Alpha blockers and calcium channel blockers Flashcards Preview

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Flashcards in Alpha blockers and calcium channel blockers Deck (29):
1

the two classes of adrenergic receptors and their affinites

alpha and beta
alpha: NE > epinephrine >> isoprotenol
Beta: Isoprotenol > epinephrine > NE

2

Alpha 1 receptors

postsynaptic, vasoconstriction, (veins and arterioles) inc BP
alpha 1 a = prostate, VSM
alpha 1 b = VSM
alpha 1 d

3

alpha 2 receptors

pre and post synaptic
inhibit norepinephrine and insulin release
alpha 2 a
alpha 2 b
alpha 2 c

4

alpha 1 antagonists

Doxazosin, prazosin, terazoin (block all alpha 1 subtypes)
vasodilatation, hypotension
Tamsulosin (alpha 1 a specific), so helpful in reducing prostate size when increased whereas doxazosin will also have an effect on BP

5

alpha 2 antagonism

not used clinically

6

combined alpha 1 and 2 antagonists

phenoxybenzamine

7

alpha blockers indications

hypertension
- essential hypertension
useful in combination therapy (e.g. diuretic, ACEi and alpha blocker)
- pheochromocytoma --> alpha blockers useful here, this is also a tumor of the SNS usually in the adrenal gland, where too much adrenaline and noradrenaline produced treatment is surgery but perioperativly use alpha-blockers

8

Doxazosin

reversible alpha blockade alpha1 >>>> alpha2
- vasodilator: blocks tonic sympathetic activity on resistance vessels
- reduce prostatic symptoms
start low dose an titrate
od
oral
first pass hepatic metabolism

9

Why aren't prazosin and terazosin as good as doxazosin?

prazosin has very short half life and so needs to be taken twice to 3x daily, and terazosin has slightly more side effects than D

10

alpha blockers adverse effects

hypotension - give first dose at night
Dizziness
Lassitude (tiredness)
Nasal stuffiness
Dry mouth
Urinary incontinence in women

11

rarely used alpha blockers: phenoxybenzamine

oral
irreversible alpha blocker antagonist alpha1 > alpha2
blocks serotonin receptors
used in pheochromocytoma
used preoperatively
marked side effects
- postural dec BP, tachycardia
- nasal stuffiness
- CNS

12

Rarely used alpha blockers: phentolamine

poorly absorbed, give in IV
competitive antagonist alpha 1 = alpha 2
increase NE release
5HT antagonist
- limited use, hypertensive crisis e.g. phaeco and cocaine OD

13

combined alpha and beta blocker: labetalol

reversible antagonist
hypertension in pregnancy
phaecochromocytoma

14

combined alpha and beta blocker: carvedilol

also antioxidant properties

15

specific alpha blockers: tamsulosin

oral
competitive antagonist
alpha1a and d
Relax bladder and prostate smooth muscle
less postural hypotension
long t1/2, given once daily

16

Calcium channel blockers - indications

hypertension (vasodilation)
angina (decreased cardiac work, vasodilatation)
arrhythmias (SVT tachcyarythmias)
- atrial fibrillation / flutter rate control
- SVT termination
Vasospasm
e.g. raynauds phenomenon, cerebral vasospasm

17

Calcium channel blocker mechanism and selectivity

block voltage gated L type Ca2+ channels - cardiac and smooth muscle (decrease arteriolar smooth muscle tone, decrease peripheral vascular resistance, decrease BP)
cardiac cells --? decrease sinus node rate and AVN transmission
some selectivity
- resistance vessels
- Myocardium
- conducting tissue

18

The dihydropyridines

e.g. Nifedipine --> are pure vasodilators, useful in lowering BP and in angina as they also dilate coronary arteries. resistance vessels (flushing, headaches, oedema)

19

e.g. of a benzothiazepine

diltiazem = in between effects

20

phenylalkylamine example

verapamil
very little effect on calcium channels in resistance vessels, its mechanism on calcium channels in conducting tissues
- cardiac tissue = heart block, negative inotrope
constipation because peristalsis in bowel inhibited

21

Ca2+ blocker pharmacokinetics

oral = all
IV preparations = diltiazem and verapamil
Significant first pass hepatic metabolism: cytochrome P450 system
Variable half life:
nifedipine/ diltazem few hours so do slow release capsule
amoldipine = long in days

22

Nifedipine

hypertension
vasospasm e.g. raynauds
Oral, do not use sublingual = too intense
SR tablets
hepatic metabolism protein bound
renal excretion
oedema, flushing, headache
* no effect on conducting system of the heart therefore no use in slowing e.g. atrial fib

23

Diltiazem

effects on conducting tissue therefore can slow HR and vasodilator activity
Angina, hypertension, tachyarrythmias
Oral and IV
hepatic metabolised, fecal excreted
Various delayed release preparations
oedema, flushing, headache, bradycardia

24

verapamil

tachyarrythmias (SVT, AF rate control)
hypertension
Oral and IV
hepatic metabolism + renal excretion
decreased bioavailability
S/E - bradycardia, -ve inotrope, constipation

25

verapamil blocker interactions

do not use with beta blockers - both too potent, can cause forms of heart block
care with statins,
e.g. simvastatin
cytochrome P450
also inhibits P glycoproteins which excrete drugs out of system e.g. digoxin so this can cause digoxin toxicity

26

niche market: clevidipine

acute hypertension
parenteral
IV infusion with lure, and after measuring BP at the same time titrate
- hydrolysed by plasma esterase's, rapid onset and offset of action

27

Why in a patient with asthma and stable angina would you use calcium channel blockers

beta blockers can cause exacerbation of asthma

28

Conclusion Alpha blockers use when?

3rd line use for hypertension
combination therapy with ACEi and diuretic
consider if concurrent potassium

29

conclusion: Ca channel blockers use when?

2nd or 3rd line use for hypertension
combination therapy with ACEi and diuretic
use if concurrent angina
rate and SVT control