Pharmacological treatment of hypertension Flashcards
Yeah you’re gonna need to just take notes on this one can’t lie.
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When should you treat hypertension
DIAGNOSIS (REMINDER): • Clinic BP • AND ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) average day time • End organ damage? • Secondary hypertension diagnosis?
STAGE 1 HYPERTENSION • End organ damage? (<80 years old?) • Cardiovascular disease? • Renal disease? • Diabetes? • 10 year CV risk of ≥10%
If no,
• Lifestyle modifications
• Monitor BP
If yes or stage 2 hypertension,
• Lifestyle modifications
• Therapeutic interventions
Discuss lifestyle modifications as a treatment strategy
- Weight loss
- Reduced salt (Na+) intake <6g/day
- Reduced alcohol consumption
- Increased aerobic exercise
- Increased fruit and vegetable intake
- Smoking cessation
- (Stress reduction / relaxation techniques)
Discuss therapeutics as a treatment of hypertension
- Angiotensin converting enzyme inhibitors (ACE inhibitors)
- Angiotensin II receptor blockers (ARBs)
- Diuretics
- Calcium channel blockers (CCBs)
- (a1-adrenergic receptor blockers)
- b1-adrenergic receptor blockers
- K+-sparing diuretics
Have a peek at the NICE/British hypertension society guidelines
And Rockwood frailty score
List antihypertensive drugs for treatment of hypertension
- Antihypertensive drugs:
- Angiotensin converting enzyme inhibitors (ACE inhibitors)
- Angiotensin II receptor blockers (ARBs)
- Thiazide diuretics
- K+ sparing diuretics
- a-adrenergic receptor blocker
- b-adrenergic receptor blocker
- Calcium channel blockers (CCBs)
Discuss filtration/reabsorption in the kidney
Blood is filtered at the glomerulus
Ultrafiltrate enters tubule and flows along distinct segments
Reabsorption (as well as secretion) of ions, solutes and water occurs along the length of the tubule
Remainder of ultrafiltrate flows to bladder and will leave as urine
Reminder: movement of Na+ important for determining blood volume.
Excretion must match intake (balance).
Discuss Na+ reabsorption in the kidney
Path is: Proximal convoluted tubule (PCT) Thick Ascending Limb (TAL), Loop of Henle Distal convoluted tubule (DCT) Cortical collecting duct (CCD)
- Na+ is reabsorbed in distinct segments along the tubule of the nephron
- Creates an osmotic gradient for H2O to follow
Discuss angiotensin II - salt retention
- Angiotensin II stimulates Na+ absorption, particularly in the proximal convoluted tubule (PCT)
- Angiotensin II stimulates Na+ absorption, particularly in the proximal convoluted tubule (PCT)
- Ang II stimulates aldosterone release which further stimulates Na+ reabsorption in the cortical collecting duct (CCD)
Discuss ACE inhibitors
• First or second line anti-hypertensive treatment
• e.g. ramipril, captopril, enalapril, perindopril, lisinopril
N.B. Increased bradykinin can cause bronchoconstriction which can give rise to a dry cough. Often patients are then prescribed an ARB instead.
Discuss angiotensin II receptor blockers (ARBs)
- Also first or second line anti-hypertensive treatment
- e.g. losartan, irbesartan, valsartan, olmesartan, candesartan
- Due to specific effects on AT1 receptors, there are no effects on bradykinin, therefore no side-effect of cough
Discuss diuretics
- Diuretics – substances that help the body get rid of water (target Na+ absorption to do this)
- Reduce blood pressure by decreasing ECV
- LOOP DIURETICS
- THIAZIDE DIURETICS
- K+ SPARING DIURETICS
Discuss loop diuretics
• Most powerful class of diuretic
• “torrential urine flow”
• e.g. Furosemide, Bumetanide
• Inhibits the NKCC2
(Na+/K+/2Cl- co-transporter) in TAL
• Only used in treatment of hypertension where renal function is impaired
• Sometimes used in other fluid overload conditions e.g. heart failure
Discuss thiazide diuretics
- Less powerful than loop diuretics
- e.g. Bendroflumethiazide, Indapamide, Hydrochlorothiazide
- Inhibits the NCC in the DCT (Na+/Cl- co-transporter)
- 2nd / 3rd line treatment
Discuss K+ sparing diuretics
- Limited diuretic action alone, but powerful in combination with loop/thiazide diuretics
- Inhibits ENaC in the CCD (Epithelial Na+ channel)
2 types: Aldosterone antagonists • Spironolactone, eplerenone ENaC inhibitors • Amiloride, triamterene
• Rarely used due to also blocking K+ excretion (coupled to ENaC), causing hyperkalaemia (K+ sparing)
Discuss calcium channel blockers in treatment for hypertension
- Inhibits contraction
- Cardiac muscle
- Vascular smooth muscle
- Na+ enters cell via slow Na+ channel in pacemaker cell (funny current)
- Small depolarisation
- Ca2+ enters cell via T-type voltage gated Ca2+ channel (VGCC)
- Further depolarisation
- Ca2+ enters cell via L-type voltage gated Ca2+ channel (VGCC)
- Large depolarisation
- Depolarisation spreads through gap junctions
- To both pacemaker and contractile cells
- Depolarisation occurs in neighbouring cell
- Ca2+ is released from sarcoplasmic reticulum (SR) in contractile cell
- These are also L-type Ca2+ channels
- This causes CONTRACTION of the cardiomyocyte
Same concept in vascular smooth muscle contraction
Discuss b(beta)-adrenoreceptor antagonism
• non-selective b-adrenoceptor antagonists have side effects
• E.g. bronchoconstriction, important in asthmatics
• b1-selective antagonists:
• Bisoprolol, Atenolol
HR/force of contraction CO BP
• Also inhibits renin release from granular cells
Ang II vasoconstriction & Na+ and H2O retention
TPR
• Why are b-blockers not first line treatment?
• Less effective than comparators in reducing CV risk
• Less effective than ACEis and CCBs at reducing risk of diabetes
• Less well tolerated than ACE inhibitors/ARBs
• However, they are useful for antihypertensive patients with additional need for b-blockade including angina or heart failure
What are the potential side effects of calcium channel blockers
Flushes
Headaches
Ankle oedema
Dizziness
What are the potential side effects of thiazide diuretics
Hypokalaemia Hyponatraemia
Gout Impotence Monitor for dehydration
Ineffective in moderate to severe renal impairement
What are the potential side effects of ACE inhibitors
Persistent dry cough Dizziness Tiredness Headaches Risk of angioedema (Afro-Caribbean ) Hypokalaemia Hyponatraemia Gout Impotence Monitor for dehydration Risk of hyperkalaemia Renal impairment Avoid in bilateral artery stenosis teratogenic
What are the potential side effects of ARBs
Dizziness Headaches Back/leg pain Hyperkalaemia Renal impairment Avoid in bilateral artery stenosis Teratogenic
What are the potential side effects of K+ sparing diuretics
Hyperkalaemia
Renal impairment
GI upset
Spironolactone – oestrogen related side effects
Discuss mutidrug treatment of hypertension
- Reduced mortality / morbidity
- Each drug class working at different sites – can achieve BP treatment more quickly
- Reduces dose burden of individual drugs thereby minimising side effects
- Concordance a problem
- “I felt fine before I started these drugs!”
- “I keep forgetting to take all these drugs”
- Side effects may be more frequent
- Increased drug costs to NHS
Learning outcomes
I missed out a fair bit of calcium shit in this one so look over it
TO IDENTIFY THE STEPPED PHARMACOLOGICAL MANAGEMENT OF HYPERTENSION
TO UNDERSTAND THE MECHANISM AND ACTION OF: ACE INHIBITORS AND ARBs
DIURETICS
CALCIUM CHANNEL BLOCKERS b1-ADRENOCEPTOR ANTAGONISTS
TO IDENTIFY THE ADVANTAGES AND DISADVANTAGES OF MULTI-DRUG TREATMENT
