Pharmacology 9: Hypertension and heart failure drugs Flashcards
Verapamil- a Ca2+ channel blocker for hypertension, should not be given with a beta blocker- used in hypertension and HF, WHY?
severe bradycardia and/or hypotension can occur
what is the threshold for drug tment for hypertension?
> or =160mmHg systolic and > or =100mmHg diastolic
tment threshold for hypertension in diabetic patient, and target level on tment?
140mm systolic or 90mm diastolic
and target is <130/80mmHg
most common cause of secondary hypertension?
chronic kidney disease
BHS classification of hypertension?
Grade 1 (mild) 140-159 systolic, 90-99 diastolic Grade 2 (moderate) 160-179, 100-109 Grade 3 (severe) >=180, >=110
lifestyle therapy for patients with hypertension?
Patient education Maintain normal body weight (BMI 20-25 kg/m2 ) Reduce salt intake to 30 minutes/day Consume >5 portions of fresh fruit/vegetables daily Reduce intake of total and saturated fat (Smoking cessation) (Relaxation therapies)
step 1 hypertensive tment in patient <55yrs?
ACEI, or AngII receptor blocker if ACEI not tolerated
if both CI or not tolerated, can use a beta blocker
ACEIs also preferred therapy in hypertensive diabetic as delay onset and progression of diabetic glomerular disease
how do ACEIs reduce BP?
competitive inhibitors of ACE, causing…
decrease AngII: so cause areteriolar vasodilation, which decreases systemic resistance.
reduces salt and water retention by PCT at kidney, and by decreasing aldosterone, promote a natriuresis to reduce intravascular volume.
reduce ADH release
reduce SNS activation
increase bradykinin, which causes vasodilation
can also cause venodilation
examples of ACEIs?
ramipril
lisinopril
ADRs of ACEIs?
persistent dry cough renal failure hyperkalaemia angio-oedema hypotension
action of angiotensin II receptor antagonsits (AT1 antagonists)
E.g. Losartan, Valsartan Bind to angiotensin AT1 receptor Inhbit vasoconstriction and aldosterone stimulation caused by angiotensin II Well tolerated, few side effects
ADRs of AngII receptor antagonists (AT1 antagonists)?
renal failure
hyperkalaemia
hypotension e.g. dizziness
don’t get dry cough- as don’t interfere with ACE responsible for bradykinin degradation
step 2 hypertensive tment in patient aged <55yrs?
combine step 1 ACEI/AngII receptor blocker with Ca2+ channel blocker, or thiazide-related diuretic if Ca2+ blocker not tolerated or high risk of HF.
3 main groups of Ca2+ channel blockers?
Dihydropyridines (Nifedipine, Amlodipine)
Benzothiazepines (Diltiazem)
Phenylalkylamines (Verapamil)
where do Ca2+ channel blockers act in hypertension?
bind to specific alpha subunit of L-type calcium channel, reducing cellular calcium entry.
oral agents used in LT tment of hypertension
how do the dihydropyridine agents e.g. amlodipine primarily act to decrease BP?
vasodilators- peripheral, coronary and pulmonary arteries
block Ca2+ induced smooth muscle contraction, hence cause vasodilation
how do verapamil and diltiazem primarily act to decrease BP?
-ve inotropes and chrontropes, decreasing myocardial contractility and HR, and impulse conduction.
Verapamil depresses SA node, prolongs effective refractory period, and is used as an anti-arrhythmic drug.
diltiazem has less inotropic effect than verapamil, and is used to treat angina.
PK properties of dihydropyridine Ca2+ channel blockers?
Good oral absorption
Protein bound > 90%
Metabolised by the liver- CYP450?
Few have active metabolite
ADRs of dihydropyridine Ca2+ channel blockers?
Sympathetic nervous system activation – tachycardia and palpitations Flushing, sweating, throbbing headache Oedema Gingival hyperplasia (rare)