Pharmacology of HTN 1

• What is isolated systolic HTN?

  Systolic > 140

  Diastolic < 90

  High pulse pressure

  Most common
• What is isolated diastolic HTN?

  Systolic < 140

  Diastolic > 90

  Least common
• What is mixed HTN?

  Systolic > 140

  Diastolic > 90
• What is the percentage of each HTN?

  Essential HTN > 90%

  Secondary HTN < 10%
• What is essential HTN?

  Idiopathic HTN (no clear causative factor)
• What is secondary HTN?

  High blood pressure that is caused by an underlying medical condition or medication

  • renal disorders
  • endocrine disorders (primary hyperaldosteronism, phaechromocytoma, Cushing's syndrome)
  • drug-induced (abuse (cocaine), iatrogenic (combined oral contraceptive, glucocorticoids))
  • pregnancy - pre-eclampsia
• What are the consequences of HTN?

  Increased risk of many CV disorders (stroke, heart failure, peripheral arterial disease, CKD etc.)
• What are the mechanisms that underlie HTN?

  Cardiac output

  Peripheral resistance

  Autonomic NS

  Endothelium

  Vasoactive peptides

  RAAS
• Arterial BP = CO x TPR
• CO = SV x HR
• How does the autonomic NS impact HTN?

  Heart - b1 receptor -> increases HR -> increased CO

  Vessels - a1 receptor -> vasoconstriction, b2 receptor -> vasodilation

  Short-term regulation (e.g. baroreceptor reflex)
• What do endothelial cells produce?

  Vasoactive agents (NO, PGI2, endothelin)
• What is the effect of NO?

  Vasodilation

  by binding to guanylyl cyclase -> increase cGMP -> increase PKG -> smooth muscle relaxation
• What does prostacyclin (PGI1) do?

  Vasodilation
• What does enothelin do?

  Vasoconstriction
• Give 3 examples of vasoactive peptides.

  Bradykinin

  Natriuretic peptides (A, B & C)

  Vasopressin (ADH)
• What is the effect of bradykinin?

  Vasodilation

  ACE inhibtors block bradykinin inactivation
• What is the effect of vasopressin (ADH)?

  Vasoconstriction
• What is renin produced by?

  Juxtaglomerular cells
• RAAS is a target for many important & effective drugs used to treat HTN.
• What is Liddle syndrome?

  Rare autosomal dominant disorder that causes severe HTN at an early age

  Caused by mutations in beta & gamma subunits of ENaCs -> prevents channel internalisation & degradation -> overexpression of ENaCs -> excess Na+ reabsorption
• What is the treatment of Liddle syndrome?


  ENaC channel blockers (e.g. amiloride)
• Fill in the blanks

  A) peptides

  B) receptors

  C) AT-II

  D) AT1

  
• Different classes of drugs used to treat HTN?

  Diuretics

  Renin inhibitor (-kiren)

  ACE inhibitor (-pril)

  Angiotensin Receptor Blocker (ARB) (-sartan)

  Ca+2 channel blocker (-dipine)

  Beta blockers (-lol)

  Centrally acting a2 agonists

  Vasodilators
• What is Stage 1 HTN?

  140/90 < ABP < 159/99
• What is Stage 2 HTN?

  160/100 < ABP < 180/120
• What is Stage 3 HTN?

  SBP > 180 OR DBP > 120
• What do natriuretic peptides do?

  Increase Na+ & water excretion (in urine)
• What is hexamethonium?

  Analogue of ACh

  Target: nicotinic receptor

  Activity: channel blocker

  Blocks sympathetic & parasympathetic NS
• What are the functions of voltage-gated Ca+2 channels?

  Cardiac AP/pacemaker

  Smooth/skeletal muscle contraction

  Endocrine (e.g. insulin secretion)

  Ntr release