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Y2 - BRS - Pharm > Pharmacology of Hypertension > Flashcards

Pharmacology of Hypertension Flashcards

1
Q

What are the 4 anti-hypertensive drug classes?

A
  1. ACEi (angiotensin converting enzyme inhibitors)
  2. Calcium channel blockers
  3. Thiazide or thiazide-like diuretics
  4. ARB (angiotensin receptor blockers)
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2
Q

What are some examples of ACEi?

A

Ramipril

Lisinopril

Perindopril

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3
Q

What is the primary mechanism of action of ACEi?

A

Inhibit the angiotensin converting enzyme

Prevent the conversion of angiotensin I to angiotensin II by ACE

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4
Q

What is the drug target site of ACEi?

A

ACE (angiotensin converting enzyme)

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5
Q

What are the main side effects of ACEi?

A

Cough

Hypotension

Hyperkalaemia (care with K+ supplements or K+ sparing diuretics)

Foetal Injury (AVOID IN PREGNANT WOMEN)

Renal failure (in patients with renal artery stenosis)

Urticaria / Angioedema (fluid buildup and swelling under the skin)

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6
Q

What is some extra information about ACEi?

A

Most ACEi (not lisinopril) are pro-drugs - require hepatic activation to generate active metabolites

eGFR and serum potassium must be regularly monitored when prescribing ACEi

Most trials indicate that ARBs are not as effective as ACEi

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7
Q

What are some examples of calcium channel blockers?

A

Amlodipine

Felodipine

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8
Q

What is the primary mechanism of action of calcium channel blockers?

A

Block L-type calcium channels – predominantly on vascular smooth muscle

Results in a decrease in calcium influx = inhibition of myosin light chain kinase and cross-bridge formation

Results in vasodilation = reduces peripheral resistance

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9
Q

What is the drug target site of calcium channel blockers?

A

L-type calcium channel

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10
Q

What are the main side effects of calcium channel blockers?

A

Ankle oedema

Constipation

Palpitations

Flushing/Headaches

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11
Q

What is some extra information about calcium channel blockers?

A

Dihydropyridine type calcium channel blockers demonstrate a higher degree of vascular selectivity

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12
Q

What are some examples of thiazide or thiazide-like diuretics?

A

Bendro-flumethiazide (thiazide)

Indapamide (thiazide-like)

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13
Q

What is the primary mechanism of action of thiazide or thiazide-like diuretics?

A

They block the Na+, Cl- co-transporter in the early DCT = Na+ and Cl- reabsorption is inhibited

Osmolarity of the tubular fluid increases = decreasing the osmotic gradient for water reabsorption in the collecting duct

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14
Q

What is the drug target site of thiazide or thiazide-like diuretics?

A

Sodium/chloride cotransporter

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15
Q

What are the main side effects of thiazide or thiazide-like diuretics?

A

Hypokalemia

Hyponatremia

Metabolic alkalosis (increased hydrogen ion excretion)

Hypercalcemia

Hyperglycemia (hyperpolarised pancreatic beta cells).

Hyperuricemia

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16
Q

What is some extra information about thiazide or thiazide-like diuretics?

A

Thiazide and thiazide-like diuretics both lose their diuretic effects within 1-2 weeks of treatment

Continuing anti-hypertensive action appears to be due to vasodilating properties (these are more pronounced for the thiazide-like diuretics)

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17
Q

What are some examples of ARB?

A

Losartan

Irbesartan

Candesartan

18
Q

What is the primary mechanism of action of ARB?

A

Act as insurmountable (i.e. non-competitive) antagonists at AT1 receptors (found on kidneys and on the vasculature)

19
Q

What is the drug target site of ARB?

A

Angiotensin receptor

20
Q

What are the main side effects of ARB?

A

Hypotension

Hyperkalaemia (care with K+ supplements or K+ sparing diuretics)

Foetal Injury (AVOID IN PREGNANT WOMEN)

Renal failure (in patients with renal artery stenosis)

21
Q

What is some extra information about ARB?

A

Most trials indicate that ARBs are not as effective as ACEi

Losartan and candesartan are pro-drugs = require hepatic activation to generate the active metabolites

22
Q

Case Study: Mrs Turner

64F - Rheumatoid arthritis for 9 years, in the last year her mobility is severely restricted, in pain even at rest

Pre-op for arthroplasty (replacement) revealed: BP = 149/93mmHg

GP measures 147/92mmHg and 145/91mmHg on 2 different occasions.

She is offered ambulatory blood pressure monitoring by her GP. Apart from RA pain, Mrs Turner feels well, although she does smoke (< 10 per day). She is 167cm and 85kg.

What is the patient’s problem?

A

BMI = 30.4

Pain from RA
Hypertension

23
Q

What is a q-risk score?

What are the 5 biggest risk factors for cardiovascular-related events?

A

Large database from which the algorithm can find your risk for cardiovascular related diseases / conditions e.g. strokes, MIs, CVD

Hypertension
Hypercholsterolaemia
Family history
Diabetes
Smoking
24
Q

What is Mrs Turner’s calculated q-risk score?

A

14.9

25
Q

What is the therapeutic objective for Mrs Turner?

A

Lower her BP - to reduce risk of long term consequences e.g. cardiovascular related diseases

Pain management of her RA

26
Q

Why is compliance lower for patients to take hypertension medication compared to e.g. inhalers?

A

Hypertension medications = no immediate effects
Short-term makes you feel worse due to everyday side effects
They offer future protection that patients sometimes do not realise

V. rarely patients sometimes have hypertensive encephalopathy (general brain dysfunction due to significantly high blood pressure), in which case the medication will have quick short term and long term effects

Whereas inhalers = feel better within a few hours

27
Q

What would you do next for Mrs Turner?

A

Firstly, give her lifestyle modifications e.g. stop smoking, reduce her BMI etc.
Check for diabetes

Do an ambulatory 24-hr reading

Find out whether she has hypertension, and if she does - stage 1 or stage 2?

28
Q

What are Stage 1 and Stage 2 hypertension?

When do you decide to treat (give hypertension medication to) patients?

A

Stage 1 = 135-150 systole
Stage 2 = 150+ systole

Stage 2 = get treated
Stage 1 = only get treated if they also have target end organ damage, renal disease, 10 year risk of greater than 10%, CVD or left ventricular hypertrophy

29
Q

Why would Mrs Turner be treated with calcium channel blockers instead of ACE inhibitors?

A

The NICE guidelines for the treatment of hypertension would suggest that Mrs Turner is treated with a calcium channel blocker - >55 y/o and ethnicity (black)

30
Q

The two most commonly prescribed calcium channel blockers are amlodipine and felodipine (both 2.5mg once daily as a starting dose)

What is the mechanism of action of calcium channel blockers in the treatment of hypertension?

A

Calcium channel blockers prevent calcium from entering the heart muscle cells

Leads to less contractility of the heart and vasodilation

Relaxes smooth muscle, reduces resistance of the blood vessels, reduces cardiac output

31
Q

What is meant by the term clearance in general?

A

Clearance = the measure of the ability of the body to eliminate a drug

Clearance by means of various organs of elimination is additive

Elimination of drug may occur as a result of processes that occur in the liver, kidney, and other organs

32
Q

What is meant by plasma clearance?

What is elimination half-life?

What is meant by time to peak plasma levels?

A

Plasma clearance = how much blood goes through the kidney in a given time to filter out the drug

Elimination half-life = time it takes for the concentration of the drug in the body to half

Peak plasma levels = time it takes for the medication in the blood plasma to accumulate and reach peak concentration, the faster the absorption rate the lower the time to peak plasma concentration

33
Q

What is the relationship between plasma clearance and elimination half-life?

A

As plasma clearance (ml/min/kg) decreases elimination half life increases

Time to peak plasma levels increase

Conc. of drugs with a long half life remains fairly stable

34
Q

Felodipine:
Plasma clearance (mL/min/kg) - 38
Elimination half-life (hrs) - 6-8
Time to peak plasma levels (hrs) - 1-3

Amlodipine:
Plasma clearance (mL/min/kg) - 11
Elimination half-life (hrs) - 35-50
Time to peak plasma levels (hrs) - 6-12

What are the differences between amlodipine and felodipine?

So which is more suitable between Felodipine and Amlodipine?

A

Felodipine = cleared faster, quicker accumulation of the medication in the blood plasma

Amlodipine = cleared slower, effects last longer and more or less consistently, but takes longer to accumulate in the blood to cause the effects

Amlodipine = more suitable = stays in the blood longer and more consistently throughout the day

35
Q

Mrs Turner = suffering with swollen ankles since she started on amlodipine, too painful on her knee.

GP mentions the angiotensin converting enzyme (ACE) inhibitors.

What is the mechanism of action of ACE inhibitors in the treatment of hypertension?

A

Targets ACE - mainly in the lungs and some in the renal endothelium

Stops conversion of angiotensin-1 to angiotensin-2

Angiotensin-2 is a very potent vasoconstrictor, so if this is inhibited, the peripheral vessels remain vasodilated

Angiotensin-2 also induces aldosterone, which increases Na+ absorption resulting in increased H2O absorption, which increases blood volume. So lack of angiotensin-2 leads to increased urine output = lowered blood volume = lowered BP

36
Q

What are ARBs?

A

Angiotensin receptor blockers - block the action of angiotensin-2

37
Q

Why do ACEi cause a cough, but ARBs do not?

A

ACE = has functions other than converting angiotensin-1 to angiotensin-2, it also breaks down bradykinin, which accumulates and can lead to a cough

ARBs block angiotensin-2 action directly, so ACE are still free to break down bradykinin

38
Q

If Mrs Turner were to start an ACE inhibitor, the advice would be to check renal function (eGFR), serum electrolytes (especially blood potassium) and blood pressure 1-2 weeks after starting treatment

Why might ACE inhibitors have a negative effect on eGFR and serum potassium?

A

Afferent arteriole needs to be more open than the efferent arteriole to produce the pressure in the glomerulus that filters out the blood

Lack of angiotensin-2 = lack of constricted efferent arteriole = lowered pressure = lowered eGFR

Lack of angiotensin-2 = lack of aldosterone = more Na+ and water in the urine output = more K+ remains in the blood = hyperkalaemia. Increased K+ in the blood = can affect the heart

39
Q

Mrs Turner and her GP decide against the ACE inhibitors as increase in serum K+ = cancellation of her knee replacement

Mrs Turner agrees to switch to a thiazide-like diuretic – indapamide (1.25mg orally once a day)

What is the mechanism of action of indapamide?

A

Block the sodium chloride co-transporter in the distal tubule

More Na+ remains in the filtrate, which leads to increased water passed in the urine output

For the first few weeks it leads to reduced cardiac output due to reduced venous return (due to lowered blood volume)

But long term, reduces peripheral resistance

40
Q

How is there Na+ excreted into the filtrate if sodium chloride channels are blocked in the kidneys?

A

Earlier on in the distal tubule, the sodium chloride channel is blocked - preventing reabsorption of Na+ and Cl-

But in the later part of the distal tubule, it is a different set of sodium transporters, which eliminate Na+ from the blood at the expense of K+ (As in K+ reabsorbed as Na+ excreted)

This increases water reabsorption in the distal tubule

Increased urine output
Decreased cardiac output

41
Q

What happens after you take thiazide diuretics for a while?

A

After a while a mechanism adapts to overcome the reduction in cardiac output

Cardiac output goes back to normal

So in reality they work by decreasing total peripheral resistance

42
Q

Indapamide (and other thiazide-like diuretics) are excreted unchanged in the urine

Why is this a vital part of the therapeutic action of thiazide-like diuretics?

A

These drugs work in the kidneys, therefore must remain unchanged as they pass through the liver, when they reach the kidneys so they can have their therapeutic effect?

(I think)

Y2 - BRS - Pharm (9 decks)

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