Antihypertensives Flashcards
What alpha blockers are used in the treatment of hypertension?
- azosins
- Prazosin
- Doxazosin
- Terazosin
What non-specific beta blockers are used in the treatment of hypertension?
-lol’s
- Propanolol
- Carvedilol
- Pindolol
- Timolol
What specific beta blockers are used in the treatment of hypertension?
• Which are 2st generation? 3rd generation?
-lol’s
- Metoprolol (2nd gen)
- Atenolol (2nd gen)
- Bisoprolol (3rd gen)
- Nebivolol (3rd gen)
What groups of drugs affect sympathetic activity in the nervous system?
Alpha and Beta Blockers
What 4 ace inhibitors do we need to know?
-pril’s
- Captonopril
- Lisinopril
- Enalapril
- Ramipril
What 5 AT-R blockers do we need to know?
–sARTan’s
- Losartan
- Valsartan
- Irbesartan
- Telmisartan
- Candesartan
What drug acts as a renin inhibitor?
• Aliskerin
What are the 3 classes of Calcium Channel Blockers?
- Phenylaklyamine
- Benzothiazepine
- Dihydropyridine
What drug falls under the category of a phenylalklamine?
• Verapamil
What drug falls under the category of a benzothiazepine?
• Dilatiazem
What are the 4 Dihydropyridines?
-dipine’s
- Amoldipine
- Nifedipine
- Nicardipine
- Nimodipine
What 2 drugs act as alpha-2 agonists?
- Clonidine
* Methyldopa
What drugs act as Direct Vasodilators?
- Minoxidil
- Na-Nitroprusside
- Hydralazine
- Fenoldopam
Who should be put on blood pressure medicine according to JNC VIII?
Give Therapy
• Pts. older than 60 with 150/90
• Pts. under 60 with greater than 90 diastolic
Probably Don’t Give therapy
• Systolic of less than 140 is not
Alpha-1 Adrenergic Receptor Blockers
• Mechanism of Action
• Pharmacological Effects (specify by drug)
MOA:
• Block alpha-1 receptors on peripheral arteries and veins causing vasodilation
Phamacological Effects:
• PRAZOSIN - reduction in TPR and BP
• TERAZOSIN and DOXAZOSIN - Benign Prostatic Hyperplasia (BPH)
Alpha-1 Adrenergic Receptor Blocker
• Side effects
• Clinical Utility in HTN
Side Effects:
• First Dose Hypotension (orthostatic) so give at BEDTIME
Clinical Utility:
• NOT FRONT LINE IN TREATMENT OF HTN
Which of the Beta blockers are CARDIOSELECTIVE?
BisAM!!!
- Bisoprolol
- Atenolol
- Metoprolol (also lipid soluble)
Which of the Beta blockers are most LIPOPHILIC?
Most:
• Propanolol
• Metoprolol
Pretty Lipophilic:
• Pindolol
• Timolol
Which of the Beta blockers show ISA (intrinsic sympathomimetic activity)?
Pindolol (and acebutolol)
Agonizing Ace-Pin
Which Beta Blockers would you definitely not want to use on someone with asthma?
Any of the 1st generations or non-specific 3rd generations
- Propanolol
- Timolol
- Pindolol
What Beta blocker would you use in pheochromocytoma or in preeclampsia?
• Drug Selectivity?
• Administration?
Labetalol - given IV in emergencies
Selectivity: Non-selective ß; Alpha-1 selective
“Labor-talol”
Note: Non-specific alpha and beta blockers must be given in pheochromocytoma because of excessive catecholamine stimulation that would happen on unblocked receptors*
What is one of the best Beta blockers you could give someone with Congestive Heart Failure?
• Drug Selectivity?
• why?
Best Beta Blocker = Carvedilol
Selectivity: Non-selective ß; Alpha-1 selective
Why:
• Antioxidant (scavenges ROS) => Protects membrane from lipid Peroxidation
• REDUCES LDL uptake in to coronary vessels
Nebivolol
• Selectivity
• Extra Functions?
- BETA-1 SELECTIVE
* stimulates NO production for Vasodilation
For Beta Blockers with NO sympathomimetic activity what is there general function on:
• Heart
• Kidney
***what patient population benefits the most from the use of these drugs?
Heart:
Function to Block Beta-1 activity causing:
• Decreased HR (less active Funny Channels b/c less cAMP)
- Decreased Contractility (Calcium Channel and Calcium channel inhibitor not phosphorylated by cAMP dependent Kinsase)
- Reduced Cardiac Output
Kidney:
• Decreased Renin secretion from Juxtaglomerular App.
Most useful in patient with HIGH RENIN HYPERTENSION
Clinically, when are Beta blockers used?
• do they need to be administered with diuretics?
JNC says you shouldn’t generally use Beta Blockers as First line therapy and IF you do, then used 3rd generation (less side effects)
• NO - beta blockers CAN be administered with diuretics but this is not necessary
if they are given with a diuretic, then the effect is additive
In what cases would use of a Beta blocker be preferred to the use of other antihypertensives?
Beta Blocker HIGHLY PREFERRED in cases of:
• Myocardial Infarction (MI)
• Ischemic Heart Disease
• Congestive Heart Failure
PREFERRED in cases of:
• Hyperthyroidism
• Migraines
Specifically what Beta blocker would you used in Congestive Heart Failure?
- Carvedilol (reduction of LDL, and antioxidant effect)
* Metoprolol-XL (long acting)
What Beta blocker would you use in Open Angle Glaucoma?
Timolol
Besides use to prevent HTN, what can Beta Blockers be used for?
- Myocardial Infarction
- Congestive Heart Failure
- Open Angle Glaucoma
- Stage Fright
- Altering Memory
Which Beta Blockers have the most adverse effects?
• First and Second Generation
What are some side effects of using beta blockers?
4 major effects
- COLD EXTREMITIES (more alpha-1 acted on by Catelcholamines => peripheral constriction, more blood in central compartment)
- BRADYCARDIA (less AV nodal conduction)
- CNS EFFECTS (Bad Dreams), depression
- METABOLIC EFFECTS - Blocks glycogenolysis, Blocks HSL in adipocytes, increased LDL, Reduced HDL, Increased TGs
T or F: its okay to pull someone off their Beta blocker if they experience a lot of adverse effects?
False, you should taper the drug back slowly
What does ACE act on?
Angiotensin Converting Enzyme (ACE) works on… Angiotensin I
**Also acts on Bradykinin which is counterproductive to the overall effects of the drug because Bradykinin is important for vasodilation*
T or F: angiotensin II is the most potent vasoconstrictor we have.
True
How do the “prils” act to depress blood pressure?
prils = ACE inhibitors
- Prevent Angiotenin I conversion to Angiotensin II
- Depress Aldosterone (Temporary effect only)
- Increase RENAL blood flow but not GFR
- RENOPROTECTIVE - increased prostaglandin synthesis
What are the pharmacological effects of the ACE inhibitors?
- angiotensin effects inhibited, No BV thickening
- ARTERIES AND VEINS DILATED
- NO Postural HYPOTENSION
- CHF = increased longevity
Why is dilation of both arteries and vein important in CHF?
• why is postural hypotension not an issue?
CHF:
• ARTERIAL dilation = REDUCED afterload
• VENOUS dilation = INCREASED preload
Postural Hypotension:
• Baroreceptors are not effected so body can change vessel tone on standing
How can angiotensin cause venous thickening?
• Activation of PKC which acts as a growth factor
What are 5 effects of angiotensin II?
- Cardiac and Vascular Hypertrophy
- Release of ADH (antidiuretic hormone) from Hypothalmus
- Release of Aldosterone from Adrenal Cortex
- Systemic Vasconstriction
- Increase Thirst
Which of the Ace inhibitors are pro-drugs?
RamEn
Prils that require activation in LIVER
• Ramipril
• Enalapril
***Advantageous because of long half life
What are some important side Effects of ACE inhibitors?
- Hyperkalemia (monitor close in ppl. taking K+ or using K+ diuretics)
- Dry Cough (related to inhibition of bradykinin)
- Angioedema (also may be related to bradykinin)
- Fetotoxicity
- RENAL DYSFUNCTION (monitor SERUM CREATININE)
What would you substitute for an ACE inhibitor in a patient who experienced dry cough?
• Why?
- Angiotensin Receptor Blocker (ARB)
- ARB’s do not change the activity of ACE on Bradyknin
Could give to patient that experience ACE induced angioedema, BUT chance of Recurrence is 1/10
What is the MOA of the -sartans?
• Major Contraindication in all Sartans?
- Blockage of Angiotensin II Receptors
- Induce Vasodilation and increased Na+ and H2O secretion
Contraindication:
• FETOTOXICITY
Losartan
• Drug Class
• Unique Features
Drug Class:
• Angiotensin Receptor Inhibitors
Unique Features:
• PROMOTES Urinary excretion of Uric Acid
• Competitive TXA2 antagonist (thus, prevents platelet aggregation)
Which of the Calcium Channel Blockers would be most effective in the treatment of hypertension?
• Why?
• MOA of Calcium Channel Blockers?
• Name all 3 classes
Dihydropyridines = Most Effect because they act mostly on the VASCULATURE
MOA:
• Blockage of L-type Ca++ Channels prevents Smooth Muscle contraction
3 Classes:
• Dihydropyridines
• Benzothiazepines (Heart)
• Pheynlalkylamines (Heart)
What patients respond best to Blood Pressure therapy by Ca++ Channel Blockers?
Patients with LOW RENIN HYPERTENSION
- Elderly Patients - ESPECIALLY THOSE WITH SYSTOLIC HYPERTENSION
- African Americans
Dihydropyridine Effects on:
• Blood Pressure
• Heart
Blood Pressure - Reduced by smooth muscle relaxation (calcium channel blocked)
NO EFFECT ON HEART rate because no baroreceptor-mediated discharge
How does the action of clonidine and methyldopa differ from that of many other drugs that work on alpha and beta receptors?
- These drugs act mainly through the CNS
* Specifically they are alpha-2 agonists
When would you use clonidine in antihypertensive therapy?
• what are some of the adverse effects?
Tertiary Use in HTN (would be the 3rd drug you added to a combo. to lower BP)
Side Effects:
• Sedation (drowsiness, fatigue, erectile dysfunction)
• HYPERTENSION ON WITHDRAW
Clonidine
• MOA
• Agonists of Postsynaptic Adrenoreceptors in the Rostral Ventrolateral Medulla (RVLM)
- DECREASE sympathetic impulses from RVL Medulla to Heart and BVs
- DECREASE in peripheral Vascular Resistance and DECREASE in HR.
Hydralazine
• Drug Class
• MOA
• Side Effects
Drug Class:
• Vasodilator
MOA:
• Arteriolar Smooth Muscle Relaxer
• REFLEX sympathetic stimulation
• Increases Catacholamine/Renin Release
Side Effects:
• Tachycardia (from reflex sympathetic stimulation)
• DRUG INDUCED LUPUS (autoimmune rxn)
Fenoldopam
• Drug Class
• MOA
• Utility
Drug Class:
• Vasodilator
MOA:
• Partial Agonist of D1
Utility:
• Good in Hypertensive Emergencies
MINOXIDIL • Drug Class • MOA • Utlility • Adverse Effects
Drug Class:
• Vasodilatory
MOA:
• Opens up ATP K+ channels to Relax Smooth muscle
• ONLY ACTS ON ATERIOLES (no veins) causes REFLEX sympathetic stimulation => Renin/Catecholamine Secreteion
Utility:
• ONLY USED IN SEVERE HTN (very rarely used)
Adverse Effects:
• HIRSUTISM
Which of the vasodilators are sometimes used in preecampsia?
• Hydralazine
Why vasodilators often have to be used in combination with other drugs?
• what other drugs are they administered with?
- Reflex Sympathetic Stimulation = major problem for the vasodilators
- BETA blockers and Diuretics are typically administered to prevent the sympathetic system from kicking in and to attenuate the effects of hypervolemia (diuretics)
Nitroprusside
• MOA
•Difference between Nitroprusside and most vasodilators?
- Nitric Oxide Pro-drug
- Stimulates GUANYLATE CYCLASE in smooth muscles
- more cGMP = smooth muscle Relaxation
Nitroprusside stimulates BOTH arterial and venous relaxation
Nitroprusside
• Pharmacological Effects (CHF vs. Normal pts)
• Utility
• Side Effects
Pharm Effects:
• Reduction in TPR and Increased in Venous Pooling
• Normal people = Reduced CO
• Left Ventricular Failure = Increased CO
Utility:
• given IV in HYPERTENSIVE EMERGENCIES
Side Effects:
• Cyanide Accumulation in patients with RENAL FAILURE
How useful are diuretics in the treatment of HTN?
• Most common diuretic?
- Very Effective - they can either be used alone or in combination with other drugs
- MORE effect that CCB (calcium channel blockers) or ACE inhibitors
Most Common:
• Thiazide-Type Diuretics
What groups of Hypertensive patients would you want to give Diuretics to in addition to other therapies?
Pts. with Edematous Conditions
• Heart Failure
• Renal Insufficiency
Pts. with Low Renin HTN
• AFRICAN AMERICANS
• OLD PEOPLE
Why might a patient respond as expected to thiazide diruretics?
- May eat too much Sodium
* May not have renal capacity to excrete sodium (old ppl)
Over how many days should you taper the dose of a Beta Blocker?
• 10-14 days
What is the MAJOR advantage to using a beta blocker to treat HTN?
• Protection is conferred against Coronary Artery Disease as well
**Usefule in hyperthyroidism, migraine, and glaucoma
What is the 1st line therapy against essential hypertension?
• Ideal patient to use these drugs on
Ideal Patient:
• Young and Middle Aged Caucasians
- ACE Inhibitors
- ARBs
In what patients is it particularly necessary to administer a Thiazide along with their ACE inhibitor?
• African Americans
*Typically you will want to use a Calcium Channel Blocker in this population
T or F: Beta blockers are 1st line antihypertensive therapy for people with CHF.
False, ACE inhibitors and ARB’s should be 1st line antihypertensive therapy in these patients
ALSO 1st LINE THERAPY IN PATIENTS WITH NON-DIABETIC NEPHROPATHIES or CHRONIC KIDNEY DISEASE*
In what cases would you defer from using ACE inhibitors, Renin inhibitors, and ARB’s as 1st line therapy?
- People that Hyperkalemic
* Pregnant women/ANY woman of CHILDBEARING age
What are the 4 Dihydropyridine calcium channel blockers?
• Which SHOULD NOT be used in treatment of HTN?
• why not?
Amoldipine
Nicardipine
Nimodipine
Nifedipine***
*Don’t use Nifedipine - its too SHORT ACTING
T or F: if someone is hypertensive you’ll want to start them on the full effective dose immediately.
False, must buildup slowly or these people will get problems with Sexual Dysfunction and Headaches etc.
