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

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

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)

Nicorandil

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

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

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 G_i 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

Hydralazine

This reduces blood pressure directly by relaxing arteriolar muscle

Sodium Nitroprusside

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

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

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

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