L46 – Calcium antagonist, α and β adrenergic blocking agents Flashcards Preview

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Flashcards in L46 – Calcium antagonist, α and β adrenergic blocking agents Deck (76):
1

Explain the action of Ca2+ during membrane doplarization?

membrane depolarization > Ca2+ channel undergo conformational change > Ca2+ influx down electrochemical gradient into cell

2

Explain the action of CCB?

Block L-type Voltage gated Ca2+ channels > decrease Ca2+ entry (down electrochemical gradient) into cell

3

Result of CCB on cardiac muscle and blood vessels?

CCB Decreases force of contraction and decreases vasoconstriction > decrease TPR

4

What specific type of calcium channel is targeted by CCBs?

Ca v1.2
L-type
High voltage activated dihydropyridine sensitive channels

5

2 roles of cardiac L-type voltage- gated calcium channels in cardiac myocytes?

Regulate HR (pacemaker potential at SA node and AV node conduction)

Regulate force of contraction of heart

6

Role of cardiac L-type voltage- gated calcium channels in vascular smooth muscle cells?

Regulate force of smooth muscle contraction

increase intracellular Ca2+ > trigger further release in stored Ca2+ > vasoconstriction

7

CCBs are used in which three pathological conditions?

Angina
Arrhythmia
Hypertension

8

Name of three structural classes of CCB? dbp

dihydropyridines

Benzothiazepine

Phenylalkylamine

9

Name 1-2 common CCBs in each structural class?

Dihydropyridine= nifedipine, amlodipine

Benzothiazipine= diltiazem

Phenylalkylamine= verapamil

10

Which CCB class is cardiac selective?

Benozothiazipine

Phenylalkylamine

11

Which CCB class is vascular selective?

Dihydropyridine

12

How does the dosage of dihydropyridine affect its function on CVS?

Low dosage = block vascular L-type channel

High dosage = block cardiac L-type channel

13

How does dosage of cardiaic selective CCBs affect their function on CVS?

Cardiac selective CCB = benzothiazipine, phenylakylamine

At low dosage = cardiac selective

At high dosage = vascular selective

14

Why is vascular selective CCB used for treatment of angina?

Dilate coronary vessels too > relieve angina

15

Vascular -selective CCB may alter myocardial contractility. Why?

Not a direct effect

CCB decrease TPR, heart senses drop in resistance and adjusts to lower contractility

16

Why does Nifedipine cause slight decrease in HR when it is a vascular -selective CCB?

Nifedipine is not very vascular-selective > slight effect on cardiac L-type CC > decrease HR

17

Why does Amlodipine increase HR when it is vascular selective?

Drop in TPR > sensed by baroreceptors > stimulate sympathetic NS > reflex tachycardia > ensure sufficient blood to brain and kidney

18

Effect of vascular selective CCB on SA node and AV node conduction?

Zero

19

3 effects of vascular selective CCBs.

increase coronary flow
Increase vascular dilatation
Increase neurohormonal activation

20

Effect of vascular selective CCB on renal system?

mild natriuresis

due to increase in renal blood flow and intraglomerular pressure

21

Compare effects of cardiac selective CCBs with vascular selective CCBs?

Cardiac selective causes similar increase in coronary flow, vascular dilatation and neurohormonal activation

But also decrease in SA node, AV node conduction and HR

22

Which vascular selective drug causes a similar effect on HR as cardiac selective CCBs?

Nifedipine

23

What are some side effects of vascular-selective CCBs on vascular dilatation?

High dosage = oedema

Mismatch in vasodilation between arteriole and venous (High Ra and normal Rv) > blood volume increase in capillary > Pc increase > increase filtration > oedema

24

Some side effects of cardiac selective CCBs when given in very high dosage?

Very high dosage> HR and contractility drop too much > trigger reflex tachycardia > heart failure/ arrhythmia

25

Apart from oedema, what are some common adverse effects of CCB?

Flushing
Dizziness

26

Why is nifedipine not favored for clinical use? (think half-life...)

Short half- life (rapidly metabolized in body) > cause surges/ oscillations in BP and sympathetic reflex activity within dosage interval > increase risk of CVS damage and high frequency of admin. = low compliance

27

Why are sustain-release CCBs used instead of start half life ones?

Reduce adverse effect (flushing, dizziness, peripheral oedema)

Reduce fluctuations in BP

28

Change in TPR causes what BP change? How about change in stroke volume?

Change in TPR = diastolic increase, systolic unchanged

Change in SV = increase in diastolic + even bigger increase in systolic

29

Which type of hypertension is CCB best used for?

Isolated systolic hypertension - increase in systolic, normal diastolic

30

Which patient groups can use CCB best as hypertensive treatment?

Patients with low renin status e.g. elderly

31

Explain the adverse action of CCB on gastroesophageal reflux

CCBs inhibit contraction of lower esophageal sphincter > lead to gastroesophageal reflux

32

Which CCBs are used as anti-arrhythmic dugs?

Only cardiac selective CCBs

e.g. verapamil , diltiazem

Decrease HR, SA node and AV node conduction

33

Which type of arrhythmia is CCB most effective for?

Delayed-afterdepolarization (DAD)- mediated arrhythmia

CCB can reduce calcium overload
(DAD: Ca2+ accumulation exceeds storage capacity > trigger extra heart beat)

34

What are 2 precautions when using CCB as antiarrhythmic drug?

Caution in patients with hepatic dysfunction (increase plasma conc.)

Avoided in patients with Ventricular tachycardia
(drug can worsen hypotension > cardiac arrest)

35

What does a1 receptor signal?

Formation of IP3 and DAG > increase intracellular Ca2+

36

What does a2 receptor signal?

Inhibition of adenylyl cyclase > decrease cAMP

37

What do b1, b2, b3 receptors signal?

Stimulate adenylyl cyclase > increase cAMP

38

Name two common a-Adrenergic receptor blockers

Prazosin
Doxazosin

39

How is Prazosin/ Doxazosin used to manage hypertension?

Both a1- Adrenergic receptor blockers > inhibit a1 adrenergic receptors in arterioles and venules > dilate arterioles and veins > decrease peripheral vascular resistance

40

What is the normal action of a1- adrenergic receptors?

Stimulate = vasoconstriction

41

General adverse effects of a1-adrenergic receptor blocker ?

dizziness, palpitations, headache

42

Explain the "first dose phenomenon" caused by a1- adrenergic receptor blocker.

Orthostatic hypotension (huge drop in BP from supine to upright posture)
with initial dose/ after dosage increase

because vasoconstriction from baroreceptor reflex is inhibited

43

What drug worsens orthostatic hypotension caused by a1 adrenergic receptor blockers?

Diuretics > hypovolemia already causes hypotension

44

How does the body compensate after first dose of a1 adrenergic receptor blockers?

Sympathetic nervous system compensate > increase systemic vascular resistance

Activate RAAS > Decrease renal sodium excretion > Na+ and water retention

Both compensations oppose drug action

45

Why is a-blocker used with diuretics and b-adrenergic receptor blockers?

Diuretics : body counteract a - blocker by salt retention > oedema

B-adrenergic receptor blocker: prevent effect of sympathetic NS on heart

46

Is a - blocker used as long term antihypertensive drug?

No

Body keeps counteracting drug > reduce efficacy

47

Name 3 common B-adrenergic receptor blockers

Propranolol

Metoprolol

Pindolol

48

What is the normal action of B1 adrenergic receptor activation on heart?

Stimulate adenylyl cyclase > increase cAMP > enhance activity of L-type channels > increase HR and force of contraction

49

Which b-receptors are in vascular smooth muscle?

B2

50

What is the action of B2 receptor activation and why is it different from B1?

Activate B2 > stimulate adeylyl cyclase > increase cAMP > INHIBIT myosin light chain kinase (MLCK) > reduce contraction on vascular SM > vasodilation

B2 REDUCES contraction
B1 INCREASES contraction

51

Explain action of B-blockers on heart?

Inhibit B- adrenergic receptors in heart > decrease rate and force of contraction > decrease cardiac output

52

Explain action of B-blockers on kidneys?

b-block in kidneys> decrease activation of renin production > decrease Na+ and water retention

53

Explain action of B-blockers on peripheral vascular resistance?

Inhibit peripheral presynaptic B-adrenergic receptors > decrease release of noradrenaline > decrease sympathetic vasoconstrictor nerve activity > decrease peripheral vascular resistance

54

Which 5 conditions is B-blockers used in?

Angina,
Arrythmia
Heart failure
Hypertension
Myocardial infarction

55

Why is b-blockers not used in patients with asthma or COPD?

Inhibit B-adrenergic (esp. B2) receptors in respiratory tract > BRONCHOSPASM

56

Why is b-blockers not used in patients with insulin-dependent diabetes?

Inhibit B-receptor in LIVER > affect glucose metabolism > increase risk of HYPOglycaemia

57

Why is b-blockers not used in patients with vasospastic disorders/ severe peripheral vascular diseases?

Inhibit B- receptor in vascular smooth muscle > decrease vasodilation

58

Summarize 3 patients groups which B-blockers is not used in?

patients with asthma or COPD

patients with insulin-dependent diabetes

patients with vasospastic disorders/ severe peripheral vascular diseases

59

Which B-blocker is less likely to have adverse effects?

B1- selective receptor blockers > higher cardiac selectivity

60

How could B-blocker lead to arrhythmia and HF? Why is pindolol used ?

Inhibit B-adrenergic receptor in heart > decrease HR and contractility > increase risk of arrythmia and HF

Pindolol has intrinsic sympathomimetic activity > partial agonist, slight activating effect on receptor

61

How can B-blockers cause psychiatric depression? How to manage?

inhibit B1 and B2 receptros in CNS > CNS disturbance > depression

Less likely with B-blockers with low lipid solubility > cannot cross BBB into brain

62

List 3 mental effects of B-blockers?

mild sedaiton
vivid dreams
depression

63

Classify the 3 generations of B-blockers and their action.

First generation = non selective = inhibit B1 & B2

Second generation = cardiac selective = inhibit B1

Third gen. = b-blockers with vasodilating effects = inhibit a and b receptors/ B1 + release NO from endothelium

64

Name some first gen and second gen B blockers

First gen = propranolol

Second gen = metoprolol, bisoprolol

65

Name some 3rd gen drugs with diff. functions

Inhibit a & b receptors = labetalol, carvedilol
OR
inhibit B1 + release NO = nebivolol

66

What are partial agonists B-blockers?

B-blockers with intrinsic sympathomimetic activity

67

Name some partial agonist B-blockers?

Pindolol > acebutolol

68

Why are partial agonists B-blockers used?

Inhibit + slightly activate B-receptors = lower risk of arrhythmia and HF

69

What are 3 main precautions with B-blockers?

Withdrawl syndrome

Drug interaction

Concurrent condition

70

How does body counteract b-blocker after long term use?

Body upregulate (increase no. of receptors) and super-sensitize B-receptors > increase sensitivity to sympathetic activation by endogenous noradrenaline

71

What happens when B-blocker is suddenly withdrawn after long term usage?

Body compensate by increase sensitivity of B-receptors

Withdrawal = rebound hypertension, tachycardia, nervousness

72

How to discontinue patient from B-blocker?

Gradual dosage reduction

73

Which drugs can interact with B-blockers?

Adrenaline and Cocaine

Both can activate a&b receptors
Cocaine DEcrease uptake of noradrenaline > activate a&b

Also nonsteroidal anti-inflammatory drugs (NSAID)

74

How can B-blocker cause severe hypertension when taken with adrenaline or cocaine?

B- receptor blocked > shift the endogenous noradrenaline to a-receptors > severe hypertension

75

Why does B-blocker mask insulin-induced hypoglycemia in diabetics?

insulin-induced hypoglycemia > result in tachycardia (warning sign)

B-blocker slow HR > mask the warning sign

76

What concurrent conditions result in severe hypertension with non-selective B-blockers?

Pheochromocytoma

Clonidine withdrawal (antihypertensive drug)

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