Alpha Blockers & Calcium Channel Blockers (Dawes) Flashcards
What do Alpha Blockers do?
Alpha blockers antagonize post-synaptic a-adrenergic receptors to mediate blood pressure lowering effects. It is used probably as third-line to treat patients with hypertension
What do Calcium channel blockers do?
Ca2+ Channel blockers block voltage-mediated calcium channels.
Describe the 2 familities of adrenergic receptors
Two families of adrenergic receptors are alpha and beta, which are based on affinity to adrenergic agonists
- _Alpha affinit_y are
- norepinephrine > epinephrine >> isoproterenol
-
Beta affinity are
- isoproterenol > epinephrine > norepinephrine
Describe the actions of a1 and a2 receptors and where they are found.
a1 Receptors (Post-Synaptic)
Its actions include vasoconstriction, i_ncrease BP_.
Its subclass includes:
- a1a found in prostate SM
- a1b found in v_ascular smooth muscle_ (increase with age)
- a1d
a2 Receptors (Mainly Pre-Synaptic, Some Post-Synaptic)
Its actions include inhibiting norepinephrine and i_nsulin release_. (inhibiting/negative feedback)
Its subclass includes a2a, a2b, a2c.
What is the most common a1 anatognist in NZ?
What does it do?
Doxazosin
(block all a1 subtypes). - inc prostate SM
- It results in vasodilation, hypotension.
Name a drug that act as both a1 and a2 antagonist
phenoxybenzamine
What are the indications of Alpha Blockers
Alpha Blockers Indications
It is indicated in:
-
Hypertension
- Essential hypertension
- Phaeochromocytoma (rare tumour of sympathetic nervous system, usually adrenal gland leads to excessive production of adrenaline or noradrenaline)
- Useful in combination therapy,
- e.g. diuretic + ACEi + alpha blocker
-
Prostatism (tamsulosin)
- Symptoms = hesitency, frequency, dribbling etc.
Describe the features of Doxazosin
Doxazosin
Doxazosin is r_eversible alpha blockade_ (a1>>>>>>a2). It blocks all a1 subtypes
- Vasodilator (blocks tonic sympathetic activity on resistance vessels) (particularly useful in elderly men with hypertension)
- Reduce p_rostatic symptoms_
It starts with low dose and titrate, once daily. Route via oral (1-16mg once daily).
- Peak plasma levels 2-3 hours. Linear kinetics. First pass hepatic metabolism (active metabolites)
- Mainly faecal elimination. Protein bound. Elimination half-life 22 hours.
What are some adverse effects of alpha blockers
-
Orthostatic hypotension (decrease BP so dizziness when standing up)
- Can give first dose at night (helps prostate symptoms)
- Start at low dose and titrate
- Lassitude (lack of energy)
-
Nasal stuffiness
- b/c of vasodilation of the nasal mucosa
- Dry mouth
- Urinary incontinence (women)
Describe the Phenoxybenzamine
Include marked side effects
- Route via oral
- Irreversible a-blocker antagonism (a1>a2)
- Antagonists for histamine (H1 receptor), cholinergic (ACh receptor), serotonin (5HT receptor)
- Used in phaeochromocytoma, pre-operatively
- Marked side effects include
- postural hypotension,
- tachycardia;
- nasal stuffiness;
- CNS (sedation)
What drug is often used in pregnancy?
Labetalol
- reversible antagonist (b1=b2 a1>a2)
- Hypertension in pregnancy (very safe drug)
- Phaeochromocytoma
65 year old man has hypertension and nocturia.
Already on bendrofluazde (thiazide diuretic) 2.5mg and cilazapril (ACEi) 5mg.
Poorly controlled hypertension 174/94mmHg.
What would you prescribe him?
What would you warn him?
Additional antihypertensive drug includes alpha blocker (e.g. doxazosin) may help with BP and prostatic symptoms (nocturia)
Warnings include orthostatic hypotension (when you stand up, don’t stand up too quickly), take the drug before bed.
What are the indicators of Calcium Channel Blockers
-
Hypertension
- (vasodilation)
-
Angina
- (decreases cardiac work, vasodilation)
-
Arrhythmias
-
(supraventricular tachyarrhythmias)
- _Atrial fibrillation/flutte_r rate control (not antiarrhythmic!)
- _Supra Ventricular Tachycardia (S_VT) termination
-
(supraventricular tachyarrhythmias)
-
Vasospasm
- __e.g.
- Reynaud’s phenomenon
- disease causes some areas of your body — such as your fingers and toes — to feel numb and cold in response to cold temperatures or stress
- cerebral vasospasms
- Reynaud’s phenomenon
- __e.g.
Where do Calcium blockers work on and what are the consequences of these drugs?
It blocks v_oltage-operated L-type Ca2+ channel_s (does not affect receptor-regulated channel) on smooth muscle and cardiac muscle.
- Some selectivity
- Resistance vessels
- Myocardium
- Conducting tissue
- Vascular smooth muscle actions include:
- Decrease arteriolar smooth muscle tone
- Decrease peripheral vascular resistance
- Decrease blood pressure, decrease afterload
- Other smooth muscle actions (some drugs) such as bowel smooth muscle, therefore constipation due to inhibition of gut peristalsis
- Cardiac cells actions include:
- Decreases contractility
- Decreases sinus node rate and AV node transmission
There is some selectivity on resistance vessels, myocardium, and conducting tissue.
What are the consequences of calcium channel blockers on cardiac cells?
Cardiac cells actions include:
- Decreases contractility
- Decreases sinus node rate and AV node transmission
Describe the mechanism of Calcium blockers
- It blocks voltage-operated L-type Ca2+ channels (does not affect receptor-regulated channel) on smooth muscle and cardiac muscle
-
Vascular smooth muscle actions include:
- Decrease arteriolar smooth muscle tone
- Decrease peripheral vascular resistance
- Decrease blood pressure, decrease afterload
- Other smooth muscle actions (some drugs) such as bowel smooth muscle, therefore constipation due to inhibition of gut peristalsis
-
Cardiac cells actions include:
- Decreases contractility
- Decreases sinus node rate and AV node transmission
-
Vascular smooth muscle actions include:
Name the 3 groups of calcium channel blockers
Dihydropyridine
Benzothiazepine
Phenylalkylamine
Describe the dihydropyridine calcium channel blockers
1) Drugs
2) Where they preferntially act on
3) Side effects
- They include nifedipine, felodipine, amlodipine.
- They act preferentially on calcium channels on resistance vessels. (little effect on heart)
- Side effects include
- flushing,
- headache,
- oedema.
- Reversed by dose reduction, not diuretics
Describe the Phenyloakylamine drugs
1) Drugs
2) Act on..
3) Effects
It includes verapamil. This act preferentially on:
-
Cardiac tissue
- heart block,
- Used in rate control
- negative inotrope
- Therefore never use verapamil on patients with HF
- heart block,
-
Gut
- __Cause constipation
Describe Benzothiazepine drugs
1) Drug
2) Effect
It includes diltiazem.
This some vasodilator properties and cardiac effects.
Describe the Pharmacokinetics of Calcium Channel Blockers (general)
All can be given via oral route. IV preparations for diltiazem and verapamil.
Significant first pass hepatic metabolism (cytochrome P450 system, less active metabolites)
There is variable half-life
- Nifedipine and diltiazem (short, hours) (sl_ow-release_ preparations)
- Amlodipine (long, days)
Describe the Pharmacokinetics of Nifedipine
(Type of Dihydropyridine)
It is used in hypertension and vasospasm (e.g. Reynaud’s)
Route via oral (do not use sublingual).
Half-life of few hours.
- Hepatic metabolism, protein bound
- Renal excretion
SR (bd) and LA (od) preparations
Side effects include oedema, flushing, headache.
- Diuretics do not help in this case
Describe the pharmacokinetics of Diltizaem
(Type of Benzothiazepine)
It is used in hypertension, angina, tachyarrhythmia (AF rate control).
- Route via oral (and IV)
- Hepatic metabolism, Faecal excretion
- Various delayed release preparations.
- Can be used with beta-blockers.
- Side effects include
- oedema, flushing,
- headache,
- bradycardia.
______ should never be used with Betablockers.
Explain why
Do not use verapamil with beta blockers!
Beta blockers and verapamil both slow HR, results in heart block.
- Caution with simvastatin!
- Verapamil inhibits cytochrome P450 3A4, thus inhibit breakdown of statin (increase rhabdomyolysis)
- Caution with digoxin/cyclosporine!
- Verapamil inhibits p-glycoproteins, which increases digoxin/cyclosporin concentrations.
- p-glycoproteins are channels in kidneys, gut, BBB, which excrete drugs out of body such as digoxin/cyclosporin
- Some tumours are resistant to chemotherapeutic agents due to presence of p-glycoprotein channels for excretion
- Verapamil inhibits p-glycoproteins, which increases digoxin/cyclosporin concentrations.
Describe the pharmacokinetics of Verpamil
(Type of Phenylalkylamine)
It is used in hypertension, tachyarrhythmia (SVT/AF rate control).
Route via oral (and IV). Half-life of 7hr.
- Hepatic metabolism
- Renal excretion
Given tds or SR (bd) preparations
Side effects include bradycardia, negative inotrope, constipation (don’t use in patients with HF)
Do not use with betablockers!
75-year-old man with asthma and s_table angina_. Currently on aspirin. Pulse 84 bpm, BP 156/80 mmHg.
What drug for exertional angina symptoms?
First line therapy for angina is beta-blockers, but can cause exacerbation of asthma
Therefore, use second line therapy of calcium channel blocker
- Diltiazem lowers BP and also has cardiovascular effects, no adverse effect on asthma
- Could use verapamil instead but reduces contractility
56-year-old man with hypertension and increased lipids. Current treatment is bendrofluazide (diuretic) 2.5mg, cilazapril (ACEi) 5mg, simvastatin (vasodilator) 80mg. Pulse 96bpm, BP 164/96 mmHg.
Treatment options?
- Ask if he has any prostatic symptoms, then add alpha blocker (tamsulosin)
- If no problem with prostate, can add another calcium channel blocker:
- Nifedipine LA (purely a vasodilator)
- Diltiazem LA (mild simvastatin interaction)
- Do not prescribe Verapamil SR (caution with simvastatin interaction)
Alpha blockers are:
- ___ line use for hypertension
- Combination therapy with ____ and ____
- Consider if concurrent _____
Alpha blockers are:
- 3rd line use for hypertension
- Combination therapy with ACEi and diuretic
- Consider if concurrent prosatism
Ca channel blockers are:
- ____ or ____ line use for hypertension
- Combination therapy with _____ and ____
- Use if concurrent _____
- Useful for____ control and ____control
Ca channel blockers are:
- 2nd or 3rd line use for hypertension
- Combination therapy with ACEi and diuretic
- Use if concurrent angina
- Rate control and SVT control
