Pharmacology Flashcards
what are the classes of antidysrhythmics
- what is used to treat bradycardia
class 1 - na+ channel blockers class 2 - beta blockers class 3 - k+ channel inhibitors class 4 - ca2+ channel blockers
“nice boys kick cats”
brady cardia - muscR blockers (rarer)
class 1 antidysrhythmics - what are they
how do they work
examples
- what is their effect on the effective refractory period
Na+ channel blockers
- decrease the phase 0 slope
- decrease the peak of ventricular action potential
they all have different effects on ERP
class 1a - quinidine - ↑ERP
class 1b - lignocaine - ↓ERP - clinical use = topical anaesthetic, very narrow therapeutic range if IV (only use in emergency)
class 1c 0 flecainide - no effect on ERP
class 2 antidysrhythmics - what are they
how do they work
effects
adverse effects
examples
class 2 - beta blockers
block the stimulation by the SNS on cardiac electrical activity
also stabilises the membrane in Purkinje fibres (similar to class I - can block Na+)
effects
- ↓sinus rate
- ↓conduction velocity
- ↓aberrant pacemaker activity
adverse effects
- hypotension
- bradycardia
- can’t increase HR to meet extra demand
- bronchoconstriction
examples - “olols”
class 3 antidysrhythmics - what are they
how do they work
what do they increase risk of?
examples
K+ channel inhibitors
- stop the efflux of K+ (phase 3)- prolong the cardiac action potential
- ↓incidence of re-entry
increase risk of triggered events (in refractory period)
example: amiodarone (also blocks sodium, calcium)
class 4 antidysrhythmics - what are they
how do they work
examples
calcium channel blockers
mechanism
- preferentially acts on SA/AV nodes
- decreases Ca2+ entry for action potential activation
- slow phase 0
example - varapamil (cardio-selective)
- preferentially acts on SA/AV nodes
- treats atrial tachy
Hypertension - risk factors
Treatment
Smoking Diet Weight Stress Sex - male Age
Treatment
- lifestyle modification - smoking, diet, weight, stress
- drugs
describe the cardiac cycle
Split into diastole (filling) and systole (ejection)
1) AV valves are open, semilunar valves are closed
- passive filling of the ventricles
- atrial contraction
- end with EDV in the ventricles
2) Isovolumetric contraction
- AV valves close as intraventricular P > atrial
- ventricular P < aortic P
- volume remains constant because all valves closed
6) rapid filling - AV valves open
- ventricle P still falling because muscle is still relaxing
- rapid flow in by bood
7) reduced filling - less compliant, pressures are rising
how much volume is EDV of LV normally
~120ml
what sounds is sometimes heart that signifies atrial contraction?
4th heart sound
- reduced ventricle compliance
- eg ventricular hypertrophyt
Heart sounds
- 1st
- 2nd
- 3rd
- 4th
1st = closure of AV valves
2nd = closure of aortic/pulm valves
3rd = (sometimes - normal in kids) - during rapid filling, indicates ventricular dilatation
4th (sometimes) - atrial contraction
described jugular wave form
2 positive waves seen with each beat
- a wave - reflect atrial contraction
- v wave - reflex atrial venous filling (happening at same time as ventricular contraction)
raised JVP indicates
jvp reflects right atrium pressure
- resistance to right atrial emptying
eg. - pulmonary hyptertension
- fluid overload
- RVF
- bradycardia
- tricuspid stenosis/regurgitation
ECG
- what electrical events does it measure?
- configuration of the leads
- what do the different waves mean
12 leads
6 - precordial (V1, V2, V3, V4, V5 and V6)
6 - limb
up = depolarisatin down = repolarisation
p wave - atrial depolarisation
pr interval - time for electrical impulse to travel through atria, cross AV node
qrs wave - ventricular depolarisation
t wave - ventricular repolarisation
approach to reading ecg
- examine rate
- examine rhythm
- examine axis, intervals, segments
- examine everything else
examining rhythm on ecg
sinus rhythm = p wave on lead II is upright
electrical conduction through heart
1) spontaneous depolarisation at sinus node (high in right atrium)
2) wave of depolarsiation spreads through RA and across intra-atrial septum into LA
3) atria + ventricles are separated by electrically inert fibrous ring - only conduction is through AV node
AV node delays signal for a short time
4) wave of depolarisation spreads down interventricular septum (via bundle of his + right and left bundle branches) into ventricles + down purkinje fibres
depolarise and contract from apex up
intrinsic beats
- SA node
- AV node
- ventricles
SA - 100
AV - 50 bpm
ventricles - 30
What is AV block?
What are the types? what do you see on ECG
impaired transmission from the AV node to the rest of the heart
First degree - slow conduction through AV junction
- elongated PR interval
- causes: MI, some drugs
Second degree - sometimes no contraction of ventricle at all
type 1 - get a gradual prolongation of PR interval, until you skip a ventricle contraction all together
type 2 - get PR intervals are constant, until a nonconducted p wave occurs - get a ratio of p:qrs
Third degree - total AV block
- just see p waves - no qrs
What is Stokes-Adam syndrome?
collapse into unconsciousness due to complete AV block
return to consciousness as purkinje kicks into gear
Digoxin (cardiac glycosides)
- mechanism
- why is it not used much
- when is toxicity increased
- main use
increase contractility by increasing intracellular Ca2+ (more ca released from SR with each ap - more contractility)
Mechanism
- inhibits Na+/K+ ATP-ase = increase intracellular [Na2+]
- Na+ is exchanged wtih Ca2+ as well (pump calcium out, sodium in)
- high intracellular Na2+ -> less calcium is being pumped out
=> increase Ca2+
Problems
- narrow therapeutic index + low selectivity
- targets are widely distributed - may block AV conduction; and increase ectopic pacemaker activity -> risk of ventricular arrhythmia
side effects:
- nausea, vom, diarrhoea, anorexia, confusion, drowsiness
- ventricular dysrhythmias
- AV block
Increased toxicity with
- low K+ (be careful with diuretics) (K+ competes for target site)
- high Ca2+ (decrease gradient for Ca efflux)
- renal impairment
main use = AF (increase vagal outflow to reduce AV conduction rate)
Which ionotropes can be used in acute heart failure?
how do they work
adverse effects
Acute = emergency = use IV for acute HF and cardiogenic shock
1) Beta-adrenoceptor agonists
= adrenaline, noradrenaline - activate a- and b-adrenoceptors - increase contractility
= dobutamine - selective for b1
adverse effects
- increase O2 demand
- risk of arrhythmia
- only SR - chronic overactivation of b1-adrenoceptors occurs in chronic HF -> reduced sensitivity to these
2) Phosphodiesterase inhibitors (PDE)
= amrinone
works through reducing phosphorylation of b1-adrenoceptors - less reduced sensitivity to agonists/sympathetic drive
what happens to b1-adrenoceptors in chronic heart failure?
because there is chronic overstimulation by the SNS - b1 adrenoceptors are downregulated
+ there is impaired b1-adrenoceptor coupling (this can be improved by PDE inhibitors)
=> over time the cardiac cells become less sensitive to stimulation by SNS and b1-adrenoceptor agonists
Diuretics - what are they
what are their classes
drugs that increase Na+ and water excretion
- decrease Na+ and Cl- into blood
- secondary H2O secretion
Classes:
- Loop diuretics
- Thiazide diuretics
- Potassium sparing diuretics
- Osmotic diuretics
Osmotic diuretics - how do they work
- where is their main effect
examples
clinical uses
Pharmacologically inert - exert osmotic effects
- are filtered but not reabsorbed, stay in lumen
- reduce passive water reabsorption
- main effect is in water-permeable parts of nephron
- prox tubume
- desc. loop of henle
- collecting tubules
eg. mannitol - small sugar molecule (polar - not reabsorbed)
clinical uses:
- decrease fluid load - ↑ICP, ↑inctraoc pressure
- prevent acute renal failure (if can’t play around with Na+)
which are the most powerful diuretics and why
loop diuretics
act on thick ascending limb of loop ofhenle
result in excretion of 15-20% of Na+ in filtrate = torrential urine flow
-> double effect of local reduced osmotic pressure and distal effects in distal tubule
Loop diuretics
- where do they act
- how do they work
- adverse effects
- clinical uses
- example
act in thick ascending limb of loop of Henle
mechanism
- inhibit Na+/K+/2Cl- carrier into cells (from lumen)
- Na+ stays in lumen, water excreted
distal effects
- increased Na+ in the distal tubule
- less water reabsorbed again (where is normally reabsorbed)
adverse effects
- hypokalaemia = need supplement (Na+ is more concentrated in distal tubule - so want to increase Na+ reabsorption there - to reabsorb Na+ - secrete K+ (Na/K ATP-ase) ))
- metabolic alkalosis
- hypovolaemia + hypotensio in elderly
clinical uses
- hypertension
- salt, water overload (acute pulm oedema, chronic HF, ascites, renal failure)
example - frusemide
Thiazide diuretics
- where do they act
- how do they work
- adverse effects
- clinical uses
- example
distal convoluted tubule
mechanism
- inhibit Na+/Cl transporter
- Na+ stays in lumen - water goes wtih
adverse effects
- hypokalaemia - take supplement (Na+ is more concentrated in distal tubule - so want to increase Na+ reabsorption there - to reabsorb Na+ - secrete K+ (Na/K ATP-ase) )-
- increased plasma uric acid - gout
clinical use
- hypertension
- severe resistant oedema (in combo w/loop)
examples
- true thiazides: bendrofluazide, hydrochlorothiazide
- thiazide-like - indapamide
Potassium-sparing diuretics
- where do they act
- when are they used
- example
act distally (where there is limited reabsorption of na+) => their diuretic effect is limited - collecting tubule + ducts
mainly used to prevent K+ loss (coadminister with K+ losing diuretics)
exammples: 2 groups
- spironolactone
- triamterene + amiloride
spironolactone
- how it works as diuretic
- where does it work
- adverse effects
- clinical uses
- example
aldosterone receptor antagonist (complex can’t bind DNA - can’t stimulate synth of Na/K channels)
aldosterone - normally stimulates synthesis of Na/K channel on basolateral membrane -> gradient for Na+ to flow through
- also activates Na+ channel on apical surface
spironolactone - block this, K+ stays in intersititium
woirks in collecting ducts/tubules
adverse effects
- hyperkalaemia if used alone
- GI upset
clinical use
- with loop/thiazide diuretic
- heart failure
- hyperaldosteronism
Triamterene and amiloride
- how it works as diuretic
- where does it work
Block luminal sodium channels in collecting ducts/tubules
- less reabsorption of Na+
=> by proxy less exchange for K+ at the basolateral surface -> less loss of K+
How do Angiotensin receptor antagonists work in treating hypertension?
What is their suffix
side effects
“sartans”
- block AT1 receptors
- > reduce vasoconstriction
- > reduce aldosterone
- > reduce cardiac hypertrophy
- > reduce sympathetic activity -> more so than ACE inhibitors
side effects
- hyperkalaemia
How do beta-blockers work in treating hypertension?
Block effects of sympathetic activity on kidney + heart (b1 adrenoceptors)
kidney
- decreased renin release -> decreased downstream effects of AngII/aldosteronne
heart
- decrease CO (rate, contractility)
which beta adrenoceptors are present in kidney, heart
both b1
adverse effects of beta blockers and why do they occur
cold extremities (reflex a-adrenoceptor constriction to decreased CO + blocking b2 receptors in peripheries)
fatigue
- cant increase HR
dreams, insomnia
bronchoconstriction (contraindicated in asthma)
why are beta blockers contraindicated in diabetes
diabetics use HR to signal blood sugar level requirements
=> beta blockers can cause hypoglycaemia
Calcium channel blockers + hypertension - how do they work, which ones are better for hypertension
block L-type ca2+ channels in myocardium + vasculature
dihydropyridines - considered vascular selective
- block constriction - reduce vascular resistance
How do diuretics work in treatment of hypertension?
- increase Na+ and water excretion by decreasing their reabsorption into blood stream
- > reduce preload
