Pharm Cram Flashcards
Cholesterol Drugs
All mechanisms aim to reduce blood cholesterol levels. Cholesterol plays a key role in the formation of foam cells, hence is a risk factor for artherosclerosis. A 10% raise results in a 20% raise in chd events. This risk is elevated by smoking, diabetes, hypertension.
It is a key MODIFIABLE risk factor in the pathogenesis of heart disease, cerebrovascular disease and peripheral vascular disease.
Indications: High LDL, low HDL, risk of cardiac disease, obesity, smoking.
Statins are HMG-CoA Reductase inhibitors. This halts the rate-limiting effect of the cholesterol synthesis pathway. Further down the pathway, both cholesterol and proteins that aid in LDL creation are produced. Statins inhibit the production of both. LDL receptors are then up-regulated on the liver, increasing LDL intake from the blood. RULE OF 6. Don’t lower too much, may cause memory and cns problems. Statins have good and bad effects, and also do other things like anti-inflammatory.
Fibrates are PPAR alpha receptor antagonists. Acts on liver, increase HDL.
Nicotinic Acid, not good
CETP Inhibitor, CETP convert HDL to LDL.
PCSK9 inhibits LDL receptor - good for familial hypercholesterolaemia.
Artherosclerosis
Manifests as coronary heart disease (Angina Pectoris, Myocardial Infarction, sudden cardiac death), cerebrovascular disease (stroke/tia), and peripheral vascular disease (intermittent claudication and gangrene).
Process: Endothelial damage results in the production of cellular adhesion molecules. Monocytes and T cells attach and migrate to the subendothelial space. Macropages then take up oxidised LDL to form lipid rich foam cells. These have fatty streaks, and form plaques.
Haemostasis & Thrombosis
Thrombosis and Artherosclerosis are both pathophysiological processes arising from the mechanism of haemostasis.
Thrombosis results in red thrombi, high in fibrin, and predominantly affects the venous system.
Artherosclerosis results in white thrombi, high in platelets, and predominantly affects the arterial system.
The causes of these processes occurring can be summarised by Virchow’s Triad. This consists of slow blood flow, as blood factors aren’t rapidly replenished, a natural inconsistency between anti and pro-coagulants, and endothelial integrity.
Stages of Coagulation
Three stages of coagulation can be targeted by drugs.
1) Initiation, the small scale production of thrombin. Targeted by anti-coagulants
2) Amplification, the large-scale production of thrombin on platelets. Targeted by anti-platelets
3) Propagation, thrombin-mediated generation of fibrin.
Drugs targeting the first stage of coagulation
Target the initiation stage, the production of a small amount of thrombin.
ANTICOAGULANTS, target any factor involved in thrombin production
Warfarin and Heparin
Indicated in DVE, PE, when thrombosis occurs during surgery and in patients with atrial fibrillation as a prophylactic for stroke.
Drugs targeting the second stage of coagulation
The large scale production of thrombin on platelets.
ANTIPLATELETS
Clopidogrel antagonises ADP/P2Y12r
Aspirin is an irreversible COX1 Inhibitor
Indicated in Acute coronary syndromes, such as MI, and as a prophylactic for stroke in atrial fibrillation.
Drugs targeting the third stage of coagulation
Thrombin-mediated generation of platelets.
THROMBOLYTICS
Used to remove pre-formed clots.
Alteplase is a recombinant tissue type plasminogen activator.
First line treatment for stroke, and STEMI cases.
Vascular Tone Regulation
RAAS, ANG II constricts blood vessels via ATI receptor. Alpha I activity also causes vasoconstriction.
Vasodilation is mediated by NO.
Anti-Hypertensives - Reducing plasma volume and vasoconstriction.
ACE inhibitors, useful in HT, HF, post-MI, diabetic nephropathy, progressive renal insufficiency, patients with high CVD risk.
ARBs/AT1 Antagonists - Recent, insurmountable drug type.
Aldosterone Antagonists, Spironolactone is a key example. Causes unwanted steroid like effects and hyperkalaemia.
Beta Blockers - Lower cardiac output, inhibit renin release by blocking B1 receptors.
Antihypertensives - Vasoconstrictors
Calcium channel blockers, such as dihydropyridines.
Organic nitrates and potassium channel openers
Alpha Blockers inhibit vasoconstricting effect of alpha-1, however can lead to postural hypotension.
Contrarily, alpha-2 agonists used to be used, with the moa of decreasing sympathetic discharge.
Vasoconstricting Drugs
5HT-1D Receptor agonists cause vasoconstriction. This can be used to treat migraines. ERGOT ALKALOIDS
Adrenaline, used in cardiac arrest and anaphylactic shock.
Regulation of cardiac output and rhythm.
HR:
- If channels are activated upon hyperpolarisation. They exist in the SAN and stimulate the autonomous initiation of individual heartbeats. Na+
- Transient and Long Ca2+ channels mediate fast calcium influx.
- Ik are potassium channels that mediate repolarisation.
- SNS increases cAMP, increasing If and Ica activity.
Contractility:
-Beta-1 stimulation induces cAMP and PKA formation. PKA stimulates Ca2+ influx into the SR via ryanodine receptors. More Ca2+ = higher contractility.
Drugs affecting Heart Rate
Aim to decrease If and Ica by decreasing the sympathetic drive.
This can be done with:
Beta 1 Antagonists.
Calcium Antagonists
Drugs affecting contractility
Beta-Blockers reduce contractility
Calcium antagonists can be rate slowing or non-rate slowing.
Drugs affecting myocardial supply and demand
Need to alter preload and afterload and increase ocygen supply trhough coronary arteries.
Organic nitrates supply no, increasing cGMP which causes vasodilation
Potassium Channel Openers stimulate hyperpolarisation in coronary arteries, hence increase oxygen flow.
