Pharmacology Antihypertensives Flashcards
The Clinical Management of Hypertension is one of the most common interventions in primary care.
What are the types of Hypertension medications used?
3 angiotensin converting enzyme inhibitors
7 β-adrenoceptor antagonists
8 calcium channel entry blockers
18 thiazide and related diuretics
24 α-adrenoceptor antagonists
25 angiotensin receptor antagonists
60 aldosterone antagonists
6P (63) potassium sparing diuretics with other diuretics
Explain the Renin Angiotensin System.
Explain how ACE inhibitors work
ACE inhibitors inhibit the action of angiotensin-converting enzyme (ACE) which reduces the conversion of angiotensin 1 to angiotensin 2.
Angiotensin 2 is the vasocontrictor and stimulates aldosterone secretion therefore we want to block this action.
This reduces the peripheral resistance of blood vessels and increases the excretion of salt and water.
What are the most widely prescribed ACE inhibitors in UK?
Ramipril, Lisinopril, and enalapril.
What type of drug is Ramipril and Enalapril?
ACE inhibitors
They are specifically Liver Pro drugs.
What are some adverse effects of ACE inhibitors?
(3 different ones)
1- Bradykinin-mediated - . A persistent cough and angioedema are both attributed to enhancing bradykinin activation of peripheral nerves. The persistent cough which occurs in 1 in 5 patients will require a change in antihypertensive therapy and the angioedema is much less frequent but more serious and potentially life-threatening event.
2- Angiotensin Lack - . In patients with renal artery stenosis, the reduction in angiotensin II can induce renal failure
3- A reduction in aldosterone reduces potassium excretion. Risk of hyperkalaemia - do not use with K-sparing diuretics.
ACE inhibitors also are known for breaking down the bradykinin, so when a person takes a ACE inhibitor bradykinin are thought to collect and create which symptom
A cough reflex
Taking ACE inhibitors means that there is decreased aldosterone production. What is aldosterone important for and what can the reduction of this result in ?
Aldosterone causes sodium to be absorbed and potassium to be excreted.
Hyperkalemia
Other than Hypertension when else can ACE inhibitors be used ?
- To treat heart failure
- Secondry prevention of major adverse cardiovascular events eg after an MI.
Explain how Angiotension Receptor Blockers (ARBs) work.
Instead of inhibiting the conversion of angiotensin 1 to angiotensin 2 like ACE inhibitors do..
ARBS block the action of Angiotensin 2 from binding to receptors.
What are the most common ARBS prescribed in the UK ?
losartan, candesartan and irbesartan which are all liver prodrugs
Explain how calicum channel blockers work to reduce hypertention.
Calcium channel blockers reduce the entry of calcium across the cell membrane of vascular smooth muscle inducing vasodilatation, and reducing peripheral resistance.
What is the most common Calcium Channel Blocker Prescribed?
Today, amlodipine is by far the most widely prescribed CCB in primary care in the UK having a longer half-life allowing once daily therapy with improved patient compliance
When would calcium channel blockers be indicated?
Therapeutic Use
Hypertension
peripheral vasodilator
monotherapy of mild hypertension in
- the elderly (55+)
- Afro/Caribbean patients of any age
co-existing - airway disease, peripheral vascular disease, ischaemic heart disease not a problem
disadvantage - co-existing heart failure
What adverse effects are associated with calcium channel blockers ?
Adverse Effects
flushing, headache
(arteriolar dilatation)
ankle oedema
(reduced capillary hydrostatic pressure)
palpitations
(reflex tachycardia)
Explain NICE recommended guidance for hypertension (step 1).
What type of Diuretic can be prescribed for hypertension?
Give an example …
Thiazide Diuretic
Indapamide
How does a Thiazide Diuretic work as an antihypertensive
The effect of thiazide inhibiting the reabsorption of sodium and therefore increasing sodium excretion is an effective antihypertensive mechanism.
Thiazides increase sodium excretion generating about 2 litres of urine, reducing the extracellular fluid volume back to normal
What are some adverse effects of prescribing thiazide diuretics ?
Risk of hypokalemia - K should be monitored and controlled, potentially use potassium supplements or combined with potassium-sparing diuretics.
What BP value is typically indicates to starts drug therapy ?
140/90
Explain typical drug therapy steps for anyone aged 55 and under suffering from hypertension.
1 - ACE Inhibator
2 - ACE + Calcium channel blocker
3- ACE + CCB + Thiazide-like diuretic.
If blood pressure still remains over 140/90 mm/Hg with the patient taking 3 antihypertensive drugs, the hypertension is defined as resistant hypertension and a fourth drug maybe required. Step 4 is to add either a further diuretic or inhibit the sympathetic nervous system with alpha or beta adrenoceptor blockers
Explain typical drug therapy steps for anyone aged 55 and over or a black person of African or Caribbean family origin of any age suffering from hypertension.
Step 1 - Calcium- Channel Blocker
Step 2- CCB + ACE
Step 3 - CCB + ACE + Thiazide-like diurtetic
If blood pressure still remains over 140/90 mm/Hg with the patient taking 3 antihypertensive drugs, the hypertension is defined as resistant hypertension and a fourth drug maybe required. Step 4 is to add either a further diuretic or inhibit the sympathetic nervous system with alpha or beta adrenoceptor blockers
What is the fourth drug that can be given for resistance hypertension?
The additional diuretic is spironolactone, an aldosterone receptor antagonist.
Spironolactone antagonises the effect of aldosterone on the distal nephron, inhibiting sodium reabsorption, enhancing its excretion. However, potassium excretion is reduced potentially leading to hyperkalaemia. If the plasma potassium exceeds 4.5 mmol/l , the dose of the thiazide may be increase since it enhances potassium excretion.
If the fourth line of treatment (spiralactolone) for resistance hypertension is ineffective what else can be given ?
A beta blocker or an alpha-blocker may be prescribed.
Beta-blockers reduce systemic blood pressure by a combined effect on the heart and kidney. Antagonism of the beta1 adrenoceptor in the heart decreases cardiac output producing negative inotropic and chronotropic effects.
The effect on the kidney is also mediated through the beta1 adrenoceptor by inhibition of the release of renin, reducing the level of angiotensin II.
