Ca Antagonists; Alpha And Beta Adrenergic Blocking Agents

Front 1

what are calcium channel-blocking agents?

Back 1

Ca antagonists, Ca channel blockers

Front 2

Give 3 examples of calcium channel-blocking agents.

Back 2

Cardiac ~ verapamil, diltiazem

Vascular ~ dihydropyridines (dipines). All Ca blockers
e.g. amlodipine, felodipine, isradipine, nifedipine

Front 3

mechanism of action of calcium channel-blocking agents? (5)

Back 3

1. Ca channels (L-type) control Ca entry
2. Ca regulates force of contraction
3. Blocks L-type Ca channels, ↓ entry of Ca
4. Vascular effect: ↓ resistance of BV
5. Cardiac effect: ↓ force of contraction

Front 4

Properties of calcium channel-blocking agents

Back 4

1. Slight difference between Ca channels in smooth muscle & cardiac cells. Dihydropyridines are vascular selective. Verapimil & diltiazem are cardiac selective (also some vasc. effect)

2. orally active

3. some: high plasma protein binding
(potential interaction: compete w. other drugs for binding)

4. most undergo extensive metabolism
(potential interaction: compete in drug metabolism)

5. Nifedipine is short acting: only sustained release formulation used

Front 5

Uses of calcium channel-blocking agents
A. (3)
B. (2)

Back 5

A. vascular effects
1. angina (relax smooth muscle, ↓ spasm)
2. HT (vascular effect: vasodilation. cardiac effect: affected calcium channel ↓ contractility so ↓ cardiac output; thus both effects: ↓ BP)
3. combine w. diuretics for HT if needed

B. cardiac effects
1. abolish reentrant supraventricular tachycardia,
(slow conduction in atria & AV node ↑ conduction block, so abolishing reentrant arrhythmia)
2. control ventricular rate in atrial fibrillation & flutter
(slow AV conduction, ↑ AV block.

Front 6

Side effects of CCB
A (4)
B (3)

Back 6

A. vascular (all due to vasodilation)
1. hypotension
2. dizziness, flushing
3. reflex tachycardia
4. ankle oedema [precapillary dilatation ↑ filtration]

B. cardiac
1. cardiac depression [↓ Ca influx in heart]
2. bradycardia, cardiac arrest, AV block, heart failure
3. care when used with B blockers (worsens cardiac output & contractility)

hence we usually use vascular blockers

Front 7

give example of a adrenergic blocking agents (a adrenoceptor antagonists, a blockers)
(4)

Back 7

-osins: Prazosin, Doxazosin, Terazosin
Phentolamine (older, non-selective)

Front 8

Mechanism of action & properties of a adrenergic blocking agents

Back 8

1. a1 is for vasoconstriction of BVs
2. block a1 adrenoceptor in arteries and veins, dilating both arteries and veins
3. commonly used are competitive antagonists
4. phentolamine non-specific, blocks a1 & a2
5. others are selective for a1 receptor

Front 9

how are a adrenergic blocking agents used? (3)

Back 9

1. Reduce BP
2. Pheochromocytoma (increases catecholamine release -> hypertensive crisis)
3. phentolamine: reverses pheochromocytoma and reduce BP, e.g. before surgical removal of pheochromocytoma. patient may also need to use b blocker.

Front 10

sE, limitations of a adrenergic blocking agents (3)

Back 10

1. reflex tachycardia
2. salt and fluid retention (so use w. diuretic)
3. postural hypotension [usually 1st dose phenomenon], esp. ladies & elderly

Front 11

specific use of selective a blockers
1. a1A receptor
2. a1B receptor
3. non-specific

Back 11

1. found in prostate
~ relax UT smooth muscle, ↓ resistance to urine outflow
~ tamsulosin & silodosin (treats BPH only, little or no effect on BP)

2. found in BV
~ reduce BP (for chronic HT)

3. Prazosin, phenolamine: both BPH and HT

Front 12

give examples of B adrenergic blocking agents
1. NS (1)
2. Specific (2)
3. glaucoma (1)
4. ISA (2)
5. others (2)

Back 12

NS: propanolol
Specific; atenolol, metoprolol
Glaucoma: timolol
Intrinsic Sympathomimetic Activity: pindolol, acebutolol
Others: atenolol, nadolol

Front 13

properties of B adrenergic blocking agents (5)

Back 13

1. NS (propanolol), Specific (atenolol, metoprolol)

2. membrane stabilizing effects; propanolol has some LA effect. Timolol doesn't though.

3. ISA (partial agonist effect); acebutolol, pindolol
~ less reduction in HR compared to other

4. all therapeutic effects due to b block
↓ contractility, ↓ CO, ↓ HR

5. different in metabolism, duration of action, and clinical uses

Front 14

uses of B blockers (7)

Back 14

1. ↓ of cardiac workload (HT, angina)
2. ↓ mortality in post-MI patients
3. cardiac arrhythmias
4. glaucoma (topical timolol), ↓ aqueous humor
5. hyperthyroidism: B blocker reverses the increased sympathetic activity
6. prophylaxis of migraine (little effect in acute attack)
7. Reduce tremor (↑ sympathetic, ↑ tremor)

Front 15

SE & limitations of B blockers (5)

Back 15

1. depress cardiac performance, bradycardia
2. contraindication asthma (even B1 selective)
3. problems w sudden withdrawal (poss. due to upregulation of receptors after prolonged use, ↑ sympathetic)
4. CNS effects: sedation, sleep disturbance, depression
5. hypoglycaemia in insulin dependent (b involved in glucose metabolism)

Front 16

properties and examples of new, 3G B blockers
1. examples (4)
2. properties (3)

Back 16

Examples: carvedilol, labetalol
(under investigation: bopindolol, bucindolol)

Additional properties (multiple effects)
1. block a1 receptor
2. antioxidant
3. vasodilator (NO production, block Ca entry, K channel opens)

Front 17

effects of labetalol & carvedilol

Back 17

1. competitive blockers of a1 & B receptors (actions as predicted)

2. treat HT with little/no reflex tachycardia (compared to a blockers)

3. ↓ cardiovascular complications and mortality by carvedilol in HF patients

Front 18

SE of labetalol, carvedilol

Back 18

same consideration for a and B blockers.
more frequent postural hypotension

Front 19

Summary of HT drugs
1. definition of HT
2. HT increases risk of?
3. BP depends on?

Back 19

1. 140/90 mmHg
2. increased risk of cardiovascular diseases
3. BP = CO x PVR (PVR depends on BV)

Front 20

Diuretics effect (5)

Back 20

1. ↑urine output so ↓BV

2. ↓venous return & cardiac output. ↓BP

3. thiazide: less effective ~ longer acting, less SE (chronic use)

4. loop: shorter acting, slightly more SE

5. ↓ fluid retention associated w. other antihypertensive tx

Front 21

CCB effects (2)
1. smooth muscle (4)
2. cardiac (4)

Back 21

1. block Ca channel (smooth muscle)
↓ Ca entry, ↓ BV constriction, ↓ resistance, ↓ BP

2. block Ca channel (cardiac)
↓ Ca entry, ↓ force of contraction, ↓ CO, ↓ BP

Front 22

1. mechanism of beta blockers
2. B blockers effects (1)

Back 22

1. blocking B1 receptor in heart [which control HR, contractility)
2. ↓ cardiac output (↓ HR, ↓ contractility) so ↓ BP

Front 23

1. mechanism
2. effects of a blockers (1)

Back 23

1. block a1 in BV which control BV contraction
2. ↓ constriction of BV, so ↓ resistance (↓ BP)

Front 24

1. mechanism
2. effects of angiotensin converting enzyme (ACE) inhibitors (1)

Back 24

1. blocking angiotensin: vasoconstriction, control aldosterone levels

2. block conversion of angiotensin I to II
↓ angiotensin II, ↓ constriction & ↓ fluid retention
(↓ BP)

Front 25

1. mechanism
2. effects of angiotensin II receptor blockers

Back 25

1. block action of angiotensin II effect at receptor level ↓ BP
2. similar to ACE inhibitors: ↓ constriction, ↓ fluid retention

Front 26

what is the ABCD tx of HT?

Back 26

Alpha blockers
ACE inhibitors
Angiotensin II receptor blockers
Beta blockers
CCB
Diuretics

Front 27

when to use ABCD?

Back 27

1. AB for young (<55) and non-black, CD for old and black

2. A (or B) + C or D (try not to use B due to DM onset)

3. A (or B) + C + D

4. add a blocker, or spironolactone or diuretic

Front 28

what is mono and combination therapy for HT tx?

Back 28

1. avoid high doses in mono-therapy.

2. monotherapy for ↓~10 mmHg

3. use combination for additional BP lowering
e.g. Diuretics + ACE inhibitor/AR/BB/CCB

4. avoid drugs w. overlapping mechanisms:
ACE inhibitor + ARB (both RAAS: rarely combined)