Lec 18- HTN Flashcards
Definition of HTN
- An elevation of arterial BP above normal
- Normally dependant on total peripheral resistance
- Linked to increase risk of CVS disease and mortality
- Definitions are based upon CVS risk- BP is normally distributed variable
- A sign, not a disease state
What is normal BP
- High 140+/90
- Pre-high 120-140/80-90
- Ideal 90-120/60-80
- Low <90/<60
Classification of hypertension
- Primary HTN (essential) - unknown Aetiology
- Secondary HTN (Non-essential) known aetiology
- Renal HTN
- Endocrine HTN
- Hypertension of pregnancy
- Latrogenic hypertension (caused drug induced)
Signs and symptoms
- Generally no signs or symptoms of HTN
- Can be difficult therefore patients to adhere or want to take there medication
- In extreme cases (180/90 +): severe headache; fatigue; vision problems; arrhythmias; pounding sensations; pain discomfort; blood in urine
- If left untreated may present with: organ damage; stroke; AMI: HF; dementia or peripheral arterial disease
Risk factors for essential HTN
NON-MODIFIABLE -Age -Race -Gender -Family history MODIFIABLE -Sedentary lifestyle -Poor diet -High Na -Obesity -High alcohol consumption -Smoking -Stress
Objectives of therapy
- Not to just reduce BP- to reduce CVS outcomes of HTN
- BP not only factor in deciding therapy
- Outcome data is essential
- Risk/benefit analysis is critical
- Need to achieve long term, 24 hour reduction in BP, monitoring critical
Holistic measures
- Maintain normal weight for adults
- Reduce salt intake <100mmol/day
- Limit alcohol intake <3 units for men <2 for women dd
- Engage in regular aerobic physical exercise for >30 min dd
- Consume at least 5 fruit and veg dd
- Reduce the intake of total and saturated fats
- Reduce stress
- Stop smoking
Risk assessment
Assessing organ damage
- Urine dip for protein&blood
- ACR (albumin to creatinine ratio)
- Bloods for U&E’s; ChE and lipid profile
- Optometrist: fundoscopy to view retina for damage
- 12 lead ECG
- QRISK 3 score for 10yr CVD risk assessment
- More detail required if: HIV: autoimmune disease; family hypercholesterolaemia; U40 with stage 1 HTN
Thresholds for diagnosis and treatment of HTN
- Stage 1 HTN –> target organ damage; CVD or 10 yr CVD risk >20% if yes then treat/ if NO then lifestyle advice then review in 1 year
- Stage 2= treat
- Severe hypertension >180/110 must treat immediately don’t wait for ABPM
- Accelerated HTN >180/110 + retinal haemorrhage or papilloedema- must refer to specialist
BP treatment target
- Use clinical BP to monitor BP control
- Optimal clinical BP control is <140/90 mmHg
- In people with white coat effect- can be 20/10 more than home average so use a home monitor- target home <135/85
- Review BP control at least annually once BP treatment is stable
Ideal antihypertensive
- Slow, controllable onset of action
- Sustained control- supine and standing
- 12-24hr duration of action- compliance
- Orally active (for long term therapy)
- No -ve inotropic action/reflex bradycardia
- No adverse reactions suitable for long term
- No development of tolerance
- Beneficial effects on morbidity and mortality
Ideal antihypertensive
- Slow, controllable onset of action
- Sustained control- supine and standing
- 12-24hr duration of action- compliance
- Orally active (for long term therapy)
- No -ve inotropic action/reflex bradycardia
- No adverse reactions suitable for long term
- No development of tolerance
- Beneficial effects on morbidity and mortality
NICE GUIDELINES- HTN
AGED <55 yrs 1) ACEI 2) ACEI + CCB 3)ACEI + CCB + thiazide 4)ACEI + CCB + thiazide + further diuretic advice AGED <55 1) CCB 2)CCB+ ACEI 3) CCB + ACEI+ thiazide
Resistance HTN- step 4
- A clinical BP that remains higher than 140/90 mmHg with the optimal or best tolerated doses of a drug from group A,C and D
- Expert advice may be needed and further review to exclude endocrine and other causes of HTN
- After this agents used may be from other such as: BB; Alpha blocker; Spspironolactone; vasodilator
ACEI in HTN (group A)
Haemodynamically arterial vasodilators
-All agents are equally effective
-decreased BP doesn’t correlate with changes in plasma renin or all some effect in anaphoric individuals
Best haemeodynamic profile
-Increase in renal blood flow
-Cerebral and coronary flow well maintained. Improve arterial compliance (SBP)
-Aldersterone release well controlled
ACEI- advantages
Effective- equal reduction DBP to all other anti-HTN greater effect on SBP
- Generally well tolerated, high acceptability: no adverse metabolic effects
- Raggression of LV hypertrophy and of vascular remodelling: highly beneficial in LV systolic dysfunction- use in all HTN with LVSD even if asymptomatic
- Retard progression of diabetic nephropathy: use in all patients with nephropathy, all diabetic
ACEI- diadvantages
-Deterioration of renal function in renal stenosis
Bilateral and unilateral one kidney. May be exacerbated by NSAID’s
-ACE is not selective for angiotensin formation; reduced metabolism of kinins and neuropeptides: skin rash; dry cough; angioneurotic oedema
-Foetopathic potential
-Hyperkaleamia
Angiotensin receptor blockers ARB’s
- Competitive antagonists at AT1 receptors
- More precise pharmacological control of RAS
- Highly selective- no effect on kinins on SNS
- Well tolerated: slow onset of action with minimal first dose effect
- Do not produce cough associated with ACEI
- Otherwise similar to ACEI: don’t use in pregnancy; in renal failure; if there is renal artery stenosis
Renin antagonist
- Directly inhibits renin
- Essential HTN
- Similar side-effect profile as ACEI/ang ||
- Not recommended for use with ACEI/Ang||
- ALTITUTE study found adverse CV and renal events when used in combination with ACEI/Ang||
- In practice rarely used-very select patient under specialist advice
- Not for use with P-gp inhibitors
- Interactions with grapefruit juice
- No fruit juices to be taken at the same time
- Used as a reserve agent when other fail to achieve control
Calcium entry blockers
- CEBs are one of a group of vasodilators
- Block voltage gated Ca2+ channel
- Main group differ in vascular selectivity- verapamil- dihydopyridines are most widely used to reduce TPR
- Direct action on VSM to reduce TPR
- Effect action of all vasoconstriction- not receptor antagonists (distal action)
- Action independent of sympathetic tone
- Good haemaerodynamic profile- Increase RBF and maintain or improve renal function, maintain cerebral and coronary flow
CEB
-Effective anti-hypertensive- used for chronic control but also may be used for rapid reduction in BP (acute control) e.g. HTN emergency or surgical control of BP
The Dihydropyridines
- Nifedepine- rapid action, starts in 20 mins with half-life of 3 hours. MR/SR preps
- Amlodipine- slow onset, half life 35-48 hrs. OD
- Nicardipine and felodipine most vascular selective
- Nimodipine- mainly used for sub-arachnoid haemorrhage
Advantages of Dihydropyridines
- Effective- comparable with other major agents
- May be used in: Asthma + COPD; peripheral vascular disease; gout; diabetes
- Positively indicated in: cerebrovascular disease; peripheral vascular disease
Disadvantages of Dihydropyridines
- Number of side effects due to vasodilation: facial flushing; headache; nausea; ankle oedema
- Myocardial depression with verapamil
- Coronary Ischemia with short-acting DHPs
Diuretics in HTN
Thiazides most widely used
- Alone will control BP in about 50% of all ESH’s. Adding other diuretics doesn’t improve efficacy
- A flat DRC with maximum AH effect around 2.5mg bendrofluazide. Linked to diuresis (no effect anaphoric dependant on Na+ intake) but different DR releationship
- Loop diuretics- torasemide only loop diuretic licensed for hypertension when renal function is poor (GFR<60% normal, serum creatinine >150
Diuretic mechanism of action
- Onset of anti-HTN slow- Mac at around 12 weeks. Early fall in CO and extracellular volume (10%)
- At peak anti-HTN action, fall in TPR. Attributed to auto regulation of tissue blood flow (normalises CO and tissue blood flow)
- Anti-HTN action reduced NSAID
- Undesirable effects- minimised by low dose: Decresase K/Na/Mg/Ca, glucose intolerance; hyperuricaemia and hyperlipoproteinaemia
Diuretic risk profile +ve indications and general advantages
\+ve indications -Old age- strong evidence -Congestive HF -For loop (thiazide add on therapy) General Advantages -Cheap -Widely effective -Generally well tolerated -Substantial evidence base
Diuretic Risk Profile -VE INDICIATIONS
- Diabetes
- Gout
- Obesity
- Hyperlipdaemia
- Where hypokalaemia may be a problem e.g. cardiac dysrhythmias
Choice of diuretic
- Chlortalidone (12.5-25mg OD) or indapamide in preference to bendroflumethazide
- Evidence review found no evidence in clinical outcome trials of benefits with bendroflumethazide
- Most recent trials showing benefit with lower dose diuretics have used thiazide-like diuretic e.g. indapamide
- No need to change diuretic in people stable on treatment and in whom BP is controlled
Anti-sympathetic Drugs
- Autonomic ganglion Blocking agent
- Adrenergic neurone blocking agent
- a1- adrenoreceptor antagonist e.g. prazosin; doxazosin; terazosin
- B-adrenoceptor antagonists - propranolol (B1 and B2), atenolol (B1 selective)
- Centrally acting a2-agonists e.g. clonidine, methyldopa and monoxide
B-adrenoceptors antagonists (group B)
- Not designed an anti-HTN- action recognised in clinical trials for angina
- Anti-HTN action associated with action at B1-adrenoceptors
- Many of the undesirable actions are linked to effect at B2-adrenoceptors: bronchoconstriction- pulmonary B2 receptors; Hypoglycaemia- B2 hepatic glycogenolysis
B-adrenoceptor antagonists
Consider for younger people particularly
- Women of child bearing age
- Where there is evidence of increased sympathetic drive
- Where intolerance to ACEI or ARB|| Antagonists
- May be compelling reason to use e.g. angina
- No reason to withdraw where BP controlle , if withdrawing do so slowly
Mode of action in HTN
- Reduction of CO: acute- may precede anti-HTN action; general effect all agents
- Suppression of renin release : very rapid does’t correlate well with decreased BP
- Central inhibitory action on sympathetic outflow
- Action on peripheral nerves- blockade of pre-synaptic B-receptors
B-antagonists disadvantages
- Recent trials: less effective at reducing major CVS outcomes, particularly stroke
- Reduce cardiac sympathetic: care in failure/disease; CI conductivity defects
- Unfavourable on blood lipids and blood glucose. care hyperlipidaemia
- CNS disturbances- linked to lipophilicity
- Impotence in males
- Effects on B2 receptors: care asthma/COPD; care PVD
B-antagoinsts advantages
- Cheap
- Effective in high output HTN e.g. labile
- Effective in young ESH
- Good in co-existing angina without cardiac failure
- 12/24 hr dosing easy
- Good high renin ESH
- Side effects- bradycardia, cold
a1-adrenoceptors antagonist e.g. doxazosin- advantages
- Well tolerated
- Few metabolic effect: favourable on blood lipids; no effect on glucose tolerance
- No bronchospasm
- +ve indications: PVD; diabetes; elderly males in prostatic hypertrophy
a1-adrenoceptor antagonist- disadvantages
- First dose effect- may see precipitate fall in BP (worst prazosin)
- Vasodilator side effects e.g. flushing
- Less effect upon CVS events particularly HF (ALLHAT study)
Centrally active a2- agonist e.g. clonidine and methyldopa- advantages
- Good BP control
- No postural hypotension
- a-methyldopa is well established. useful in pregnancy
- No effect bronchial smooth muscle (asthma)
- No direct cardiac action
Centrally active a2- agonist e.g. clonidine and methyldopa- disadvantages
- Rebound HTN
- Dry mouth
- Constipation
- Impotence in males
- Tolerance may occur
- a-methyldopa only: sedation; blood dyscarsias; hypersensitivity
Other direct vasodilators
Sodium Nitroprusside
-Active only by IV infusion
-Very short duration of action
-Highly effective for short term use
-Toxicity- thiocyanate (chronic); cyanide (acute)- dangerous
Diazoxide (k channel activator)
-Chemically related to thiazide diuretics
-Major action on arteriolar muscle
-Can be used IV (emergency) and active orally
-Problems: hyperglycaemia; volume expansion; decrease K
-Main use: emergency treatment of increased intra-ocular pressure
Other direct vasodilator advantages
- Direct reduce TPR. Potent anti-HTN
- Good side effect profile: no -ve isotropy; favourable on blood lipids
- A number of specific uses e.g. HTN crisis
Other Direct vasodilators disadvantages
- Can produce precipitate fall in BP
- Activation of baroreceptor reflex producing reflex tachycardia and increased plasma renin activity
- Na+ and H20 retention 2ndary to inc. plasma renin activity
- Care in IHD- may precipitate angina- avoid after AMI
- Range of drug specific side-effects and contra-indications
Renovascular HTN
- Reduction of blood supply to one or both kidneys
- A number of causes of reduced flow: stenosis (fibromuscular dysplasia); 2ndary to atherosclerosis; obstruction due to tutors, thrombosis etc
- One kidney “vasoconstriction driven’ (activation of RAAS)
- 2 kidney- volume expansion
Endocrine HTN
Normally due to problems with pituitary or adrenal glands (to much cortisol)
- Phaeochromocytoma (rare tutor of adrenal gland, excess NA)
- Cushings: 2ndary or primary (benign tumor pituitary gland; excess ACTH; resulting in excess aldosterone); HTN in 75%; volume loaded HTN
- Conns syndrome; adrenal adenoma with aldersterone release
- Hyperthyroidism: classical high output HTN
HTN in pregnancy
- Chronic HTN: antedates pregnancy but may be exacerbated. 30-50% of all cases
- Gestational HTN (PIH): Normotensive individual before pregnancy. BP at least on 2 occasions 6hrs apart
HTN in pregnancy- in pre-eclampsia/eclampsia
- Pre-eclampsia: with proteinuria and oedema
- Eclampsia (toxaemia of pregnancy) extensive intravascular clotting; convulsion; hepatic and renal dysfunction
- 65% in primagravidas. 5-10% all pregnancies
- Risks:>40 years age, previous history; DBP >80 at start
Drug treatment of PE/PIH
-Challange
-No proven benefit 110, SBP >170 mmHg
Therapy: ACEI and ARB|| antagonists contra-indicated; diuretics undesirable
Early pregnancy: methyldopa; Beta-blocker- labetalol; CEB- nifedipine
Late pregnancy: methyldopa; CEB- nifedipine slow release
