Pharmacology Flashcards
sympathetic nervous system acts on __ receptors mediated by __ causing ___
B1 adrenoceptors
adrenaline and noradrenaline
increase in heart rate and contractility
sympathetic nerves innervate nodal and myocardial cells true/false
true
how do beta-adrenoceptors increase heart rate and contractility
activate G protein coupled receptors - activates adenylyl cyclase - increases cAMP - increases number of L-type channels - triggers release of calcium from SR
increase in heart rate is known as
positive chronotropic effect
increase in heart contractility is known as
positive inotropic effect
parasympathetic nervous system acts on __ mediated by __ causing ___
M2 muscarinic cholinoceptors
mediated by ACh
decrease in heart rate
parasympathetic nerves innervate nodal and myocardial cells true/false
false only on nodal cells - therefore only has effect on heart rate but not contractility
how does parasympathetic nerves decrease heart rate in nodal cells
when M2 binds to ACh making G protein - cAMP is reduced and potassium channels open decreasing contraction slope
what are the stages occurring for cardiac muscle contraction to occur
Ca L-type channels open during phase 2 - influx of Ca - triggers release of Ca from SR (CICR) - Ca binds to troponin C moving tropomyosin causing contraction
describe calcium induced calcium release
increasing the intracellular concentration of calcium causes further increase in its concentration from the sarcoplasmic reticulum
how does relaxation of cardiac muscle occur
repolarisation in phase 3 and 4 closes L-type channels. Ca influx stops and Ca dissociates from troponin C causing relaxation of muscle
what is the purpose of vagal manoeuvres
suppress conduction through the AVN - therefore decreasing heart rate
what are vagal manoeuvres used for
SVTs such as atrial fibrillation and atrial flutter
what is the funny current mediated by
HCN channels
which drug selectively blocks the HCN channel
ivabradine - decreasing slope on pacemaker potential
which conditions is ivabradine used for
angina - lowers oxygen requirements
which two areas can drugs act on to alter heart rate and contractility
beta-adrenoceptors
muscarinic receptors
what is the effect of B1 adrenoceptor agonists
activated adenylyl cyclase increasing cAMP which increases heart rate
name two examples of B-adrenoceptor agonists and their uses
dobutamine - IV for heart failure
adrenaline - cardiac arrest and anaphylaxis
what is the effect of beta-blockers
either selectively or non-selectively block beta-adrenoceptor slowing conduction through AVN reducing heart rate/oxygen requirement
name a non-selective beta-blocker and what does it act on
propanolol acting on B1 and B2 adrenoceptors
name some selective beta-blockers
atenolol, bisoprolol, metoprolol
what are the clinical uses of beta-blockers
angina
arrhythmias - esp AF
heart failure - start low and go slow as reduces sympathetic drive
(hypertension if extreme)
what are the side effects of beta-blockers
bradycardia can trigger bronchospasm esp in asthmatics fatigue hypoglycaemia can aggravate heart failure cold extremities
what is the effect of muscarinic ACh receptor antagonists
block parasympathetic action therefore increase heart rate
name two drugs that are muscarinic receptor antagonists
atropine
digoxin
what is the clinical use of atropine
used for extreme bradycardia following an MI
what is the clinical use of digoxin
treatment of heart failure as increases contractility
what are the side effects of digoxin
can cause heart block
arrhythmias
GI disturbances
disturbance to colour vision
what are the classifications of drugs that have direct effect on vasculature and BP
organic nitrates
calcium channel blockers
ACEi and ARBs
how does smooth muscle contraction occur in vasculature
Ca through L-type channels activates MLCK causing contraction
how does relaxation occur in smooth muscle vasculature
myosin light chain phosphatase activated by protein kinase G causes relaxation of smooth muscle
what is the action of organic nitrates
organic nitrates metabolised into nitric oxide causing venorelaxation and arteriolar dilatation causing increased coronary blood flow
name a short acting organic nitrate and its use
GTN (glycerintrinitrate) administered sublingually
used for symptomatic relief of angina and acute MI
name a long acting organic nitrate and its use
isosorbide mononitrate administered orally
used for prophylaxis of angina
how can organic nitrates improve symptoms of angina
reduces myocardial oxygen requirement decreasing preload and afterload
what are some of the side effects of organic nitrates
over dilatation of blood vessels causing hypotension, headaches, dizziness and nausea
what is the effect of repeated administration of organic nitrates
can cause diminished effect - therefore nitrate free period overnight is recommended
which calcium channel blocker has an effect on cardiac L-type channels
verapamil
which calcium channel blocker has an effect on smooth muscle L-type channels
amlodipine
what is the overall effect of blocking Ca channels
reduction in intracellular Ca causing arteriolar dilatation
what are Ca channel blockers used for
hypertension
angina
arrhythmias
what are the side effects of calcium channel blockers
excessive vasodilation causing hypotension, dizziness and ANKLE OEDEMA
what is haemostasis
the stopping of blood flow through a damaged vessel
what is thrombosis
pathological haemostasis - formation of blood clot
thrombin from coagulation cascade is activated from ___ by ___ enzyme
prothrombin
prothrombinase
describe arterial thrombus
white thrombus mainly containing platelets
where is an arterial thrombus most likely to detach and travel to
heart
arteries
brain - stroke
describe venous thrombus
red thrombus mainly containing fibrin
where is a venous thrombus most likely to detach and travel to
lung from lower limbs
arterial thrombus is treated with
antiplatelets
venOus thrombus is treated with
anticOagulants
what is the mechanism of anticoagulants
block different points of the coagulation cascade typically prothrombinase, thrombin and factor Xa
name the clinical uses of anticoagulants
DVTs and PE
atrial fibrillation prophylaxis
post-op thrombosis
name some anticoagulants
warfarin
rivaroxaban
epixaban
heparin
what type of drug is warfarin classed as
vitamin K antagonist
what is one of the major side effects of taking anticoagulants
increased risk of haemorrhage
what factors can lessen the effects of warfarin
anything increased risk of thrombosis:
- pregnancy
- hypothyroidism
- vitamin K consumption (green salad vegetables)
which factors of the coagulations cascade does warfarin interact with
factor II, VII, IX and X
heparin and LMWHs are which type of anticoagulants
antithrombins
what is the mechanism of heparin
binds to antithrombin III increasing affinity for clotting factors
when is the only time heparin is preferred over LMWHs
when the patient has renal failure
name some examples of antiplatelets
aspirin
clopidogrel
ticagrelor
what are some of the side effects of antiplatelets
haemorrhage
aspirin also causes GI upset
when are fibrinolytic drugs used
as thrombolysis to reopen occluded arteries in acute stroke or MI
name an example of fibrinolytic drug
streptokinase
what causes renin to be released from the kidneys
drop in blood pressure - body thinks there is not enough fluid and so will retain it
what is ACE and its function
enzyme converting angiotensin I to angiotensin II
acts as a vasoconstrictor and inactivates bradykinin
what is bradykinin
vasodilator inactivated by ACE
what is the effect of an ACE inhibitor
blocking the conversion of angiotensin causes arteriolar dilatation and venous dilatation - overall reduces blood pressure and cardiac load
what is an ARB
angiotensin receptor blocker - very similar effect however doesn’t activate bradykinin
what are the clinical uses of ACEis and ARBs
hypertension
heart failure following MI
what is a common side effect of an ACEi but not an ARB and why
dry cough due to the activation of bradykinin
are ACEis and ARBs safe in pregnancy
no as the have foetal toxicity
name two examples of alpha blockers
prazosin and doxazosin
what is the effect of alpha blockers
through blocking A1 channel throughout the rest of the body - sympathetic vasoconstriction is prevented - prevents blood pressure from getting too high
what is the indication for alpha blockers
severe hypertension
or patient with benign prostatic hyperplasia and hypertension
what is an adverse effect of alpha blockers
postural hypotension
what is the purpose of diuretics
acts on kidneys to increase Na, Cl and water excretion - indirectly relaxing vasculature
what are the two types of diuretics
thiazide diuretics
loop diuretics
give an example of a thiazide diuretic and its main uses
bendroflumethiazide
used mainly for hypertension as not as effective for removing fluid
give an example of a loop diuretic and its main uses
furosemide
has strong diuresis and used for acute pulmonary oedema and chronic heart failure
what are the main side effects of diuretics
can cause severe hypokalaemia and require K supplements or can lead to gout
also thirst and dizziness
