5. Pharmacology of Anti-hypertensive Agents Flashcards
What is hypertension?
Blood pressure over 140/90 mmHg
BP = CO x TPR
CO (L/min) = SV x HR
TPR = Resistance to blood flow across all systemic vasculature
Main mechanisms involved in arterial blood pressure regulation
Heart: CO - rate & force of contraction
Vasculature: TPR - vasoconstriction & dilation
Kidney: TPR - blood volume
A: Renin-Angiotensin System
- Renin release is rate limiting step - released from Juxtaglomerular cells (kidneys)
- ACE found in lungs
- Ang II - primarily acts on AT 1 receptor
AT1 mediated vasoconstriction
Ang II acts on AT1 (Gq receptor) triggering IP3 resulting in Smooth muscle contraction
ACE-inhibitors
- Prevent conversion of Ang I to Ang II
- Reduce level of Ang II
- Indirect acting vasodilators
- Other effects including reduced sodium retention
ARBs
AT1 receptor agonist:
- Prevents Ang II binding
- Prevents receptor coupled IP3 production
Renin inhibitor
Aliskiren is a new agent used for primary hypertension
- Inhibition of the level of renin - better control of RAAS
Renin Ang II pathways - Side effects
- Hyperkalaemia - increase K+ in blood
- Teratogenicity
- Dizziness
- Nausea
- Fatigue
ACE-inhibitors - dry cough
Renin inhibitors - diarrhoea
B: Beta adrenoreceptor antagonists
Act on both within the heart & juxtaglomerular cells in the kidney
Beta blockers
Selective beta blockers: Metoprolol
- Prevent NA binding to B1 on cardiomyocytes
- Prevents activation of cAMP/PKA downstream pathways
- Reduces chronotropy (speed of contraction - HR & inotropy (force of contraction - SV)
Non-selective beta blocker: Carvedilol
- In addition to beta blocking effects also has alpha blocking
- Reduces vasoconstriction
Alpha1 adrenorecpetor antagonists
- Vascular smooth muscle
- Inhibits IP3 medicated contraction
Prazosin produces vasodilation with little/no effect on CO
- Reserved for crisis
Beta blocker/alpha blocker side effects
- Fatigue
- Dizziness
- Lightheaded
- Poor circulation - cold fingers/toes
- Nausea - GI issues
Calcium channel blockers
Cardiac - decrease chronotropy (speed of contraction - HR) & inotropy (force of contraction - SV) to block the voltage gated sodium channel & prevent downstream calcium release
Vascular - smooth muscle relaxation which blocks L-type Ca2+ channel, preventing calcium entering & binding
- Prevent cardiomyocyte contractile machinery
- Promote vasodilation
CCB: 3 classes
- 1st generation – Nifedipine
- 2nd generation – Isradipine, Nicardipine, Felodipine
- 3rd generation – Amlodipine
- Phenylalkylamines – Verapamil
- Benzothiazepines – Diltiazem
Benzothiazepines - Diltiazem
- Vasodilates coronary & peripheral vessels
- Cardiovascular effects:
+ Decrease contractility
+ Lower heart rate
+ Slows conduction through AV node - Reduced peripheral resistance & after load
+ Pressure is reduced so less blood is pumped out - Less potent as dihydropyridine CCBs
