Flashcards
Drug List for Pharmacology 2 Exam
Cards in this deck (161)
- 1Drugs for AnaemiaIron deficient Anaemia
Ferrous fumarate
Ferrous sulfate
Iron polymaltose
Iron sucrose
Ferric carboxymaltose
B12 and Folic Acid Deficient Anaemia
Cyanocobalamin
Hydroxocobalamin
Folic acid
Anaemia linked to Chronic Disease
Epoetin
Darbepoetin - 2Ferric carboxymaltoseIV least likely to cause an immune reaction to the carbohydrate shell or toxic effects of labile iron from the iron oxyhydroxide core
- 3Cyanocobalamincyanide moiety
synthetic
shorter half life
oral or IM - 4Hydroxocobalaminhydroxy group
naturally occurring
longer half life
IM injection - 5EpoetinRecombinant Human Erythropoietin
Epo agonist
mimics erythropoietin to stimulate erythropoiesis in the bone marrow, by binding to Epo receptors on progenitor cells.
shorter half life - 6darbepoietin alfasynthetic erythropoietin analogue
Epo agonist
mimics erythropoietin to stimulate erythropoiesis in the bone marrow, by binding to Epo receptors on progenitor cells.
longer half life, less frequent dosing - 7drugs for dyslipidaemiaStatins;
Atorvastatin
Rosuvastatin
Simvastatin
Pravastatin
Fluvastatin
Fibrates:
Fenofibrate
Gemfibrozil
Cholesterol Absorption Inhibitors
Ezetimibe
Bile Acid Binding Resins:
Cholestyramine
Colestipol
Nitrates:
Nicotinic acid (Niacin)
PCSK9 inhibitors:
Alirocumab
Evolocumab
Omega-3 fatty acids - 8Statins (DRUGS)Shorter HALF LIFE
Pravastatin
Simvastatin
Fluvastatin
Longer Half life
Rosuvastatin
Atorvastatin - 9Statins MOACompetitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (a rate-limiting enzyme in cholesterol synthesis).
Increase hepatic cholesterol uptake from blood, reduce concentrations of total cholesterol, LDL and triglyceride (modest), and produce a small increase in HDL concentrations. - 10PravastatinClass: statin ( HMG-CoA reductase inhibitors)
MOA:
Competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (a rate-limiting enzyme in cholesterol synthesis). Increase hepatic cholesterol uptake from blood, reduce concentrations of total cholesterol, LDL and triglyceride (modest), and produce a small increase in HDL concentrations.
Metabolised:
CYP450 - 11SimvastatinClass: statin ( HMG-CoA reductase inhibitors)
MOA:
Competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (a rate-limiting enzyme in cholesterol synthesis). Increase hepatic cholesterol uptake from blood, reduce concentrations of total cholesterol, LDL and triglyceride (modest), and produce a small increase in HDL concentrations.
Metabolised:
CYP3A4 - 12FluvastatinClass: statin ( HMG-CoA reductase inhibitors)
MOA:
Competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (a rate-limiting enzyme in cholesterol synthesis). Increase hepatic cholesterol uptake from blood, reduce concentrations of total cholesterol, LDL and triglyceride (modest), and produce a small increase in HDL concentrations.
Metabolised:
CYP2C9 - 13RosuvastatinClass: statin ( HMG-CoA reductase inhibitors)
MOA:
Competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (a rate-limiting enzyme in cholesterol synthesis). Increase hepatic cholesterol uptake from blood, reduce concentrations of total cholesterol, LDL and triglyceride (modest), and produce a small increase in HDL concentrations.
Metabolised:
CYP2C9 - 14AtorvastatinClass: statin ( HMG-CoA reductase inhibitors)
MOA:
Competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (a rate-limiting enzyme in cholesterol synthesis). Increase hepatic cholesterol uptake from blood, reduce concentrations of total cholesterol, LDL and triglyceride (modest), and produce a small increase in HDL concentrations.
Metabolised:
CYP3A4 - 15Adverse Effects of StatinsPravastatin & Rosuvastatin less lipophilic = less myopathy
Common AE’s:
mild gastrointestinal symptoms, headache, changes to liver function tests, muscle-related adverse effects
Monitor liver function tests
Muscle-related side effects (myopathies)
Myalgia - muscle pain
Myositis – muscle inflammation
Rhabdomyolysis – can be life threatening
Destruction of striated muscle cells
Myoglobin, K+, creatinine kinase (+more) released
High myoglobin in bloodstream = kidney injury - 16Fibrates (drugs)Fenofibrate
Gemfibrozil - 17Fibrates MOAFibrates activate the peroxisome proliferator activated receptors (PPAR) and modulate lipoprotein synthesis and catabolism. PPAR alters expression of lipid metabolism in genes.
PPAR alpha activation leads to increased lipoprotein lipase in muscle
Increased uptake and oxidation of fatty acid in muscle cells
Increased fatty acid and oxidation in liver
reduced TGI synthesis and incased Apoprotein 1 and 2 ligands for specific receptors, increasing HDLs - 18FenofibrateClass: Fibrate
MOA:
Activate peroxisome proliferator-activated receptors (PPAR) & modulate lipoprotein synthesis & catabolism--> PPAR alters expression of lipid metabolism genes - 19GemfibrozilClass: Fibrate
MOA
Activate peroxisome proliferator-activated receptors (PPAR) & modulate lipoprotein synthesis & catabolism--> PPAR alters expression of lipid metabolism genes - 20Fibrates: AEsMetabolite of fenofibrate = fenofibric acid → photoexcitation → intersystem
crossing to triplet excited state
→ damage to cellular components
→ inflammation - 21Cholesterol Absorption InhibitorEzetimibe
- 22Ezetimibelass: Cholesterol Absorption Inhibitor / other drugs for dyslipidaemia
Mode of action
reduces binding of AP2 clathrin to NPC1L1 to ↓ cholesterol absorption
Reduces absorption of dietary and biliary cholesterol by inhibiting its transport across the intestinal wall. This leads to an increased demand for cholesterol, an increase in LDL uptake and its removal from the plasma.
Doesn’t interfere with absorption of triglycerides, fat-soluble vitamins or fat-soluble drugs
Metabolised:
in liver, excreted in bile to GI lumen where it can work again → enterohepatic circuit increases half-life - 23Bile Binding Acid Resins (Drugs)Cholestyramine
Colestipol - 24Bile Acid Binding Resins (MOA)Cholesterol is converted to bile acids in the liver
Bile acids are secreted into the GI tract, can be reabsorbed
Bile acid binding resins sequester bile
in GI tract = ↑ excretion in faeces
More LDL cholesterol moves from blood stream to liver to form bile acids
Mode of action
Bind bile acids in intestinal lumen, preventing reabsorption, and increasing bile acid excretion in the faeces. Increased demand for cholesterol for bile acid synthesis results in an increase in LDL uptake and removal from plasma. - 25Cholestyramine and ColestipolCholesterol is converted to bile acids in the liver
Bile acids are secreted into the GI tract, can be reabsorbed
Bile acid binding resins sequester bile
in GI tract = ↑ excretion in faeces
More LDL cholesterol moves from blood stream to liver to form bile acids
Mode of action
Bind bile acids in intestinal lumen, preventing reabsorption, and increasing bile acid excretion in the faeces. Increased demand for cholesterol for bile acid synthesis results in an increase in LDL uptake and removal from plasma. - 26Bile acid binding resins - precautionsMay increase triglycerides, cause steatorrhoea & reduce absorption of fat-soluble vitamins
Less bile acids available for digestion
May need to sup ADEK
Ineffective if complete biliary obstruction
No bile reaching the resins in the GI lumen
May worsen constipation, diverticular disease, haemorrhoids Adding bulk to the stool
May bind to & alter absorption of other rx
Warfarin, digoxin, thyroxine – need to separate doses - 27Nicotinic Acid / Niacin *Nitrates*Class: ~ Other drugs for dyslipidaemia
Mode of action
Mechanism of action is unclear
Thought to decrease VLDL, ILD, LDL by:
* Suppressing fatty acid release from adipose tissue
* Reducing TG synthesis, via inhibition of DGAT2 enzyme
* Increasing apoprotein B catabolism
Thought to increase HDL by:
* Increasing hepatic uptake of & production of apoprotein A
* Reducing cholesteryl ester transfer protein
* Reducing HDL uptake by inhibiting beta chain ATP synthase - 28Adverse effects of Nicotinic acidNicotinic acid induced flushing
Nicotinic acid binds to receptor on epidermal Langerh cells → prostaglandin release → vasodilation
Prevented by pre-administration of aspirin
Hyperglycaemia
Niacin receptor GPR109A found on islet cells → islet cell dysfunction
Hyperuricaemia, may precipitate gout Increases urate resorption in kidney
decreases urate excretion
Nicotinate functions as counter-ion for main uric acid transporter URAT1
Myopathy (rare) - 29Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (DRUGS)alirocumab
evolocumab - 30Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors MOAMode of action
Human monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9). It inhibits PCSK9 degradation of LDL receptors which increases the number of LDL receptors thereby increasing hepatic LDL uptake and reducing serum LDL. - 31alirocumabClass: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors
MOA:
Human monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9).
It inhibits PCSK9 degradation of LDL receptors which increases the number of LDL receptors thereby increasing hepatic LDL uptake and reducing serum LDL.
SUBCUT every 2-4 weeks - 32evolocumabClass: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors
MOA:
Human monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9).
It inhibits PCSK9 degradation of LDL receptors which increases the number of LDL receptors thereby increasing hepatic LDL uptake and reducing serum LDL.
SUBCUT 2-4 weeks - 33Omega-3 fatty acids - Fish oil derivatives MOA + AEMOA
Inhibit release of TGs from the liver
Reduces VLDL and therefore LDL
Stimulate lipoprotein lipase to increase clearance of TGs from plasma
May have anticoagulant and anti-inflammatory effects
Adverse effects:
gastrointestinal upset, fishy aftertaste - 34drugs for thrombosisAspirin
ADP, P2Y12 antagonists
Clopidogrel
Prasugrel
Ticagrelor
PDE Inhibitor
Dipyridamole
Glycoprotein IIb/IIIa antagonists
Abciximab
Tirofiban
Warfarin
Indirect Thrombin Inhibitors
Unfractionated heparin
Enoxaparin
Fondaparinux
Direct Thrombin Inhibitors
Dabigatran
Factor Xa inhibitors
Apixaban
Rivaroxaban
Tissue plasminogen activator (t-PA) analogues
Alteplase
Tenecteplase
haemostatic agent / Antifibrinolytic
Vitamin K
Tranexamic acid
Protamine
Idarucizumab - 35Aspirin - anti platelet (Cyclo-oxygenase (COX) inhibitors)Mode of action
Inhibits platelet aggregation by irreversibly inhibiting cyclo-oxygenase, reducing the synthesis of thromboxane A2 (an inducer of platelet aggregation) for the life of the platelet.
Non-selective COX I & II inhibitors can cause adverse effects via reduced production of off-target prostaglandins - 36Adenosine diphosphate (ADP, P2Y12) antagonists (drugs)Antiplatelets
Clopidogrel
Prasugrel
Ticagrelor - 37Adenosine diphosphate (ADP, P2Y12) antagonists MOAMode of action:
(clopidogrel, prasugrel)
The active metabolite of the thienopyridines irreversibly binds to the platelet P2Y12 receptor and inhibits platelet aggregation for the life of the platelet.
MOA:
Ticagrelor binds reversibly to the P2Y12 receptor. - 38ClopidogrelClass: Adenosine diphosphate (ADP, P2Y12) antagonists
The active metabolite of the thienopyridines irreversibly binds to the platelet P2Y12 receptor and inhibits platelet aggregation for the life of the platelet.
Prodrug - 2 CYP450 Dependent Steps
Daily Dosing - 39PrasugrelClass: Adenosine diphosphate (ADP, P2Y12) antagonists
MOA:
Delivered as Prodrug: 1x plasma esterase + 1 CYP450 dependent step to become active metabolite.
The active metabolite of the thienopyridines irreversibly binds to the platelet P2Y12 receptor and inhibits platelet aggregation for the life of the platelet. - 40TicagrelorClass: Adenosine diphosphate (ADP, P2Y12) antagonists
MOA:
Ticagrelor binds reversibly to the P2Y12 receptor. Non-competitively inhibits ADP dependent platelet activation & aggregation - 41Phosphodiesterase (PDE) inhibitors drug and MOADipyridamole
Mode of action
Inhibiting reuptake of adenosine
Inhibiting PDE to increase cAMP
within platelets -> decreases Ca2+
Platelet aggregation and activation inhibited
Inhibits platelet function by inhibiting phosphodiesterase, which increases platelet cAMP. - 42DipyridamoleClass: Phosphodiesterase (PDE) inhibitors
Mode of action
Inhibiting reuptake of adenosine
Inhibiting PDE to increase cAMP
within platelets -> decreases Ca2+
Platelet aggregation and activation inhibited
from AMH
Inhibits platelet function by inhibiting phosphodiesterase, which increases platelet cAMP. - 43Glycoprotein IIb/IIIa antagonists drugs and MOAAbciximab
Tirofiban
Mode of action
Prevent binding of fibrinogen to platelet, by occupying glycoprotein IIb/IIIa receptor, thereby blocking platelet aggregation. - 44AbciximabClass: Glycoprotein IIb/IIIa antagonists
Mode of action
Prevent binding of fibrinogen to platelet, by occupying glycoprotein IIb/IIIa receptor, thereby blocking platelet aggregation. Abciximab is a chimeric monoclonal antibody. - 45TirofibanClass: Glycoprotein IIb/IIIa antagonists
Mode of action
Prevent binding of fibrinogen to platelet, by occupying glycoprotein IIb/IIIa receptor, thereby blocking platelet aggregation.
Tirofiban is a non-peptide antagonist - 46WarfarinClass: Vitamin K Antagonist
Mode of action
Vitamin K antagonist; inhibits synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and the antithrombotic factors protein C and protein S.
Racemic mix: S-warfarin 2-5x more anticoagulant Narrow therapeutic index
Susceptible to drug-drug & drug-food interactions - 47indirect thrombin inhibitors drugs and MOAheparin
enoxaparin
fondaparinux
Induce conformational change to increase in antithrombin III to its efficacy inhibiting Xa (and thrombin for heparin) - 48heparinClass: indirect thrombin inhibitors
MOA:
inhibits factor Xa and thrombin by Inducing conformational change to increase in antithrombin III to its efficacy inhibiting Xa and thrombin - 49enoxaparinClass: indirect thrombin inhibitors
MOA:
inhibits factor Xa and thrombin by Inducing conformational change to increase in antithrombin III to its efficacy inhibiting Xa - 50fondaparinuxClass: Factor Xa inhibitor // indirect thrombin inhibitors
MOA:
inhibits factor Xa and thrombin by Inducing conformational change to increase in antithrombin III to its efficacy inhibiting Xa
Selectively inhibit factor Xa, blocking thrombin production, conversion of fibrinogen to fibrin, and thrombus development. - 51Direct thrombin inhibitors Drugs and MOAdabigatran
MOA:
Reversibly inhibit both free and fibrin-bound thrombin, preventing conversion of fibrinogen to fibrin, preventing thrombus formation. Thrombin-induced platelet aggregation is also inhibited.
Reversible, competitive inhibitor of thrombin → prevents conversion of fibrinogen to fibrin: - 52dabigatranClass: Direct Thrombin Inhibitor
MOA:
Reversibly inhibit both free and fibrin-bound thrombin, preventing conversion of fibrinogen to fibrin, preventing thrombus formation. Thrombin-induced platelet aggregation is also inhibited.
Reversible, competitive inhibitor of thrombin → prevents conversion of fibrinogen to fibrin - 53Factor Xa inhibitors drugs and MOAapixaban
rivaroxaban
MOA:
Selectively inhibit factor Xa, blocking thrombin production, conversion of fibrinogen to fibrin, and thrombus development.
Both metabolized CYP3A4 & both substrates of P-gp -> risk of drug interactions - 54apixabanClass: Factor Xa Inhibitors
MOA:
Selectively inhibit factor Xa, blocking thrombin production, conversion of fibrinogen to fibrin, and thrombus development.
metabolized:
CYP3A4 & both substrates of P-gp -> risk of drug interactions - 55rivaroxabanClass: Factor Xa Inhibitors
MOA:
Selectively inhibit factor Xa, blocking thrombin production, conversion of fibrinogen to fibrin, and thrombus development.
metabolized:
CYP3A4 & both substrates of P-gp -> risk of drug interactions - 56Tissue plasminogen activator (t-PA) analogues drugs and MOAAlteplase
Tenecteplase
Fibrinolytic/thrombolytic agents.
Convert plasminogen to plasmin, which catalyses the breakdown of fibrin.
Analogues of human tPA developed
More specific to clot-bound plasminogen, no immune response - 57AlteplaseClass: Fibrinolytic/thrombolytic agents // Tissue plasminogen activator (t-PA) analogues
MOA:
Convert plasminogen to plasmin, which catalyses the breakdown of fibrin.
Exact copy of human t-PA
Short half-life, need IV infusion - 58TenecteplaseClass: Fibrinolytic/thrombolytic agents // Tissue plasminogen activator (t-PA) analogues
MOA:
Convert plasminogen to plasmin, which catalyses the breakdown of fibrin
Higher binding affinity for plasmin vs alteplase
Longer half-life, can give IV bolus
Not inactivated by plasminogen activator inhibitor (PAI-1) - 59Tissue plasminogen activator (t-PA) analogues adverse effects and risksAlter haemostasis more profoundly than any other anticoagulants
→ Greatest risk for bleeding complications Many contraindications to fibrinolysis
Concurrent antiplatelet or anticoagulant drugs increase risk of bleeding but combinaGons can be required - 60haemostatic agent / AntifibrinolyticTranexamic acid
Vitamin K - 61Tranexamic AcidClass: haemostatic agent / Antifibrinolytic
Mode of action
Inhibits breakdown of clots by blocking binding of plasminogen and plasmin to fibrin.
Inhibits fibrinolysis:
Competitive inhibitor of plasminogen activation
At high doses = non-competitive inhibitor of plasmin
Onset of action 5-15 min
Cleared renally – may require dose adjustment - 62Vitamin KClass: haemostatic agent / Antifibrinolytic/ antidote reversal agent
Mode of action
Essential cofactor in the synthesis of blood clotting factors II, VII, IX and X, and proteins C and S; reverses effect of vitamin K antagonists.
Indications
Haemorrhage or threatened haemorrhage due to severe hypoprothrombinaemia, eg from excessive dose of warfarin, hypovitaminosis K
Prevention and treatment of haemorrhagic disease of the newborn - 63Drugs for reversing anticoagulationIdarucizumab
Protamine
Vitamin K - 64Protamineclass: Drugs for reversing anticoagulation
Mode of action
Combines with heparin to form a stable inactive complex, reversing its anticoagulant effect.
heparin & enoxaparin reversal
Indications
Heparin, dalteparin or enoxaparin overdose in patients with, or at high risk of, severe haemorrhage - 65Idarucizumabclass: Drugs for reversing anticoagulation
Mode of action
Humanised monoclonal antibody fragment (Fab) that binds with dabigatran and its metabolites to form a stable inactive complex, reversing their anticoagulant effect.
Indications
Rapid reversal of anticoagulant effects of dabigatran: in life-threatening or uncontrolled bleeding
for emergency surgery or urgent procedures - 66drugs for Ischaemic Heart DiseaseBBs
Metoprolol
Atenolol
CCBs
Amlodipine
Nifedipine
Diltiazem
Verapamil
organic nitrates
Glyceryltrinitrate
Isosorbide mononitrate
Isosorbide dinitrate
other drugs for angina
Nicorandil
Ivabradine
Perhexiline - 67Beta Blockers drugs to know for exam and basic MOAMetoprolol
Atenolol
Competitive antagonism of beta-adrenoceptors Reduce myocardial oxygen demand
Reduced heart rate Reduced contractility - 68Atenololclass: beta blocker
Beta-1 selective ‘cardioselective’ antagonists
Competitive antagonism of beta-adrenoceptors
Reduce myocardial oxygen demand
Reduced heart rate Reduced contractility
renal clearance longer half life - 69Metoprololclass: beta blocker
Beta-1 selective ‘cardioselective’ antagonist
Competitive antagonism of beta-adrenoceptors
Reduce myocardial oxygen demand
Reduced heart rate Reduced contractility
hepatic Clearance
short half life - 70Calcium channel blockers Dihydropyridines (end with ‘pine’ )Amlodipine
Nifedipine
Dihydropyridines act mainly on arteriolar smooth muscle to reduce peripheral vascular resistance and BP. They have minimal effect on myocardial cells.
Block inward current of calcium into cells in vascular smooth muscle, myocardium and cardiac conducting system via L‑type calcium channels.
Act on coronary arteriolar smooth muscle to reduce vascular resistance and myocardial oxygen requirements, relieving angina symptoms. - 71Calcium Channel Blockers Non-dihydropyridineDiltiazem (a Benzothiazepine)
Verapamil (a Phenylalkylamine) - 72AmlodipineClass: Calcium Channel Blocker - Dihydropyridines
Block inward current of calcium into cells in vascular smooth muscle, myocardium and cardiac conducting system via L‑type calcium channels.
Act on coronary arteriolar smooth muscle to reduce vascular resistance and myocardial oxygen requirements, relieving angina symptoms.
Dihydropyridines:
* act mainly on arteriolar smooth muscle to reduce PERIPHERAL vascular resistance and BP.
* They have minimal effect on myocardial cells. - 73nifedipineClass: Calcium Channel Blocker - Dihydropyridines
Block inward current of calcium into cells in vascular smooth muscle, myocardium and cardiac conducting system via L‑type calcium channels.
Act on coronary arteriolar smooth muscle to reduce vascular resistance and myocardial oxygen requirements, relieving angina symptoms.
Dihydropyridines:
* act mainly on arteriolar smooth mscle to reduce PERIPHERAL vascular resistance and BP.
* They have minimal effect on myocardial cells. - 74diltiazem ( a Benzothiazepine)Class: Calcium Channel Blockers /
non-dihydropyeridine
MOA:
Block inward current of calcium into cells in vascular smooth muscle, myocardium and cardiac conducting system via L‑type calcium channels.
Act on coronary arteriolar smooth muscle to reduce vascular resistance and myocardial oxygen requirements, relieving angina symptoms.
Non-dihydropyridines:
diltiazem acts on cardiac and arteriolar smooth muscle to reduce cardiac contractility, heart rate and conduction. - 75Verapamil (a Phenylalkylamine)Class: Calcium Channel Blockers /
non-dihydropyeridine
MOA:
Block inward current of calcium into cells in vascular smooth muscle, myocardium and cardiac conducting system via L‑type calcium channels.
Act on coronary arteriolar smooth muscle to reduce vascular resistance and myocardial oxygen requirements, relieving angina symptoms.
Non-dihydropyridines:
Verapamil acts on cardiac and arteriolar smooth muscle to reduce cardiac contractility, heart rate and conduction, with verapamil having the greater effect. - 76Calcium Channel Blockers AEsDepend on type/properties of CCB
Headache, flushing, peripheral oedema Constipation, dyspepsia
Gingival hyperplasia
Overgrowth of gums
Rare, most common with nifedipine
Reversible when CCB ceased
Most CCBs susceptible to CYP3A4 mediated drug interactions - 77organic nitrates - drugs and MOAGlyceryltrinitrate (GTN or nitroglycerin) Isosorbide mononitrate (ISMN)
Isosorbide dinitrate (ISDN)
Mode of action
Decrease myocardial oxygen demand
Dilates veins to decrease preload
At high doses dilates arteries to reduce afterload
Improve myocardial oxygen supply by Inducing coronary vasodilation
Relaxation of coronary vessels decreases spasms (variant angina) - 78Glyceryltrinitrate (GTN or nitroglycerin) Provide exogenous source of nitric oxide (which mediates vasodilator effects). Predominantly venodilators; reduce venous return and preload to the heart, reducing myocardial oxygen requirement..
DFD = Sublingual spray & tablets, transdermal patch, IV infusion
metabolism:
1. Denitration to dinitrates
(t1/2 = 40 min)
2. Glucuronidation
very very short half life 1- 3 minutes - 79Isosorbide mononitrate (ISMN)Provide exogenous source of nitric oxide (which mediates vasodilator effects). Predominantly venodilators; reduce venous return and preload to the heart, reducing myocardial oxygen requirement.
DFD = Controlled release tablets
Metabolism:
1. Denitration to isosorbide
2. Glucuronidation - 80 Isosorbide dinitrate (ISDN)Provide exogenous source of nitric oxide (which mediates vasodilator effects). Predominantly venodilators; reduce venous return and preload to the heart, reducing myocardial oxygen requirement.DFD = sublingual and oral tablets
Metabolism:
1. Denitration to mononitrates (t1/2 2-4 h)
2. Glucucronidation - 81Tolerance to nitratesTolerance to vasodilator effect develops in 60% of patients if used continuously to prevent angina
Need a nitrate free period each day to maintain efficacy GTN patch on 0800, off 2000 or min 8 h off each night
Time nitrate free period when symptoms least likely
Mechanism of tolerance not fully understood ?? Related to reduced production of nitric oxide (NO) - 82Potassium channel activators drug and MOANicorandil
Mode of action
Produces venous and arterial dilation due to its nitrate moiety and its effect on potassium channels in vascular smooth muscle; improves myocardial oxygen balance and decreases angina. - 83Nicorandillass: Potassium Channel Activator / drugs for angina
Opens K+ channels of vascular smooth muscle → K+ moves
out of cell → hyperpolarisation → muscle contraction inhibited
Also a nitrate donor
Decreases myocardial oxygen demand
Dilation of arteries to reduce afterload
Some dilation of veins to decrease preload - 84IvbradineClass; other drugs for angina
MOA: simple
Blocks sodium channels in the sino-atrial node
Increases interval between depolarisation
Reduces heart rate
Decreases myocardial oxygen demand
Mode of action: technical
Ivabradine inhibits a current regulating the interval between depolarisations of the sinoatrial (SA) node. It reduces heart rate (by about 10 beats/minute) which in turn lowers cardiac workload and myocardial oxygen demand. - 85PerhexilineMOA:
Inhibits enzyme involved in long-chain fatty acid metabolism in the heart → Glucose metabolism predominates
Oxidation of glucose requires less oxygen than oxidation of fatty acids = reduces myocardial oxygen requirements
Narrow therapeutic index
Requires therapeutic drug monitoring Non-linear pharmacokinetics
Adverse effects: neurotoxicity, hepatotoxicity
Metabolised by polymorphic CYP2D6 = large interindividual variation in dose required - 86Drugs for Heart FailureACE inhibitors
Captopril
Enalapril
Perindopril
Ramipril
Sartans
Candesartan
Irbesartan
Neprilysin Inhibitor
Sacubitril
BBs
Bisoprolol
Carvedilol
Metoprolol
Diuretics
Frusemide (furosemide)
Aldosterone Antagonist
Spironolactone
Digoxin - 87Angiotensin I converting enzyme (ACE) inhibitors drugs and MOACaptopril - active drug
Enalapril - prodrug
Perindopril - prodrug
Ramipril - prodrug
ACE inhibitors block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. They reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors. - 88CaptoprilMOA: ACE inhibitors block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. They reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
Shorter Half Life - Active Drug, chance of rash due to sulphur moiety - 89EnalaprilClass: ACE inhibitor
MOA: ACE inhibitors block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. They reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
Prodrug - 90RamiprilClass: ACE Inhibitor
MOA: ACE inhibitors block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. They reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
Prodrug - 91PerindoprilClass: ACE inhibitors
MOA: ACE inhibitors block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. They reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
Prodrug - 92Angiotensin II receptor blockers (ARBs) or ‘Sartans’Irbesartan
Candesartan
Mode of action
Competitively block binding of angiotensin II to type 1 angiotensin (AT1) receptors. They reduce angiotensin II-induced vasoconstriction, sodium reabsorption and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors. - 93IbersartanClass: Sartan /ARB
Mode of action
Competitively block binding of angiotensin II to type 1 angiotensin (AT1) receptors. They reduce angiotensin II-induced vasoconstriction, sodium reabsorption and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors. - 94CandesartanClass; Sartan / ARB
MOA:
Mode of action
Competitively block binding of angiotensin II to type 1 angiotensin (AT1) receptors. They reduce angiotensin II-induced vasoconstriction, sodium reabsorption and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
Prodrug - 95Neprilysin inhibitorssacubitril
Mode of action
The active metabolite of sacubitril inhibits neprilysin reducing degradation of natriuretic peptides. It also increases angiotensin II concentration which is blocked by valsartan. The combination produces vasodilation, increases glomerular filtration rate, reduces sympathetic tone and aldosterone release, and increases bradykinin levels. - 96SacubitrilClass: Neprilysin Inhibitor
Mode of action
The active metabolite of sacubitril inhibits neprilysin reducing degradation of natriuretic peptides. It also increases angiotensin II concentration which is blocked by valsartan. The combination produces vasodilation, increases glomerular filtration rate, reduces sympathetic tone and aldosterone release, and increases bradykinin levels.
Heart Failure - 97beta blockers for heart failureBisoprolol β1
Carvedilol β1, β2, α1
Metoprolol β1 - 98BisoprololClass: Beta Blocker -
β1 selective (hepatic CL + renal CL)
Indication: heart failure
MOA: Competitively block beta receptors in heart, to slow heart rate. Beta-blockers reduce heart rate, BP and cardiac contractility; also depress sinus node rate and slow conduction through the atrioventricular (AV) node, and prolong atrial refractory periods.
The affinity of individual beta-blockers for beta receptors varies - 99metoprololClass: Beta Blocker
selective β1 - hepatic clearance
Indication: heart failure
MOA: Competitively block beta receptors in heart, to slow heart rate. Beta-blockers reduce heart rate, BP and cardiac contractility; also depress sinus node rate and slow conduction through the atrioventricular (AV) node, and prolong atrial refractory periods.
The affinity of individual beta-blockers for beta receptors varies - 100Carvedilol β1, β2, α1Class: Beta Blocker
non selective (β1, β2, α1) hepatic CL
Indication: heart failure
MOA: Competitively block beta receptors in heart, to slow heart rate. Beta-blockers reduce heart rate, BP and cardiac contractility; also depress sinus node rate and slow conduction through the atrioventricular (AV) node, and prolong atrial refractory periods.
The affinity of individual beta-blockers for beta receptors varies - 101frusemide (loop diuretic)Class: Loop Diuretic
Indication: heart failure / oedema related to heart failure
MOA: Inhibit reabsorption of sodium and chloride in the ascending limb of the loop of Henle. This site accounts for retention of approximately 20% of filtered sodium; therefore, these are potent diuretics.
Produce a rapid and intense diuresis and have a short duration of action (4–6 hours). They are effective over a wide dose range with a dose-related response. - 102loop diuretics most potentloop diuretics most potent, increase water and sodium excretion in kidney, reducing intravascular volume, reducing preload.
- 103Aldosterone AntagonistSpironolactone
Indication: heart failure
MOA: Inhibit sodium absorption in the distal tubule by antagonising aldosterone, increasing sodium and water excretion and reducing potassium excretion; they are weak diuretics.
Aldosterone may contribute to the pathophysiology of heart failure; by reducing aldosterone activity, aldosterone antagonists improve outcome. - 104DigoxinClass: Antiarrhythmic
Indication: heart failure
MOA: Slows heart rate and reduces AV nodal conduction by an increase in vagal tone and a reduction in sympathetic activity. Increases the force of myocardial contraction by increasing the release and availability of stored intracellular calcium.
inhibits Na+/K+ ATPase transport pump, increases intracellular calcium, increasing ejection fraction and cardiac output. - 105drugs for allergic rhinitisCromoglycate
Nedocromil
Ipratropium
Dexchlorpheniramine
Promethazine
Loratadine
Cetirizine
Fexofenadine - 106Cromoglycateclass: other drugs for rhinitis
intranasal / inhaled / eyedrops
allergic rhinitis only
mast cell stabiliser - prevents then degranulation and release of histamine from mast cells - 107Ipratropiumanticholinergic
Class: Other Drugs for Rhinitis
Dries nasal secretions and may reduce rhinorrhoea. - 108Nedocromilcromone
mast cell stabilisation
Act by inhibiting release of inflammatory mediators from mast cells. - 109sedating antihistainesDexchlorpheniramine
Promethazine
inverse agonist
MOA: Reduce the effects of histamine by binding to the H1 receptor and stabilising it in an inactive form.
Promethazine also has anticholinergic activity and alpha-blocking activity - 110Dexchlorpheniramine Promethazinesedating antihistamines
inverse agonist
MOA: Reduce the effects of histamine by binding to the H1 receptor and stabilising it in an inactive form.
Promethazine also has anticholinergic activity and alpha-blocking activity - 111less-sedating antihistaminesLoratadine
Cetirizine
Fexofenadine
Class: less sedating antihistamine
inverse agonist
Reduce the effects of histamine by binding to the H1 receptor and stabilising it in an inactive form. - 112Loratadine Cetirizine FexofenadineClass: less sedating antihistamine
inverse agonist
Reduce the effects of histamine by binding to the H1 receptor and stabilising it in an inactive form. - 113Drugs for GlaucomaLatanoprost
Bimatoprost
Timolol
Betaxolol
Apraclonidine
Brimonidine
Acetazolamide
Brinzolamide
Dorzolamide - 114prostaglandin analogues (eye)Latanoprost
bimatoprost
indication: glaucoma
MOA: Reduce intraocular pressure by increasing uveoscleral outflow of aqueous humour. - 115beta blockers for glaucomaTimolol (non selective)
Betaxolol (β1 selective)
MOA: Reduce aqueous humour formation, probably by blockade of beta receptors on the ciliary epithelium. - 116Timolol (non selective)Class - beta blockers for glaucoma
MOA: Reduce aqueous humour formation, probably by blockade of beta receptors on the ciliary epithelium. - 117Betaxolol (β1 selective)Class - beta blockers for glaucoma
MOA: Reduce aqueous humour formation, probably by blockade of beta receptors on the ciliary epithelium. - 118α2 agonists for glaucomaapraclonidine and brimonidine
MOA: Reduce intraocular pressure by suppressing formation and increasing uveoscleral outflow of aqueous humour. - 119apraclonidinesympathomimetic / vasoconstriction
Indication: Glaucoma
MOA: Reduce intraocular pressure by suppressing formation and increasing uveoscleral outflow of aqueous humour. - 120brimonidineclass: α2 agonist
sympathomimetic / vasoconstriction
Indication: Glaucoma
MOA: Reduce intraocular pressure by suppressing formation and increasing uveoscleral outflow of aqueous humour. - 121Systemic carbonic anhydrase inhibitor drug and MOAAcetazolamide
Inhibits carbonic anhydrase and therefore bicarbonate synthesis; in the eye this reduces aqueous humour secretion and thereby intraocular pressure; in the brain this leads to the accumulation of carbon dioxide, reducing the spread of seizure activity. - 122carbonic anhydrase inhibitorsBrinzolamide
Dorzolamide
MOA: Inhibit carbonic anhydrase II (predominant subtype found in the eye), which reduces aqueous humour formation. - 123BrinzolamideClass: Carbonic anhydrase inhibitors
Indication: Glaucoma
MOA: Inhibit carbonic anhydrase II (predominant subtype found in the eye), which reduces aqueous humour formation. - 124DorzolamideClass: Carbonic anhydrase inhibitors
Indication: Glaucoma
MOA: Inhibit carbonic anhydrase II (predominant subtype found in the eye), which reduces aqueous humour formation. - 125Other eye drugs:Atropine
Cyclopentolate
Tropicamide
Phenylephrine
Naphazoline
Tetrahydrozoline
Carmellose
Hypromellose - 126anticholinergics (eyes) drugs and MOAatropine, cyclopentolate, tropicamide
MOA: Reversibly block acetylcholine receptors on iris sphincter and ciliary muscle. - 127Atropine (eye)Class: anticholinergic
Indications from Anticholinergics
Mydriasis (dilation of pupil): examination of peripheral lens and retina; prevention or breakdown of posterior synechiae from iritis; prevention of pupil constriction in iritis
Cycloplegia (relaxation of ciliary body): diagnostic refraction; pain relief in uveitis; chemical occlusion for treatment of suppression amblyopia; ciliary block glaucoma (rare)
MOA: Reversibly block acetylcholine receptors on iris sphincter and ciliary muscle. - 128Cyclopentolateanticholinergic
Reversibly block acetylcholine receptors on iris sphincter and ciliary muscle. - 129Tropicamideanticholinergic
Reversibly block acetylcholine receptors on iris sphincter and ciliary muscle. - 130vasoconstrictors (eyes) drugs and MOAphenylephrine,
naphazoline,
tetrahydrozoline
MOA: Alpha-adrenoreceptor agonists constrict conjunctival blood vessels, reducing ocular redness and discomfort. - 131phenylephrine,MOA: Alpha-adrenoreceptor agonists constrict conjunctival blood vessels, reducing ocular redness and discomfort.
- 132naphazoline,MOA: Alpha-adrenoreceptor agonists constrict conjunctival blood vessels, reducing ocular redness and discomfort.
- 133tetrahydrozolineMOA: Alpha-adrenoreceptor agonists constrict conjunctival blood vessels, reducing ocular redness and discomfort.
- 134Carmellose & Hypromelloseocular lubricants
- 135Urigenitory DrugsPropantheline
Imipramine
Oxybutynin
Tolterodine
Solifenacin
Mirabegron
Oestrogen/estrogen
Finasteride
Tamsulosin
Prazosin
Tadalafil - 136ImipramineClass: Tricyclic antidepressants
Indiction: *for urinary issues* Nocturnal enuresis
MOA: TCAs inhibit reuptake of noradrenaline and serotonin into presynaptic terminals. Although unrelated to the therapeutic effects of the TCAs, they also block cholinergic, histaminergic, alpha1-adrenergic and serotonergic receptors.
beta3 mimetic properties to RELAX detrusor muscle - 137anticholinergics (genitourinary) drugsPropantheline
Oxybutynin
Tolterodine
Solifenacin
Darifenacin - 138OxybutyninClass: anticholinergic (genitourinary)
Indication: urinary urge incontinence
works by blocking muscarinic receptors, inhibiting spontaneous detrusor contractions - 139TolterodineClass: anticholinergic (genitourinary)
Indication: urinary urge incontinence
works by blocking muscarinic receptors, inhibiting spontaneous detrusor contractions - 140SolifenacinClass: anticholinergic (genitourinary)
Indication: urinary urge incontinence
works by blocking muscarinic receptors, inhibiting spontaneous detrusor contractions - 141DarifenacinClass: anticholinergic (genitourinary)
Indication: urinary urge incontinence
works by blocking muscarinic receptors, inhibiting spontaneous detrusor contractions - 142beta 3 agonist (genitourinary)Mirabegron
indication: Urinary urge incontinence
MOA: Beta3-adrenoceptor agonist; relaxes bladder muscle during the storage phase of micturition, increasing bladder capacity. - 143Oestrogen/estrogenRatio of plasma oestrogen to testosterone increases with age
This may result in stromal (the supporting tissue) overgrowth
Greater amount of hormone receptors in the stroma compared with the epithelium
This theory explains why BPH is chiefly a stromal disease - 144Selective alpha blockers (genitourinary)Tamsulosin
Prazosin - 145TamsulosinClass: selective alpha blocker (genitourinary)
Indication: Symptom relief in BPH
MOA: Block alpha1 receptors, relaxing smooth muscle in the bladder neck and prostate, and decreasing resistance to urinary flow. Tamsulosin is more selective for the alpha1-receptor subtypes found in the bladder and prostate. - 146PrazosinClass: selective alpha blocker (genitourinary)
Indication: Symptom relief in BPH
MOA: Block alpha1 receptors, relaxing smooth muscle in the bladder neck and prostate, and decreasing resistance to urinary flow. Tamsulosin is more selective for the alpha1-receptor subtypes found in the bladder and prostate.
Prazosin and terazosin are also arterial and venodilators due to blockade of postsynaptic alpha1 receptors and therefore inhibition of catecholamine-mediated vasoconstriction.
Unlike nonselective alpha-blockers (eg phenoxybenzamine), they have little effect on presynaptic alpha2 receptors and are therefore less likely to cause reflex tachycardia. - 147Phosphodiesterase 5 inhibitorsTadalafil
Finasteride
MOA: Inhibit 5‑alpha-reductase, which converts testosterone to dihydrotestosterone (a potent cellular androgen that stimulates prostate growth). They reduce prostate size and improve symptoms and urinary flow rate. - 148FinasterideClass: Phosphodiesterase 5 inhibitors
MOA: Inhibit 5‑alpha-reductase, which converts testosterone to dihydrotestosterone (a potent cellular androgen that stimulates prostate growth). They reduce prostate size and improve symptoms and urinary flow rate. - 149TadalafilClass: Phosphodiesterase 5 inhibitors
MOA: Inhibit 5‑alpha-reductase, which converts testosterone to dihydrotestosterone (a potent cellular androgen that stimulates prostate growth). They reduce prostate size and improve symptoms and urinary flow rate. - 150drugs for skin conditionssteroids etc
- 151HydrocortisoneMildly potent topical corticosteroid. Alters transcription of inflammatory mediators
Reduce inflammation and itching.
TCS misuse associated with skin atrophy and corticoid acne (unlikely) - 152phenergan (promethazine)Dermatitis is not caused by histamine release.
Reduces awareness of itchiness resulting in less scratching and skin damage
Drowsiness, dry mouth. - 153Betamethasone diproprionateVery potent topical corticosteroid. Alters transcription of inflammatory mediators
Reduce inflammation and itching, and minimises skin thickening
TCS misuse associated with skin atrophy and corticoid acne (possible) - 154Methotrexatedihydrofolate reductase inhibitor, direct keratolytic and reduced T-cell activity
Reduce inflammation and keratinisation
Severe liver, kidney, lung, WBC and mucosal DNA damage. Cytotoxic!! - 155Calcipotriol (+/- betamethasone)Vitamin D analogue, controls keratinocyte proliferation / differentiation.
Returns cells to normal function. Reducing, inflammation, erythema and itching.
Dry / irritated skin and mucosal layers Hypocalcaemia, - 156Benzoyl peroxideAntibacterial effect by free radical formation and desquamation
Reduce bacterial load, unblock comedones and clear spots
Skin redness, peeling. - 157DoxycyclineAntibacterial and anti-inflammatory effect. Bind to 30s microbial ribosome subunit
Reduce lesion number and appearance, swelling, pain associated with acne.
Photosensitivity, incorporation into calcifying tissue in under 8 year olds. - 158AdapaleneInteract with retinoid receptors.Modulate cell proliferation
Modulate cell differentiation
Reduce sebum secretion, Reduce P. acnes load, Anti-inflammatory
Skin redness, peeling in the first 6 -8 weeks. Teratogen? - 159MiconazoleImidazole antifungal. Fungistatic, inhibits Lanosterol 14-alpha demethylase
Reduce itching, broken skin, smell.
Safe, minimal risk of drug interactions if used topically - 160TerbinafineAllylamine antifungal. Fungicidal. Inhibits squalene epoxidase.
Reduce itching, broken skin, smell.
Safe, minimal risk of drug interactions if used topically. (oral tablets, liver issues) - 161GriseofulvinHalts fungal mitosis, by altering mitotic spindle formation.
Used for resistant fungal infections
Potentially cause mutation of DNA.