Lecture 1- Intro To Module And Antihypertensive Drugs Flashcards
Hypertension
Hypertension has NO cure- treatment can modify its course
Changes in lifestyle are some examples;
-controlling weight by diet and exercise
-smoking cessation
-decreasing alcohol and sodium intake
-exercising regularly
-resting and avoiding stress
Aetiology of hypertension
-some patients have primary hypertension- persons bp has no clear cause
-stressful lifestyle, high dietary intake of sodium and smoking are factors that make hypertension occur
Mechanisms for controlling BP
-bp needs to stay in normal range - high enough to give body oxygen but not so high it causes damage
BP = CO X PR
-baroreflexes mediated by the sympathetic nervous system
-the renin-angiotensin-aldosterone system
^ two control mechanisms to regulate cardiac output and peripheral resistance
-most antihypertensive drugs lower BP by reducing CO and/or decreasing PR
Baroreceptors and the sympathetic nervous system
-baroreceptors located in blood vessels are sensitive to changes in bp
-a fall in bp causes baroreceptors to send fewer messages to cardiovascular centres in the CNS —> increased sympathetic activity output to the heart and blood vessels
-sympathetic output in the heart and blood vessels = vasoconstriction and increased cardiac output
- body is trying to fix a problem
-system quickly adjusts bp form moment to moment
Renin-angiotensin-aldosterone system
-kidney= help control bp in long term by adjusting how much water is in your body
-baroreceptors located in the kidney= reduced bp by releasing an enzyme = Renin
-Renin= responsible for the production of a substance known as angiotensin I —> converted into angiotensin II through the action of the enzyme Angiotensin Converting Enzyme (ACE)
-Angiotensin II- strongest substance in the body that can tighten blood vessels
-angiotensin II stimulates aldosterone production
Classification of antihypertensive drugs
Examples of drugs; slide 12
- Diuretics= reduce circulating blood volume by blocking the reabsorption of sodium and water= more water being retained in the kidney and excretion of excess fluid
-bendroflumethiazide, benzthiazide and hydrochlorothiazide - Beta-adrenoceptor blocking agents= reduce bp by decreasing cardiac output in the heart
-labetalol, metoprolol and atenolol - ACE inhibitors= lower bp by reducing peripheral resistance through the blockage of angiotensin converting enzyme (ACE)
-captopril, cilazapril and enalapril
Classification carried over
Examples of drugs; slide 13
- Angiotensin-II receptor antagonists= antagonise the effects of angiotensin II
-losartan and eprosartan - Renin inhibitors= directly inhibits renin, acts earlier in the renin-angiotensin-aldosterone system than ACE inhibitors or angiotensin receptor blockers **ALISKIREN
- Centrally-acting antihypertensive drugs= able to reduce the sympathetic outflow from the CNS—> diminished peripheral resistance and cardiac output *CLONIDINE + METHYLDOPA
- Vasodilators= produce a direct relaxation of vascular smooth muscle. Does not depend on the innervation of vascular smooth muscle
*HYDRALAZINE + MINOXIDIL
Classification carried over
Examples of drugs; slide 14
- Alpha-adrenoreceptor blocking drugs = block adrenergic receptors on blood vessels which decrease peripheral resistance and lower blood pressure by causing relaxation of vascular smooth muscle
*DOXAZOSIN, PRAZOSIN, TERAZOSIN, PHENOXYBENZAMINE, PHENTOLAMINE - Calcium channel blockers
*AMLODIPINE, FELODIPINE, NIFEDIPINE
Diuretics; Thiazide diuretics
-diuretic action is achieved by blockade of distal renal tubular sodium reabsorption
-they reduce blood pressure by reducing circulating blood volume which leads to a reduce in long term peripheral resistance
-treatment for mild/moderate hypertension
-can be used in combination with sympathetic blockers and vasodilator drugs for severe hypertension
B-adrenoreceptor blocking agents
-reduce cardiac output
-reduce blood pressure in mild-moderate hypertension
-reduce sympathetic outflow from the CNS and inhibit renin release from the kidneys
Example= propanolol= first B-blocker to be effective in hypertension which has now been replaced by atenolol (cardioselective B-blocker)
-acts B1 + B2 receptors, therefore B2 bronchodilator for asthmatic patients will not work
Angiotensin converting enzyme (ACE) inhibitors
-recommended when diuretics/B-blockers are ineffective
-reduce blood pressure by reducing peripheral resistance
-blocks the enzyme that changes AG1 into AG2
-by reducing angiotensin II levels= ace inhibitors also decrease the secretion of aldosterone —> decreased sodium and water retention
-degrades bradykinin
-accumulation of bradykinin in airways stimulates cough reflex via vagal nerves
ACE inhibitors side effects
-dry cough= due to increased levels of bradykinin in the pulmonary tree
-rash
-fever
-hypotension
-hyperkalemia- potassium levels must be monitored
Calcium channel blockers (CCBs)
-recommended when other treatments are ineffective
-interfere with vascular tone by decreasing cytosolic calcium concentration and release of Ca2+ from the sarcoplasmic reticulum
*Diphenylalkylamines (verapamil)= least selective CCB, has significant effects on both cardiac and vascular smooth muscle cells
*Benzothiazepines (diltiazem)= affects both cardiac and vascular smooth muscle cellls, less negative effect on the heart compared to verapamil
*Dihydropyridines (nifedipine, felodipine and amlodipine)= drug sticks more strongly to CCB in blood vessels than in the heart
Calcium channel blockers side effects
-verapamil= constipation
-verapamil= avoid in patients with congestive heart failure because of its negative inotropic effect
-dihydropyridines= dizziness, headaches, fatigue and a decrease in blood pressure
A-adrenoreceptor blockers
-selectively block a-adrenoreceptors to produce a competitive block of a-adrenoreceptors
-decrease peripheral vascular resistance and lower arterial bp by causing relaxation of both arterial and venous smooth muscle
*prazosin, doxazosin and terazosin = examples
Centrally-acting drugs: Clonidine + side effects
*clonidine= a2-agonist- acts pre-synaptically to inhibit noradrenaline release from adrenergic nerve terminals
-acts to diminish central adrenergic outflow
-bp lowering results from reduction of cardiac output and peripheral resistance
-treats hypertension in combination with two or more drugs
Side effects:
-sedation
-drying of the mouth nasal mucosa
-rebound of hypertension occurs with withdrawal symptoms
-caution in patients with mental depression
Centrally-acting drug: a-Methyldopa + side effects
*a-methyldopa= a2-agonist which converts into methylnoradrenaline to diminish central adrenergic outflow from the CNS
-reduces bp by reducing peripheral resistance with a variable reduction in heart rate + cardiac output
Side effects:
-sedation and drowsiness
-long term treatment-impaired mental concentration
-nightmares, mental depression, vertigo + extrapyramidal signs
