Pharm - 11: Drugs Used In Hypertension

Front 1

What is the definition of Hypertension?

Back 1

Persistent Diastolic > 90 mmHg and Systolic > 140 mmHg

Front 2

What are the stages of HTN?

Back 2

Pre-HTN: 120-139 Systolic or 80--89 Diastolic; No target-organ damage. Can be >140/90 occas.

Stage 1: Resting BP S: 140-159 or D: 90-99

Stage 2: Sustained resting BP S: >/=160 or D: >/=100

Front 3

What is the hydraulic equation for Blood Pressure?

Back 3

CO x TPR = BP

Drugs that decrease CO or TPR will decrease BP

Front 4

Sympatholytic agents

Back 4

Methyldopa, Clonidine, guanfacine, alpha blockers, B blockers, Ganglion blockers, Postganglionic adrenergic blockers
-----
Decrease TPR or CO

Front 5

Diuretics

Back 5

Loop and Thiazide Diuretics
-----
Decrease volume

Front 6

Vasodilators

Back 6

Hydralazine, Minoxidil, Sodium Nitroprusside, Diazoxide, Ca channel blockers.
-----
Decrease TPR

Front 7

Angiotensin antagonists: ACE Inhibitors + Ang II Receptor blockers

Back 7

Captopril, Enalapril, Lisinopril, Losartan
-----
Decrease TPR and Volume (by decreasing Aldosterone secretion)

Front 8

MOA on: Sympathetic Nerve Terminals

Back 8

Guanethidine
Reserpine

Front 9

MOA on: B-Receptors of Heart

Back 9

Propranolol + other Beta blockers

Front 10

MOA on: Angiotensin Receptors of Vessels

Back 10

Losartan

Front 11

MOA on: Alpha-receptors of Vessels

Back 11

Prazosin and other Alpha1 blockers

Front 12

MOA on: Vasomotor Center

Back 12

Methyldopa
Clonidine

Front 13

MOA on: Sympathetic Ganglia

Back 13

Trimethaphan

Front 14

MOA on: Vascular Smooth Muscle

Back 14

Hydralazine
Minoxidil
Nitroprusside
Diazoxide
Verapamil
Other Ca2+ Channel blockers

Front 15

MOA on: Kidney Tubules

Back 15

Thiazides etc.

Front 16

MOA on: B-receptors of JG cells that release Renin

Back 16

Propranolol adn other B-blockers

Front 17

MOA on: ACE

Back 17

Captopril + other ACE inhibitors

Front 18

Sympathoplegics reduce...

Back 18

Venous tone
HR
Contractile Force of the Heart
CO
TPR

Front 19

What Compensatory Effects occur when giving antiHTN Drugs?

Back 19

Increased SNS Tone ---> Tachycardia
---------------
Increased Renin ---> Salt and water Retention

Front 20

What are the different Kinds Sympathoplegics?

Back 20

CNS-Active Agents
Ganglion-Blocking Drugs
Postganglionic Sympathetic Nerve Terminal Blockers
Adrenoceptor Blockers

Front 21

What are the 5 main classes of drugs used for hypertension?

Back 21

Diuretics
Sympatho-blockers
Vasodilators
Angiotensin Antagonists
Renin inhibitors

Front 22

Are most cases of HTN primary or secondary?

Back 22

Primary or Essential (Unknown) HTN

Front 23

What are some primary causes of HTN

Back 23

Pheochromocytoma
Coarctation of aorta
Renal vascular disease
Adrenal cortical tumors/Cushings

Front 24

What are the main goals when prescribing and antihypertensive?

Back 24

Reduction of Blood volume, sympathetic tone, vasc. smooth muslce tone, and angiotensin effects

Front 25

Which diuretics are mainly used for mild hypertension?

Back 25

Thiazides

Hydrochlorothiazide

Front 26

Which diuretics are used for moderate, severe, and malignant hypertension?

Back 26

Loop Diuretics

Furosemide

Front 27

When do thiazides achieve their maximum antihypertensive effect?

Back 27

at doses BELOW those required for max. Diuretic effect

Front 28

What Compensatory Responses do diuretics have when used for HTN

Back 28

Minimal campensatory responses

Front 29

What are the side effects seen with Diuretics?

Back 29

HYPOkalemia

Front 30

What are Clonidine, methyldopa, and guanfacine?

Back 30

CNS-Active Agents

Front 31

MOA of CNS-Active Agents

Back 31

Alpha 2- Selective Agonists

Act in the CNS to inhibit sympathetic vasomotor centers. When given i.v. or topically (nasal spray) they cause vasoconstriction, but when given orally, the accumulate in teh CNS and reduce SNS & BP.

Front 32

What is the active form of methyldopa?

Back 32

get converted to Methylnorepinephrine in teh brain

Front 33

In general, what is the main compensatory response of sympathoplegics?

Back 33

Salt and water retention

Front 34

What happens if you suddenly stop use of Clonidine?

What would you use to treat this?

Back 34

Rebound Hypertension

Use Phentolamine (alpha-blocker), or re-start clonidine

Front 35

What is the main side effect of Clonidine?

Back 35

Dry mouth

Front 36

What are the main side effects of Methyldopa?

Back 36

Hemolytic anemia
+ Coombs Test
Sedation

Front 37

What class of drugs are Hexamethomium and trimethaphan?

Back 37

Ganglion-Blocking Drugs

Nicotinic blockers that act in the ganglia

Efficacious, but lots of adverse effects

Front 38

Why aren't ganglion blockers used anymore? What side effects do they cause?

Back 38

They block both
PNS: Blurred vision, constipation, urinary hesitancy, sexual dysf
&
SNS:Sex dysf. Orthostatic HYPOtension

Front 39

What are the 2 Post-ganglionic SNS Terminal Blockers?

Back 39

Reserpine
&
Guanethidine

Front 40

MOA of Reserpine

Back 40

Blocks STORAGE of catecholamines by blocking the vesicle transporter that transports the NE/Epi into the vesicle

Front 41

MOA of Guanethidine

Back 41

Blocks RELEASE of catecholamine stores by blocking vesicle fusion with axon terminal membrane

Front 42

Major compensatory response of post-ganglion SNS blockers

Back 42

Salt and water retention

Front 43

Are Reserpine and guanethidine still used?

Back 43

Reserpine sometimes in low doses as adjunct to other drugs.
Guanethidine rarely

B/c of severe adverse effects

Front 44

Side effects of Reserpine (in low dose)

Back 44

DEPRESSION
Diarrhea
nasal stuffiness
sedation

Readily enters CNS

Front 45

Side effects of Guanethidine

Back 45

Orthostatic hypotension
Sexual dysfunction

Doesn't readily enter CNS

Requires Uptake1, so drugs that block Uptake1 interfere w/its action (Cocaine, Tricyclic antidepressants)

Front 46

Prazosin =

Back 46

Alpha1-selective blockers

Front 47

Propranolol =

Back 47

Beta-blocker

Front 48

Alpha-blockers reduce...

Back 48

Vascular resistance and venous return

Front 49

Main compensatory responses of Alpha1 blockers and Beta-blockers

Back 49

Alpha1: Salt & Water retention + slight tachycardia

Beta-blockers: Minimal comp. responses

Front 50

Why are NON-selective alpha blockers of NO use for HTN?

Back 50

They cause too many compensatory effects like tachycardia

Front 51

Side effects of Alpha1 blockers

Back 51

Not many, just Orthostatic hypotension usu with the first few initial doses.

Front 52

Beta-blockers reduce...

Back 52

CO initially
After a few days, start to reduce vasc. Resistance

Front 53

What effect do Beta-blockers have on teh kidney?

Back 53

Reduce Renin release from the Kidney, which might cause the deacreased vasc. Resistance after a few days of use

Front 54

How would a Beta-blocker affect your CBC, Blood Chem or Lipid panel results?

Back 54

Slightly Increased Glucose, LDL, Triglycerides

Low HDL levels

Front 55

Side effects of Beta blockers

Back 55

Sleep disturbances
Sedation
Impotence
Cardiac disturbances
Asthma

Front 56

How do the "Vasodilator" class of antihypertensives work?

Back 56

directly on the smooth muscle, by non-ANS ways.

Front 57

What are the 4 mechanisms used by Vasodilators

Back 57

- NO release
- Opening of K+ channels (hyperpolarization)
- Blockade of Ca2+ channel
- Activation fo D1 dopamine receptors

Front 58

Which Vasodiltors have marked Compensatory responses?

Back 58

Hydralazine: Na & H2O Retention + Marked Tachy

Minoxidil: Marked Na&H2O Retention + Marked Tachy

Nifedipine: Minor
Nitroprusside: Na&H2O ret.

Front 59

Hydralazine and Minoxidil have more of an effect on

Back 59

Arterioles

Front 60

What kind of HTN are Hydralazine and Minoxidil used for?

Back 60

Hydralazine for Chronic HTN

Minoxidil for Severe HTN (b/c very efficacious)

Front 61

MOA of Hydralazine

Back 61

Releases NO from endothelial cells

Front 62

Major Toxicity of Hydralazine, and at what dose?

Back 62

Drug-induced Lupus at doses ABOVE 200 mg/d

Reversible, and doesn't have the renal effects

(+ Compensatory tachy and salt,water ret.)

Front 63

What is Minoxidil's metabolite?

Back 63

Minoxidil sulfate

Minoxidil = prodrug

Front 64

MOA of Minoxidil

Back 64

Potassium channel opener that hyperpolarizes and RELAXES vascular smooth muscle.

Front 65

Toxicities of Minoxidil

Back 65

Hirsutism & Pericardial effusion

(+ Comp. markes Tachy + marked Salt,water ret.)

Front 66

What kind of HTN are Calcium channel blockers good for?

Back 66

Chronic HTN

They are effective vasodilators

Front 67

MOA of Calcium Channel blockers

Back 67

Decreased Intracellular [Ca2+] so decrease contractility of smooth muscle --> Vasodilation

Front 68

Why are Ca2+ Channel Blockers preferred over hydralazine and minoxidil?

Back 68

Less Compensatory responses

Front 69

Side effects of Ca2+ Channel blockers

Back 69

Constipation
Cardiac disturbances
FLUSHING

Front 70

Examples of Ca2+ Channel blockers

Back 70

NIFEDIPINE
Verapamil
Diltiazem

Front 71

What kind of HTN are Sodium Nitroprusside and Diazoxide used for? How are they adminitered?

Back 71

Hypertensive EMERGENCIES
and CHF

Parenterally
Nitroprusside must be infused continuously - short DOA

Front 72

MOA of Sodiun Nitroprusside

Back 72

Releases NO from itself

NO stim. Guanylyl cyclase to INCREASE [cGMP] in smooth muscle --> decreased intracell. Ca --> relaxation of smooth muscle.

Both arterial and Venous

Front 73

Toxicity of Nitroprusside

Back 73

CYANIDE, THIOCYANATE tox.

XS hypotension, tachy
Metaboloic acidosis

Front 74

How do you treat Cyanide/thocyanate toxicity?

Back 74

Rhodanese

An enzyme that combines cyanide and thisulfate --> Thiocyanate, a less toxic metabolite

Front 75

Sx of Thiocyanate toxicity

Back 75

Weakness
psychosis
muscle spasm
convulsions

Front 76

MOA od Diazoxide

Back 76

Opens Potassium channels -> hypoerpolariaze -> prevent arterial smooth muscle contraction

Front 77

What other action does Diazoxide have?

Back 77

It prevents insulin release from the Pancreas, so can be used to treat hypoglycemia caused by Insulin-producing tumors.

Front 78

Side effects of Diazoxide

Back 78

Hypotension
Reflex Tachycardia
Hyperglycemia

Front 79

What is the clinical use of Fenoldopam?

Back 79

For Hypertensive emergencies

Front 80

MOA of Fenoldopam

Back 80

Dopamine D1 receptor Activation to cause quick, marked arteriolar vasodilation.

Short DOA, 10mins

Front 81

What are the 2 types of Angiotensin antagonists?

Back 81

ACE Inhibitors
&
Angiotensin II receptor blockers

Front 82

What is Captopril?

Back 82

ACE Inhibitor

Front 83

What are the other names of ACE?

Back 83

kininase II

peptidyl dipeptidase

Front 84

ACE inhibitors decrease levels of what? and Increase levels of what?

Back 84

DECREASE: Ang II, and aldosterone

INCREASE: Bradykinin; endogenous vasodilators of the kinin family

Front 85

ACE inhibitors are absolutely contraindicated in who?

Back 85

Pregnant pts.

Front 86

Side effects of ACE inhibitors

Back 86

- Cough
- Renal damage in pts w/existing renal vasc. disease
- Renal damage in Fetus

*They PROTECT the Diabetic kidney*

Front 87

What is Losartan?

Back 87

Ang II receptor blocker

Competetively inhibits Ang II at the AT1 receptor sire

Front 88

What is the advantage of Ang II inhibitors?

Back 88

Less incidence of cough

Front 89

Ang II inhibitors are contraindicated in in who?

Back 89

Pregnant pts.

They still cause Fetal renal toxicity like ACE inhibitors

Front 90

What is Aliskiren?

Back 90

Inhibits Renin's action on its substrate, Angiotensinogen

Thus decreases Ang I, and thus Ang II as well

Front 91

Toxicities of Aliskiren

Back 91

Headache
Diarrhea

Front 92

What is the normal physiological role of ACE?

Back 92

Converts Ang I (inactive) to Ang II
&
Converts Bradykinin to Inactive metabolites

Front 93

What are the effects of Ang II and Bradykinin on the vasculature?

Back 93

They are Active Vasoconstrictors

So, ACE promotes the activation of Ang II, and the inactivation of Bradykinin

ACE inhibitors block ACE, so cause an accumulation of Bradykinin, which causes cough.

Front 94

How do Angiotensin inhibitors in general effect the kidney?

Back 94

They cause Potassium accumulation, b/c you're decreasing the levels of Aldosterone (which normally causes Na reabsorption and K+ secretion) so w/o Aldost. you're keeping your K in

Front 95

What is "Stepped Care"

Back 95

Treating pts with severe HTN with lower doese of a bunch of drugs, to lessen the compensatory effects of 1 drug at high doses.

1.) Lifestyle measures: Na restriction, wt. loss
2.) Diuretics
3.) Sympathoplegics: usu. an alpha or an a, B combined - CARVEDILOL
4.) ACE Inhibitors
5.) Vasodilator: Ca Channel blocker

Front 96

Which drug reduces the tachycardia induced by hydralazine?

Back 96

Propranolol

Front 97

What is monotherapy used for?

Back 97

Mild and moderate HTN

Ace inhibitor
Ca2+ channel blocker
a-B combined blocker

Front 98

What drugs do older pt's respond better to?

Back 98

Diuretics and B-blockers

than to ACE inhibitors

Front 99

What drugs do African Americans respond better to?

Back 99

Diuretics and Ca2+ channel blockers

than ACE inhibitors

Front 100

What is Malignant Hypertension?

Back 100

Rapidly progressing severe HTN with associated target-organ vascular damage: Hypertensive Encephalopathy, retinal hemorrhages, Angina

Front 101

How is malignant HTN treated?

Back 101

Initially you want to reduce the BP by 25% (to avoid hypoperfusion of the brain) with i.v. diazoxide, sodium nitroprusside, and labetalol.

Then you can remove XS fluid with loop diuretics or if needed, dialysis.

Front 102

* Inhibit angiotensin-converting enzyme (ACE)

Back 102

* ACE Inhibitors

Front 103

* Captopril and enalapril (-OPRIL ending) are

Back 103

* ACE Inhibitors

Front 104

* SE of ACE inhibitors

Back 104

* Dry cough, hyperkalemia

Front 105

* ACE inhibitors are contraindicated in

Back 105

* Pregnancy and with K+

Front 106

* Losartan and valsartan block

Back 106

* Angiotensin receptor

Front 107

* Angiotensin receptor blockers do NOT cause

Back 107

* Dry cough

Front 108

* Agents that block L-type calcium channel

Back 108

* Calcium Channel blockers

Front 109

* CCB contraindicated in CHF

Back 109

* Verapamil

Front 110

* CCB with predominate effect on arteriole dilation

Back 110

* Nifedipine

Front 111

* SE of CCB

Back 111

* Constipation, edema, and headache

Front 112

* Agents that reduce heart rate, contractility, and O2 demand

Back 112

* Beta-blockers

Front 113

* B-blockers that are more cardioselective

Back 113

* Beta 1 selective blockers

Front 114

* Cardioselective Beta 1-blockers

Back 114

* Atenolol, acebutolol, and metoprolol

Front 115

* Beta-blockers should be used cautiously in

Back 115

* Asthma (bronchospastic effects), diabetes (block signs of hypoglycemia) and peripheral vascular disease

Front 116

* Non-selective Beta-blocker also used for migraine prophylaxis

Back 116

* Propranolol

Front 117

* SE of beta blockers

Back 117

* Bradycardia, SEXUAL DYSFUNCTION, decrease in HDL, and increase in Triglycerols (TG)

Front 118

* Alpha 1selective blockers

Back 118

* Prazosin, terazosin and doxazosin (-AZOSIN ending)

Front 119

* Non-selective Alpha1blockers use to treat pheochromocytoma

Back 119

* Phenoxybenzamine

Front 120

* For rebound HTN from rapid clonidine withdrawal

Back 120

* Phentolamine

Front 121

* A1a-selective blocker with no effects on HTN used for BPH

Back 121

* Tamsulosin (Flomax)

Front 122

* SE of alpha blockers

Back 122

* Orthostatic hypotension (especially with first dose) and reflex tachycardia

Front 123

* Presynaptic Alpha 2 agonist used in HTN, and acts centrally

Back 123

* Clonidine, and methyldopa

Front 124

* SE of methyldopa

Back 124

* Positive Comb's test, depression

Front 125

* Methyldopa is contraindicated in

Back 125

* Geriatrics due to its CNS (depression) effects

Front 126

* SE of clonidine

Back 126

* Rebound HTN, sedation, dry mouth

Front 127

* Direct vasodilator of arteriolar smooth muscle

Back 127

* Hydralazine

Front 128

* SE of hydralazine

Back 128

* Lupus like syndrome

Front 129

* Arterial vasodilator that works by opening K+ channels

Back 129

* Minoxidil

Front 130

* SE of minoxidil

Back 130

* Hypertrichosis

Front 131

* IV Drug used Hypertensive Crisis

Back 131

* Nitroprusside

Front 132

* Nitroprusside vasodilates

Back 132

* Arteries and veins

Front 133

* Toxicity caused by nitroprusside and treatment

Back 133

* Cyanide toxicity treated with sodium thiosulfate