Case 5 - Anti-Hypertensives

Front 1

Regulation of Blood Pressure

Back 1

1. Blood Volume - Sodium Intake/ Renal excretion
2. Cardiac Output- heart rate/ stroke volume.
3. Peripheral Resistance

Front 2

Tissue Targets for BP lowering

Back 2

1. Kidney - Regulate blood volume
2. Heart - alter CO
3. Arterioles - peripheral resistance
Also:
-CNS centres regulating BP control
-Sympathetic nerves- release NA

Front 3

Vascular smooth muscle

Back 3

1. Vasoconstrictors
a) activate voltage gated Ca2+ channels
b)receptor operated Ca2+ channels
c) receptor mediated increase in IP3
2.Vasodilators
a)block voltage gated Ca2+ channels
b)hyperpolarise cell membrane.
c)interfere with mechanisms linking Ca2+ to contraction - increased cAMP and cGMP

Front 4

Adrenergic Receptors

Back 4

1. 4 main types - a1, a2, B1, B2
2. B-adrenoceptors coupled to adenylate cyclase increase cAMP
3. a1 adrenoceptors increase IP3 - a2 receptors decrease cAMP

Front 5

Norepinephrine vs. epinephrine

Back 5

1. Norepinephrine
-released from sympathetic nerve terminals
- a>B
2. Epinephrine
- circulating hormone released from adrenals
-B>a effects

Front 6

Hypertension Drugs

Back 6

A ACEI/ARBs Enalapril, lisinopril, losartan
B Beta Blockers Atenolol
C CCBs Nifedipine Amlodipine
D Diuretics (thiazide) Bendroflumethiazide
Alpha Blockers Prazosin, Doxaziosin

Front 7

Thiazide Diuretics

Back 7

1. Bendrofluethiazide
-Drug of first chocie for >50 age.
2. Increase excretion of Na, Cl K and water. via blockade of Na-Cl cotransporter at distal nephron. Leads to excess K+ loss.
3. BP lowering due to decreased peripheral resistance, not Na loss
Also:
-decreased renal excretion of Ca2+, increased plasma glucose
- adverse effects: orthostatic hypotension, gout, impotence, diabetes, hypokalaemia

Front 8

Beta Blockers

Back 8

1. Atenolol
2. Decreased heart rate - slow conduction AV node, less spotaneous firing.
3. Inhibition of renin-angiotensin system
4. Decreased peripheral resistance
Also:
-in hypertension cardio selective (B1) drugs are used.
- can precipitate or exacerbate heart failure.

Front 9

Alpha Blockers

Back 9

1. Prazosin, doxazosin
- Block a1 adrenoceptors
-Produce vasodilation decrease BP
- Baroreceptors increase HR.
-First dose phenomenon.

Front 10

Calcium Channel Blockers

Back 10

1. Act on L-type voltage sensitive Ca2+ channels.
2. Inhibit the slow calcium current in sinus and AV node.
3. Haemodynamic effects - decreased PR/HR/coronary vascular resistance
Also:
-adverse effects: flushing, nausea, oedema, bradycardia, heart failure

Front 11

ACE Inhibitors

Back 11

1. Mechanism of Action
-Inhibits angiotensin I to ang II
-Inhibits degradation of bradykinin.
-Reduces aldosterone secretion
-renal vasodilation
2. Commonly used in heart failure.
Adverse Effects
-Renal Failure
-Cough
-Hyperkalaemia
-Angioedema
-Urticaria
-Fetal Injury

Front 12

Angiotensin Receptor Blockers

Back 12

1. Mechanism of Action
-Inhibit Ang II
-Vasodilation,
Increasingly used with ACEIs, most commonly in heart failure

Front 13

ABCD

Back 13

AB drugs = renin-angiotensin
CD drugs = reduce peripheral resistance

-Start with D or A in younger patients
- Combine A or B with C or D
- Avoid combination of B and D- increased risk of diabetes.