Anti-Hypertensive Pharmacology Flashcards
Hypertensive values
>130/80
Blood pressure equations
BP is the pressure exerted against the arterial wall
BP=[EDV-ESV] x HR] x SVR
or
BP=CO x SVR
Ways to reduce cardiac output?
Reduce blood volume
Reduce heart rate
Reduce stroke volume
Ways to reduce SVR?
Dilate systemic vasculature
What are the four anatomic sites of BP control?
- Resistance arterioles
- Capacitance venules
- Pump heart output
- Volume kidneys (Renin-angiotensin-aldosterone)

Mechanism of action of Diuretics
- Deplete body of sodium and H2O
- Reduce blood volume (decrease stroke volume)
Type of Diuretics?
- *1. Loop diuretics
2. Thiazide diuretics
3. Potassium sparing diuretics**
4. Osmotic diuretics
5. Carbonic anhydrase inhibitors (renal specialists)
6. Vasopressin (ADH) antagonists
Where do loop diuretics act?

Blocks the Na/K/Cl exchanger in the ascending Loop of Henle, accounts for 25% less Na/K/Cl retention because it inhibits this pump. 25% more Na/K/Cl is excreted in the urine.
Uses:
Treatment/prevention of edamatous conditions (heart failure), hyperkalemia, HTN (2nd line)
Adverse effects (mainly dehydration):
Na/volume depletion leading to hypotension
Hypokalemia (arrhythmias), hypocalcemia (tetany), hypomagnesemia (arrhythmias), metabolic alkalosis
Ototoxicity (tinnitus, vertigo, deafness) in high concentrations
Hyperuricemia (gout) when used chronically

Where to thiazide diuretics act?
Act on a Na/Cl pump in the distal convoluted tubule (DCT) where 5% Na/Cl is excreted to the urine. First line of defense against hypertension because it is less potent, can augment the loop effect
Thiazides to remember:
Hydrochlorothiazide
Chlorthalidone
Indapamide
Metalazone (never used alone)
Adverse effects: Hypovolemia, hypokalemia, hyponatremia (common), hypochloremia, hypomagnesemia, hypercalcemia, hyperuricemia (gout), metabolic acidosis

Where do potassium sparing diuretics act?
Work in the collecting duct of the nephron by inhibiting aldosterone (antagonist) or blocking a Na/H/K exchanger. Pretty weak diuretics unless used for specific disease states, can cause hyperkalemia
Na Channel Blockers: triamterene and amiloride, inhibitors of renal epithelial Na+ channels
Aldosterone receptor antagonists: Indicated in HF, spironolactone and eplerenone (indirect effect)*
*Do not act on the luminal side of the tubule

What is the root cause of hypertension?
Sympathetic overdrive

Sympathetic receptor review

Drugs that alter sympathetic nervous system function?

Mechanism of action of a2 agonists
Stimulate a2 receptors on presynaptic neuron, reduces central sympathetic flow and increased parasympathetic flow
Adverse effects: Dry mouth, drowsiness/sedation, lethargy, constipation, sexual dysfunction, bradycardia, rebound HTN with withdrawal

Clonidine’s central mechanism of action?
Activation of a2 receptor initiates more firing of vagus nerve (decreases HR/SV) and decreases firing of sympathetic nerves leading to decrease in BP
Clinical use: Hypertension (not a first line of defense), resistant hypertension
Hypertensive urgency without acute organ damage
ADHD (guanfacine)
Treatment of withdrawal (Narcotics, alcohol)

What are the more a2 agonist specific drugs?

Alpha 1 adrenergic antagonists mechanism of action?

Inhibit binding of NE to postsynaptic alpha1 receptors by relaxing smooth muscles and decreasing peripheral vascular resistance and venous return
Uses: Mostly used for reducing resistance to urinary flow (relaxes smooth muscle), useful in benign prostatic hypertrophy, n__ot recommended for initial monotherapy
Adverse effects: Drowsiness, fluid retention, diarrhea, postural hypotension, syncope, tachycardia, can increase risk of HF with chronic use
First dose phenomenon: faintness or syncope 30-60min after first dose, use low initial dose (bedtime) and titrate slowly

Beta-Blocker effects/adverse effects? Clinical uses?
Adverse effects:
- Smooth muscle spasm (bronchospasm especially with non-selectives)
- Exaggeration of cardiac therapeutic actions (too much bradycardia/hypotension)
- CNS penetration (insomnia, depression, some more lipid soluble than others)
- Worsened quality of life (weight gain, fatigue, ED)
- Adverse metabolic side effects (loss of glycemic control, masks hypoglycemia)
- Withdrawal phenomenon
Clinical uses: Ischemic heart disease, HF with reduced EF (only metoprolol, carvedilol, bisoprolol), tachyarrhythmias, controlling acute panic symptoms, glucoma, variceal bleeding from portal hypertension/cirrhosis

Non-selective/cardioselective/vasodilating B-Blockers

What are the vasodilating B-Blockers, and what do they do?
BP reduction from decrease in HR and SVR
a1 and B1 antagonist

What are the two types of Ca channel blockers?
T (transient) type: opens at more neg. potentials, involved in initial depolarization of SA/AV nodes
L-type: located on vascular smooth muscle, cardiac myocytes, cardiac nodal tissue
Dominant in AV node, required for CICR from SR, Phase 0 and Phase 2 of action potential
Activity increased by catecholamines

Difference between DHPs and Non-DHPs

Dihydropyridines (DHP): -pine suffix, act on on arterioles
Non-DHPs: Act directly on the heart decreasing HR and contraction

B-blockage effects vs. CCBs

Clinical uses of verapamil or diltiazem?
- Hypertension
- Supraventricular tachyarrhythmias
- Coronary spasm
- Chronic stable angina






