Week 9 Pharmacology

Anti-hypertensive agents:


What classes of antihypertensives are you aware of ? (x4).

  • ACE inhibitors – reduce angiotensin 2 –> reduced peripheral resistance and decreased blood volume (preload)
  • B Blockers – reduce HR and cause peripheral vasodilation ( venodilation leading to decreased pre load too)
  • Ca Channel blockers – reduce peripheral resistance
  • Diuretics – reduce preload
  • Nitrates – venodilate (to reduce pre load) and dilate arteries – drop peripheral resistance.


Tell me about the drugs used in hypertensive emergencies

  • Malignant HTN
    • SBP> 200 and DBP>120 with end organ failure eg encephalopathy, nephropathy/AKI, severe headache, confusion, apprehension, blurred vision, nausea, vomiting, focal neurology. Untreated can progress –> convulsions, coma, death.
  • HTN with haemodynamic compromise –> CCF, stroke, dissecting aortic aneurysm
  • Treatment
    • Parenteral antihypertensives then convert to oral once BP stabilised
    • Needs art line and strict fluid balance
    • Goal is to reduce BP by 25% and DBP shouldn’t drop below 110-100. Normal BP should be aimed in several weeks not acutely.
    • Sodium Nitroprusside – commonest
    • Labetalol, GTN, fenoldopam, Ca channel blockers, hydralazine – also used.
    • Concurrent diuretics used to prevent volume expansion in reaction to the vasodilators.
    • Periop – esmolol is often used to control BP.



  • Centrally acting sympathoplegic – reduce sympathetic outflow from vasomotor centres in the brain but retain baroreceptor control so are less likely to cause postural hypotension. Reduces renal vascular resistance.
  • Used in pregnancy induced HTN, pre eclampsia
  • Analog of L-dopa, paralells NA pathway of production.
  • PD – Released from adrenergic nerves –> replaces NA–> peripherally this doesn’t make a difference cos it still causes vasoconstriction at alpha receptors, but centrally it can cause antihypertensive effects.
  • PK – max effect 4-6hrs post, action persists after parent drug gone, t1/2 2hrs, bioavail 25%, start 1g/d, no reduction required in renal imp
  • Toxicity – sedation esp at onset of treatment, lactation, positive coombs test (reversible)



  • Another central sympathoplegic
  • Partial agonist at alpha adrenoceptors
  • PD – IV injection –> immediate hypertension due to agonist action at alpha adrenoceptors in arterioles –> more sustained hypotension cos it stops other agonists acting there.
  • It also exerts hypotensive effect via alpha receptors in medulla –> hypotension + bradycardia (more than methyldopa).  Reduces renal vascular resistance. Not much postural hypotension.
  • PK – lipid soluble, increasing increases effect, t1/2 8-12hrs, bioavail – 95%, dose reduce in renal imp
  • SE – dry mouth, sedation, depression(should be withdrawn), withdrawal after long term use can result in lifethreatening HTN,


Sodium Nitroprusside

  • PD – powerful parenteral antihypertensive used in hypertensive crisis and severe heart failure. Dilates arteries and veins –> decrease TPR and venous return. Acts like nitrates –> activate guanyl cyclase –> increase cGMP –> relax vascular smooth muscle.
  • In normal ppl BP decreases but in ppl with heart failure the drop in afterload is so significant that BP increases
  • PK – complex of nitrate, iron and cyanide. Cyanide metabolised by mitochondria and distributed to ECF and slowly renally cleared.
  • Effect dissapears within 1-10mins after ceasing meds. So Given as IV infusion. Needs art line to monitor during infusion.
  • Photosensitive so made up fresh each time and covered.
  • SE – hypotension, cyanide accumulation(disorientation, weakness, psychosis, muscle spasm, convulsions), metabolic acidosis, arrhythmias, death. Can combat cyanide build up with injection of sodium thiosulfate.



  • PD – opens K channel –> hyperpolarises/stabilises membrane potential so prevents vascular smooth muscle from contracting –> reflex tachycardia and increased CO.



  • PD – dilates arterioles not veins, useful in heartfailure and severe HTN, can be combined with nitrates.
  • PK – rapidly metabolised by liver(low bioavail), t1/2 1.5-3hrs,
  • SE – rapidly develops tachyphylaxis, headaches, nausea, anorexia, palpitations, sweating, flushing. Reflex tachycardia–> may worsen angina or cause tachyarrhythmias.
  • Toxicity – esp in slow acetylaters – arthralgia, myalgia, skin rashes, fever – SLE like syndrome. Reversible by stopping drug.


ACE inhibitors:

    • Normal physiology : Reduced renal arterial pressure, increased sympathetic tone, increased sodium concentration/decreased sodium abount at distal renal tubule –> renin release –> activate angiotensinogen –> Angiotensin to angiotensin 1 –> ACE in endothelium converts ACE1 to ACE 2 –> vasocontrictor, sodium retainer and stimulate aldosterone that further increase Na retention.
    • PD – ACEI stop peripheral conversion of Angiotensin 1 to 2. More bradykinin(vasodilator). Anti hypertensive by reducing TPR. CO and HR not changed much. No reflex tachycardia so safe in angina patients.
    • Good in CKD cos reduces proteinuria and stabilises renal function.
    • Captopril – the original
    • Enalapril, perindopril, ramipril are all predrugs converted in liver by hydrolysis.
    • SE – severe hypotension if started in volume depleted patient. Acute renal imp(esp in bilateral renal artery stenosis), hyper K, dry cough(bradykinin), angio-oedema. CI in 2nd and 3rd trimester of pregnancy.
    • PK
Drug T1/2 (Hrs) Oral Bioavailablity Dose reduc in renal imp
Captopril 2 65% Yes
Lisinopril 12 25% Yes
Losartan (ARB) 1-2 36% No


Angiotensin receptor blockers

  • Losartan/telmisartan/candesartan/valsartan
  • Angiotensin 2 receptor blocker. No effect on bradykinin so less cough and angio oedema.


Beta-blockers – Week 4 pharmacology

Alpha1 blockers (Prazosin). – Week 4 pharmacology

Alpha1&2 blockers (Phentolamine, Phenoxybenzamine) – Week 4 pharmacology

Ca2+ blockers – Week 10 pharmacology