Blood Pressure Drugs

Used in many heart conditions, these drugs reduce arteriolar constriction and thus afterload

 

Nitrovasodilators

e.g. Amyl nitrate + Glyceryl trinitrate + Isosorbide dinitrate

These drugs are converted to nitric oxide in vascular smooth muscle cells

– This activates cGMP-dependent kinases –> PKG –> phosphorylation of MLCK –> smooth muscle relaxation –> vascular dilation

– They dilate veins reducing cardiac preload but also arterioles reducing afterload

– Unlike other vasodilators, these drugs preferentially dilate collaterals in ischaemic areas rather than well-oxygenated areas. It helps the areas which need blood most preventing “coronary steal.”

 

  • Amyl nitrate – volatile liquid inhaled for acute attacks
  • Glyceryl trinitrate + Isosorbide dinitrate – these are taken sublingually
Side effects
  • Hypotension with reflex tachycardia

  •  Throbbing headache

  • Dizziness

  • Development of tolerance

Contraindications
  • Hypotension (BP<90)
  • Aortic stenosis

Dihydropyridines 

e.g. Amlodipine + Nifedipine + Nimodipine

These are L-type calcium channel blockers, that bind to the inactive form of the channel.

– As they bind inactive form of channel, this gives them selectivity for vascular smooth muscle rather than cardiac muscle, meaning that they give vasodilation and decrease afterload

– They are often combined with beta-blockers in order to prevent a reflex tachycardia

 

Side effects
  • Vasodilation –> flushing and headaches

  • Ankle oedema

Alpha receptor antagonists

These lower total peripheral resistance by stopping sympathetic system action on a1 receptor

Phentolamine

This is a non-selective a-antagonist, gives vasodilation but also a reflex tachycardia 

Prazosin + Terazosin

These are alpha-1-selective antagonists.

– Do not cause a reflex tachycardia but can give orthostatic hypotension (when patient stands) 

Labetalol

This is a mixed alpha – and B- adrenoceptor antagonist 

K+ channel openers

These act on ATP-sensitive K+ channels in vascular smooth muscle

– ATP usually closes these channels, these drugs open the channels enhancing outward K+ current

– This causes cell hyperpolarisation –> muscle relaxation –> vasodilation

 

e.g. Minoxidil

This is used to treat refractory hypertension + hair loss (causes hirsutism)

Side effects
  • Causes reflex tachycardia so combined with a B-blocker + Diuretic.

Nicorandil

This is used in angina to open cardiac KATP channels to improve coronary blood flow

Side effects
  • Flushing + Headache, nausea + vomiting, rectal bleeding

Dipyridamole

This is a phosphodiesterase inhibitor and so dilates resistance vessels

– Also interferes with adenosine breakdown which stops platelet aggregation

– Used in acute coronary syndrome as an antiplatelet agent (second line after clopidogrel)

    Central Sympathetic Agents

    These drugs work on different levels of the sympathetic nervous system to decrease peripheral vascular resistance

    Reserpine [Storage]

    Prevents vesicle storage of Na by inhibiting the VMAT transporter

    – Therefore, NA leaks out of the terminal causing depletion from the sympathetic nerve terminal

    – This leads to less sympathetic outflow causing vasodilation

    Methyldopa [Release]

    This is a variant of Dopa, a precursor in the noradrenaline synthesis pathway

    – This instead gets converted to methyl-noradrenaline which is a false neurotransmitter

    – It binds presynaptic inhibitory a2 receptors which are Gi coupled, causing hyperpolarisation

    –  This inhibits the presynaptic terminal reducing NA release decreasing sympathetic outflow, leading to downstream vasodilation

    – It is used to manage hypertension during pregnancy

    Clonidine + Monoxidine [Release]

    These are a2 receptor agonists which stimulate pre-synaptic a2– adrenoceptors

    – They inhibit the synaptic terminal in the CNS decreasing sympathetic outflow, leading to downstream vasodilation

     

    Hydralazine

    This reduces blood pressure directly by relaxing arteriolar muscle

     

    Side effects
    • Can cause lupus-like (SLE) syndrome

    Sodium Nitroprusside

    This is metabolised to NO, causing dilation of arterioles + veins.

    Side effects
    • Can be converted to cyanide –> risk of toxicity

    Pulmonary hypertension drugs

    Many of these drugs work by inhibiting the endothelium to stop making endothelin

    – Endothelin is a vasoconstrictor and activates local renin-angiotensin systems in lungs.

     

    • Ambrisentan – selective endothelin A receptor competitive antagonist
    • Bosentan – antagonises both endothelin A and B receptors to lower BP
    Side effects
    • Interact with ciclosporin
    • Can cause oedema/elevated LFTs

    Erectile Dysfunction drugs

    Some vasodilators are used to decrease pelvic vessel resistance to treat erectile dysfunction.

    e.g. Sildenafil (Viagra) + Tadalafil

    These drugs inhibit phosphodiesterase type V

    – Increases cGMP levels –> phosphorylates MLCK –> smooth muscle relaxes –> vasodilation

    – They can also be used to treat pulmonary hypertension + Raynaud’s phenomenon

    Side effects
    • Back pain and myalgia

    • Headache + Flushing

    • Nasal congestion

    • Blurred vision with blue tint

    Contraindications
    • Degenerative retinal disorders

    • Recent stroke, MI or unstable angina

    • Hypotension (systolic <90mmHg)

    Disclaimer

    The intended purpose of this website is to be used as a resource for revision for exams. It should not be used as a guideline or reference for clinical practice/decision making or by patients looking for medical information or advice. In2Med takes no responsibility for any loss or damaged resulting from the use of information from this website.

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