P13: Pharmacological Management of Hypertension Flashcards
What are the normal blood pressure ranges
90-120/60-80 mmHg
Equation for arterial blood pressure
Arterial Blood Pressure = Cardiac Output x Peripheral vascular resistance
Name the symptoms of Hypertension
There usually are none lol
Name risk factors for hypertension
Stress
Dietary salt
High saturated fat intake
High alcohol intake
What BP is considered hypertension
140/90
Name some of the potential consequences of hypertension
- Most important cause of occlusive stroke
- Major cause of haemorrhagic stroke
- Kidney disease/failure
- Angina, heart disease and cardiac infarction
- Blindness through hypertensive retinopathy
- Sexual dysfunction
How and where does hypertension cause hypertrophy in the heart
- Thickening in left ventricle wall
- Hypertension causes greater pressure load on the heart to induce left ventricular hypertrophy
Name some drugs that can cause hypertension
- Oral contraceptives (estrogen, progesterone)
- Monoamine oxidase inhibitors
- Indirectly acting sympathomimetic amines
- Carbenoloxone (treatment of gastric/duodenal ulcers)
- Steroids (glucocorticoids)
Name some diseases that result in hypertension
- Phaeochromocytoma (adrenal chromaffin cell tumour)
- Cushing’s syndrome (excess cortisol) - renal hypertension
- Conn’s syndrome (excess aldosterone) - renal hypertension
What 2 things are pathogenesis factors for hypertension
Increased cardiac output
Increased peripheral resistance
What causes increased preload
Increased fluid volume
Excess sodium intake
Renal sodium retention
What causes increased venous constriction
- excess renin/aldosterone/angiotensin stimulation
- SNS over-activity
- endothelial derived factors
What 3 major sites are pharmacological agents used to treat hypertension
- Sympathetic nervous system
- Vascular smooth muscle
- Renal system
What are the aims of hypertension treatments
- Suppress renin/angiotensin activity
- Suppress heart rate and/or vasoconstriction
- Increase vasodilation
- Increase diuresis
What are the effects of Angiotensin II
- Direct vasoconstrictor, acting on AT1 receptors on the vascular smooth muscle - Gq, IP3, Ca2+ mobilisation, muscle contraction
- ADH release from anterior pituitary
- Acts on hypothalamus to increase desire for water(dipsogen) and salt
- Increases aldosterone release
- Directly acts on PCT to enhance Na+ uptake
What are the effects/actions of aldosterone
- Promotes Na+ and Na+/K+ channel expression in the DCT and CD through mineralocorticoid receptor (MR) actions
- Enhances Na+ reuptake and K+ excretion
- Water follows Na+
What are the effects of Angiotensin II from Aldosterone
Aldosterone is rapidly upregulated by the action of ATII in response to decreased plasma Na+
Name some Angiotensin Converting Enzyme (ACE) inhibitors
Enalapril
Captopril
Name an Angiotensin II (AT1 type) receptor antagonists
Iosartan
Why are there no usable renin inhibitors
too many side effects
How does Angiotensinogen form Angiotensin II
Angiotensinogen to ATI using renin
ATI to ATII using ACE
Overall effects of ATII
Increased vasoconstriction
Increased aldosterone
Increased sympathetic function
Increased ADH
How do diuretics reduce hypertension
Reduce hypertension by reducing blood volume and depleting sodium
How do thiazide diuretics work and give an example
- Inhibits reabsorption of Na+ and Cl- in the DCT
- Increased Na+ in the CD leading to increased Na+/K+ antiporter activity - hypokalaemia
- Hydrochlorothiazide
How do Potassium-sparing diuretics work and give an example
- Inhibits aldosterone effect on Na+ reabsorption and K+ excretion in DCT
- MR antagonists
Describe the mechanism of hypertension drugs that target the heart
Primary approach is to block Beta1 adrenoceptors in the heart, causes bradycardia
Name some hypertension drugs that target the heart
Atenolol Oxprenolol Pindolol Acebutolol Celiprolol (these are kinds of beta blockers)
When are hypertension drugs that target the heart used (first line etc)
Not first line except in patients who do not tolerate ACE inhibitors or AT1 antagonists
What are potential side effects of hypertension drugs that target the heart
Anxiety
Insomnia
Bronchospam in asthamtics/COPD patients
Describe the mechanism of Ca2+ channel blockers
- Inhibits influx of extracellular Ca2+ into cardiac and smooth muscle cell
- Block L-type Ca2+ channels - coronary and peripheral vasodilation
Where are N-type and L-type calcium channels found
N-type = in presynpatic terminals L-type = in the T-tubules
What type of calcium channels do Ca2+ channels block
No binding to N-type
Large excess of L-type Ca2+ channels in skeletal muscle - limited effect
What are the 2 classes of Ca2+ channel blockers and give examples of each
Dihydropyridines - nifedipine, amlodipine
Non-dihydropyridines - diltiazem, verapmil
Describe the actions of Dihydropyridines
- Favours vasculature over the heart
- Reflex tachycardia due to potent vasodilation
- No effect on AV condition, (not effective in supraventricular tachyarrythmias)
Describe the actions of Non-Dihydropyridines
- Favours heart over the vasculature
- Decrease the heart rate by slowing the AV node conduction (may treat supraventricular tachyarrythmias)
What are the adverse effects of Non-Dihydropyridines
Bradycardia
Atrioventricular block
When are Ca2+ channel blockers used (first line etc)
First line treatment in older patients, or if ACE inhibitors cant be used
Name some centrally acting hypertension drugs that work at the medullary CVS regulatory centres
Clonidine, alpha-methyldopa
Moxonidine
Describe the mechanism and effects of clonidine
- selective alpha2 agonists
- stimulation of alpha2 receptors in medulla reduces SNS outflow
- causes centrally mediated vasodilation and reduction in heart rate
- sedative in ~50% of patients
Describe the mechanism and effects of Moxonidine
- Selective agonist at the imidazoline subtype 1 (I1) receptor
- ^^receptor found in depressor areas of the medulla
- activation = decrease in SNS activity and so BP
- used in moderate hypertension when other approaches fail
What are the 3 types of peripheral nerve modulator hypertension drugs and give examples
- Ganglionic transmission - trimethaphan
- False neurotransmitters - guanethidine
- Non-selective alpha-adrenoceptor antagonists - phenoxybenzamine and phentolamine
How do peripheral nerve modulators that affect ganglionic transmission work
- short-acting N1 nicotinic receptor antagonist
- prevents SNS activity in the vasculature = vasodilation
- net tachycardia; loss of vascular resistance governs overall effect on BP
What are the side effects of peripheral nerve modulators that affect ganglionic transmission (trimethaphan)
Postural hypotension
Loss of visual accomodation
Constipation
Urinary Retention
How do peripheral nerve modulators that are false neurotransmitters work
- Taken up by NA transporters, accumulates in vesicles
- Displaces NA, reducing effect of sympathetic stimulation
- Used in acute hypertensive crisis, rarely long term
What are the side effects of peripheral nerve modulators that are false neurotransmitters (guanethidine)
Postural hypotension
Fluid Retention
Inhibits Ejaculation
When are peripheral nerve modulators that are non-selective alpha-adrenoceptor antagonists used (phentolamine)
- not used for treatment of hypertension - postural hypotension and tachycardia
- Used in treatment of hypertensive crisis due to MAOI or phaeochromocytoma
What kind of hypertensive drugs are used in hypertensive crisis and give some examples
Direct vasodilators
Hydralazine
Sodium Nitroprusside
Describe the mechanism of Hydralazine
- Liberates NO from vascular endothelium, stimulates cGMP production in vascular smooth muscle
- cGMP activates PKG, which phosphorylates Ca2+ channels
- Preventing their activation and induing relaxation (arterioles>veins)
Side effects of Hydralazine
Tachycardia with palpitations, often hypotension
Describe the mechanism of Sodium Nitroprusside
- Stimulates soluble guanylate cyclase
- Increasing vascular smooth muscle cGMP
- Causes very rapid vasodilation
Risk of using Sodium Nitroprusside
Metabolism releases cyanide ions - narrow therapeutic window
