Pulmonary Hyper/Hypotension

  1. Group I PAH
    • Cause: long term vasoconstriction of the pulmonary arteries; can be secondary to cirrhosis, hepatic portal hypertension, certain anemias; drug-induced by cocaine or fen-phen
    • Presentation: vessels become stiff and think, loss of endothelium, smooth muscle proliferates, and fibrosis
  2. Fenfluramine-Phenteremine
    • Sympathomimetic amines designed to induce serotonin release
    • ADEs: Cardiac valve fibrosis and pulmonary hypertension, when Fen and Phen are taken together
    • Wasn't tested in combination before selling
    • MoA: targets 5-HT2B
  3. BMPR2
    • Bone morphogenic receptor protein type II = serine/threonine kinase
    • Key role in cellular differentiation/maturation
    • Gene that encodes this protein also encodes 5-HT2B 
    • Disruption of the gene produces cellular overgrowth particularly in small arteries
  4. Pulmonary Hypertension Definition
    • Normal PAP = 12-16 mmHg
    • PH = >25 upon exercise

    • Terminology:
    • Idiopathic Pulmonary Arterial Hypertension (IPAH)
    • Familial Pulmonary Arterial Hypertension (FPAH)
  5. Group II PVH (Pulmonary Venous Hypertension)
    • Causes: left heart insufficiency leads to volume back-up in pulm vein; decreased PA emptying and thus pressure rises;
    • Presentation: pooling of blood in lung, edema, effusions
    • What used to be "Secondary Pulmonary Hypertension"
  6. Group III Hypoxic Pulmonary Vasoconstriction
    • Causes: vasoconstriction in the face of hypoxia; Acute Mountain Sickness = low O2 lvls in air, so lung thinks you're not using the whole lung and responds by lowering blood flow to lungs.
    • V/Q matching
  7. Group IV Thrombotic or Embolic Disease
    • Blockage or narrowing of vessels, often occult
    • Similar to Group 1 in terms of presentation (stiff vessels, fibrosis)
    • i.e. Airplane employees
  8. Group V Miscellaneous
    yep, way to go Venice...
  9. Sleep Apnea
    • Usually only mild hypertension
    • Pickwickian syndrome: hypoxia, hypercapnia (too much CO2), acidosis, obstruction
  10. Tx Group II PVH
    • Treat the cause = congestive heart failure
    • Diuretics, β-blockers, ACE inhibitors, Valve replacement
    • Conventional: lifestyle, digoxin, oxygen, diuretics
  11. Calcium Channel Blockers
    • Goal: to reduce smooth muscle contraction, but it is not specific enough
    • Ends up slowing down delivery of oxygenated blood to the rest of the body, and these patients are already hypoxic from PH!
    • Only 5% of IPAH is vasoreactive
  12. Epoprostenol
    • Synthetic prostacyclin
    • PGI= most effective Tx for PAH
    • Continuous infusion via in-dwelling central venous catheter
  13. Treprostinil
    • IV or SC
    • Synthetic prostaglandin
    • Tx PAH
  14. Remodulin
    • Synthetic prostaglandin
    • Tx PAH
  15. Iloprost
    • Synthetic prostaglandin
    • MoA: systemic and pulmonary vasocontrictor
    • Specificity achieved via Nebulizer delivery
  16. Endothelin Receptor Antagonists
    • Bosentan- acts at both ETA and ETB sites
    • Ambrisentan- specific for ETA (good because ETB antagonism on endothelial cells can inhibit prostacyclins and NO-induced relaxation)
  17. Phosphodiesterase V Inhibitors
    • Sildenafil
    • Tadalafil- longer half life
    • Unknown specificity and effectiveness
  18. Vasoactive Intestinal Peptide
    • Binds to GPCRs VPAC1 (lung) & 2 (heart)
    • Potential vasodilator, but also potential positive chronotrope&inotrope
    • Tx PAH?
  19. Serotonin antagonism
    • PRX-08066 specific 5HT2B receptor antagonist
    • Opposes hypoxic vasoconstriction
    • Phase II trials
  20. Endothelial Progenitor Cells
    Under investigation for PAH, which has a loss of endothelial cells
  21. Persistent Pulmonary Hypertension of Newborns
    • Not based on remodeling;
    • When neonates don't transition from in utero-style breathing (high PVR w/ hypoxic constriction) to outdoors breathing (low PVR w/ more blood flow)
    • = high PVR and PAP, low Qp, shunting continues
    • Causes: Zoloft effect (mothers taking Zoloft), Capillary dysplasia, Maternal diabetes; meconium aspiration; lung hypoplasia (lung doesn't fully inflate)
  22. Tx PPHN
    • Oxygen
    • Correct acidosis w/ bicarbonate, THAM
    • Dilate the lung w/ dopamine
    • High Frequency Oscillating Ventilation
    • Extracorporal Membrane Oxygenation (not a good option, hooking up the lil one to machina)
  23. iNO
    • Tx PPHN
    • Beware rebound hypertension, takes 3 days to wean off
  24. NONOates
    • Liquid based, but arterial oxygenation does not get better since V/Q gets mismatched
    • Reduces PAP and PVR
    • iNO preferred?
  25. Shock
    • Inadequate perfusion of vital capillary beds
    • Key elements: hypoperfusion --> cellular injury --> systemic damage; Reperfusion injury; Infammatory response to cellular injury
    • Lactic acid accumulation: anaerobic metabolism
    • Metabolic acidosis: vasoconstriction
    • Intracellular lysosomes released: efflux of potassium, but influx of sodium/water
  26. Four Stages of Shock
    • Initial: shift to anaerobic metabolism
    • Compensatory
    • Progressive: failure to compensate leads to more injury
    • Refractory: organ shock occurs, and Tx cannot be applied
  27. Hypovolemic Shock
    • Most common form
    • Significant loss in preload
    • Attempts to correct BP end up decreasing organ perfusion (i.e. vasoconstriction + RAS)
    • Classes I-IV based on blood pressure, % blood loss, pulse, respiratory rate, and urine output
  28. Cardiogenic Shock
    • Primary pump failure, but no always MI
    • Causes include: loss of myocardium, reduced contractility, filling anomalies, acute valvular failure, dysrhythmias
    • Peripheral vasoconstriction
    • Oliguria
  29. Distributive Shock
    • High cardiac output
    • Systemic hypotension
    • Decreased vascular resistance
    • Perfusion/metabolic demand mismatch
  30. Neurogenic Shock
    • Subset of Distributive Shock
    • Loss of autonomic control due to spinal injury: hypotension, bradycardia, warm dry skin
    • Euvolemic with reduced peripheral tone
    • Tx: Atropine
  31. Anaphylaxis
    • Subset of Distributive shock
    • Respiratory obstructive processes can result in myocardial depression
    • Usually low central venous pressure
  32. Four main things to correct in shock:
    • 1. Preload: crystalloid vs colloid fluids
    • 2. Contractility: Ca2+/glucagon if β-blocked
    • 3. Afterload: 
    • 4. Oxygen delivery
  33. Dopamine
    • Catecholamine Tx Contractility
    • Low dose improves renal fxn
    • Medium dose increases cardiac contractility & HR
    • High dose increases systemic blood pressure
  34. Dobutamine
    • Catecholamine Tx Contractility-help shock
    • Minimal chronotropy
    • Increased inotropy
    • Systemic vasodilator
  35. Norepinephrine
    • Positive chronotropic
    • Positive inotropic
    • Systemic vasoconstrictor
  36. Levosimendan
    • Inodilator
    • MoA: binds to troponin C (but Ca2+ dependent), thus sensitizing the myocyte to calcium; opens ATP-K channels in smooth muscle
    • ADE: renal impairment
  37. Arginine Vasopressin
    • Normally released in posterior pituitary in response to severe hypotension
    • Septic patients have low lvls of AVP
    • MoA: blocks ATP-K channel, which restores responsiveness to catecholamines in the septic patient
  38. Reduction in Afterload
    • Improves cardiac function, but can cause hypotension
    • Nitroprusside/nitroglycerin IV
    • ACEIs "-prils"
    • Mechanical aids
Card Set
Pulmonary Hyper/Hypotension
For Rutgers P2 students studying for the second Pharmacology II exam