Lecture 4 - Hypertensive Drugs Flashcards
What is the equation for Mean Arterial Pressure?
MAP = Cardiac output x TPR
MAP = Diastolic BP + 1/3(Systolic BP - Disastolic BP)
Systolic BP - Diastolic BP = Pulse pressure
What regulates blood pressure?
Autonomic sympathetics
Renin Angiotensin Aldosterone System (RAAS)
What are some autocoids (locally acting compounds) produced by vascular endothelium mon vascular smoooth muscle?
Bradykinin
Nitric oxide
How are radius and resistance of a blood vessel related?
Smaller the radius the larger the resistance
With vasoconstriction of vascular smooth muscle what must happen to BP to keep supplying blood at the same rate in systemic circulation?
Inc Peripheral resistance would mean BP needs to increase to meet the systemic demands
How does hyperinsulinaemia and hyperglycaemia lead to hypertension?
Leads to endothelial dysfunction
Increased ROS which leads to less NO signalling
NO is a potent vasodilator
What are the long term effects of hypertension on the body?
Hypertrophy of vasculature
Decreased compliance of vessels
End organ damage (renal, peripheral vascular disease, aneurysm, vascular dementia and retinal disease)
Hypertensive heart disease (Left Vntricular hypertrophy)
Why does hypertension and disease related to hypertension more prevalent in men than women before menopause?
Oestrogen has a protective affect on the vasculature but once menopause has been reached risk becomes similar
What is the definition of hypertension?
An elevated blood pressure that treated will do more good than harm
140/90 mmHg
Normal range: 90/60 - 120/80 mmHg
How do we increase awareness and increase the amount of people we can diagnose with hypertension?
Screening those at risk
Inc public awareness of risk factors
Appropriate lifestyle changes
Regular monitoring and refinement of meds once initiated
Reliable measurements based on clinical guidelines!!
How do we clinically diagnose hypertension?
Sitting relaxed and arm supported
Measure both arms and use higher reading arm, if theres more than a 15mmHg
When measuring someone’s BP what systolic and diastolic measurements should we need emergency treatment if they have clinical signs?
SBP > 180
DBP > 120
What is the target BP for someone younger than 80 with T2DM?
<140/90 mmHg
What is the target BP for someone older than 80 with T2DM?
<150/90 mmHg
What is the target BP for someone with the highest Urine albumin to creatinine ratio of 70mg/mmol or more?
<130<80mmHg
What are the 3 stages of Hypertension?
Stage 1 hypertension. 140/90 - 159/99 mmHg
Stage 2 hyper tension 160/100 - 180/120mmHg
Stage 3 severe hypertension 180/120mmHg >
What do we consider prehypertension?
120/80 - 140/90 mmHg
What interventions should be put in place for those who are classified as having pre hypertension?
Regular exercise
Modify to o have healthy balanced diet
Reduce stress
Reduce alcohoool
Smoking cessation
Reduce caffeine
Reduce dietary sodium
What are the main categories of primary hypertensive therapeutic agents?
ACEi
ARBs (Angiotensin Receptor Blockers)
Calcium Channel Blockers
Diuretics (thiazide and thiazide like)
Other agents
What is ACE?
Where is it found?
What is its functon?
Angiotensin converting enzyme located on the capillary endothelial cells mainly int he lungs
It converts Angiotensin 1 to angiotensin 2
What receptors does Angiotensin 2 act on?
AT1 mainly
AT2
What is the effect of angiotensin II acting on AT1 receptors?
Inc aldosterone production which increases reabsorption of ions and water in DCT
Inc ADH production
Vasoconstrictor
What is the mechanism of action ACEi in acting as an anti-hypertensive?
Limits conversion of angiotensin I -> Angiotensin II
Less angiotensin II =
-vasodilation (less vasoconstriction)
-reduced aldosterone release (more Na+ and H20 lost)
-reduced cell growth and proliferation
What is also a substrate for ACE?
What can be a side effect of ACEi?
Bradykinin
Dry cough due to bradykinin build up
What are some potential side effects for ACEi?
Hypotension
Dry cough
Hyperkalaemia (decreased aldosterone)
Worsen renal failure
Angioedema
What are some contraindications for using ACEi?
Renal artery stenosis
AKI
Pregnancy
CKD (Caution)
Idiopathic angioedma
What are some drug-drug interactions you have to be careful of with ACEi?
K+ sparing drugs
NSAIDs
Other anti-hypertensive agents
What are 2 ACEi (ace inhibitors)?
Ramipril
Lisinopril
What are 2 Angiotensin Receptor Blockers (ARBs)?
Losartan
Candesartan
What is the mechanism of action of Angiotensin Receptor Blockers (ARBs)?
Prevents angiotensin II from binding to AT1 (mainly) and AT2 receptors prevents production of aldosterone by the RAAS system
So overall reduced vasoconstriction and less ENAC expression
What are the adverse/side effects of Angiotensin Receptor Blockers (ARBs)?
Hypotension
Hyperkalaemia (Low aldosterone means higher K+)
Cause/worsen renal failure
Why do ARB (Angiotensin Receptor Blockers) not causes a dry cough?
Bradykinin levels are unaffected since ACE is still functional which can use bradykinin as a substrate
ARBs block the AT1 (AT2) receptors
When are ARB (angiotensin receptor blockers) contraindicated?
Renal artery stenosis
AKI
Pregnancy
CKD (Caution)
What are some drug-drug interactions that you need to know for ARB (angiotensin receptor blockers)?
So what drugs cant be used with ARBs?
Drugs increasing K+ (Potassium sparring drugs)
NSAIDs
What is the function of L-type calcium channels?
Allow inward Ca2+ flux into cells
Where are L-type calcium channel/voltage operated calcium channels located in the body?
Vascular smooth muscle
Cardiac myocytes
SA + AV node
What are the 3 classes of Calcium Channel Blocker?
Dihydropyridines
Non-dihydropyridines:
-Phenylalkyamines
-Benzothiazapines
What are the 2 types of non-dihydropyridines?
Phenylalkylamines
Benzothiazapines
How do dihydropyridines act as an antihypertensive?
Calcium channel blocker that is selective for peripheral vasculature
How do dihydropyridines affect the heart?
Very little chronotropiic or inotropic effects
How do Phenylalkyamines act as an antihypertensive drug?
What class of drug are they?
Calcium channel blocker in the non-dihydropyridine category
They depress the SA node and slow AV conduction having a negative inotropic affect
How do Benzothiazapines act as antihypertensive?
Calcium channel blocker that’s not really selective to either peripheral vasculature or the heart
When are calcium channel blockers normally given as a hypertensive?
When a patient has low renin
What is the key difference between dihydropyridines and Phenylalkyamines?
Dihydropyridines are selective to peripheral vasculature and dont affect the heart
Phenylalkyamines affect the heart selectively
What are some drugs that are dihydropyridines?
Amlodipine
Nimodipine
Nifedipine
What is special about the dihydropyridine nimodipine as a hypertensive drug?
Selective for cerebral vasculature so is useful for tthe ischaemic effects of a subarachnoid haemorrhage
What are some adverse/side effects of dihydropyridines?
Ankle swelling/oedema
Flushing
Headaches (vasodilation)
Palpitations (compensatory tachycardia)
What are some contraindications for use of dihydropyridines as an antihypertensive?
Unstable angina (vasodilation of blood vessels leads to Inc demand on heart so it would pump harder and faster worsening any ischameic heart damage)
Severe aortic stenosis
Cardiogenic shock (mismatch between preload and after load)
What drugs should not be paired with dihydropyridines and why?
Amlodipine (dihydropyridine) with Simvastatin
This increases the effect/ plasma concentration of the statin
What type of drug are Phenylalkyamines?
Class IV anti-arrhythmic agent/ prolongs the action potential and effective refractory period
What are Phenylalkyamines used for?
Arrythmias
Angina (hypertension)
What is the main Phenylalkyamine that can be used as an antihypertensive and Arrythmias?
Verapamil
What affect do Phenylalkyamines have to act as antihypertensives?
Negative chronotropy
Negative inotropy
Less peripheral vasodilation
What are some adverse effects of Phenylalkyamines?
Constipation
Bradycardia(i.v)
Heart block
Cardiac failure
What are some contraindications for using Phenylalkyamines like verapamil?
Poor LV function
AVN conduction delay
What drugs should not be used with Phenylalkyamines like verapamil?
B blockers (only cardiologists)
Caution with other anti hypertensives or antiarrythmics
What is an example of Benzothiazapines?
Diltiazem
What are 2 examples of thiazide and thiazide like diuretics that can be used as an antihypertensive?
Indapamide
Bendroflumethiazide
How do Thiazides and Thiazide like diuretics act as antihypertensives?
Inhibts Na+/Cl- transporter in the DCT
Means less Na+ and H2O reabsorbed into the body
Na+ and Cl- increases osmotic pressure in filtrate
What are some adverse efffects of using thiazides and thiazide like diuretics as antihypertensives?
Hypokalaemia
Hyponatraemia
Hyperuricemia (GOUT)
Arrythmias
Inc glucose
Inc cholesterol and triglyceride
What is a contraindication to using thiazides and thiazide like diuretics as antihypertensives?
Hypokalaemia
Hyponatraemia
Gout
What are the drug-drug interactions you need to be carful of when using thiazides and thiazide like diuretics as antihypertensives?
NSAIDs
K+ losing drugs like loop diuretics
When deciding to pharmacologically treat primary hypertension what drugs do you normally give to people with hypertension and T2DM OR younger than 55 and not of African or African-Caribbean family origin?
Give an example of each drug:
ACEi or ARB as first approach
So ramipril or Losartan
What type of antihypertensive drug is first given to patients that DONT have T2DM that are older than 55 or of black African or African-Caribbean family origin?
Calcium Channel Blocker
Why is the treatment for patients with hypertension and T2DM considered a two prolonged approach?
The ACEi (ramipril) and ARB (Losartan) decrease peripheral vascular resistance leading to decrease in BP and dilatin of efferent glomerular arterioles in kidney reducing the intraglomerular pressure helping with diabetic nephropathy
At a basic level how doACEi and ARB help reduce diabetic nephropathy?
Dilated efferent glomerular arteriole of kidney
If a patients hypertension is resistant what drug can be tried?
Spironolactone
What type of drug is Spironolactone?
Aldosterone receptor antagonist
What contraindications for Spironolactone have?
Hyperkalaemia
Addisons disease
What drugs shouldn’t be paired with Spironolactone?
K+ sparringi drugs (need monitoring)
Pregnancy
What is Addisons disease?
Body doesn’t produce enough Mineralocorticoids like cortisol and aldosterone
What other drugs can be considered instead of Spironolactone if K+ is high?
A and B blockers
What are some examples of B-adrenoceptor blockers?
Bisoprolol
Metoprolol
Labetalol
Atenolol
Propanolol
How do B blockers act as antihypertensives?
Decreased sympathetic tone by blocking the action o f noradrenaline and reducing myocardial contraction reducing cardiac output
Means less renin secreted
What are some adverse affects of using B blockers as antihypertensives?
Bronchospasm
Heart block
Raynauds (cold hands)
Lethargy
Importance
May mask tachycardia
What are some contraindications to usingi B blockers as antihypertensives?
Asthma
COPD
Haemodynamic instability
Hepatic failure
What drugs shouldn’t be paired with B blockers?
Non-dihydropyridine Calcium Channel Blockers like verapamil and diltiazem since cause asystole
How do alpha adrenoceptor blockers act as antihypertensives?
Selective antagonism of alpha 1 adrenoceptors
Reduces peripheral vascular resistnace
What is an example of a adrenoceptor blockers as antihypertensives?
Doxazosin
Tamsulosin (often used with BPH affecting internal urethral sphincter)
What are the adverse effects associated with alpha blockers?
Postural hypotension
Dizziness
Syncope
Headache and fatigue
What are somecontradincatins of using alpha blockers?
Postural hypotension
What drug-dug nteractions need to be considered witht alpha blockers?
Dihydropyridine CCBs. Inc oedema