Hypertension Flashcards
Name the major risk factors for cardiovascular disease (CVD)
Diabetes mellitus Hypertension Obesity Smoking Dyslipidemia Family hx of primary hypertension or premature CVD in men <55yo and women <65yo
Name examples of target organ damage (TOD) seen in hypertensive disease
Left ventricular hypertrophy
Microalbuminuria
Elevated creatinine levels
Name associated clinical conditions (ACC) of hypertensive disease
Ischaemic heart disease - angina - prior myocardial infarction Heart failure Stroke/TIA Chronic kidney disease Retinopathy Peripheral arterial disease
What is the cause of a treatment-resistant state in hypertensive disease?
Vascular damage
Renal damage
Each 2mmHg rise in SBP is assoc with increased risk of mortality due to?
7% from heart disease
10% from stroke
Complications of hypertension
Stroke (60-70%) Heart failure (50%) Heart attack (25%) Kidney failure (20%) Dementia Sexual dysfunction
Epidemiology of hypertension
Influenced by age + lifestyle factors
50% of those over 60yo have HT
As population ages, HT and required treatment increases
Clinical signs of high blood pressure?
Fatigue Decreased activity tolerance Dizziness Palpitations Angina Dyspnoea
Organs that undergo target organ damage from hypertensive disease?
CVS (heart and blood vessels)
Kidneys
Nervous system
Eyes
Definition of primary hypertension
AKA essential hypertension
95% of hypertensive cases
Idiopathic
Definition of secondary hypertension
Secondary to other potentially rectifiable causes Less common (5%)
Lifestyle change recommendations to reduce blood pressure and/or cardiovascular risk factors in hypertensive disease
Salt intake (restrict 5-6g/day)
Moderate alcohol intake (limit to 20-30g/day men OR 10-20g/day women)
Increase vegetables, fruit
Low fat dairy intake
BMI (<25kg/m2)
Waist circumference (men <102cm/40in; women<88cm/34in)
Exercise (>30min/day 5-7 days/week)
Hypertension pharmacotherapy options
Central agents Catecholamine inhibitors Vasodilators Aldosterone blockers Diuretics ACE inhibitors Angiotensi-1 receptor blockers
Factors influencing pharmacotherapy choice to treat hypertension
Concomitant diseases
Patient’s ethnicity
Drug profile S/E
Allergy
Thiazides
Type
Examples
Mechanism of action
Low ceiling diuretics
Hydrochlorothiazide, chlorthalidone
Main: Inhibit Na+ and Cl- transporter in distal convoluted tubules -> increased Na+ and Cl- excretions
Other:
a) weak inhibitors of carbonic anhydrase -> increased HCO3- excretion
b) increased K+/Mg2+ excretion
c) decreased Ca2+ excretion
Thiazides
Type
Examples
Mechanism of action
Low ceiling diuretic
Hydrochlorothiazide, chlorthalidone, chlorothiazide, indapamide, metozalone
Main: Inhibit Na+ and Cl- transporter in distal convoluted tubules -> increased Na+ and Cl- excretions
Other:
a) weak inhibitors of carbonic anhydrase -> increased HCO3- excretion
b) increased K+/Mg2+ excretion
c) decreased Ca2+ excretion
What is the brand name of hydrochlorothiazide?
Microzide
What is the brand name of chlorothiazide?
Diuril
Name potential side effects of thiazides
Hypokalemia Hypovolemia Hyperuricemia Metabolic adverse drug reaction (ADR) -> mostly after high dose -> impaired glucose tolerance + dyslipidaemia Erectile dysfunction
Aldosterone receptor blockers
Type
Examples
Mechanism of action
Potassium sparing diuretics
Spirinolactone
Binds and blocks aldosterone receptors -> reduce Na+ and water reabsorption -> decreased SVR -> decreased BP
Considered a weak diuretic
Often used on cinjunction w/ more potent K+ depleting diuretics
Name potential side effects of aldosterone receptor blockers
If patient has renal impairment, uses ACE drugs or potassium supplement -> MONITOR CLOSELY for hyperkalemia Gynecomastia Amenorrhoea Post-menopausal bleeding Dizziness Cramps Nausea Diarrhea
Calcium channel blockers
Examples
Mechanism of action
Amlodipine, nifedipine, verapamil
Act on voltage dependent Ltype Ca2+ channels -> reduce Ca2+ influx -> smooth muscle relaxation + vasodilation
Effectively treat systolic HT
Potentially superior to other antiHT for stroke prevention
Effective in patient’s with comorbid conditions e.g Reynaud’s, migraine
Particularly effective in the elderly and african americans
Which class of antihypertensive drug is particularly effective in the elderly and african americans?
Calcium channel blockers
Which class of antihypertensive drug effectively treats systolic hypertension?
Calcium channel blockers
Which class of antihypertensive drug is the potentially superior antiHT drug for stroke prevention?
Calcium channel blockers
Which class of antihypertensive drug is effective in patient’s with comorbid conditions e.g Raynaud’s, migraine?
Calcium channel blockers
Classification of calcium channel blockers
Phenylalkylamines
Benzothiazepines
Dihydroxypyridines
Classification of calcium channel blockers
Phenylalkylamines
Verapamil
Classification of calcium channel blockers
Benzothiazepines
Diatezem
Classification of calcium channel blockers
Dihydropyridines
1st generation - nifedipine 2nd generation - isradipine - nicardipine - felodipine 3rd generation - amlodipine
Cardiovascular effects of diatezem
Calcium channel blocker (benzothiazepines) Vasodilation +++ Suppression of cardiac contractility ++ Automaticity suppression (SA node) +++++ Conduction suppression (AV node) ++++
Cardiovascular effects of verapamil
Calcium channel blocker (phenylalkylamines) Vasodilation ++++ Suppression of cardiac contractility ++++ Automaticity suppression (SA node) +++++ Conduction suppression (AV node) +++++
Cardiovascular effects of nifedipine
Calcium channel blocker (dihydropyridines) Vasodilation +++++ Suppression of cardiac contractility + Automaticity suppression (SA node) + Conduction suppression (AV node) 0
Cardiovascular effects of amlodipine
Calcium channel blocker (dihydropyridines) Vasodilation +++++ Suppression of cardiac contractility + Automaticity suppression (SA node) + Conduction suppression (AV node) 0
Which of the following drugs results in the most vasodilation? Verapamil Diatazem Nifedipine Amlodipine
Nifedipine
Amlodipine
(the dihyropyridines)
Which of the following drugs results in the least vasodilation? Verapamil Diatazem Nifedipine Amlodipine
Verapamil
Which of the following drugs results in the most suppression of cardiac contractility? Verapamil Diatazem Nifedipine Amlodipine
Diatazem
Which of the following drugs results in the least suppression of cardiac contractility? Verapamil Diatazem Nifedipine Amlodipine
Nifedipine
Amlodipine
Which of the following drugs results in the most automaticity suppression? Verapamil Diatazem Nifedipine Amlodipine
Verapamil
Diatzaem
Which of the following drugs results in the least automaticity suppression? Verapamil Diatazem Nifedipine Amlodipine
Nifedipine
Amlodipine
Which of the following drugs results in the most conduction suppression? Verapamil Diatazem Nifedipine Amlodipine
Diatazem
Which of the following drugs results in the least conduction suppression Verapamil Diatazem Nifedipine Amlodipine
Nifedipine
Amlodipine
What are potential side effects of dihydropyridines?
Peripheral oedema Reflex tachycardia Flushing Headache Hypotension
What are potential side effects of non-dihydropyridines?
Constipation
Conduction abnormalities
Angiotensin converting enzyme (ACE) inhibitors
Examples
Mechanism of action
Enalapril, benazepril, captopril, lisinopril, fosinopril, quinapril, ramipril, moexipril, trandolapril, perindopril
Prevents conversion of angiotensin I -> angiotensin II -> prevents vasoconstriciton + aldosterone release
What are advantages of using ACE inhibitors?
Reduce mortality in left ventricular dysfunction
Prevent progressive post-infarct cardiac failure
Reduce cardiovascular outcomes in high risk patient
Reno-protective in diabetics + renal disease w/ proteinuria
Lack deleterious effect on glucose tolerance + blood lipids
What are side effects of using ACE inhibitors?
Dry cough Angioedema Hyperkalemia First dose hypotension Reversible taste disturbance
What are contraindications for using ACE inhibitors?
Renal artery stenosis
Pregnancy
When must one take caution when using ACE inhibitors?
Pre-existing eGFR <20
ACE-inhibitors versus angiotensin receptor blockers (ARB)
ARBs do not prevent bradikinin inactivation -> less dry cough + angioedema
75% ACE-I vs 95% AB RAAS blockade
No difference in clinical endpoints
Choice of therapy guided by cost + tolerability
Angiotensin receptor blockers
Examples
Losartan, valsarta, irbesartan, telmisartan, candesartan, eprosartan
Direct vasodilators
Hydralazine
Minoxidil
Sodium nitroprusside
Diazoxide
Direct vasodilators
Mechanism of action of hydralazine
Dilates arterioles but not veins
Direct vasodilators
Mechanism of action of minoxidil
Opens K+ channels in smooth muscles with its active metabolite
Direct vasodilators
Mechanism of action of sodium nitroprusside
Increases intracellular GMP ad dilates both aa and vv
Direct vasodilators
Mechanism of action of diazoxide
Stimulates opening of K+ channels
Which direct vasodilator is a powerful vasodilator for treatment of hypertensive emergencies? And an alternative to this?
Sodium nitroprusside
Can also use diazoxide
Centrally acting agents
Examples
Mechanism of action
Side effects
Alpha agonists, adrenergic receptor blockers
Stimulates central alpha 2 receptors which results in inhibiting efferent sympathetic activity
Should be used 3rd/4th line
Can be addictive (e.g clonidine, methyldopa)
Sedation, orthostatic hypotension
Centrally acting agents
Clonidine
Mechanism of action
S/E
Alpha-2 agonist -> reduces norepinephrine production w/o stimulating sympathetic nervous system -> vasodilation -> decreased BP
S/E sedation, dry mouth, Na+ retention, water retention
Centrally acting agents
Alpha-methyldopa
Mechanism of action
S/E
Alpha-methylnorepinephrine stored in neurosecretory vesicles instead of NE -> released -> alpha-receptor agonist
S/E sedation, lassitude, nightmares, lactation (due to dopaminergic neuron inhibition)
Examples of beta 1 selective adrenergic receptor blockers
Atenolol, bisoprolol, metoprolol
Examples of beta 1 + 2 adrenergic receptor blockers
Propanolol (lipophilic)
Examples of alpha, beta 1 and beta 2 receptor blockers
Carvedilol (lipophilic), labetolol
What is the name of the active metabolite of alpha-methyldopa?
Alpha-methylnorepinephrine
What is the significance of a lipophilic adrenergic receptor blocker?
Can cross the blood brain barrier
Name mortality reducing beta blockers
Carvedilol
Bisoprolol
Nebivilol
Metoprolol
Atenolol
Class
Caution
Contraindications
4th line antihypertensive - ONLY use in pt with comorbid angina or uncontrolled hypertension
Cardioselective beta blocker (least lipophilic)
Caution: elderly, renal failure
Contraindications: asthma, symptomatic cardiac failure, Av block, bradycardia
When is the only time you give atenolol as antihypertensive treatment?
ONLY use in pt with
(1) comorbid angina or
(2) uncontrolled hypertension
Why do you take caution when prescribing atenolol to an elderly or renal failure patient?
Excreted unchanged in urine
Can accumulate if low GFR
How is carvedilol excreted?
Via bile
What is the use of beta blockers in COPD patient with severe hypertension?
Benefit versus risk assessment
Little reversibility + not severe COPD -> carvedilol benefit outweighs bronchospasm risk
Definition and classification of severe hypertension
SBP>180mmHg and DBP >110mmHg
- Asymptomatic severe
- Hypertensive urgency
- Hypertensive emergency
Definition of asymptomatic severe hypertension
SBP>180mmHg and DBP >110mmHg
Asymptomatic
No TOD
No ACC
Definition of hypertensive emergency
SBP>180mmHg and DBP >110mmHg
Assoc w/ acute and ongoing damage to kidneys, brain, heart, eyes or vascular system
What grade retinopathy qualifies as TOD during hypertensive emergency
Grade 3/4
Definition of hypertensive urgency
SBP>180mmHg and DBP >110mmHg
Severe headache, SOB, oedema
No immediate life-threatening neuro, renal, eye or cardiac complications
Glyceryl trinitrate Drug class Mechanism of action Side effects Contraindications
Organ nitrates
Venodilation -> decrease preload via coronary vasodilation
SE: hypotension, headache
CI: hypertrophic obstructive cardiomyopathy (HOCM)
Which common drug does glyceryl trinitrate interact with?
Sildenafil (potentiates vasodilation)
PDE5 inhibitor with tadalafil, verdenafil
Furosemide Drug class Mechanism of action Side effects Caution
High ceiling loop diuretic
Inhibits Na+ and Cl- reabsorption in the ascending limb of Henle -> venodilation -> decreased venous return
IV is very fast acting
SE:: hypotension, hypovolemic shock, ototoxicity if given in large IV doses therefore give slow at 4mg/min
Why must you give furosemide slowly at 4mg/min?
Can cause hypotension, hypovolemic shock, ototoxicity if given in large IV doses
How does decreased renal function affect furosemide treatment?
Patient requires a higher dose
What site do organic acids compete with drug transport for?
Lumen side of ascending limb of Henle
Special populations to consider in antihypertensive treatment
Africans Left ventricular hypertrophy (LVH) Elderly Pregnancy Children/adolescents
What is important to remember when providing african patients with anti-hypertensive treatment?
Response to diuretics + CCB > ACE-I, ARB, beta blockers
Angioedema 2x-4x more
What is important to remember when providing elderly patients with anti-hypertensive treatment?
Isolated systolic hypertension
Same general principles
Thiazide/CCB may be better tolerated
What is important to remember when providing pregnant patients with anti-hypertensive treatment?
Methyldopa, beta-blockers + vasodilators (hydralazine) are options
Avoid ACE-Is and ARBs
What is important to remember when providing left ventricular hypertrophy patients with anti-hypertensive treatment?
Aggressive BP control allows LVH to regress but NOT w/ hydralazine or minoxidil
What is important to remember when providing children/adolescent patients with anti-hypertensive treatment?
Avoid ACE-I or ARBs in pregnant or sexually active girls
Safest anti-hypertensive options for pregnant woman with pre-existing hypertension?
Methyldopa
Nifedipine
Labetalol
Diuretics + beta blockers still C/I from 2nd trimester because of fetal growth retardation and electrolyte imbalances
Pre-eclampsia
Time of onset
Clinical presentation
Treatment
Usually after 20 weeks of pregnancy
Hypertension, oedema, proteinuria,hyperuricemia
Bed rest + antiHT
Pre-eclampsia
Complications
Convulsions Cerebral haemorrhage Abruptio placentae Pulmonary oedema Renal failure
Recommended anti-hypertensives in heart failure
Diuretic
Beta blocker
ACE-I
ARB
Recommended anti-hypertensives in post MI
Beta blocker
ACE-I
Recommended anti-hypertensives in high coronary disease risk
Diuretic
Beta blocker
ACE-I
CCB
Recommended anti-hypertensives in diabetes
Diuretic
ACE-I
ARB
CCB
Recommended anti-hypertensives in chronic kidney disease
ACE-I
ARB
Recommended anti-hypertensives in recurrent stroke prevention
Diuretic
ACE-I
“Compelling indications” for a drug means?
Literature has proven it superior treatment in that medical situation
