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CV - Vasodilators - Vascular Tone - Coggle Diagram
CV - Vasodilators - Vascular Tone
Physiology of Vascular Tone
Endothelium Mediators
Nitric oxide
Prostacyclin
Endothelin
Sympathetic NS
Vasocontrictor Norepinephrine α receptors
Neurohormonal Mediators
Epinephrin
Angiotensin II
Vasopressin
Blood Pressure
Vasodilators
Angiotensin Converting Enzyme (ACE) Inhibitors
Reduce IP3 CA2+ release
Angiotensin II Receptor Antagonists
Renin Inhibitors
Phosphodiesterase (PDE) Inhibitors
Increase cGMP
Calcium Channel Blockers
Close L-type Ca2+ channels
Potassium Channel Openers
Endothelin Receptor Antagonists
α-1 Adrenoreceptor Antagonists
Nitrates NO donors
ACE Inhibitors
Captopril :cat:
Enalapril, ramipril
Lisinopril
Actions of Angiotensin II (5)
Vasoconstriction
Activation of Gq AT1 receptors
IP3 pathway increases Ca2+
Facilitates NE release
Degrades bradykinin
Stimulate Aldosterone release from adreanl cortex
Stimulate ADH release from pituitary
MOA
Inhibits angiotensin converting enztme
Angiotensin II not produced
3 Dilation of arteries and veins (Gq AT1 receptors not activated)
Down regulation of sympathetic activity
Promotion of renal excretion
Use (4)
Hypertension
MI
Heart failure
Decreased Mortality
Diabetic Nephropathy
Adverse Effects (6)
Hyperkalaemia
Increased creatinine
Dry cough - Bradykinin
Fainting
Hypotension
Teratogenic
Angiotensin II Receptor Blockers (ARBs)
Losartan :arrow_down_small:
Candesartan :candy:
Valsartan :mountain:
MOA
Blocks activation of Gq AT1 receptor preventing Ca2+ increase, and therefore contrcation
Dilation of arteries/veins
Downregulation of Sympathetic NS
Promotes renal excretion
Use
Heart failure
MI
Hypertension
When ACE can't be used
Renin Inhibitors
Aliskiren
High Risk
MOA
Inhibits Renin, preventing conversion of Angiotensinogen to Angiotensin I
Nitrates / NO Donors
Glyceryl trinitrate (GNT)
Nitroglycerin
Isosorbide mononitrate
MOA
Activates Guanylyl cyclase
GC converts GTP to cGMP
cGMP activates protein kinases that activates MLC phosphatase
MLC phosphatase dephosphorylates Myosin LC, reducing crossbridge formation and contraction
Preferentials
Dilates large vessels
Venous dilation
Reduced EDV / decreased volume preload
Arterial dilation (High dose)
Decreased systemic resistance
Pharmacokinetics
GNT
Low oral bioavailability - 1st pass metabolism
Transdermal patch - prophylaxis
Sublingual spray - acute angina symptoms
Isosorbid mononitrate
GI
Up to 100% bioabailability
Tolerance
Continous exposure causes tolerance development
Less likely with short acting agents
Free periods - 8hrs recommended
Mechansism (6)
Dimished ability to convert nitrate to NO
Diminished release of NO bc depletion of endogenous sulfydryl compounds
Alterations in GC activity
Endothelial vascular changes (opposing vasocontrictor repsponses)
Oxidative stress
6 .Plasma volume expansion - baroreceptor reflex
PDE Inhibitors
Sildenafil
Tadalafil
Vardenafil
MOA
Inhibits PDE-5
Prevents cGMP breakdown hydrolysis to GTP
cGMP activates MLC phosphatase
MLC phosphatase dephosphorylises ML, decreasing crossbridge formation and contraction
Side Effects (4)
Flushing
Headaches
Dyspepsia
Decreased BP
Use
Erectile dysfuntion
Calcium Channel Blockers
Dihydropyradines
Phenylalkylamines
Benzothiazepines
MOA
Inhibition of L-type Ca2+ channels :zap:
Vasodilation + Inhibition of cardaic contraction
Potassium Channel Openers
Nicorandil
Minoxidil
MOA
Opens ATP-sensitive K+ channels
Hyperpolarisation of smooth muscle cells
Closure of Voltage-gated Calcium channels - decrease Ca2+ influx
Less activation of MLC kinase, and phosphorylation of ML
Relaxation and vasodilation
Endothelin Receptor Antagonists
Bosentan
Non-selective ET-1 receptor antagonist (blocks ETA and ETB receptors)
MOA
Antagonises Gq ET receptors
Prevents IP3 casacade and Ca2+ increase
Vasodilation / relaxation
α-1 adrenoreceptor antagonists
MOA
Antagonises Gq α1 receptors
prevents IP3 cascade and Ca2+ increase
Vasodilation and relaxation
Prazosin
Treatment
CV disease - Angina
Hypertension
Cardiac failure
Pulmonary hypertension
