Cardiac DRUGS Flashcards
Outline the process of platelet plug formation & inhibition
- Platelets (1a,1b,2b,3a) adhere to damaged subendothelium
- 1a - Collagen 1,2&3
- 1b - vWF & microfibrils
- 2b/3a - vWF & fibrinogen
- Form monolayer, spheres & release a & b granules
- ⇒ ADP, thromboxane A2 & 5HT
- ⇒ Aggregation & vasoconstriction
- Inhibited by PGI2 & NO
- Inhibits vasoconstriction
- Inhibits ADP, TcA2 & 5HT release
Outline the class & mechanism of Aspirin
Antiplatelet drug
- Blocks thromboxane A2 pathway of platelet activation by irreversibly acetylating cyclo-oxygenase
- Effects exist for lifespan of platelet (8-9d)
What are the indications for Aspirin
- Primary prevention - less clear due to bleeding risk, only in high risk pts
- Secondary prevention - ALL CV disease
- AF: 75-300mg
Outline the adverse affects/ risk factors/ contraindications of Aspirin
- Bronchospasm in up to 20% asthmatic adults [caution]
-
Gastric side-effects
- Nausea ⇒ GI bleeds
- Bleeding from Duodenal > Gastric ulcers
- [Active/recent ulcer/ bleeding contraindicate]
- Prophylaxis with PPIs should be considered if Hx
- Nausea ⇒ GI bleeds
- Any bleeding disorder contraindicate
*
What is Aspirin resistance?
- 10% of pts
- Affects effectiveness of Aspirin
- Testing of platelet activity not common so rarely identified
What drug interactions occur with Aspirin
- Analgesics: concomitant use
- Anticoagulands: bleeding risk
- Antidepressents: bleeding with
- SSRIs
- Venlafaxine
- Cytotoxics: aspirin reduces excretion of methotrexate
Outline the mechanism of Thienopyridines
Thienopyridines mechanism;
- Irreversibly block the binding of ADP to platelet reception
- ⇒ Prevent expression of the active glycoprotein IIb/IIa receptor
Give examples of thienopyridines
- Ticlopidine (first)
- Clopidogrel
- Prasugrel
- Ticagrelor
Outline the class & mechanims of Clopidogrel
Thienopyridine, mechanism;
- Irreversibly block the binding of ADP to platelet reception
- ⇒ Prevent expression of the active glycoprotein IIb/IIa receptor
What are the indications for Clopidogrel?
Indications;
- 2º prevention of CV events
- post-MI/ post-stroke/ **PVD **(75mg)
- post-PCI + stent insertion (+ Aspirin, 300-600mg loading dose, 75mg)
-
ACS
- +Aspirin
- 300-600mg loading dose, 75mg
Outline contraindications & cautions & adverse effects for Clopedigrel
Contraindications
- Hypersensitivity
- Bleeding problems
- Severe hepatic impairment
Cautions
- Bleeding risk
- Renal impairment
Adverse effects
- **Skin rash **(distinguish from self-limiting X-ray contrast-media-induced skin rash which occurs 1wk post PCI)
- GI side effects
- Bleeding & bruising
Outline the class & mechanism of Prasugrel
Compare to Clopidogrel
Thienopyridine, mechanism;
- Irreversibly block the binding of ADP to platelet reception
- ⇒ Prevent expression of the active glycoprotein IIb/IIa receptor
Compared to Cloppidogrel;
- **Earlier onset of anti-aggregatory effects **(<½hr) & less inter-patient varibility
- P is better in ACS & diabetics
- P is worse in stroke/ TIA (contraindication)
What are the indications for Prasugrel?
Outling dosing
- **1º or delayed PCI **for ACS
- Stent thrombosis during clopidogrel therapy
- Diabetes
Dosing;
- 60mg loading, 10mg
- 5mg in <60kg >75yrs
Outline contraindications & cautions & adverse effects of Prasugrel
Contraindications;
- Hx of CVA/ TIA
- Hypersensitivity
- Bleeding problems
- Severe hepatic impairment
Cautions
- Bleeding risk
- Renal impairment
- Pregnancy & lactation
Adverse effects
- Skin rash (distinguish from self-limiting X-ray contrast-media-induced skin rash which occurs 1wk post PCI)
- GI side effects
- Bleeding & bruising
Outline examples and mechanism of actions of Glycoprotein IIb/IIIa receptor inhibitors
- Abcliximab
- Monoclonal AB
- Eptifibatise/ tirofiban
- Small-molecule GPIIb/IIIa inhibitors
Outline the mechanism of action of Eptifibatise
Outline its indiations
IV antiplatelet agent: Small-molecule GPIIb/IIIa receptor inhibitor
Indication:
- Prevention of early MI in patients presenting with ACS
Outline the mechanism of action of Tirofiban
Outline its indiations
IV antiplatelet agent: Small-molecule GPIIb/IIIa receptor inhibitor
Indication:
- Prevention of early MI in patients presenting with ACS
Outline the mechanism of action of Abiciximab
Outline its indiations
Intravenous antiplatelet agent: Monoclonal AB
Indications;
- Pre-PCI: prevents ischaemic complications
Outline the mechanism of action of angiotensin-converting enzyme inhibitors
Outline AG2 function
ACEi block conversion of Angiotensin 1 to Angiotensin 2.
Angiotensin 2 functions;
- Massive vasoconstriction
- ADH secretion from posterior pituitary
- Aldosterone secretion from adrenal gland cortex
- Sympathetic activity increase
- Renal
- Na+Cl- reabsorption in proximal tubule (and hence H2O)
- K+ exretion
Give examples of ACEi
- Captopril
- Analapril
- Lisinoprl
- Ramipril
- Perindopril
Outline the indications for ACEi’s
- Hypertension [all non-black <55yrs]
- HF [all LVF]
- Post-MI 2º prevention [all post-MI]
- CV risk reduction [all CVD]
Outline the contraindications & cautions & adverse effects of ACEi’s
Contraindications
- Valvular stenosis
- Angioedema
- Hypersensitivity
- Bilateral renal artery stenosis
- Pregnancy
Cautions
- Hypotension (systolic <90mmHg)
- Patients on high-dose diuretics (ie furosemide >80mg daily)
- Breast feeding
- Moderate to severe renal impairment
Adverse effects
- First-dose hypotension [use long-acting, 1st dose at night, avoid diuresis]
- Dry cough [may resolve, switch]
- Angioedema [stop]
- Rash [switch, stop]
Outline the key drug interactions with ACEi’s
- Ciclosporin & potassium: inc risk of hyperkalaemia [low K+ diet]
- Diuretics: enhances hypotensive effect
- Lithium: increases lithium levels
What monitoring is important for patients on ACEi’s
- Baseline BP & U&Es
- 2wks then annually
- Serum creatinine >20% |or| eGFR drops >15%
Outline the mechanism of Angiotensin receptor blockers (ARBs)
aka AG2 receptor antagonists, AIIRAs
- Bind to angiotensin 2 receptors and block action of angiotensin 2
Angiotensin 2 function
- Angiotensin 2 functions;
- Massive vasoconstriction
- ADH secretion from posterior pituitary
- Aldosterone secretion from adrenal gland cortex
- Sympathetic activity increase
- Renal
- Na+Cl- reabsorption in proximal tubule (and hence H2O)
- K+ exretion
For ARBs, outline;
- Indications
- Contraindications & Cautions & Adverse affects
- Monitoring
- Drug interactions
Indications
- 2nd line to ACEi
Contraindications & Cautions & Adverse affects
- Same as ACEi
Monitoring
- Same as ACEi
Drug interactions
- Same as ACEi
Give examples of ARBs
Sartan’s
- Candesartan
- Irbesartan
- Losartan
- Telmisartan
- Valsartan
Outline the mechanism of Aldosterone antagonists
Aldosterone functions
Structurally similar to aldosterone & competitively binds to mineralocorticoid receptor
Aldosterone function;
- Upregulates and activates basolateral Na+/K+ pumps
- Upregulates epithelial sodium channels
- Secretes K+
- Secretes H+ for Na+ (regulating plasma bicarbonate HCO3-)
Normal mechanism;
- Stimulated by angiotensin 2
- Released from adrenal gland cortex
Give examples of Aldosterone antagonists
- Eplerenone
- Spironolactone
Outline the indications for aldosterone antagonists
- HF (25-50mg)
- Post-MI HF (EF <40%, 3-14d of MI)
- Hypertension (step 4)
Outline the contraindications & cautions & adverse affects of Aldosterone antagonists
Contraindications
- Hypersensitivity
- Serum K+ >5mmol/L
- Renal/ hepatic failure (severe, mod=caution)
- Anuria
Adverse affects
- Hyperkalaemia [common, diet]
- Renal dysfunction [common, withdrawal]
- Gynaecomastia [eplerenone has no progesterone effects]
- GI…
- Menstral irregularities
- Rash
Outline drug interactions with aldosterone antagonists
- Hyperkalaemia
- ACEi & ARBs
- Potassium
- Ciclosporin
- Eplerenone plasma levels
- Antiarrhythmic’s
- Antibacterial’s
- Antidepressant’s
- Antifungal’s
- Antiviral’s
- Lithium
Outline the mechanism of action of Beta-adrenoceptor blokers (B-blockers)
- Block action of noradrenaline at B-adrenoceptors
- Located in;
- Myocardium
- Throughout circulatory system
- Inhibit sympathetic stimulation of HR & myocardial contractility
- -ve chronotropic [speed]: slow SA node firing
- -ve inotropi [contractility]
- Anti-arrhythmic & anti-ischaemic
- Lower BP (unclear, lowers renin/ sympathetic tone?)
Give examples of B-blockers
- Atenolol
- Bisoprolol
- Metoprolol
- Nebivolol
- Carvedilol
Outline the indications for B-blockers
- HF (bisopro, carvedi, nebivo)
- Post-MI 2º prevention
- Angina (1st line, HR 50-60)
- AF (1st line)
Outline the contraindications & cautions & adverse effects of B-blockers
Contraindications
- Asthma/ bronchospasm
- 2nd/ 3rd degree heart BLOCK
- PVD
- Patients on Verapamil
Cautions
- COPD
- uncontrolled HF, sick sinus syndrome, hypotension, bradycardia
- Prenancy/ breast feeding
Adverse effects
- Bradycardia (HR <50bpm)
- Symptomatic hypotension
- Bronchospasm (swap + supervise)
- Fatigue
- Cold-extremities (gloves/ socks)
- Sleep disturbances (water-soluble agent)
Outline the mechanism of action of calcium-channel blockers (CCBs)
- Inhibit inward movement of calcium ions through slow channels in myocardial cells
- Dihydropyridine (DHP): Affinity for vascular smooth muscle
- peripheral vasodilation
- Reduced BP
- Reduced afterload
- non-DHP: Affinity for myocardial cells & conduction system
- Negative inotropy
- Myopcardial depression
- AV conduction delay
Give examples of calcium channel blockers & their types
Dihydropyridine (DHP) CCBs
- Amlodipine
- Nifedipine
- Felodipine
- Lacidipine
Non-DHP CCBs
- Diltiazem
- Verapamil
Outline the indications for CCBs
- Angina
- 2nd to B-blockers or DHPs in conjunction
- Hypertension
- 2st line in black/ >55yrs
- AF (2nd line, non-DHP: verapamil)
Outline the contraindications & cautions & adverse effects of CCBs
Contraindications
- Cardiogenic shock/ aortic stenosis/ post-acute MI/ ACS
- non-DHPs: dangeous arrhythmias/ LVF
Cautions
- Worsening HF
Adverse effects
- non-DHP: Bradycardia (reduce)
- Symptomatic hypotension (reduce)
- Flushing (dissipates/ time)
- GI disturbances
- Ankle oedema (reduce/ +ACEi/ ARB)
- Gingival hypeplasia (change)
Outline the mechanism of Nitrates
- Vaso/ veno dilatory efects
- Inc coronary blood flow
- Reduce preload & afterload
- (Low workload = low oxygen demand)
- Prevent coronary spasm & vasoconstriction induced by exercise
Give examples of nitrates
- Glyceryl trinitrate (GTN)
- Isosorbide mononitrate
- Isosorbide dinitrate
Outline the indications for nitrates
- Angina
outline the contraindications & cautions & adverse effects of nitrates
Contraindications
- Hypersensitivity
- Any hypovolaemic/ tensive condition
- Any containing heart disease (restrictive/ constrictive/ stenosed)
- Cerebral haemorrhage
Cautions
- Hypothyroidism
- Closed-angle glaucoma
Adverse effects
- Hypotension
- Headache (cerebral vasodilation)
Outline the mehanism of action of potassium-channel activators
Opening potassium channels leads to arterial vasodilation and reduced afterload
Nicorandil also has nitrate-like action: venous dilation & reduced preload
Give examples of potassium-channel activators
- Nicorandil
Outline the indications for potassium-channel activators
- Angina (adjunct or alternative)
Outline the contraindications & cautions & adverse effects of potassium-channel activators
Contraindications
- Cardiogenic shock
- LVF/ hypotension
- Hypertensitivity
- Pregnancy & breast feeding
Cautions
- Haemodynamically unstable/ MI/ failure/ low pressure
- No driving/ machinary until sure not affects
Adverse effects
- Headache
- Dizziness & hypotension
- Peripheral vasodilation
- Ulceration (GI/ skin/ mucosa, change)
- Angiodema
