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Year 2 - Pharm Lectures 11+ > Drugs & The CVS - The Heart > Flashcards

Drugs & The CVS - The Heart Flashcards

1
Q

3 different mechanisms regulating HR?

A

If

Ica (T or L)

Ik

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2
Q

If?

A

Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels
•’funny’ channels
• predominantly a Na+ channel (initates depolarisation)
• switches on during hyperpolarisation
• utilises cAMP

BUT not enough on its own to initiate FULL depolarisation

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3
Q

Ica (T or L)?

A

Transient T-type Ca2+ channel
OR
Long-lasting L-type

• mediates fast calcium influx

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4
Q

Ik?

A

Potassium channels

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5
Q

What is Phase 4 during HR regulation in SA Node?

A

ONENOTE!!

Spontaneous depolarisation (pacemaker potential) that triggers the AP

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6
Q

SN and PSN effect on HR?

A

SN
• INCREASES cAMP
SO
• INCREASES If & Ica

PSN
• DECREASES cAMP
SO
• INCREASES Ik

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7
Q

How is contractility regulated?

A

B1-receptor stimulation activates AC which creates cAMP which activates PKA - 2 main actions:
• phosphorylates proteins in the myofibril
• induces CICR in the SR (via stimulating Ca2+ influx into SR via. RyR)

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8
Q

Where does the majority of Ca2+ come from in the cardiac muscle?

A

75% - from CICR (aka SR)

25% - from the outside

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9
Q

How is Ca2+ then removed for contractility regulation?

A

Either
• pumped back into the SR (via. ATPase Ca2+ channel)
• removed via. Na/Ca exchanger (w. the help of Na/K ATPase)

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10
Q

What influences myocardial oxygen supply?

A

PRIMARILY
• coronary blood flow
(pathologically more important)

AND also
• arterial O2 supply

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11
Q

What regulates myocardial oxygen demand?

A

Myocyte contraction - primary determinant

  • increased HR = increased contractions
  • increased afterload = increased force of contraction
  • increased preload = small increase in force of contractions
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12
Q

Drugs influencing HR?

A

• BETA-BLOCKERS (predominantly B1)
- decrease If & Ica

• CA2+ ANTAGONISTS
- decrease Ica

• IVABRADINE

  • decrease If
  • less pronounced as Ca2+ is the main driver
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13
Q

Drugs influencing contractility?

A

• BETA-BLOCKERS

  • decreases contractility
  • reduces phosphorylation & cross-bridge formation

• CALCIUM ANTAGONISTS

  • decreases Ica
  • stops further entry of Ca2+ into myofibrils
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14
Q

What are the two classes of calcium antagonists?

A

RATE SLOWING
• CARDIAC & VSM action
• Phenylakylamines - e.g. Verapamil
• Benzothiazepines e.g Diltiazem

NON-RATE SLOWING
• VSM action - more potent!
• Dihtdropyridines e.g. amlodipine

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15
Q

What can occur with non-rate slowing calcium antagonists?

A

Have NO effect on the heart (just VSM)
BUT
the profound vasoDILATION produced can lead to REFLEX TACHYCARDIA

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16
Q

Drugs influencing myocardial O2 supply/demand?

A

• ORGANIC NITRATES

  • DIRECTLY supply NO
  • increases cGMP = stimulates K+ channel opening = relaxation
  • can stimulate K+ channel directly as well!

• POTASSIUM CHANNEL OPENERS

  • stimulates hyperpolarisation (ability of coronary arteries to contract is impaired)
  • -VE feedback on Ca2+ channels
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17
Q

Ultimately what do organic nitrates & potassium channel openers affect?

A

INCREASE coronary blood flow!

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18
Q

What 2 different effects of nitrates/potassium openers influence preload & afterload?

A

DECREASE preload/afterload (demand)
AND
INCREASE O2 supply (increase blood supply)

VASOdilation = decreased afterload
VENOdilation = decreased preload
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19
Q

Classically what is angina defined as?

A

Classic mismatch between myocardial O2 supply & demand!

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20
Q

How can the drugs be used than for angina treatment?

A
  1. Beta-blocker OR CCA
    • background treatment
    • e.g. Ivabradine - more specific
  2. Nitrate
    • symptomatic treatment (i.e. exercise)
  3. Other
    • e.g. K-channel openers if intolerant to other drugs
21
Q

What aspects of the myocardial O2 supply and demand do the drugs affect?

A

Ivabradine
• HR

Beta-blocker
• HR
• Contractility

CCB
• HR
• Contractility

Nitrate & K-channel opener
• Coronary blood flow
• Preload
• Afterload

22
Q

What are possible criteria should be aware of if on beta-blockers?

A

Worsening HF
• CO reduction & increased vascular resistance can affect it for the worst!

Bradycardia
• if heart block, decreased conduction through AV node so can worsen it

MAINLY due to B2 as are vasoDILATORS so are blocking that!

23
Q

What can be used to lessen the 2 big beta-blocker side-effect?

A

Pindolol (non-selective)
• has ISA

Carvedilol (mixed B&A-blockers)
• A1 blockade gives additional vasoDILATOR properties!!

24
Q

Other possible SEs of beta-blockers in relation to certain conditions?

A 
ALWAYS want to know if patient is either
 • asthmatic 
OR
 • diabetic
BEFORE giving beta-blockers

as can lead to
• bronchoconstriction
• hypoglycaemia (masks the early warning sign of this)
• cold extremities

25
Q

Why does beta-blocker use lead to cold extremities?

A

Cold extremities/worsening of peripheral artery disease

LOSS of B2-receptor mediated cutaneous vasodilation in extremities

26
Q

Other general SEs of beta-blocker use?

A 
Fatigue
Impotence (sexual dysfunction)
Depression
CNS effects (lipophilic agents)
 • e.g. nightmares

ALTHOUGH RCTs question the validity of these

27
Q

SEs of CCBs in relation to B-blockers?

A

Said to be ‘safer’ than b-blockers

28
Q

SEs of Verapamil?

A

CCB - rate-limiting

Bradycardia & AV-block
• heart Ca2+ channels blockers

Constipation
• gut Ca2+ channels blocked

29
Q

SEs of Dihydropyridines?

A

CCB - non-rate limiting

Ankle oedema
• vasodilation means more capillary pressure in extremities

Headache/flushing
• due to vasodilation

Palpitations
• reflex SNS adrenergic activation due to vasodilation

30
Q

SEs of K+-opening channels/nitrates?

A

Ankle oedema
• vasodilation means more capillary pressure in extremities

Headache/flushing
• due to vasodilation

31
Q

What are the aims of rhythm disturbance treatment?

A

Reduce sudden death
Alleviate symptoms
PREVENT STROKE!!

32
Q

Simple classification of arrhythmias?

A

Based on site of origin
• Supraventricular (above ventricles)
- e.g. Amiodarone, Verapamil

• Ventricular
- e.g. Flecainide, Lidocaine

• Complex (supra + ventricular)
- e.g. Disopyramide

33
Q

What is the Vaughan Williams Classification and what is interesting about it?

A

Classification of anti-arrhythmic drugs separated into 4 areas:
• Class 1 = Na+-channel blockade
• Class 2 = Beta-blockers
• Class 3 = K+-channel blockade (prolong repolarisation)
• Class 4 = Ca2+-channel blockade

Classification is of LIMITED clinical significance due to the significance of cross-overs in rhythm disturbance

34
Q

Potential selective anti-arrhythmic drugs?

A
  • Adenosine
  • Verapamil
  • Amiodarone
  • Digoxin
35
Q

MOA of Adenosine?

A

Activates A1 receptors in the SA & AV node
•Gi protein activation = reduces AC conversion of ATP to cAMP
• = decreased cAMP = decreased ionotropic & chronotropic effect

Also causes relaxation in VSMCs by increasing cAMP instead (Gs-protein)

36
Q

Use of Adenosine?

A

Targets SVT!!
• IV-given
• short-action (thus safer than Verapamil)
• Class IV drug

37
Q

Use of Verapamil?

A

Reduces ventricular responsiveness to atrial arrythmias

38
Q

MOA of Verapamil?

A

Blocks VGCC
• depresses SA firing and subsequent AV node conduction

Class IV drug

39
Q

Uses of Amiodarone?

A

SVT & VT
• due to RE-ENTRY

(onenote for explanation!!)

40
Q

MOA of Amiodarone?

A

Complex but probably invovles multiple ion-channel block
• most likely prolongs hyperpolarisation which reduces chance of re-entry

Class I, II, III & IV
• SO limited clinical importance

41
Q

Adverse effects of Amiodarone?

A

Accumulation in body (t1/2 10-100days)
Skin rashes (photosensitive)
Hypo OR hyper-thryoidism
Pulmonary fibrosis

42
Q

What 2 broad affects does Digoxin have on?

A
  1. INHIBITS NA+/K+ ATPase

2. Central vagal stimulation

43
Q

What effect does Digoxin have on inotropy in regards to (1)?

A 
Inhibits Na+/K+ ATPase
 • increases IC Ca2+
 • reversal of Na+/Ca2+ exchanger
 • Na efflux & Ca influx
 • POSITIVE INOTROPIC EFFECT

Ca2+ struggles to leave the cardiac muscle so remains for longer = contraction becomes STRONGER

44
Q

What effect does Digoxin have on inotropy in regards to (2)?

A

Central vagal stimulation
• increases refractory period
AND
• reduced rate of conduction through the AV node

SO slows the HR down!

45
Q

What is the double whammy of Digoxin?

A

Improving rhythm control of the heart
WHILST ALSO
improving CO (by increasing contractility)

46
Q

Uses of Digoxin?

A

In atrial fibrillation & flutter leads to a rapid ventricular rate that can
• impair ventricular filling (due to reduced filling time)
&
• reduce CO

Digoxin via. vagal stimulation reduces the conduction of electrical impulses within the AV node
• fewer impulses reach the ventricles and ventricular rate falls

47
Q

SEs of digoxin?

A

Dysrhythmias

e.g. AV conduction block, ectopic pacemaker activity

48
Q

Why does hypokalaemia (usually due to diruetic use) lower threshold for digoxin toxicity?

A

Digoxin is a K+-receptor competitive antagonist
SO
low blook K+ means less competition and so the effect of digoxin are enhanced

(onenote for more info!)

49
Q

Digoxin?

A

Cardiac glycoside

Year 2 - Pharm Lectures 11+ (23 decks)

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