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What are the factors that control BP?
- BP = CO x TPR
- CO - volume of blood flow from heart
- Blood volume
- Blood viscosity – thickness of blood
- TPR – resistance of blood vessels
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As TPR rises, structural changes in bv occur
- Hypertrophy of smooth muscle
- Reduced lumen diameter
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Why is it important for optometrists to know about hypertension?
- HTN can result in ophthalmic vascular changes
- Affecting the retina and choroid
- It may be a warning sign of organ damage
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Ophthalmic conditions associated with HTN
- HTR - 50-80%
- HTC - less common cf HTR
- RAM - 50-75%
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Why is it important to treat increased blood pressure?
- 3 million people die annually
- 30% of Australians aged >25yo
- a major risk for coronary heart disease, stroke and heart failure
- CVD = number 1 killer
- Increases morbidity/mortality from stroke, CVD, renal failure
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What is HTN?
- chronic elevated BP
- high systolic/diastolic/both
- primary/secondary
- multifactorial disease
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Approaches to lower BP
- Smoking
- Weight loss
- Alcohol
- Exercise
- Salt
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Drug types to treat HTN
- diuretics
- beta/alpha adrenoceptor antagonists
- calcium channel blockers
- affecting angiotensin system
- centrally acting hypertensives
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Diuretics MOA
- Inhibits reabsorption of Na and Cl in the loop, DCT/CT (collecting tubule) of nephron
- kidneys remove more Na and H2O
- ↓ blood volume --> ↓ BP
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Types of diuretics
- loop
- thiazides
- potassium-sparing
- osmotic
- CAI
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Diuretics treat?
- HTN
- heart failure
- kidney disease
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Adverse effects of diuretics
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β-adrenoceptor antagonists MOA
- bind to β-adrenoceptors
- block the binding of catecholamines (e.g. NE, epinephrine)
- inhibits normal sympathetic effects
- reduces CO: reduces HR, contractility
- reduces renin release: affects volume/tone
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Nonselective drugs (β1 and β2)
- Propranolol
- Timolol
- Levobunolol
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β-adrenoceptor antagonists vary in?
- selectivity – β1 vs β2 adrenoceptors
- lipid solubility
- sympathomimetic effects (can act as agonists)
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β1 selective antagonists
- Atenolol
- Metoprolol
- Betaxolol
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β1 selective antagonists used for glaucoma
- timolol
- levobunolol
- betaxolol
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Adverse effects (related to β-adrenoceptor blockade)
- Fatigue
- Aqueous tear secretion (decreased)
- Triglycerides (increased)
- Cold hands, feet
- Bronchospasm
- Dreams, insomnia
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β-adrenoceptor antagonists used in glaucoma can result in
- irritation
- dry eye from long term use
- systemic side effects (measure BP first)
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What do α-adrenoceptor antagonists bind to?
α-adrenoceptor
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What is an example of a α-adrenoceptor antagonists? What is it selective for?
- Prazosin
- α1 selective antagonist
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Prazosin MOA
- Dilates arteries, veins
- “Blocks” postsynaptic α1 receptors so NA cannot bind
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Adverse effects of Prazosin
- Postural hypotension – 1st dose effect
- Weakness
- Drowsiness
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What is the role of calcium?
- intracellular 2nd messenger
- regulates smooth muscle tone
- many cells have voltage-sensitive Ca++ channels(VOCC)
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Calcium channel blockers MOA
disrupt the movement of Ca via Ca channels
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Type of Ca channel blocker used and for what?Where are they found?
- L-type channels
- found on vascular smooth muscle and cardiac muscle
- used as antihypertensives
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Ca channel blockers have site specificity that varies from
vascular selective to vascular and cardio-selective
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Ca channel blockers that are vascular selective to vascular cardio selective are
- Dihydropyridines (e.g. nifedipine)
- Diltiazem
- Verapamil
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Adverse effects of Ca channel antagonist dihydropyridines
- oedema
- flushing
- headache
- reflex incr in symp activity
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Adverse effect of diltiazem and verapamil
bradyarrhythmia
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ACEI MOA
- blocks conversion of AI to AII
- ↓ vascular tone --> ↓BP
- ↓ aldosterone production --> ↓ salt/water retention
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Adverse effects of ACEI
- Severe hypotn
- Acute renal failure
- Hyperkalemia
- Cough
- Taste (lost)
- Rash
- Fetal malformation
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Why do angiotensin receptor antagonists work?
- AII receptors widely distributed:vascular smooth muscle,adrenal cortex, kidney, brain
- 2 types of AII receptor identified - AT1 & AT2
- MOST known actions of AII are mediatedby AT1 type Angiotensin receptors
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What is Losartan?
- selective antagonist at AT1 receptors
- inhibits CV effects of AII
- similar efficacy to ACEI
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Adverse effects of Losartan
- hyperkalemia
- headache
- dizziness
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Losartan should be avoided when the px
- has renal impariment
- is pregnant
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Centrally acting hypertensives MOA
- ↓ symp outflow from brain centres --> ↓ vascular tone
- acts at brainstem α2 receptors (agonists)
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Adverse effects of centrally acting antihypertensives
- sedation
- sleep disturbances
- dreams
- depression
- dry mouth
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Drug examples of centrally acting hypertensives and their adverse effects
- α methyldopa: hepatotoxicity, hemolytic anemia
- clonidine: withdrawal syndrome
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