Block 2-Reymann (AntiHypertensive)

Question 1

Classes of drugs

Answer 1

• 5 classes:

1. Diuretics
2. Beta-Adrenoreceptors ANTAgonists
3. Ca-channel blockers
4. Inhibitors of Angiotensin
5. Alpha adrenergic blockers (?)

• Hypertension is NOT an isolated disease &linked w:
• increased coronary artery
• MI
• Left vent hypertrophy
• Also Stroke & peripheral vascular disease
• All lead to CV remodeling in LV dysfunction

Question 2

Resperine (obsolete)

Answer 2

• _PK: _
• Oral with 1/2 life of 24 hours & can presist up to 6 weeks
• PD:
• Depletes biogenic amines from neuronal vesicles ^{<u><strong>(ALL NT)</strong></u>} by inhibiting re-uptake
• SE:
• Denervation of **SNS & PSNS **
• Nasal congestion
• Hypersecretion ^{<u><strong>(BAD FOR ULCERS)</strong></u>}
• Bronchoconstriction
• mental Depression
• Parkinsons
• SUICIDE
• Use:
• Not used due to long term presistance (6weeks)

Question 3

Clonodine (alpha-2) PK&PD

Answer 3

• Alters sympathetic activity-GI coupled-LESS NE = Lowered^{<strong> B1 effect</strong>}
• Alpha-2 autoreceptor sympathomimetic ^{<u><strong>(mimcs)</strong></u>} 2nd choice in hypertension treament
• PK:
• **Oral, IV, & Patch **
• !/2 life of 8-12 hours secreted renally
• PD:
• Centrally mediated hypotensive effects
• Reduces CO - Reduce sympathetic tone, relax of venous, reduction of peripheral resistance
• Renal blood flow maintained = Initial hypertensive episode^{<u><strong> (renin-angiotensin)</strong></u>}
• CNS effects
• Body adapts w/rebound effects ^{<u><strong>(Lowered TPR &amp; HR)</strong></u>}

Question 4

Clonodine (alpha-2) Use&SE

Answer 4

• SE:
• Seen in high doses due to ^{<strong>blockage of SNS</strong>}
• BradyCardia
• AV block
• Functional cardiac failure (left vent activity)
• Dry mouth
• Drowsiness
• Constipation
• Tricyclic Anti-depress lower effects of Anti-hyper effects
• Use:
• 2nd line for hypertension
• Treat withdrawl symptoms heroin, alcohol,benzos ^{<strong>(OPIATES)</strong>}
• prevention of alcoholic delirium
• adjunct w/analog-sedation need less of other drug ^{<u><strong>(DEXMEDETOMIDINE)</strong></u>}

Question 5

Methyldopa (alpha-2)

Answer 5

• Alters SNS w/GI coupled = LESS NE lowered Beta-1
• Centrally acting (^{<strong>act on brain from sending signals</strong>}) anti-hypertensive SAFE in pregers
• PK:
• Oral 1/2 4-6 hours
• up to 24 hours MOA
• PD:
• Centrally mediated hypotensive effects similar to clonodine (^{<u><strong>alpha 2 autoreceptor</strong></u>})
• SE:
• same as clonodine
• Coombs test MAY turn + for pregers

Question 6

Prazosin, Terazosin, Doxazosin (A1 blockers)

Answer 6

• PK:
• Oral & IV
• 1/2 life 3-4 hours (prazosin)
• OR 22hours (doxazosin)
• PD:
• Blocks alpha-1 receptors = Dialate vessels
• reflex tachycardia (B1 still works) due to lowered Arterial & venous resistance
• NO effect on Pre-synap a-2 autoreceptor
• Decrease tone on urinary sphinctors = Treat BPH
• SE:
• First dose phenomenon-Sensitive when given drug frist time = Orthostatic hypertension ^{<u>LEAD TO MI</u>}
• Dizziness & palpatations
• Test + for ANA
• Good effect on Lipid profile

Question 7

Hypertension & Diuretics

Answer 7

• Thiazide used for hypertension Even in small doses
  Use K+ supplements or combine w/K+sparring dieuretics WATCH Hyperkalemia
• Keeping pt on dry weight may further help bypertension COULD lead to dehydration:
• Mental confusion
• Aggravate COPD
• Peripheral arterial occulsive disease
• SE:
• Hypokalemia
• Hyperuricaemia
• Imparied glucose tolerance
• Hyperlipidemia (chornic usage)

Question 8

Beta Blockers

Answer 8

• Non-selective: Propranalol
• Contraindicated in pregers due to B2 in uterus = dialation premature delivery
• Contraindicated in Diabetes = hypoglycemic episodes going unseen
• Small doeses of B-blockers good for CHF
• Beta 1 (little effect on B2): Atenolol & metoprolol
• Alpha & Beta 1 blocker: Labetalol ^{<u><strong>(intensive care)</strong></u>} 4 isomers
• Beta 2 agonist-lower BP BUT does NOT constrict peripheral vessels
• Alpha & Beta 1 blocker: Carvedilol (not perscribed as often)-USED in remote cases for ^{<u><strong>lipid profile</strong></u>}
• Beta 1 agonist: Esmolol ^{<u><strong>(short acting) </strong></u>}emergency cases

Question 9

Comparing Beta to Alpha (Anti-hypertensive)

Answer 9

• _A-blockers: _
• Better @ managing lipid profile ^{<u><strong>(person w/high cholesterol)</strong></u>}
• A-1 blockers do NOT affect insulin sensitivity & will NOT cause cold extermity syndrome
• B-blockers:
• tend to increase LDL & decrease HDL = Increase TAGs
• Do NOT cause orthostatic hypotension or reflex tachycardia
• OVERALL beta-blockers are the dug of choice

Question 10

CCB (Ca+2 channel blockers) PK&PD

Answer 10

• Drugs: Verapamil, Dilitiazam, Nifedipine
• Given to pt with contraindications for B-blockers^{<u><strong> (ASTHMATIC, DIABETICS, PREGERS)</strong></u>}
• PK:
• Oral & IV
• Highly bound to serum proteins
• Hepatic metab & renal excretion
• PD:
• Blocks L-type Ca+2 channels ^{<u><strong>(work on phase2 plateu)</strong></u>}-Verapamil
• Cardiodepressant - Vasodialator ^{<u>(dilitiazam)</u>}

Question 11

CCB (Ca+2 Channel blockers) SE & use

Answer 11

• SE:
• **Dihydropyridines (Nifedipines)- **
• EXCESSIVE vasodilation = reflex tachycardia
• Tachycardia = Dizziness, headache, flushing, digital dysaethesia (numb), Edema, constipation
• Verapmil & Dilitiazem-
• Cardio depressents = Bradycardia due to NO reflex ^{<u><strong>(Antiarrthymthmic</strong></u>})
• USE:
• All used to treat hypertension
• Treat Arrythmia ^{<strong>(Verapmil & Dilitiazem)</strong>}
• Treat Angina with ALL 3 depends on what outcome u want ^{<u><strong>(bradycardia or NOT)</strong></u>}

Question 12

CCB & Beta

Answer 12

• Chronic use of CCB can result in increased risk of MI due to rebound effects-
• Aburptly STOP or forget dosage
• Can be treated with longer 1/2 lives OR gradual onset
• Amlodipine^{<u><strong><em><strong> </strong></em>(dihydropyridine)</strong></u>} long acting w/SLOW onset
• Beta & CCB routinely used in combo in treating hypertension-
• Combining the 2 = LESS of each drug leading to LESS effect of substance LOAD on BODY
• Amlodipine(vasodialation) decrease in contractile force ^{<u><strong>WHICH</strong></u>} can lead to reflex Tachycardia
• Block reflex w/B-Blocker =OVERadditive Effect ^{<u><strong>(override bodies natural mech)</strong></u>}

Question 13

Inhibitors of Angiotensin

Answer 13

• Can be used instead of CCB/B-blockers
• Include ACE-inhibitors & AT1-blockers
• AT-1 blockers Creates a perfusion shunt = Activation of Angio 2
• Vasocontriction
• Aldosterone secretion
• NE release
• Prodrugs=Lostratan/Valsar_tan _
• ACE inibitiors:
• Vasodialation-Decrease aldesterone-Decrease NE release
• BradyKinin is INACTIVE by Kinase 2 (ACE)
• Bradykinin = Vasodialation (Prostacyclin, NE, edothelial factors)-Inflammation
• Prototype Drug=Captopril, Enalapril, lisinopril

Question 14

ACE-Inhib (Captopril) PK & PD

Answer 14

• PK:
• Oral & Renal elimination
• PD:
• Angiotensin 2 Antagonism (blocks)
• Decreased vasoconstriction-NE decrease-Decrease in aldosterone
• Brady kinin=Vasodialation
• NE decrease=
• NO reflex tachy or CO change
• NO water & sodium retention
• Reduction in SNS tone

Question 15

ACE-Inhib (Captopril) SE&CI

Answer 15

• SE:
• Hypotension
• Dry cough & bronchospasm due to ++ of bradykinin
• Skin Rashes
• Angioneuroticedema^{<u><strong>(HIVES)</strong></u>}, neutropenia ^{<u><strong>(LOW NEUTROPHILS)</strong></u>}, leukipenia^{<u><strong>(DECREASED WBC)</strong></u>} DUE to inflammation via prostaglandins & bradykinin system
• Taste perversion
• Hyperkalemia (inhibition of aldesterone)
• Protenuria
• CI:
• Pts w/HIstory of renal artery stenosis & renal filaure
• Angioedema, Asthma, COPD
• Pregers cause oligohyrdaminion ^{<u><strong>(def of)</strong></u>}

Question 16

ACE-Inhib (Captopril) Interactions

Answer 16

• Drug interactions:
• NSAIDS block bradykinin pathway=reduce anti-hypertensive ^{<u><strong>(vasodialtion)</strong></u>}
• K+ sparing diuretics = accelerated HYPERkalemia
• Increased LVLs of Digoxin & Lithium
• Toxicity:
• Hypotension w/o tachy due to NE depression
• Therapeutic Drug combo:
• ACE inhib + K+wasting diuretic (low doses)
• K+ wasting diuretics = increased ACE system effect
• Over-additive antihypertensive effect

Question 17

ACE-inhib (Enalapril/Enalaprilat)

Answer 17

• Prodrug=Enalapril
• PK:
• Oral 1/2 life of 11hrs
• Renal elimination
• Enalaprilat given IV in hypertensive Emergency
• PD:similar to captopril
• SE:
• More potent w/^{<u><strong>SLOWER </strong></u>}onset & ^{<u><strong>LONGER </strong></u>}duration
• NO SULFA groups
• NO taste pervertion
• Fosinopril & Moexipril = HEPATIC elimination

Question 18

Use of ACE inhibitors

Answer 18

• ACE-Treatment of:
• Hypertension
• CHF
• Post MI (due to dead cells around the infarction generate Arrythmias)
• B-Blockers preferred POST MI but for Pts with contraindication ^{<u><strong>(asthma/Diabetics) </strong></u>}ACE inhibit given
• Progressive renal disease=Diabetic neuropathy
• AT-1 & AT-2 Blockers Treat:
• AT-1-
• normally mediate vasocontriction, NE, aldosterone
• Helps w/Vascular & cardiac remodeling(^{<u><strong>chronic CHF/Hypertension)</strong></u>}
• AT2-_ANTI-prolif effect _

Question 19

Angtiotensin 2/AT-1 Blocker (Losartan)

Answer 19

• Direct acting
• PK:
• Oral
• 1/2 life 2hrs active metabolite 6-9hrs
• Hepatic elimination
• PD:
• Like ACE inhib BUT no effect on bradykinin
• Decreased vastocontriction, decreased NE release, Decreased aldosterone
• _SE: _
• LIke ACE NO bradykinin related issues (^{<u><strong>NO angioedema &amp; NO dry cough)</strong></u>}
• CI:
• Renal artery stenosis = Renal failure
• Pregers

Question 20

Contraindication (COPD & Asthma)

Answer 20

• NO B-blockers (propanonlol)
• NO Ace-inhibitors (Enalapril)
• Reason:
• Induction of broncospams
• Dry cough
• USE AT-1 blockers (Losartan), CCB, or Alpha Blockers

Question 21

Contraindication (bradycardia)

Answer 21

• NO clonidine (beta)
• B-blockers
• Verapamil (CCB)
• Dilitiazem (CCB)
• Reason:
• Aggrevation & risk of Adam’s Stokes Syndrome (passing out due to heart arrthymia)

Question 22

Contraindication (Diabetes & gout)

Answer 22

• DM:
• NO thiazides
• NO unselective B-blockers (colonopin)
• Reason:
• Reduce glucose tolerance
• Reduce symptoms of Hypoglycemia
• Gout:
• NO Thiazides
• Reason:
• Reduction of uric acid secretion=GOUTY attack

Question 23

Contraindication (Coronary & peripheral artery disease)

Answer 23

• CAD:
• NO Hydralazine (vasodialator)
• NO Prazosin (Alpha-1 blocker)
• Reason:
• Triggered Angina-pectoris VIA reflex tachy
• PAOD:
• NO beta blockers
• Reason:
• Triggered periphery artery occulsion disease