CVS Pharmacology 1: Antihypertensives-1. Flashcards
Hypertension is an important risk factor for which conditions? (4)
1- heart disease.
2- stroke.
3- chronic kidney disease.
4- organ damage.
The risk of organ damage is directly related to what?
The extent of elevation of BP.
List the 4 classifications of hypertension?
1- normal: <120 and <80.
2- elevated: 120-139 or 80-89.
3- stage 1 hypertension: 140-159 or 90-99.
4- stage 2 hypertension: >= 160 or >=100.
List the 2 types of hypertension, and their etiology?
1- essential hypertension (90% cases).
2- secondary hypertension (10-15%).
List the 7 lifestyle modifications that can decrease blood pressure?
1- weight reduction.
2- increase in physical activity.
3- dietary sodium reduction.
4- limited fat intake.
5- increased fibre intake.
6- restriction on alcohol consumption.
7- stopping tobacco products.
Arterial blood pressure is directly proportional to what?
Directly proportional to cardiac output and peripheral vascular resistance.
Most antihypertensives lower BP by reducing _______ ____ and/or decreasing _______ _______.
Reducing cardiac output and/or decreasing peripheral resistance.
Cardiac output and peripheral resistance are controlled by what?
1- baroreflexes.
2- RAAS.
List the 10 classifications of antihypertensives?
1- diuretics.
2- ACE inhibitors.
3- angiotensin (AT1 receptor) blockers (ARB).
4- direct renin inhibitor.
5- calcium channel blockers.
6- Beta adrenergic blockers.
7- beta and alpha adrenergic blockers.
8- alpha adrenergic blockers.
9- central sympatholytics.
10- vasodilators.
List the 3 types of diuretics?
1- thiazides.
2- high ceiling “loop diuretics”.
3- K+ sparing.
List 3 examples of thiazides?
1- hydrochlorothiazide.
2- chlorthalidone.
3- indapamide.
Give an example of high ceiling “loop diuretics”?
Furosemide.
List 2 examples of K+ sparing?
1- spironolactone.
2- amiloride.
List 6 examples of ACE inhibitors?
1- captopril.
2- enalapril.
3- lisinopril.
4- perindopril.
5- ramipril.
6- fosinopril.
All end with “pril”.
List 5 examples of ARB?
1- losartan.
2- candesartan.
3- irbesartan.
4- valsartan.
5- telmisartan.
All end with “sartan”.
List an example of direct renin inhibitor?
Aliskiren.
List 7 examples of CCBs?
1- verapamil.
2- diltiazem.
3- nifedipine.
4- felodipine.
5- amlodipine.
6- nitrendipine.
7- lacidipine.
List 3 examples of Beta adrenergic blockers?
Non selective: propranolol.
Beta 2 selective: metoprolol, atenolol.
List 2 examples of beta and alpha adrenergic blockers?
Labetalol,
Carvedilol.
List 5 alpha adrenergic blockers?
1- prazosin.
2- terazosin.
3- doxazosin.
4- phentolamine.
5- phenoxybenzamine.
List 2 central sympatholytics?
1- clonidine.
2- alpha-methyldopa.
List the 2 groups of vasodilators, and give examples of them?
1- arteriolar: hydralazine, minoxidil, diazoxide.
2- arteriolar + venous: sodium nitroprusside.
Alpha adrenergic blockers work on which type of BP?
Peripheral BP.
Central sympatholytics work on which receptor?
Alpha 2 antagonist, stimulates the alpha 2 receptor in the brain.
Which type of antihypertensives are used in emergencies and in resistant hypertension?
Vasodilators.
Which vasodilator is used in emergency in 180mmHg and above with impending organ damage?
Sodium nitroprusside.
Which antihypertensives can be used as first-line drug therapy?
Diuretics, specifically thiazides.
Which type of investigations should be done in all patients receiving diuretics?
Routine serum electrolyte monitoring.
List the actions of diuretics?
Lower blood pressure by increasing Na and water excretion > which causes a decrease in extracellular volume, decrease in cardiac output and renal blood flow.
What happens to plasma volume and peripheral resistance with long term treatment of diuretics?
Plasma volume approaches a normal value, but peripheral resistance decreases.
Which type of drugs are often combined with thiazides?
Potassium-sparing diuretics.
Thiazide diuretics are particularly useful in the treatment of which groups of patients?
Black or elderly patients.
Thiazides are not effective in patients with which conditions, and what may be required in these patients?
Not effective in patients with inadequate kidney function (creatinine clearance <50 mL/min), loop diuretics may be required in these patients.
List the 4 adverse effects of diuretics?
1- hypokalemia.
2- hypomagnesemia.
3- hyperuricemia (can cause gout).
4- hyperglycemia (interferes with blood glucose management).
Which type of investigation should be done in patients who are taking diuretics and are predisposed to cardiac arrhythmias?
Serum potassium levels.
Loop diuretics act even in patients with poor ____ _____ or who have no responded to ____ or other _____.
Patients with poor renal function or who have not responded to thiazides or other diuretics.
What do loop diuretics do to renal vascular resistance and renal blood flow?
Decrease renal vascular resistance and increased renal blood flow.
Loop diuretics increase the ___ Content of urine, whereas thiazide diuretics decrease it.
Ca2+.
List the 2 groups of potassium-sparing diuretics?
1-inhibitors of epithelial sodium transport at the late distal and collecting ducts.
2- aldosterone-receptor antagonists.
List the 2 potassium sparing diuretics that are inhibitors of epithelial sodium transport at the late distal and collecting ducts?
Amiloride and triamterene.
List the 2 potassium sparing diuretics that are aldosterone-receptor antagonists?
Spironolactone and eplerenone.
List an adverse effect of spironolactone?
Gynecomastia, blocks testerone.
List a benefit of spironolactone?
Diminishing of the cardiac remodeling (caused by aldosterone) that occurs in heart failure.
(Good for cardiac patients).
How do ACE inhibitors lower blood pressure?
By reducing peripheral vascular resistance without reflexively increasing cardiac output, rate, or contractility.
What effects do ace inhibitors have on sodium and water retention?
By reducing circulating angiotensin 2 levels, ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention.
Which drugs are first line drugs in all grades of hypertension?
ACE inhibitors.
ACE inhibitors are highly effective and first choice drugs in _______ and _______ hypertension.
Renovascular and resistant hypertension.
ACE inhibitors are particularly suitable for which type of hypertension patients?
Diabetic hypertensives.
They decrease proteinuria of diabetic nephropathy.
List 7 therapeutic uses of ACE inhibitors?
1- no postural hypotension.
2- safe in asthmatics, diabetics and peripheral vascular disease patients.
3- secondary hyperaldosteronism and K+ loss due to diuretics is prevented.
4- no rebound hypertension on withdrawal.
5- left ventricular hypertrophy is reversed.
6- no hyperuricaemia, no deleterious effect on plasma lipid profile.
7- minimum worsening of quality of life parameters like general wellbeing, work performance, sleep, sexual performance ect.
List the 8 adverse effects of ACE inhibitors?
1- hypotension.
2- hyperkalaemia.
3- dry cough.
4- rashes, urticaria.
5- angioedema.
6- dysgeusia.
7- foetopathic.
8- acute renal failure: in patients of bilateral renal artery stenosis.
What causes dry cough with ACE inhibitors?
Not dose related, appears to be caused by inhibition of bradykinin/substance P breakdown in the lungs of susceptible individuals.
Angiotensin 2 receptor blockers block which receptor?
Block the AT1 receptors.
ARBs differ from ACE inhibitors in what?
Don’t increase bradykinin levels.
ARBs are contraindicated in which group of people?
Pregnant women because they are fetotoxic.
Which drug is a selective renin inhibitor, used for the treatment of hypertension?
Aliskiren.
List the adverse effects of Aliskiren?
1- Causes diarrhea, especially at higher doses.
2- Cough and angioedema.
List Aliskiren contraindications?
Pregnancy.
How do calcium channel antagonists work?
They block the inward movement of calcium by binding to L-type calcium channels > causes vascular smooth muscle to relax, dilating mainly arterioles.
Where do calcium channel blockers block calcium?
In the heart and smooth muscle of the coronary and peripheral vasculature.
CCBs are recommended first line agents in which group of people?
Blacks.
List the 3 classes of CCBs?
1- diphenylalkylamines.
2- benzothiazepines.
3- dihydropyridines.
Give an example of diphenylalkylamines CCBs?
Verapamil.
Give an example of benzothiazepine CCBs?
Diltiazem.
Give an example of dihydropyridines?
First generation: nifedipine.
Second generation: isradipine, felodipine, amlodipine, nitrendipine, nimodipine, lacidipine, lercanidipine.
(All end with dipine).
Which class of CCBs works in the blood vessels only?
Dihydropyridines.
Which classes of CCBs work both in the blood vessels and the heart?
1- diphenylalkylamines.
2- benzothiazepines.
CCBs are safe to treat hypertension in which cases?
COPD and peripheral vascular disease.
CCBs have an _____ effect and therefore don’t require the addition of a ______.
Natriuretic effect, don’t require addition of a diuretic.
List the 8 therapeutic uses of CCBs?
1- hypertension.
2- Angina pectoris.
3- cardiac arrhythmias.
4- hypertrophic cardiomyopathy.
5- premature labor.
6- nocturnal leg cramps.
7- raynaud’s episodes.
Which CCBs can be used for PSVT and supraventricular arrhythmias?
Verapamil and diltiazem .
Which CCB can be used for premature labor?
Nifedipine.
Which CCB can be used for nocturnal leg cramps?
Verapamil.
Which CCB can be used for Raynaud’s episodes?
DHPs (Dipines).
List the 7 AE of CCBs?
1- palpations, flushing, ankle edema.
2- hypotension, headache, drowsiness and nausea.
3- first degree AV block (with the CCBs that work on the heart).
4- constipation.
5- urine voiding difficulty in elderly males.
6- GER may be worsened.
7- gingival hyperplasia.
Which CCB causes urine voiding difficulty in elderly males?
Nifedipine.
Which CCB may worsen GER?
All DHPs.
Which CCB can cause gingival hyperplasia?
Nifedipine.
Which CCBs should be avoided in heart failure and AV block? And why?
Verapamil and diltiazem, due to negative inotropic effect.
How do beta blockers affect cardiac output, central sympathetic outflow from the CNS and release of renin from kidneys?
Decreases cardiac output.
Decreases sympathetic outflow from the CNS.
Inhibits the release of renin from the kidneys.
Which receptors does propranolol work on?
Acts on both beta 1 and beta 2 receptors.
Which receptors do metoprolol and atenolol work on?
Selective blockers of beta 1 receptors.
Which type of beta blockers are preferred in asthmatics?
Selective beta blockers.
Beta blockers are more effective in which race group?
Whites more than blacks.
List contraindications of beta blockers?
1- severe COPD.
2- 1st and 2nd degree heart block.
3- severe peripheral vascular disease.
List the conditions that may coexist with hypertension in which beta blockers are useful in treating?
1- supraventricular tachyarrhythmia.
2- previous MI.
3- angina pectoris.
4- migraine headache.
5- chronic heart failure.
List 5 adverse effects of beta blockers?
1- bradycardia.
2- hypotension.
3- fatigue, lethargy, insomnia, and hallucinations.
4- decrease libido and cause impotence.
5- alternations in serum lipid patterns; decrease in HDL and increase in TGs.
Abrupt withdrawal of beta blockers causes what?
May induce angina, myocardial infarction, or sudden death in patients with ischemic heart disease.
How do alpha blocking agents affect TPR and BP?
They decrease TPR and BP.
What often occurs at the onset of treatment with increase in dose of alpha blocking agents?
Reflex tachycardia and postural hypotension.
List alpha blocking agents?
Prazosin, doxazosin, terazosin.
Which receptor do alpha blocking agents work on?
Competitive blockers of alpha 1 adenoreceptors.
Labetalol and carvedilol act on which receptors?
They block alpha 1, beta 1 and beta 2 receptors.
List the 4 therapeutic effects of labetalol?
1- rapid BP reduction in hyperadrenergic states.
2- cheese reaction.
3- clonidine withdrawl.
4- eclampsia.
Which additional properties does carvedilol have?
Antioxidant/ free radical scavenging properties.
Cavedilol is used for what?
Long term treatment of CHF, and is approved as an antihypertensive as well.
List 2 centrally acting adrenergic drugs?
Clondine.
Methyldopa.
Clondine and methyldopa act on which receptors?
Both drugs are alpha 2 adrenergic receptor agonists.
How do centrally acting adrenergic drugs affect sympathetic outflow from the brain to the CVS?
They decrease it.
What is the route of administration of centrally acting adrenergic drugs?
Both are absorbed orally.
Clondine is also available as a transdermal patch.
How does clonidine affect renal blood flow?
Does not decrease renal blood flow.
Clonidine is used for the treatment of which?
- used for hypertension has not responded adequately to treatment with two or more drugs.
- useful in the treatment of hypertension complicated by renal disease.
List the 3 adverse effects of clonidine?
1- can cause sodium and water retention (Add diuretic).
2- sedation and drying of the nasal mucosa.
3- rebound hypertension on abrupt withdrawal.
Rebound hypertension caused by clonidine abrupt withdrawal is due to what?
Supersensitivity of adrenergic receptors caused by chronic clonidine-induced reduction in sympathetic outflow.
List 4 vasodilators?
1- hydralazine.
2- minoxidil.
3- diazoxide.
4- sodium nitroprusside.
How do vasodilators affect TPR and BP?
Decrease TPR and BP.
Vasodilators produce ____ _____ of the heart?
Reflex stimulation.
Reflux stimulation of vasodilators cause which AE?
1- angina pectoris.
2- myocardial infarction.
3- cardiac failure.
In predisposed individuals.
How do vasodilators affect plasma renin concentration?
Increase plasma renin concentration, resulting in sodium and water retention.
Undesirable side effects of vasodilators can be blocked by concomitant use of what?
Diuretics and a beta blocker.
Which antihypertensives are given when a patient has stable IHD?
1- beta blocker.
2- ACE inhibitor.
3- ARBs.
4- CCBs.
Which antihypertensives are given when a patient has diabetes?
1- diuretics.
2- ACEI.
3- ARBs.
4- CCBs.
Which antihypertensives are given when a patient has recurrent stroke?
1- diuretics.
2- ACEI.
3- ARBs.
Which antihypertensives are given when a patient has HF?
1- diuretics.
2- beta blockers.
3- ACEI.
4- ARBs.
5- aldosterone receptor antagonist.
Which antihypertensives are given when a patient has previous MI?
1- beta blocker.
2- ACEI.
3- aldosterone receptor antagonist.
Which antihypertensives are given when a patient has CKD?
1- ACEI.
2- ARBs.
The goal of antihypertensive therapy is to reduce what?
Cardiovascular and renal morbidity and mortality.
Antihypertensive therapy is indicated in cases where:
- SBP _______ or DBP _______ (at age 60 or more).
- SBP _______ or DBP _______ (at age <60).
- SBP >= 150 mmHg or DBP >= 90mmHg (at age 60 or more).
- SBP >= 140 mmHg or DBP >= 90mmHg (at age <60).
Current recommendation is to initiate therapy with a _____ _____, ____ ______, ___ or ____.
Thiazide diuretic, ACE inhibitor, ARB or CCB.
What do we do if BP is inadequately controlled after 1 month of therapy?
Either increase dose or add another drug.
Add a third drug if 2 drugs don’t control the BP.
If SBP is greater than 20mmHg or DBP is 10mmHg above goal, we start with how many drugs?
Start with 2 drugs.
List the 3 drug combinations in hypertension?
1- fully additive drug combinations (preferred combination).
2- questionable drug combinations.
3- preferred combinations with patients with associated conditions.
Give 4 examples of fully additive drug combinations?
1- diuretics + beta blocker.
2- diuretics + ACEI.
3- CCB + beta blocker.
4- CCB + ACEI.
List 4 questionable drug combinations?
Non-additive:
1- beta blocker + ACEI.
2- ARB + ACEI.
Side effect additive:
3- beta blocker + verapamil.
4- alpha blocker + CCB.
What is the preferred antihypertensive combinations in patients with angina?
Beta blocker + CCB.
What is the preferred antihypertensive combinations in patients with HF?
Diuretic + ACEI.
What is the preferred antihypertensive combinations in patients with diabetes?
ACEI + CCB.
What is the preferred antihypertensive combinations in patients with COPD?
Diuretic + CCB.
List the drugs which increase plasma renin activity?
Diuretics, vasodilators, CCBs, ACEI.
List the drugs which lower plasma renin activity?
Beta blockers, clonidine, methyldopa.
Why should we avoid combining verapamil or diltiazem with beta blockers?
Because of marked tachycardia, AV block can occur.
Definition: BP that remains elevated despite administration of an optimal three drug regimen that includes a diuretic?
Resistant hypertension.
List the 4 causes of resistant hypertension?
1- poor compliance.
2- excess ethanol intake.
3- concomitant conditions (diabetes, obesity, sleep apnea, hyperalsosteronism, high salt intake, metabolic syndrome).
4 concomitant medications (sympathomimetics, NSAIDs, corticosteroids), insufficient dose, use of drugs with similar mechanism of action.
What defines hypertensive emergencies?
Systolic BP > 180 or diastolic > 120mmHg, with evidence of impending or progressing end organ end damage.
Mean BP should be lowered by no more than _% over a period of ___ or a few ___ and then ___ to not lower than ________ mmHg.
Mean BP should be lowered by no more than 25% over a period of mins or a few hrs and then gradually to not lower than 160/100 mmHg.
List the 9 drugs employed in hypertensive emergencies?
1- sodium nitroprusside.
2- glyceryl trinitrate.
3- hydralazine.
4- esmolol.
5- phentolamine.
6- labetalol.
7- fenoldopam.
8- furosemide.
9- nicardipine.
