Anti-hypertensives Flashcards
Hypertension
Blood pressure that is persistently higher than the normal: 150/95 mm Hg
Normal BP
150/ 95 mm Hg
Regulation of stroke volume
Carried out by the ventricles
Regulation of heart rate
Carried out by SAN regulation
Regulation of total peripheral resistance
Controlled by arteriole constriction in the peripheries.
Factors that increase cardiac output
Increase in:
Preload
Cardiac force of contraction
Frequency of heart beats
Release of NADR
Extrinsic regulation of CO
Autonomic nervous system
Sympathetic- increases heart rate and contractility.
Parasympathetic: decreases heart rate and contractility.
Sympathetic effect on cardiac output
Acts on Beta-1 receptors
Causes an increase in cAMP—-> Increases Ca2+ released —> increases the rate and contractility in the heart.
Parasympathetic effect on cardiac output
Acts on M2 receptors:
Decreases cAMP—> less Ca2+ —> decreases rate and contractility.
Sympathetic effect on total peripheral resistance
System releases noradrenaline from adrenal medulla.
Acts on alpha-1 receptors— Increase IP3—-> Increase Ca2+ released —-> Causes vasoconstriction in arterioles.
Effect of angiotensin II on BP
Acts on AT1- R - causes vasoconstriction and arterio-constriction
Venoconstriction = increase in preload
Arterioconstriction= increase in afterload
Arterioconstriction
A factor that increases afterload, thus blood pressure.
Trigger by angiotensin II acting of AT1-R
AT1-R
Angiotensin II Type 1 receptor.
Angiotensin II is an agonist that triggers arterioconstriction and venoconstriction.
Regulation of BP by the kidneys
Kidneys sense an increase in blood flow and triggers the RAS.
Release of aldosterone and angiotensin increase preload and afterload= increase in BP
Effect of aldosterone on BP
Release is triggered when RAS is activated from an increase in renal blood flow.
Aldosterone is released from adrenal cortex and acts on AT1-R.
This causes more Na+ retention, thus more H20 retention.
This increases preload= increase in BP
Regulation of TPF by angiotensin II
Angiotensin II is made in the lungs via ACE.
Triggers an increase in IP3— > increase in Ca2+
When this occurs in arteriole muscular walls, causes vasoconstriction.
This increase TPR= increase in BP.
Aldosterone effect on aldosterone-sensitive distal nephron
Aldosterone binds to cytoplasmic receptors and activates them.
The activated receptor binds to the nucleus and triggers increased expression of Na= channels= increases water retention = increase BP.
Factors that determine what antihypertensive is given
Age
Race
Co-existing diseases
Using age to determine what antihypertensive is given
If patient is <55:
ACE inhibitor/ ARB is given
If patient is >55:
Ca2+ channel blocker is given
Using race to determine what antihypertensive is given
If the patient is Black African/American/Caribbean:
Ca2+ is given despite the age. They respond less to ACE inhibitors and beta-blockers
Side effects/ contraindications of ACE inhibitors
Dry cough
1st dose hypotension
Contraindication with bilateral renal artery stenosis
May cause hyperkalaemia
Dry cough with ACE inhibitors
ACE inhibitors prevent the breakdown of bradykinin.
ACE breaks down bradykinin in CNS/PNS/ SP/ BKergic neurone.
This prevents bradykinin to be converted to an inactive peptide. This triggers coughing response- too much bradykinin in system.
1st dose hypotension with ACE inhibitors
Side effect of ACE inhibitors
Due to an overstimulation of inhibiting the RAAS
Contraindication of ACE inhibitors
Bilateral renal artery stenosis
The kidney is already hypoperfused due to narrower efferent arteriole
ACE inhibitor dilates the efferent arteriole whilst decreasing/ keeping the afferent arteriole the same.
This decreases perfusion even more.
ARB
Angiotensin receptor blockers
Antagonises AT1-R, blocking the action of Angiotensin II
Example: Losartan
Losartan
An ARB
Spironolactone
Aldosterone antagonist- a diuretic, potassium sparing.
Blocks epithelial sodium channel (ENaC)- less absorption of Na+ in the blood.
Ca2+ channel antagonist
Blocks Ca2+ channels:
Dihydropyridines act on blood vessel smooth muscles.
Phenylalkylamines and benzothiazepines action on cardiac cells.
Dihydropyridines
Ca2+ channel antagonists that target L-type Ca2+ channels on smooth muscle of blood vessels.
Example: amlodipine.
Used to treat hypertension
Amlodipine
Dihydropyridine
Targets L-type Ca2+ channels on blood vessels.
Used to treat hypertension
Phenylalkylamines
Ca2+ antagonists that target L-type channels in the heart
Decreases heart rate and contractility.
Example: Verapamil
Benzothiazepines
Ca2+ antagonists that target L-type Ca2+ channels in the heart.
Decreases heart rate and contractility.
Example: Diltiazem
Verapamil
Phenylalkylamine that blocks L-type Ca2+ channels in the heart.
Decreases HR and contractility.
Diltiazem
Benzothiazepine that decreases HR and heart contractility.
Side effects and contraindications of Ca2+ channel antagonists.
Flushing and headaches
Combination of antagonists not recommended.
Action enhanced by grapefruit juice.
Peripheral oedema.
Peripheral oedema as a side effect of Ca2+ channel antagonists.
With specifically dihydropyridines:
-Preferential dilation of precapillary arteriole.
Impairment of pre-capillary sphincter.
This increases HP across the capillary- forcing liquid out into surrounding tissues.
Thiazide and thiazide-like diuretics.
Acts on distal convoluted tube to initiate diuretic action.
Blocks reabsorption of Na+ and Cl- back into the blood.
Activates Katp in blood vessel smooth muscle which dilates arterioles.
Example: Indapamide
Indapamide
Thiazide-like diuretic.
Prevents the release of K+ from Katp, which increases Ca2+ in smooth muscle cells.
This hyperpolarises the cell- causing dilation of arterioles= decreases TPR and BP.
Side effects and contraindications of thiazide and thiazide-like diuretics.
Hypokalaemia
Increase in urate, glucose and blood lipids.
Bendroflumethiazide
A thiazide diuretic, treats high BP.
Side effects and contraindications of beta-blockers
Bronchoconstriction
Vasoconstriction- B2 receptor
Fatigue
Increase in blood lipids
Hypoglycaemia
CNS side effects
Not efficacious in Black people.
Beta blockers and vaso/bronchoconstriction
If the inhibit Beta-2 receptors, prevents the formation of cAMP.
This prevents the relaxation of smooth muscles in the airways and peripheral arterioles.
Beta blockers and hypoglycaemia
Low blood glucose usually triggers the release of adrenaline.
This is inhibited by beta-blockers.
This keeps blood glucose low.
Therefore beta-blockers are contraindicated in diabetics.
Non-selective beta-blockers
Acts on both beta-1 and beta-2 receptors
Example: propranolol
Propranolol
Non-selective beta-blocker
Bisoprolol
Selective beta-1 antagonist.
Alpha-1 antagonists
Act as vasodilators
Blocks NADR from binding to Alpha-1 receptors.
Prevents release of IP3—> Ca2+ —-> vasoconstriction
examples: Doxazosin
Doxazosin
Alpha-1 antagonist used to treat hypertension in patients with benign prostatic hypertrophy.
Minoxidil
Vasodilator that opens K+ channels.
Hyperpolarises the smooth cell muscle cells- leading to vasodilation.
