Pharmacology Flashcards
When is digoxin used?
Rate control in AF/Atrial Flutter
Heart Failure
What is the MoA of digoxin?
Positively inotropic (increases contractility) Negatively chronotropic (decreased HR)
Inhibits the Na/K ATPase Na accumulates inside the cell Activates the Na/Ca exchanger Ca pumped into the cell Ca increases the force of contraction
Digoxin increases the vagal parasympathetic activity
What side effects are associated with digoxin?
Bradycardia
Visual disturbances (blurred/yellow vision)
Dizziness
GI disturbances
What are the main pharmacokinetics/pharmacodynamic principles of digoxin?
Narrow therapeutic window
Digoxin toxicity –> arrhythmias (life-threatening)
Long t1/2 - once daily dosing
When is aspirin used?
Secondary prevention of thrombotic events
Management of ACS
(Pain relief)
What is the MoA of aspirin?
Binds irreversibly to the cyclooxygenase (COX) enzyme
Reduces production of thromboxane –> reduces platelet aggregation and thrombus formation
Reduces endothelial prostaglandin production –> reduces nociceptive sensitisation and inflammation
What side effects are associated with aspirin?
Gastric bleeding (1%) Peptic ulceration Bronchospasm - hypersensitivity Angiooedema Reyes syndrome (rare)
What advice should be given to patients on aspirin?
PPI can be useful in LT uses
Avoid drug preparations that contain aspirin
Aspirin should be avoided in under 16s –> increased risk of Reyes Syndrome
What are the common doses of aspirin?
ACS: 300mg then 75mg OD
2ry prevention: 75mg OD
When is Clopidogrel used?
Secondary prevention of thrombotic events
What is the MoA of Clopidogrel?
Irreversibly blocks the ADP receptor on platelet cell membrane
Prevents formation of GPIIb/IIIa complex needed for platelet aggregation
Reduces thrombus formation
What side effects are associated with Clopidogrel?
Bleeding (GI, IC, post-surgery) in 1-10%
GI upset (dyspepsia, diarrhoea, abdo discomfort) in 1-10%
Rarely, thrombocytopenia
What advice needs to be given to patients on Clopidogrel?
Stop 7d prior to surgery
Don’t stop without consulting dr if have an arterial stent in-situ
Give examples of recombinant tissue plasminogen activator drugs
Alteplase
Tenecteplase
Describe the MoA of rTPA
Recombinant tissue plasminogen activator
Catalyse the conversion of plasminogen into plasmin
Lysis of the fibrin clot
What are the indications for the use of rTPA?
Within 4.5h of an acute ischaemic stroke
Within 12h of MI
Massive PE
What are the side effects associated with rTPA?
Bleeding
Allergic reaction/angiooedema (1%)
How is Alteplase administered?
Bolus-infusion regimen
How is Tenecteplase administered?
Single bolus
What pharmacodynamic interaction is associated with rTPA?
Interaction with anti-platelets and anti-coagulant drugs
Describe the MoA of unfractionated heparin
Enhances the activity of antithrombin III which inhibits thrombin
Also inhibits multiple other factors in the coagulation pathway
Has an anti-coagulant effect
What are the indications for heparin?
Treatment and prevention of thromboembolic events
Renal dialysis
Treatment of Acute Coronary Syndrome
What are the side effects associated with heparin?
Bleeding - risk as great as 3.5%
Heparin-induced thrombocytopenia
Osteoporosis
How is heparin administered?
Continuous IV infusion
SC injection
How can the anti-coagulant effect of heparin be reversed?
Protamine
How is the effect of heparin monitored?
aPTT
What are the indications for Warfarin?
Thromboprophylaxis in AF, metallic heart valves, cardiomyopathy
Treatment of thromboembolism
What is the MoA of Warfarin?
Inhibits Vit K epoxide reductase
Prevents the recycling of Vitamin K to reduced form after carboxylation of coagulation factors II, VII, IX and X
Prevents thrombus formation
What side effects are associated with Warfarin?
Bleeding (Increased risk with increasing INR)
Warfarin necrosis
Osteoporosis
What are the key PD/PK principles of Warfarin?
Multiple interactions with other drugs/foods
Requires regular monitoring of INR and dose adjustment (requires compliance)
Can be reversed with Vit K
Give an example of a direct thrombin inhibitor
Dabigatran
What is the MoA of Dabigatran?
Direct thrombin inhibitor
Inhibits conversion of fibrinogen into fibrin
Prevents thrombus formation
What are the indications for Dabigatran?
Venous thrombus prophylaxis post surgery
Thromboprophylaxis in non-valvular AF
What are the side-effects associated with Dabigatran?
Bleeding
Dyspepsia
What are the key PD/PK principles of Dabigatran?
Rapid onset
Not metabolised by cytochrome p450 so no drug/food interactions
No monitoring required
No antidote available
What is the MoA of Rivaroxaban?
Inhibits the conversion of prothrombin into thrombin
Reduces the concentration of thrombin in the blood
Inhibits the formation of fibrin clots
What are the indications for Rivaroxaban?
Venous thromboembolism prophylaxis (post-surgery)
Thromboprophylaxis in non-valvular AF
Treatment of venous thromboembolism
What side effects are associated with RIvaroxaban?
Bleeding
Nausea
What are the key PD/PK principles of Rivaroxaban?
Metabolised by cyrochrome p450
No antidote
No therapeutic monitoring required
What is the MoA of metformin?
Suppresses gluconeogenesis
Reduces amount of glucose absorbed in the gut
Increases uptake of glucose into skeletal muscle
What side effects are associated with metformin
Dose related GI upset
Lactic acidosis
What is the MoA of sulphonylureas (glipizide, gliclazide)?
Binds to the SU receptor on the surface of beta cells
Blocks K ATPase –> cell depolarises
L-type Ca channels open –> influx of Ca into cell
Exocytosis of insulin
What side effects are associated with sulphonylureas (glipizide, gliclazide)?
Prolonged severe hypoglycaemia Bone marrow toxicity Skin rashes GI upset Increased appetite --> weight gain
What is the MoA of meglitinides (Repaglitinide, nateglitinide)?
Binds to SU receptor on B cell will less potency compared to sulphonylureas (lower risk of hypoglycaemia)
What is the MoA of thiozolidinediones (Pioglitazone?)
Binds to PPAR-gamma receptor (present in adipose tissue, liver and muscle)
Increases lipogenesis
Increases uptake of fatty acid and glucose
What side effects are associated with thiozolidinediones (Pioglitazone)?
Fluid retention (worsens heart failure)
Increased risk of fracture
Increased risk of bladder cancer
Weight gain
What is the MoA of alpha-glucosidase inhibitors (acarbose)?
Delays carbohydrate absorption
What side effects are associated with alpha-glucosidase inhibitor (acarbose)?
Flatulence
Loose stools/diarrhoea
Abdominal bloating
Abdominal pain
(useful in obese patients)
What is the MoA of incretin mimics (exenatide, liraglutide)?
Increases insulin secretion
Decreases glucagon secretion
Slows gastric emptying
What side effects are associated with incretin mimics (exenatide, liraglutide)?
Hypoglycaemia
Range of GI effects
Pancreatitis
What is the MoA of -gliptans?
Competitively inhibit DDP4
Increase GLP-1 in circulation
Increase insulin secretion
Reduce glucagon secretion
What side effects are associated with -gliptans?
GI
Liver disease
Worsening of pancreatitis, heart failure
What is the MoA of SGLT-2 inhibitors (-flozin)?
Inhibit SGLT2 channel in PCT
Reduce amount of glucose reabsorbed from filtrate
More glucose lost in urine
What side effects are associated with SGLT-2 inhibitors (-flozin)?
Hypoglycaemia
UTI
Genital candidiasis
