Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

brs (phase 1b) > (pharm) pharmacology of hypertension > Flashcards

(pharm) pharmacology of hypertension Flashcards

1
Q

what are four classes of drugs that are commonly prescribed for hypertension?

A

angiotensin converting enzyme inhibitors (ACE inhibitors)

calcium channel blockers

thiazide/thiazide-like diuretics

angiotensin receptor blockers (ARBs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

give examples of ACE inhibitors

A

ramipril
lisinopril
perindopril

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

explain the primary mechanism of action of ACE inhibitors

A

inhibit angiotensin-converting enzyme

= prevent the conversion of angiotensin I to angiotensin II by ACE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the drug target for ACE inhibitors?

A

angiotensin-converting enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the main side effects of ACE inhibitors?

A

cough

hypotension

hyperkalaemia

foetal injury (AVOID IN PREGNANT WOMEN)

renal failure (in patients w renal artery stenosis)

urticaria/angioedema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how do ACE inhibitors affect serum potassium levels and why is this important?

A

can cause hyperkalaemia as a side effect so care must be take with K+ supplements or K+ sparing diuretics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how do ACE inhibitors affect foetuses?

A

can cause foetal injury as a side effect and so pregnant women cannot take them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what must occur for most ACE inhibitors to have their therapeutic effect?

A

require hepatic activation (as they are pro-drugs) to generate the active metabolites required for therapeutic effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

ACE inhibitors are pro-drugs - what does this mean?

A

require hepatic activation to generate the active metabolites required for therapeutic effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how do ACE inhibitors affect the kidneys?

A

can cause renal failure in patients with renal artery stenosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what must be regularly monitored if ACE inhibitors are prescribed?

A

serum potassium levels and eGFR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what are the more anti-hypertensive agents: ARBs or ACE inhibitors?

A

according to most trials, ACE inhibitors > ARBs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

give examples of calcium channel blockers

A

amlodipine

felodipine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

explain the primary mechanism of action of calcium channel blockers

A

binds to and blocks L-type calcium channels (found predominantly on vascular smooth muscle)

= decrease in calcium influx
= increases downstream inhibition of myosin light chain kinase + prevention of cross-bridge formation
= resultant vasodilation reduces peripheral resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the drug target for calcium channel blockers?

A

L-type calcium channels (found predominantly on vascular smooth muscle)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the main side effects of calcium channel blockers?

A

ankle oedema

constipation

palpitations

flushing

headaches

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are the two types of calcium channel blockers?

A

dihydropyridine CCBs and non-dihydropyridine CCBs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

differentiate between the two types of calcium channel blockers

A

dihydropyridine (DHP) CCBs tend to be more potent vasodilators than non-dihydropyridine (non-DHP) CCBs

(the latter have greater depressive effects on cardiac conduction and contractility and are less potent vasodilators)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

why are dihydropyridine calcium channel blockers more potent vasodilators?

A

they have a higher degree of vascular selectivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

give examples of thiazide/thiazide-like diuretics

A

bendro-flu-methiazide (thiazide)

indapamide (thiazide-like)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

explain the primary mechanism of action of thiazide/thiazide-like diuretics

A

bind to and block the Na+, Cl- co-transporter in the early DCT so Na+ and Cl- reabsorption into the blood is inhibited

= the osmolarity of the tubular fluid increases, steepening the osmotic gradient for water reabsorption in the collecting duct

= greater water reabsorption in the collecting duct reduces arterial pressure and therefore peripheral vascular resistance in the surrounding blood vessels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is the drug target for thiazide/thiazide-like diuretics?

A

sodium-chloride co-transporter in the distal convoluted tubule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what are the main side effects of thiazide/thiazide-like diuretics?

A

hypokalaemia

hyponatraemia

metabolic alkalosis (increased H+ ion excretion)

hypercalcaemia

hyperglycaemia (hyperpolarised pancreatic beta cells)

hyperuricemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

how long do the effects of thiazide/thiazide-diuretics last?

A

both lose their diuretic effects within 1-2 weeks of treatment and remaining anti-hypertensive effects are due to vasodilating properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

give examples of angiotensin receptor blockers

A

losartan
irbesartan
candesartan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

explain the primary mechanism of action of angiotensin receptor blockers (ARBs)

A

non-competitive antagonists at AT1 receptor (found on the kidneys and on the vasculature)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

which region of the body do angiotensin receptor blockers act on?

A

on the AT1 receptors found on the kidneys and vasculature

28
Q

what are the main side effects of angiotensin receptor blockers?

A

hypotension

hyperkalaemia (care w K+ supplements and K+ sparing diuretics)

foetal injury (avoid in pregnant women)

renal failure (in patients w renal artery stenosis)

29
Q

losartan and candesartan are pro-drugs - what does this mean?

A

require hepatic activation to generate the active metabolites required for therapeutic effects

30
Q

what are the classifications of hypertension?

A

stage 1 hypertension (140/90 to 160/100)

stage 2 hypertension (160/100 to 180/120)

severe hypertension (higher than 180/120)

31
Q

what is stage 1 hypertension?

A

between 140/90 to 160/100

32
Q

what is stage 2 hypertension?

A

between 160/100 to 180/120

33
Q

what is severe hypertension?

A

higher than 180/120

34
Q

what is Q risk?

A

an algorithm for predicting cardiovascular risk

35
Q

what does Q risk estimate?

A

estimated the risk of an individual developing cardiovascular diseases over the 10 years

36
Q

what is a concerning Q risk score?

A

an individual scoring above 10% is considered to be at high risk of cardiovascular disease

37
Q

what is used to predict an individual’s cardiovascular risk?

A

a Q risk score

38
Q

how would you manage a patient with a Q risk score of greater than 10%?

A

lifestyle modifications (more exercise, lose weight, improve diet, stop smoking, reduce alcohol intake)

drug treatment (maybe statin/other drugs depending on conditions)

39
Q

what are the therapeutic objectives for a patient with stage 1 hypertension?

A

reduce blood pressure levels to below 140/90 ideally

modify lifestyle factors that are associated with an increased morbidity and mortality (i.e. smoking, weight, alcohol intake)

ensure no contraindications to medication prescribed (interference w surgery?)

40
Q

why do calcium channel blockers have the greater effect on smooth muscle and cardiac muscle as opposed to skeletal muscle?

A

both smooth muscle and cardiac muscle rely on extracellular calcium (as well as intracellular calcium) for muscle contraction however skeletal muscle relies only on intracellular calcium stores

= so prevention of extracellular calcium influx will more significantly impair smooth + cardiac muscle contraction

(skeletal muscle may also have different types of calcium channels which CCBs cannot act on)

41
Q

what is the mechanism of action of calcium channel blockers?

A

bind to and block L-type calcium channels, preventing an influx of extracellular calcium into the vascular smooth muscle cells

prevent the formation of of actin-myosin cross-bridges, reducing frequency and force of muscle contraction

= subsequently less vasoconstriction reduces peripheral vascular resistance

42
Q

why is vasodilation important to tackle hypertension?

A

vasodilation will reduce the systemic vascular resistance by allowing for a increased in blood flow and therefore reduced blood pressure

43
Q

what is plasma clearance in terms of pharmacology?

A

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

44
Q

what is elimination half-life in terms of pharmacology?

A

the length of time required for the concentration of a particular drug to decrease to half of its starting dose in the body

45
Q

what is time to peak plasma levels in terms of pharmacology?

A

the time required for a drug to reach peak concentration in plasma

(i.e. faster absorption rate, less time to peak plasma concentration)

46
Q

what is the relationship between absorption rate and time to peak plasma concentration?

A

faster absorption rate, less time to peak plasma concentration

47
Q

what is the measure of plasma clearance?

A

ml/min/kg

48
Q

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

A

bind to and inhibit angiotensin converting enzyme that prevents the conversion of angiotensin I to angiotensin II

with less angiotensin II, less aldosterone synthesis is stimulated = reduced vasoconstriction + reduced Na+ retention in the kidneys

49
Q

why do calcium channel blockers cause oedema?

A

increased vasodilation = increased Starling forces within the bloodstream = increased capillary hydrostatic pressure resulting in oedema

50
Q

why are angiotensin receptor blockers preferentially used over ACE inhibitors?

A

as ARBs will not simultaneously also reduced the conversion of bradykinin to inactive metabolites

51
Q

what two factors have to be monitored in patients on ACE inhibitors?

A

serum potassium and eGFR

52
Q

explain why eGFR has to be monitored in patients on ACE inhibitors

A

less angiotensin II = less constriction of the efferent arteriole so blood does not build up in glomerulus SO glomerular pressure cannot increase

= impaired/reduced glomerular filtration

53
Q

explain why serum potassium has to be monitored in patients on ACE inhibitors

A

increased ACE inhibitors = less aldosterone synthesis

aldosterone stimulates Na+ reabsorption and K+ excretion in the renal collecting duct

so with less aldosterone, less Na+ reabsorption and LESS K+ excretion

= increased K+ retention risks hyperkalaemia

54
Q

what effect does angiotensin II have on the glomerular arterioles?

A

angiotensin II will constrict the glomerular arterioles

will constrict the efferent arteriole MORE SIGNIFICANTLY than the afferent

= forces blood to build up in the glomerulus, increasing glomerular pressure

= required for glomerular filtration

55
Q

which glomerular arteriole does angiotensin II more significantly affect?

A

efferent arteriole

56
Q

explain what happens if an ACE inhibitor is given to a patient with renal artery stenosis

A

afferent arteriole already stenosed (i.e. already less blood is entering the glomerulus)

+ combined with reduced tone of efferent arteriole (due to ACEi)

= glomerular pressure cannot increase to sufficient levels to allow glomerular filtration to efficiently occur
(GFR collapses)

57
Q

what is the mechanism of action of indapamide (thiazide-like diuretic)?

A

block the Na+, Cl- co-transporter in the early DCT

= Na+ and Cl- reabsorption is inhibited

so osmolarity of the tubular fluid increases, so steeper water potential gradient

= reduced water reabsorption in the collecting duct

= reduced arterial pressure
= reduced peripheral vascular resistance

58
Q

what effect do thiazide-like diuretic have on serum potassium?

A

reduce serum potassium levels

59
Q

what drug type is given to type II diabetes patients with hypertension and why?

A

respond better to ACEi than CCB as ACEi tend to be better for renal function which can be impaired in T2DM patients

60
Q

what dietary modifications can patients with hypertension be encouraged to make?

A

follow DASH (dietary approaches to stop hypertension)

daily sodium < 1.5 grams

61
Q

two of the most commonly prescribed ACE inhibitors are ramipril and lisinopril

ramipril (like most ACE inhibitors) is a pro-drug whereas lisinopril is not

what does this mean?

A

pro-drugs = drug is inactive until it is metabolised in the body (most commonly in the liver)

62
Q

what is the opposite of a pro-drug?

explain how

A

pro-drug = drug is inactive until it is metabolised by the liver

active drug = drug is active and it takes effect directly

63
Q

what are the three main impacts of thiazide-like diuretics?

A

as a result of the inhibition of the apical Na+/Cl- symporters, and the subsequent urinary Na+ and water loss,

1) decreased blood volume
2) decreased venous return
3) decreased cardiac output

64
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

the target site of action for thiazide-like diuretics is apical transporters in the kidney

the only way to get to this site of action is via glomerular filtration into the Bowman’s capsule and beyond

= if they are excreted unchanged, they will be able to have the desired effect at the desired site of action

65
Q

why do thiazide-like diuretics increase potassium excretion?

A

thiazide-like diuretics act on the early DCT apical Na+/Cl- symporters to increase urinary sodium loss

= increased Na+ delivery from the early DCT to the distal DCT
= subsequent increased tubular Na+ concentration activates aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium + hydrogen excretion

= increased potassium excretion

(!! increased hydrogen ion loss causes metabolic alkalosis !!)

66
Q

how long does the effect of thiazide diuretics last and why?

A

the diuretic effect lasts around 1-2 weeks

= as eventually the kidney becomes tolerant to the diuretic effect and there is subsequent rebound activation of the renin-angiotensin system which increases sodium reabsorption, counteracting the diuretic effect

67
Q

despite the diuretic effect of thiazide-like diuretics lasting only 1-2 weeks, what can the continued (after 2 weeks) antihypertensive effect be attributed to?

A

(less well understood) vasodilating effects

brs (phase 1b) (71 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions