Pharmacology Flashcards
3 beta adrenoreceptor agonists are?
dobutamine, adrenaline and noradrenaline (catecholamines)
All beta adrenoreceptor agonists will…
Produce an increase in force, rate and oxygen consumption but a decrease in cardiac efficiency.
Clinical uses of adrenaline?
IV injection in cardiac arrest
IM injection in anaphylaxis
Clinical use of dobutamine?
Acute but potentially reversible heart failure
Examples of beta blockers?
- Beta 1 and 2= propranolol
* Beta 1 only= atenolol, bisoprolol, metoprolol
Atropine is a non-selective blocker of….
All acetyl choline muscarinic receptors
Effect of atropine? It is used in?
Increase in HR in normal subjects (at all but low doses)
First line in management of severe, or symptomatic bradycardia, particularly following myocardial infarction
Why must you give at least 300mg of atropine?
In low doses it makes bradycardia even worse
What does digoxin do?
Increases heart contractility
How does digoxin work?
It blocks the sodium potassium pump which results in increased calcium induced calcium release resulting in shortening of action potential and refractory period so force of contraction is increased.
Why and what are the side effects of digoxin?
- Cardiac effects- propensity to cause arrhythmias and excessive depression of AV node conduction
- Major 4- nausea, vomiting, diarrhoea and disturbances of colour vision
DUE TO NON-SELECTIVE BINDING TO Na/K ATPase
2 classes of drugs used to relax vascular smooth muscle?
Organic nitrates
Calcium channel blockers
Two examples of organic nitrate drugs and when are they used?
Glyceryltrinitrate (GTN) and isosorbide mononitrate (ISMN)
In all types of Angina
Describe GTN spray
- Short acting only 30 mins.
- It undergoes extensive first-pass metabolism (almost completely inactivated by the liver)
- It is administered sublingually as a tablet or as a spray for rapid effect before exertion in stable angina or IV in conjunction with aspirin (in unstable angina)
- More sustained effect if delivered by transdermal patch.
Describe ISMN
- Longer-acting (t½ = 4 hours) – resistant to first-pass metabolism
- Administered orally for prophylaxis and a more sustained effect (usually in the morning and at lunch)
- Not used to relieve attacks only prevent.
Adverse effects of the organic nitrates?
- Headaches may occur initially – due to arteriolar dilatation
- Hypotension and fainting
- Reflex tachycardia – prevented by co-administration of a β-blocker (which also improves stable and unstable angina by lowering myocardial oxygen requirement)
- Formation of methaemoglobin (oxidation product of haemoglobin which does not carry oxygen) – rarely occurs.
Why is ISMN given in the morning and at lunch?
Allows a nitrate low period over night and in the evening meaning patients are less likely to develop a tolerance to it
What do calcium channel blockers do?
Calcium blockers physically block, or prevent the opening, of L-type channels in excitable tissues in response to depolarization and hence limit increased [Ca2+]i
Three main types of calcium channel blockers?
- Verapamil- relatively selective for cardiac L-type channels- decrease in cardiac force- block the pore.
- Amlodipine (dihydropyridine) compound- relatively selective for smooth muscle L-type channels)- act allosterically to prevent channel opening.
- Dilitiazem- (intermediate selectivity)
What calcium blockers are used in hypertension and why?
The dihydropyridines (amlodipine) They have selectivity for smooth muscle L-type channels are preferred minimising the negative effects on the heart.
When are calcium channel blockers used in angina?
Prophylactic treatment, often used in combination with GTN particularly if beta-blockers are contraindicated
What does aliskerin do?
Inhibit the action of renin
What do ACE inhibitors do and example of one and adverse side effect?
Block conversion of angiotension 1 to angiotension 2. They also increase amount of bradykinin in the blood. Lisinopril. Dry cough.
What do Angiotension 1 receptor blockers do and when are they useful? (ARBs)
block the agonist action of angiotensin II at AT1 receptors in a competitive manner. Are useful as in patients who find the dry cough produced by ACEIs intolerable
Clinical uses of ACE inhibitors and ARBs?
Hypertension, cardiac failure and following MI
What are beta adrenoreceptor antagonists (beta blockers) no longer first line for? When are they used?
Hypertension
Used in treatment of heart failure in combination with other drugs to suppress adverse effects associated with elevated activity of the sympathetic nervous system and RAAS
How do potassium channel openers work?
Cause hyperpolarization which switches off L-type Ca2+ channels . Act potently and primarily upon arterial smooth muscle resulting in relaxation of the smooth muscle.
Examples of potassium channel openers?
Minoxidil and Nicorandil
Examples and mechanisms of alpha 1 adrenoreceptor antagonists?
Cause vasodilatation by blocking vascular alpha 1-adrenoceptors. Reduced sympathetic transmission results in decreased MABP. The most frequently used compounds are prazosin and doxazosin – both are competitive antagonists.
Anti cholesterol drugs?
Statins
Fibrates
PCSK 9 Inhibitors (used in familial hypercholesterolemia )
Anti- hypertensive drugs?
1) Diuretics e.g. bendrofluazide and furosemide.
2) Beta blocker
3) Calcium channel blockers- dihydropyridines (amlodipine) and rate limiting calcium antagonists e.g. verapamil, dilitiazem.
4) Alpha blockers
5) ACE Inhibitors
6) Mineralcorticoid Antagonists
Coronary artery disease common drugs?
1) Nitrates
2) Nicorandil- K ATP channel activator- lots of side effects- ulcers in GI tract and mouth, headache.
3) Ivabradine- If channel modulator in the sinus node (only works in someone in sinus rhythm). Altered visual disturbance
4) Ranolazine- Late sodium channel modulator, decrease calcium load on the heart, effective in refractory angina.
Antiplatelet/thrombotic agents?
Aspirin, clopidogrel, plasugrel, ticagrelor
Anticoagulant drugs?
Heparin, fondaparinux Warfarin, Rivaroxaban, Dabigatran, Edoxaban (oral)
Heart failure drugs?
- ACE Inhibitors
- ARBs
- Beta-blockers
- Mineralocorticoid antagonists (Spironolactone, eplerenone)
- Neprilysin inhibitors (salcubitril valsartan)
- Diuretics
- Digoxin
Lipids e.g. ______1______ are insoluble in ___2____ and are transported in the plasma by _____3_____
1) triglycerides and cholesterylesters
2) water
3) lipoproteins that have a hydrophilic shell of phospholipids and free cholesterol
The surface layer of lipoproteins is stabilised by…. these also act as…..
apoproteins which also act as ligands for cell surface receptors
The four major types of lipoprotein are…
HDL, LDL, VLDL and chylomicrons
Clearance of LDL particles is dependent upon? This is mainly expressed by the?
LDL receptor expressed by the liver
Released cholesterol in the liver causes….
a decrease in LDL receptor expression
How do statins work?
These inhibit HMG coA reductase which blocks synthesis of cholesterol in the liver leading to increased expression of LDL receptors which increases the clearance of cholesterol from the plasma.
Adverse effects of statins? When are these effects more likely to occur?
Myositis (inflammation of muscles)
Very rarely rhabdomyolysis (death of muscle fibres).
Incidence is increased if the statin is combined with a fibrate.
How do fibrates work?
Act as ligands for the nuclear transcription receptor PPARalpha to enhance the transcription of several genes including that encoding LPL. They cause a marked fall in plasma triglycerides.
Fibrates are first line treatment for?
Those with very triglyceride levels.
Adverse effects of fibrates?
More likely to happen if combined with statins is the myositis and rhabdomyolysis by also more risks of GI symptoms, pruritus and rash occurring.
Examples of three bile acid binding resins?
Colestyramine, colestipol and colserelam
How do bile acid binding resins work?
Cause the secretion of bile salts resulting in more cholesterol being converted to bile salts by interrupting enterohepatic recycling.
Adverse effects of bile acid binding resins?
Can cause GI irritation
How does ezetimibe work and when is it contraindicated?
Inhibits the transport protein in enterocytes of the duodenum reducing absorption of cholesterol. Contraindicated in breast feeding females.
An arterial thrombus is __1___ and treated with ___2____
A venous thrombus is ___3___ and treated with __4____
1 white
2 anti-platelets
3 red
4 anticoagulants
5 important anticoagulant drugs
Rivaroxiban Heparin Fondaparinux Dabigataran Warfarin
What does rivaroxiban directly inhibit?
Factor Xa
Heparin inactivates both factor ____ and ____ via _____
Xa and lla
via anti-thrombin lll
Fondaparinux and LMWHs only inactivate factor _____ via ______
Xa via anti-thrombin lll
Warfarin works by blocking
Vitamin K reductase
Dabigataran directly inhibits factor ____
lla
Overdose of warfarin can be treated with
administration of vitamin K1 (as phytomenadione), or concentrate of plasma clotting factors (IV)
What makes digoxin toxicity more likely/risky?
If patient is already on a lot of drugs ie someone in heart failure
What drug can be used to treat VT?
Amiodarone
