Dawes: Alpha Blockers and Calcium Channel Blockers

Question 1

What are the function of alpha blockers and calcium channel blockers?

Answer 1

• A receptor blockers: antagonize post-synaptic alpha receptors to mediate the BP lowering effect
• Ca ²⁺ Channel Blockers: block voltage-operated Ca channels throughout the CV tree with a number of indications

Question 2

What is the function of alpha-1 receptors?

Answer 2

These are all post-synaptic and result in vasoconstriction of the veins and arterioles, thus producing an increase in blood pressure.

Question 3

Where are alpha-1 receptors found?

Answer 3

• Alpha-1 a = Prostate smooth muscles
• Alpha-1 b = Vascular Smooth Muscle (These increase with age)

Question 4

What is the function of Alpha-2 receptors?

Answer 4

These are both pre and post-synaptic receptors that inhibit the release of norepinephrine and insulin.

Question 5

What are the effects of alpha 1 antagonism?

Answer 5

This results in vasodilation and hypotension. These include drugs such as…

• Doxazosin, Prazosin, Terazosin
• Tamulosin is an alpha-1 A specific blocker and therefore targets those receptors found in the prostate (but no BP lowering)

Question 6

What are the effects of alpha 2 antagonism?

Answer 6

Increased norepinephrine release this is caused by yohimbine. (not used clinically)

Question 7

What is an example of a combine alpha-1 and aplha-2 antagonist?

Answer 7

Phenoxybenzamine​

Question 8

When is an alpha blocker used?

Answer 8

• 3rd line if the patient is suffering from essential hypertension - used in combination with an ACEi and diuretic.
• May be used in the treatment of pheochromocytoma which is a tumour of the SNS classically in the adrenal glands (rare)
• Used in the treatment of prostatism - people have poor stream, dribbling, hard to start

Question 9

What are the effects of doxazosin?

Answer 9

This is a reversible alpha blocker that has a far greater affinity for alpha-1 receptors. It blocks all alpha-1 receptors and therefore is a vasodilator that blocks the tonic sympathetic activity on resistance vessels and is used in the treatment of prostatism.

Question 10

How is doxazosin administered?

Answer 10

Doxazosin is taken orally once daily. At first, a low dose needs to be taken and slowly increased with titration.

Question 11

What are the pharmacokinetics and pharmacodynamics of doxazosin?

Answer 11

It has a peak plasma concentration 2-3 hours after administration. It displays linear kinetics and has first-pass hepatic metabolism which greatly reduces its bioavailability.

It is eliminated mainly by the faecal route and has a high protein binding percentage and therefore is eliminated with a half-life of 22 hours.

Question 12

What are the pharmacokinetics of prazosin?

Answer 12

It is taken orally and undergoes first pass metabolism. As a result, it has a half-life of 3-4 hours and needs to be given twice daily.

Question 13

What are the pharmacokinetics of terazosin?

Answer 13

It is taken orally and undergoes little first pass metabolism. As a result, it only needs to be taken once daily and has a half-life of 12 hours.

Question 14

What are the adverse effects of alpha blockers?

Answer 14

• They cause (orthostatic) hypotension which manifests as dizziness and therefore can give the first dose at night to manage prostate symptoms.
• Lassitude
• Nasal Stuffiness
• Dry Mouth
• Urinary Incontinence (in Women)

Question 15

Why is phenoxybenzamine rarely used?

Answer 15

It is irreversible and causes postural hypotension, tachycardia, nasal stuffiness and CNS problems.

It is used pre-operatively or to treat phaeochromocytoma as it also acts as H_1, ACh and 5HT antagonist.

Question 16

Why is phentolamine rarely used?

Answer 16

It is poorly absorbed and needs to be given via iv. It caused cardiac and GI side effects and it acts to increase norepinephrine release as it has competitive antagonism with both alpha-1 and alpha-2 receptors. It also acts as a 5HT antagonist and a muscarinic, H₁ and H₂ agonist.

Question 17

When is labetalol used?

Answer 17

Labetalol is a combined alpha and beta blocker used in the treatment of hypertension in pregnancy as it is a reversible antagonist that has a greater affinity for beta receptors than alpha receptors.

Question 18

When is carvedilol used?

Answer 18

Carvedilol has a greater affinity for beta receptors than alpha receptors and as a result, is used in the treatment of congestive heart failure. It also has anti-oxidant properties.

Question 19

When is tamsulosin used?

Answer 19

Tamsulosin is specific for alpha-1 a and alpha-1 d receptors and as a result, is used to treat prostatism. This is because it acts to relax the bladder and prostate smooth muscle and has NO effect on BP.

This orally administered drug has a long half-life and functions as a competitive antagonist.

Question 20

When is a calcium channel blocker used?

Answer 20

• Hypertension -(vasodilation)
• Angina -(dec. cardiac work, vasodilation)
• Arrhythmias -(supraventricular tachycyarrhythmias eg. AF)
• Vasospasm -

Question 21

What is the mechanism of a calcium channel blocker?

Answer 21

Calcium channel blockers act by blocking voltage-operated L-type Ca²⁺ channels with some selectivity: present in the resistance vessels, myocardium and conducting tissue.

Question 22

What is the effect of a L-type calcium channel clocker on vascular smooth muscle?

Answer 22

1. Decreased Arteriolar Smooth Muscle Tone
2. Decreased Peripheral Vascular Resistance
3. Decreased Blood Pressure and Afterload
4. also: other smooth muscle eg. biliary tree, uterus, bowel

Question 23

What is the effect of a L-type calcium channel blocker on cardiac cells?

Answer 23

• Decreased contractility
• Decreased Sinus Node Rate and AV Node Transmission

Question 24

What drugs fall under the dihydropyridine classification? What do they target?

Answer 24

• Nifedipine
• Felodipine
• Amlodipine

These target resistance vessels with almost no heart effect so lowering BP is its function for Hypertension or combatting vasospasm and therefore cause flushing, headaches and peripheral oedema (that is resistant to diuretics).

Question 25

What areas of the body does phenyalkykamines - such as verapamil - target?

Answer 25

• Cardiac Tissue meaning it can cause heart block and negative inotrope (slows HR in AF if beta blocker can’t be used)
• Gut meaning it is able to cause constipation.

Question 26

What are the characteristics of diltiazem?

Answer 26

Has both effects in the peripheral vasculature and so can lower BP and vasorelaxation but also has a little amount of reducion of HR and work

• This is used to treat angina, hypertension and tachyarrhythmias.
• It can be taken both orally (and iv) is hepatically metabolised and faecally excreted. There are a number of delayed release preparations available.
• It causes oedema, flushing, headaches and bradycardia and can be used in combination with beta-blockers.

Question 27

What are the pharmacokinetics of calcium channel blockers?

Answer 27

They are all taken orally but diltiazem and verapamil can be prepared in an iv. They undergo significant first-pass hepatic metabolism by cytochrome p450 and therefore don’t produce as many active metabolites.

They all have variable half-lives.

Question 28

What are the characteristics of nifedipine?

Answer 28

Nifedipine is used to treat hypertension and vasospasm - such as that witnessed in Reynauds disease.

It is taken orally, shows protein binding and undergoes hepatic metabolism. These work together in combination with its renal excretion to give it a half-life of a few hours.

Question 29

What are the characteristics of verapamil?

Answer 29

It is used to treat tachyarrhythmias and hypertension. (only chromotropes, NO vasodilator effect)

V potent on HR, don’t use with BB’s

Inhibits cc p450

inhibits P-glycoproteins and inhibits tissues ability to excrete drugs

It can be given both orally or via iv and undergoes both hepatic metabolism and renal excretion. It has a half-life of 7 hours and can cause bradycardia, negative inotrope (dont use in HF) and constipation.

Question 30

What drugs does verapamil interact with?

Answer 30

It should not be used with beta blockers!

Also inhibits cytochrome P450-3A4 and therefore should be used carefully with statins such as simvastatin is metabolised by this enzyme. The two may interact to cause rhabdomyolysis.

Also inhibits p-glycoproteins and therefore can lead to increased digoxin and cyclosporin concentrations.

Question 31

What is clevidipine?

Answer 31

This is a i.v drug used to treat acute hypertension. It has a half-life of about one minute and is hydrolysed by plasma esterases. It has a rapid onset and offset of action.

Question 32

How would you treat someone with asthma and stable angina who is taking aspirin? Pulse: 84, BP: 156/80mmHg

Answer 32

BB are used for angina but asthma is a contraindication
Diltiazem as it acts to reduce HR and vascular tone; thus improving angina and hypertension. It also doesn’t have any adverse effects on asthma.