines in the CNS as well as peripheral adrenergic neuron
• Interferes with sympathetic nervous function
• Binds to adrenergic storage vesicles and inhibits vesicular catecholamine transporter that facilitates vesicular storage → pharmacological sympathectomy

Answer 10

Reserpine

Question 11

• Centrally acting sympatholytic agents
• Stimulate the α_2A-adrenergic receptors in the brainstem
• Reduction in sympathetic outflow from the CNS → Hypotensive effect
• High Dose → activate α_2B-adrenergic receptors on vascular smooth muscle → Loss of therapeutic effect

Answer 11

Clonidine (Catapres)

Guanabenz (Wytensin)

Guanfacine (Tenex)

Question 12

• ATP K⁺ channel Opener → metabolized to active metabolite minoxidil sulfate that activates the
• *ATP-modulated K⁺ channel** in Arteriolar smooth muscle (hyperpolarize)
  
  • → little effect on Venous and Capacitance vessels
• Side effects: ↑ HR, Contractility, Plasma renin activity and Fluid retention, also ↑ oxygen demand can lead to cardiac ischemia and is contraindicated in HTN pts.
• Tx: HTN refractory, Hypertrichosis, Hyperglycemia (Diazoxide surpresses insulin release)
• Co-administed with sympatholytic agents, β-blockers

Answer 12

Minoxidil → Severe Hypertension and Baldness (Rogaine)

Diazoxide → Emergency Hypertensive

Cromakalim

Pinacidil

Nicorandil

Question 13

• Ca²⁺ channel blocker - Dihydropyridine
• Arteriolar dilators
• Decreased entry of Ca²⁺ by binding to α₁ subunit of L-type channels → intracellular [Ca²⁺] low
  → reducing activation of myosin light chain kinase, actin-myosin interaction, and smooth muscle contactility
• Arteriolar more responsive then Venous
• ↓ Contractility by reflex, ↓ SA node rate, ↓ AV node conduction velocity, ↑ HR by reflex
• Tx: HTN, HTN emerg., Angina, HF, prevent neuro deficits secondary to Cerebral Artery Spasm

Answer 13

Nifedipine (Procardia)

Question 14

• Ca²⁺ channel blocker - Non-dihydropyridine
• Arteriolar dilators
• Decreased entry of Ca²⁺ by binding to α₁ subunit of L-type channels → intracellular Ca²⁺ low
  → reducing activation of myosin light chain kinase, actin-myosin interaction, and smooth muscle contactility
• Arteriolar more responsive then Venous
• ↓↓↓ Contractility by reflex, ↓ SA node rate, ↓↓ AV node conduction velocity, ↓↓↓ HR, ↓↓↓ Ca²⁺ recovery
• Tx: HTN, HTN emerg., Agina, HF, prevent neuro deficits secondary to Cerebral Artery Spasm

Answer 14

Verapamil (Isoptin)