Antihypertensive Drugs (Dawes) Flashcards
- Hypertension is major risk factor for ….. (4)
- Hypertension is major risk factor for
- stroke,
- coronary artery disease,
- renal disease,
- heart failure
What are the arbitary levels of “hypertension”
Optimal <120/80
Pathology
- <140/90
- Some flexibility
- <130/80
- Diabetes, end organ damage (secondary prevention) (higher risk of cardiovascular diseases)
- <125/75
- Proteinuria, CKD (higher risk of cardiovascular diseases)
What are the 6 groups of Anti-hypertensive drugs?
- ACE inhibitors or angiotensin II antagonists
- Beta blockers
- Calcium channel blockers
- Diuretics (thiazide, loop, aldosterone antagonists)
- Alpha blockers
- Miscellaneous
100mmHg systolic BP fall results in….
Increased blood pressure is associated with increased CHD and stroke risk. Conversely, treatment reduces risk.
10mmHg systolic BP fall results in:
- 20% reduction CVA (cerebrovascular accident)
- 40% reduction MI
- 25% reduction CVS mortality
Describe the Hypertension Treatments
Hypertension Treatments
-
Lifestyle changes include
- diet (sodium <80mmol/day (<5g NaCl)),
- weight loss,
- exercise,
- reduce alcohol
-
Drug therapy include polypharmacy
- ACE inhibitors or angiotensin II antagonists
- Beta blockers
- Calcium channel blockers
- Diuretics (thiazide, loop, aldosterone antagonists)
- Alpha blockers
- Miscellaneous
What are some problems with treating hypertension?
Hypertension is lifelong disease (no cure) with concurrent diseases
- Perceived benefits of treatment
- Asymptomatic
- Life-long medications for asymptomatic patients can reduce long term adherence
- Therefore, prescribe as less once-daily drugs as possible and monitor conditions periodically to make sure medicines are still producing BP-lowering effect with minimal side effects
What are the first line drugs for Hypertension?
ACE inhibitors
Name some examples of ACE inhibtiors
What are some Side effects of ACE inhibitors?
Side Effects
ACEi include cilazapril 1-5mg od (enalapril, lisinopril).
Side effects include:
- Hypotension
- Cough
- Angio-oedema
- Hyperkalemia (monitor electrolytes)
AIIA include candesartan 4-32mg od (losartan, valsartan), used when ACEi is not tolerated due to cough. Side effects include:
- Hypotension
- Hyperkalemia (monitor electrolytes)
Not used in combination anymore!
Name 3 ACE inhibitors
ACEi include cilazapril 1-5mg od (enalapril, lisinopril).
What are the contradinications of ACE inhibitors?
Contraindications
- Bilateral renovascular disease
- AII maintains perfusion gradient
- ACEi/AIIA → marked hypotension
- Deterioration renal function
- Pregnancy
- Cross placenta
- Angiotensin role in renal development
Describe the mechanism of action and side effects of beta blockers
Mechanism is by antagonizing beta-adrenoreceoptors.
Mechanism of reducing BP unclear
- Reduce cardiac output
- Reset baroreceptors
- Renin inhibition
- Central actions (reduce SNS drive)
- Presynaptic actions? (beta-blocker reduces norepinephrine release)
Side Effects
- Fatigue
- Bradycardia
- Negatively inotropic
- Erectile dysfunction
- Wheeze/asthma exacerbation
- Cold peripheries
Describe the Calcium Channel Blockers
- Mechanism of action
- Classifications
Mechanism of Action
- Calcium channel blockers b_lock voltage-operated L-type Ca2+ channels_
- There is some selectivity on resistance vessels, myocardium, conducting tissue.
Classifications
-
Dihydropyridine (most common, purely vasodilating effect) include nifedipine, felodipine, amlodipine
- These act on r_esistance vessels_, which can cause flushing, headache, oedema
- Benzothiazepine include diltiazem
-
Phenylalkylamine include verapamil
- These act on cardiac tissue, which can cause heart block, negative inotrope
- These act on gut tissue, which can cause constipation
Name some types of Calcium channel blockers
Dihydropyridine (most common, purely vasodilating effect) include nifedipine
Benzothiazepine include diltiazem
Phenylalkylamine include verapamil
Name some diuretics used for Hypertension
Thiazide include endrofluazide, chlorthalidone, hydrochlorothiazide
Loop diuretics include frusemide
K+ sparing diuretics include spironolactone
Describe the Mechanism of action of Thiazide
Mechanism of Action
Thiazide include bendrofluazide, endrofluazide (2.5mg od), chlorthalidone (12.5-25mg od), hydrochlorothiazide
- _Inhibit Na+/Cl- cotransporte_r from renal Na/Cl reabsorption in DCT (distal convoluted tubule), leads to body salt and water reduction (pee more)
- Plasma volume eventually increase because body would respond to decreased volume by activating RAAS, which causes salt retention
- Common dual therapy of overcoming RAAS activation is thiazide diuretic with ACE inhibitor
- Decrease BP with subdiuretic doses (long-term BP reduction mechanism still unclear)
- Vasodilators (open vascular K+ channels à hyperpolarization-> less responsive to vasoconstriction -> open up peripheral vascular smooth muscles)
It can take 12 weeks for actions.
*Although the Blood pressure remains low, plasma volume and cardiac output returns to normal (due to the AII system.
Describe the mechanism of action of Loop Diuretics
Mechanism of Action
Loop diuretics include frusemide (40mg od), (bumetanide).
- Secreted in proximal tubule and concentrated
- Inhibit Na+/K+/Cl- cotransporter (ascending loop of Henle) (inhibit Na+/K+/2Cl- reabsorption)
- Steep dose-response curves, potent most effective diuretic (useful in treatment of heart failure where patients are fluid overloaded)
-
Little antihypertensive effect alone
- Not used as monotherapy in hypertension
- Used in severe/resistant hypertension (resistant to conventional therapy)
- Potent effect if used with ACE inhibitor
Describe the mechanism of action of Potassium-Sparing Diuretics
Mechanism of Action
K+ sparing diuretics include spironolactone (aldosterone antagonist) (12.5-25mg once daily (mild diuretic))
- Inhibits distal Na+/K+ exchange
- Acts in collecting duct
It has very potent BP lowering effect, used in resistant hypertension.
Whata are indications for Anti-Hypertensive Drug Therapy
Decision to Treat
Antihypertensive drug is indicated in patients with:
- BP >160/100mmHg
- Or BP>140/90mmHG plus:
- Target organ damage/cormorbidities
- Cerebrovascular disease (stroke)
- Coronary artery disease/peripheral vascular disease
- Left ventricular hypertrophy
- Heart failure
- Diabetes mellitus
- Proteinuria/renal impairment
- 10 year CVS risk of >20%
