VIVA: Pharmacology - Cardiovascular Flashcards
What is the mechanism of action of GTN?
- Taken up by vascular smooth muscle
- Denitrited by glutathione-S-transferase to release nitric oxide
- NO activates cGMP and reduces intracellular Ca2+, resulting in smooth muscle relaxation and vasodilation
Prostaglandins may be involved
What are the clinical effects of GTN?
Beneficial effects:
- Venodilation* -> reduced VR and decreased ventricular preload -> decreased LVEDV, LV wall tension -> reduced myocardial oxygen consumption*
- Vasodilation of epicardial coronary arteries -> increased coronary collateral flow
- Decreased systemic BP*
Adverse effects:
- Hypotension
- Tachycardia
- Headache
*2/3 to pass + 2 adverse effects
What are the indications for GTN use in the ED?
- Angina*
- Acute coronary syndrome
- Hypertensive urgencies/emergencies
- APO
- Aortic dissection (with B blockade)
*needed to pass + 2 others
What is adenosine and how does it work?
- Naturally-occurring nucleoside*
- Blocks AV conduction* by activating inward rectifier K+ current (i.e. hyperpolarises the AV node)
*needed to pass
Describe the pharmacokinetics of adenosine
- Short half-life (less than 30secs)*
- Uptake by endothelial and red cells
- Less effective in presence of adenosine receptor blockers (e.g. caffeine, theophylline)
*needed to pass
What are the side effects of adenosine?
4 to pass:
1. Cardiovascular:
- Chest tightness / burning
- Flushing
- Hypotension
- Arrhythmia
2. Neurological:
- Headache
- Paraesthesias
3. Respiratory:
- Bronchospasm
4. GIT:
- Nausea
What are the possible drug interactions with adenosine?
1/3 to pass:
- Theophylline inhibits (adenosine receptor blocker)
- Dipyridamole enhances (adenosine uptake blocker)
- Interactions with other AV nodal blocking drugs
What antiarrhythmic class does amiodarone belong to?
- Class III*
- Also has class I, II and IV effects
*needed to pass
What are the effects of amiodarone on the heart?
- Increases action potential duration due to blockade of rapid component of delayed K+ current (Ikr)*
- Chronic use also blocks slow K+ rectifier
- Prolongs QT* (due to above effects)
- Blocks inactivated Na+ channels
- Weak adrenergic and Ca2+ channel blocker
*needed to pass
What other arrhythmias is amiodarone used for?
2 to pass:
- AF
- VT
- VF
- Supraventricular (re-entrant/accessory)
What arrhythmias may amiodarone cause?
1 to pass:
- TdP (rare, <1%)
- Bradycardia
- Heart block
Describe the pharmacodynamics of digoxin
- Inhibitor of Na+/K+ ATPase*:
- Increases intracellular Na+, decreases intracellular K+
- Increased intracellular Na+ leads to reduced Na+/Ca2+ exchanger activity which leads to increased intracellular Ca2+
- Increased intracellular Ca2+ causes an increase in contractility (inotropy)
- Inhibition of Na+/K+ ATPase in vascular smooth muscle causes depolarisation, which causes smooth muscle contraction and vasoconstriction - Electrical effects*:
- Direct: shortening of action potential, leading to shortened atrial and ventricular refractoriness
- Increased automaticity of the heart muscle: leads to bigeminy, followed by VT and then VF - Parasympathetic and sympathetic effects:
- At lower doses, parasympathetic effects (early signs of toxicity = bradycardia, AV block)
- At higher doses, increased sympathetic effect which may further sensitise the myocardium to automaticity
*needed to pass
What are the non-cardiac symptoms and signs of digoxin toxicity?
- GIT:
- Anorexia
- Nausea and vomiting
- Diarrhoea - CNS*:
- Disorientation
- Hallucinations
- Yellow/green vision (or some variation of)
- Chemoreceptor trigger zones
*1 example to pass
What factors may predispose a patient to digoxin toxicity?
- Electrolyte imbalances*:
- Hypokalaemia (K+ normally inhibits digoxin binding to the Na+/K+ ATPase)
- Hypercalcaemia (potentiates digoxin toxicity by increasing the intracellular Ca2+ stores, producing automaticity)
- Hypomagnesaemia - Drugs that increase digoxin effect*:
- Amiodarone (by increasing plasma digoxin concentrate)
- Diltiazem
- Verapamil
- Quinidine
- Macrolide antibiotics (azithromycin, erythromycin, clarithromycin)
- K+ depleting drugs (including diuretics)
- Spironolactone - Organ disease:
- Renal failure (important because of kinetics)
- Hypothyroidism
*1 example of each to pass
What is digoxin’s mechanism of action in heart failure?
Ca2+ accumulation in cells * (due to Na+/K+ block*, increased intracellular Na+ reduces Na+/Ca2+ exchange):
- Increased contraction strength *
- Increased SV/CO per beat (with smaller EDSV, small heart, reduced right heart pressures/volume)
- Slower HR via effects on parasympathetic fibres/AV node, further increasing SV (particularly in AF)
*2/3 to pass
Why are patients in heart failure prone to digoxin toxicity?
- Poor renal function from low CO*
- Potential dehydration and/or other drug interactions* (e.g. ACEI, diuretics, spironolactone, Ca2+ channel blockers)
- Potential effects on effective Vd
- Low K+ from other heart failure medications, especially diuretics
- Poor cardiac reserve/output, altered digoxin handling during acute HF / fluid distribution changes / other major illnesses
*1/2 to pass + 1 other
What are the features of digoxin toxicity?
- Cardiovascular:
- Arrhythmias due to increased automaticity and AV block (particularly bradyarrhythmias, but also R-on-T)
- Severe heart block (particularly if pre-existing block)
- Worsening HF
- Hypotension - Metabolic:
- Hyperkalaemia* (associated strongly with mortality) - GIT:
- Anorexia
- Nausea and vomiting
- Diarrhoea - CNS*:
- Disorientation
- Hallucinations
- Yellow/green vision (or some variation of)
- Chemoreceptor trigger zones
- Lethargy, fatigue
- Headaches
- Paraesthesias
*1 example to pass
Describe the pharmacodynamics of propranolol that make it useful in thyrotoxicosis
Competitive non-selective B-blocker, blocking both B1 and B2 receptors*
Cardiovascular effects:
- Decreased BP
- Decreased HR (especially rate control of AF)
- Negative inotropy and chronotropy
- Decreased catecholamine effects which are prominent in hyperthyroidism
Inhibition of peripheral conversion of thyroxine to triiodothyronine (especially specific to propranolol over other B-blockers)
Also has Na+-channel blocking action (“membrane stabilisation”)
*needed to pass + 2 cardiovascular effects
What are the adverse effects of propranolol?
- CVS*:
- Bradycardia
- Hypotension
- Worsening CCF
- Worsening ischaemia in PVD
- QRS widening and arrhythmias in toxicity - CNS*:
- Sedation
- Depression
- Dreams
- Coma, seizure, delirium in toxicity - Respiratory*:
- Worsening asthma/COPD - Other:
- Decreased exercise tolerance
- Fatigue
- Impotence
- Decreased libido
- Masks symptoms of hypoglycaemia
*1 example from each
Describe the mechanism of action of verapamil
- Block voltage-gated L-type Ca2+ channels* (a1 subunit) to reduce frequency of opening when depolarised, resulting in decreased transmembrane Ca2+ current* and Ca2+ influx*
- Decreases AV node conduction and contractility*, thereby reducing CO
- Also causes vascular smooth muscle relaxation (moreso with dihydropyridines)
*needed to pass
What are the toxic effects of verapamil?
- Cardiovascular*:
- Bradycardia
- AV block
- Cardiac arrest
- Heart failure
- Hypotension - Minor*:
- Flushing
- Dizziness
- Nausea
- Constipation
- Peripheral oedema
*3 cardiovascular and 1 minor needed to pass
What antidotes can be used to treat verapamil toxicity?
1 to pass:
- IV calcium
- High-dose insulin euglycaemic therapy
What is the mechanism of enalapril?
Competitive inhibitor of angiotensin converting enzyme (ACE):
- Blocks conversion of angiotensin I to II*
- Decreases vascular tone* due to prevention of vasoconstrictive effects of angiotensin II (main effect)
- Inhibits aldosterone secretion* caused by angiotensin II leading to reduced Na+ and H2O resorption, and therefore decreased BP
- Increases bradykinin*, resulting in further vasodilation (angiotensin II normally metabolises bradykinin to its inactive form)
*2/4 to pass
What are the adverse effects of ACE inhibitors?
- Cardiovascular:
- Hypotension* (first dose, especially if hypovolaemic, diuretics, NaCl restriction, GI loss) and dizziness - Neurological:
- Headache
- Weakness
- Loss of taste - GIT:
- Nausea
- Diarrhoea - Renal:
- AKI
- Hyperkalaemia (due to decreased aldosterone secretion) - Other:
- Fever
- Rash
- Joint pain
- Angioedema
- Cough, wheeze - Reproductive:
- Teratogenic
*needed to pass + 2 others
What other drugs can interact with ACE inhibitors and how?
2 to pass:
- Diuretics: hypotension, fluid loss
- K+-sparing diuretics, K+ supplements: hyperkalaemia
- Other nephrotoxins: AKI
- Lithium: hyperkalaemia, reduced effect of ACEIs, lithium toxicity
- Anaesthetics (any): hypotension
- NSAIDs: hyperkalaemia, makes ACEIs ineffective
What advantages do angiotensin receptor blockers have over ACEIs?
- No effect on bradykinin, so reduced incidence of cough and angioedema
- More complete inhibition of actions of angiotensin II (as there are enzymes other than ACE capable of generating angiotensin II)
Describe the pharmacodynamics of irbesartan
- Competitive selective antagonist of angiotensin II type 1 (AT1) receptor*
- Results in vasodilation and inhibition of aldosterone secretion
*needed to pass + 1/2 effects
What are the specific contraindications of angiotensin II receptor blockers?
2/5 to pass:
- Non-diabetic renal failure
- Pregnancy
- Allergy / previous adverse reaction
- Hyperkalaemia
- Renal artery stenosis
What is the mechanism of action of prazosin?
- Selective alpha-1 receptor antagonist* in arterioles and venules
- Reduces arterial pressure by dilating both resistance and capacitance vessels
- a1-receptor selectivity allows noradrenaline to exert unopposed negative feedback (mediated by presynaptic alpha-2 receptors) on its own release
*needed to pass
List three non-BP effects of prazosin
- Cardiovascular:
- Postural hypotension, dizziness, syncope
- Reflex tachycardia, palpitations - Neurological:
- Headache
- Lethargy - Genitourinary:
- Reduces prostate smooth muscle tone (alleviating prostatic urinary obstruction) - Metabolic:
- Decreased LDL and triglycerides, increased HDL - Other:
- Positive serum antinuclear factor
What non-antihypertensive benefits do ACEIs have in diabetes mellitus?
- Diminishes proteinuria and stabilises renal function (even in the absence of lowering of blood pressure)
- Now recommended in diabetes even in the absence of HTN
How is ramipril eliminated? Why is this important?
- Eliminated primarily by the kidneys*
- Doses of these drugs should be reduced in patients with renal insufficiency
*needed to pass
What is the mechanism of action for beta blockers in general?
- Bind to beta receptors in the heart, lung and endocrine tissue
- Beta receptor activation by circulating catecholamines is antagonised by beta blockers*
- Selective bind beta 1 receptors, non-selective bind beta 1 and 2 receptors*
- Most are pure antagonists
*needed to pass
Describe the pharmacokinetics of metoprolol
- Absorption *:
- Rapid and complete
- Given orally (onset 1-2hrs) and IV (onset 20mins when infused over 10mins)
- Oral bioavailability 50% * due to significant first pass effect - Distribution *:
- Large (3.2-5.6L/kg, >200L)
- Crosses the BBB
- 10-12% protein binding to albumin * - Metabolism *:
- Extensive hepatic metabolism via CYP2D6
- Elimination half-life 3-4hrs * - Excretion *:
- Urine 95%
- 4/7 to pass
What are the side effects of beta blockers?
- Cardiovascular*:
- Hypotension
- Bradycardia
- Heart block
- Depressed myocardial contractility
- Heart failure
- Dizziness
- Peripheral vasoconstriction, Raynaud’s, claudication - Neurological:
- Fatigue
- Sedation
- Depression
- Nightmares
- Abrupt withdrawal effects
- Sexual dysfunction - Respiratory:
- Bronchospasm - Endocrine:
- Masks signs of hypoglycaemia (e.g. tachycardia, pupil dilatation) - Interactions:
- Exacerbates Ca2+ channel blocker effects
*cardiac + 2 others to pass
What are the cardiovascular effects of metoprolol?
- Negative inotropic and chronotropic effects*
- Slows AV node conduction with increased PR interval on ECG
- Decreases BP by a mechanism not fully understood but probably includes suppression of renin release and CNS effects
*needed to pass
How does metoprolol differ from propranolol in its receptor action?
- Metoprolol is B1 specific and propranolol is not* (equipotent at B1 and B2)
- B1 equipotent (full agonist)
- B2 50-100x less potent
- At higher doses is less specific
*needed to pass
Describe the pharmacodynamics of propranolol
Mechanism of action:
- Competitive non-selective B antagonist
Effects:
1. Cardiovascular:
- Negative inotropy and chronotropy
- Increased PR interval
- Decreased BP if high
- Decreased renin release
2. Respiratory:
- Bronchospasm
3. Eye:
- Decreased IOP due to decreased humour production
4. Metabolic:
- Glycogenolysis
- Increased VLDL, decreased HDL
Describe the effects of verapamil on the heart and blood vessels
- Reduced contractility / CO*, reduced O2 demand
- Reduced impulse generation, AV node conduction block*
- Vascular smooth muscle relaxation* (less than dihydropyridines) or reduced coronary artery spasm
*2/3 to pass
What are the indications for verapamil?
- Angina*
- HTN*
- Atrial arrhythmias*
- Migraine
*2/3 to pass
What class of drug is frusemide?
Loop diuretic
What are the pharmacokinetics of frusemide?
3 to pass:
1. Absorption:
- Well absorbed with variable oral bioavailability, 10-100%
- Onset post oral 1-3hrs, IV 15-30mins
- Peak effect oral 1hr, IV 30mins
- Duration of action oral 2-6hrs, IV 2hrs
2. Distribution:
- Highly albumin bound (>95%)
3. Metabolism:
- 50% conjugated in kidney and 50% excreted in urine unchanged
- Small amount metabolised by liver
- Elimination half-life 1.5-2hrs
4. Elimination:
- Renal (tubular secretion)
What are the adverse effects of frusemide?
- Cardiovascular*:
- Orthostatic hypotension
- Dehydration - Metabolic*:
- Hyponatraemia
- Hypokalaemia
- Hypomagnesaemia
- Hyperglycaemia
- Metabolic alkalosis
- Raised uric acid and gout
- Increased LDL and triglycerides, decreased HDL - Neurological:
- Ototoxicity (with high dose IV)
- Tinnitus
- Vertigo - GIT:
- Pancreatitis
- Jaundice
- Nausea and vomiting - Renal:
- Interstitial nephritis - Haematological:
- Thrombocytopaenia
- Eosinophilia - Allergic:
- Hypersensitivity reactions
- Rash
*1 of each to pass
What are the possible drug interactions of frusemide?
1 to pass:
- NSAIDs
- Aminoglycosides
- Anticoagulants
- Digoxin
- Lithium
- Propranolol
- Probenecid
- Thiazides
- Amphotericin B
- Cisplatin
How does frusemide exert its action?
- Selectively inhibits Na+/K+/2Cl- transporter in thick ascending limb of loop of Henle to prevent resorption of Na+ and Cl-*
- Abolishes counter-current concentrating mechanism leading to dilute urine
- Increases prostaglandin synthesis -> inhibits salt transport in thick ascending limb, increases renal blood flow, decreases pulmonary congestion, decreases LV filling pressures
*needed to pass
Why is mannitol used in the management of head injury?
Mannitol is used to reduce intracranial pressure post head injury
What is the mechanism of action of mannitol?
- Mannitol is an osmotic diuretic*
- Alters Starling forces as it does not cross the intact BBB and thus draws water out of cells to reduce intracellular volume (hence reducing intracranial volume and intracranial pressure)
What are the other clinical effects of mannitol besides its effect on intracranial pressure?
2/4 to pass:
- Reduces intraocular pressure
- Diuresis / dehydration / hypovolaemia
- Hypernatraemia
- Hyperkalaemia
What is an appropriate dose of mannitol in head injury?
1-2g/kg as an IV bolus over 15mins*
- 0.25-2g/kg acceptable range
Describe the mechanism of action of thiazides
Inhibition of Na+/Cl- transporter in the distal convoluted tubule*, leading to increased NaCl excretion and diuresis
*needed to pass
What are the major clinical indications for thiazide diuretic use?
- Heart failure*
- HTN*
- Nephrolithiasis
- Nephrogenic diabetes insipidus
- Generalised oedema
- Nephrotic syndrome
- Cirrhosis
*needed to pass
What are the potential adverse effects of thiazide diuretics?
- Cardiovascular:
- Orthostatic hypotension, hypovolaemia*
- Dehydration* - Metabolic:
- Hypokalaemia*
- Hyponatraemia*
- Hyperuricaemia
- Hypercalcaemia
- Metabolic alkalosis
- Impaired carbohydrate tolerance, hyperglycaemia - GIT:
- Pancreatitis - Allergy:
- Cross-reactivity with sulphonamides
*2/4 to pass + 1 other
What is the mechanism of action of clopidogrel?
Antiplatelet effect by inhibiting ADP pathway*:
- Irreversible blockade of ADP receptor on platelet for life of platelet
*needed to pass
Describe the pharmacokinetics of clopidogrel
- Absorption:
- Loading dose 300-600mg* or 75mg daily* - Metabolism:
- Prodrug* metabolised to pharmacologically active metabolite and inactive metabolites
- Activated in liver by cytochrome P450 enzymes* (including CYP2C19)
- 80% of platelet activity inhibited within 5hrs of oral dose
- Elimination half-life 0.5-1hrs*
- Effects last the life of the platelet* - Elimination:
- Following an oral dose: 50% excreted in the urine and 46% in the faeces in next 5 days
* 2/6 needed to pass
What are the adverse effects of clopidogrel?
- Haematological:
- Bleeding*
- Pancytopaenia, TTP (rarely) - GIT:
- Reflux
- Gastric ulcers
- Abdominal pain
- Diarrhoea - Neurological:
- Paraesthesias - Dermatological:
- Rash
*needed to pass + 2 others
How does heparin act?
- Heparin binds endogenous antithrombin and enhances its activity*
- Antithrombin inhibits factors IIa, IXa and Xa* by complexing with them and inducing a conformational change
*needed to pass
How may heparin be administered?
- Parenteral (IV or subcut)*, nebulised
- Continuously (following bolus) vs intermittent
- Therapeutic vs prophylactic
*needed to pass
What are the potential adverse effects of heparin?
- Haematological:
- Bleeding*
- Heparin-induced thrombocytopaenia* - Dermatological:
- Alopecia - Allergy
- Endocrine:
- Osteoporosis
- Mineralocorticoid deficiency
*needed to pass + 1 other
What are the advantages of low molecular weight heparins compared with unfractionated heparin?
- Have equal efficacy
- Increased subcut bioavailability
- Require less frequent dosing
- Require less monitoring
- Shorter chain heparin with less effect on thrombin (IIa)
Describe the mechanism of action of rivaroxaban
Inhibits both free and prothrombinase-bound forms of activated factor X
Describe the pharmacokinetics of rivaroxaban
- Absorption:
- Oral bioavailability >80%
- Peak levels 3hrs post-ingestion - Distribution:
- Small volume of distribution (<50L)
- Highly protein bound - Metabolism/elimination:
- Elimination renal (predominant)* and hepatic (CYP3A4) with steady state half-life 5-14hrs
- Prolonged with renal impairment
*needed to pass + 2 others
What clinical advantages does rivaroxaban offer over warfarin?
2 to pass:
- More rapid onset/offset of action
- More predictable effect = easier dosing, wider therapeutic index
- INR monitoring not required
- Fewer drug and dietary interactions
Do the pharmacokinetics of rivaroxaban present any clinical disadvantages relative to warfarin?
Predominant renal excretion means dose must be adjusted in renal failure, and is not suitable for dialysis patients
What are the classes of thrombolytic agents?
- tPA* (tissue plasminogen activator; e.g. alteplase, tenecteplase, reteplase)
- Streptokinase* (protein synthesised by streptococci)
*needed to pass
What is the mechanism of action of tissue plasminogen activator?
- tPA is an enzyme that directly converts plasminogen to plasmin*
- Plasmin is the major fibrinolytic enzyme
- Preferentially activates plasminogen bound to fibrin by several hundred fold, therefore is considered clot-specific
- Short half-life therefore heparin is an essential adjunct
- Naturally-occurring
*needed to pass
What are the adverse effects of thrombolytic agents?
- Haematological:
- Bleeding* (including cerebral haemorrhage, gastrointestinal haemorrhage, and from sites of recent surgery/wounds) - Allergy (especially streptokinase)
*needed to pass
What are the clinical uses of tPA?
- AMI*
- PE*
- Acute ischaemic stroke*
- Severe DVT
- Intra-arterial peripheral limbs
*needed to pass
Describe the mechanisms by which drugs interact with warfarin
Pharmacokinetic*:
- Enzyme inhibition (majority)
- Enzyme induction
- Altered plasma protein binding
- Altered absorption
Pharmacodynamic*:
- Synergism (impaired haemostasis)
- Competitive antagonism (clotting factor synthesis/concentration)
*1 example of each to pass
Give some examples of drugs that increase INR when administered with warfarin
1 to pass:
- Aspirin
- Heparin
- Corticosteroids
- Metronidazole
- Fluconazole
- Trimethoprim-sulfamethoxazole
- Third generation cephalosporins
- Macrolides
- Amiodarone
- SSRIs
- Tramadol
Give some examples of drugs that decrease INR when administered with warfarin
1 to pass:
- Vitamin K
- Diuretics
- Barbiturates
- Phenytoin
- Carbamazepine
- Rifampicin
- Dicloxacillin
- Azathioprine
What is flecainide’s mechanism of action?
- Na+ channel blockade *:
- Predominant action is to inhibit fast Na+ channel responsible for rapid upstroke of the myocardial action potential in cardiac conducting tissue
- Class 1C * action with minimal effect on AP duration and slow dissociation from the channel (also no effect on QT interval)
- Decreases the rate of rise of action potential with little effect on duration
Describe flecainide’s pharmacokinetics
2 point to pass:
Absorption:
- Well-absorbed orally
- Peak plasma levels at 3hrs
- Usual dose 100-200mg daily
Distribution:
- Vd 5-12.4L/kg
Metabolism and elimination:
- Elimination half-life 20hrs
- 30% excreted unchanged in urine, remainder by hepatic metabolism
In which patients is flecainide contraindicated?
- Hypotension
- LV dysfunction
Describe the mechanism of action of lignocaine on the heart
- Class 1B antiarrhythmic *
- Blocks activated and inactivated Na+ channels *, with greater effect in ischaemic tissue
- Decreases pacemaker activity
- No vagal effects
- May cause hypotension by depressing myocardial contractility in those with heart failure
*needed to pass
Describe the adverse effects of lignocaine
3 to pass:
1. CNS:
- Ototoxicity
- Tinnitus
- Dizziness
- Tremor
- Visual disturbance
- Paraesthesia
- Slurred speech
- Seizure
2. CVS:
- Bradycardia
- Hypotension
- Cardiovascular collapse
- Proarrhythmia (uncommon; includes SA arrest)
- Worsening of CCF
3. Respiratory:
- Respiratory depression
4. GIT:
- Anorexia
- Nausea and vomiting
5. Allergy
What are the clinical uses of lignocaine?
2/3 to pass:
- Type 1B antiarrhythmic
- Local anaesthetic
- Post-herpetic neuralgia
What features distinguish lignocaine from other class 1 antiarrhythmics?
- Does not prolong duration of AP *
- Dissociates from channel with rapid kinetics
- No effect on normal cells (preferentially affects ischaemic tissue)
*needed to pass
How are class 1 anti-arrhythmics classified? Give an example of each
1A (intermediate dissociation): quinidine, procainamide
1B (rapid dissociation): lignocaine, phenytoin
1C (slow dissociation): flecainide
What are the differing effects on the action potential of class 1A, B and C antiarrhythmics?
1A: prolongs
1B: nil
1C: minimal
List the classes of drugs used for the management of AF in the ED
3/5 to pass:
- B blockers
- Ca2+ channel blockers
- Cardiac glycosides
- Class 1c antiarrhythmics
- Class 3 antiarrhythmics
Describe the pharmacodynamics of sotalol
- Non-selective B-blocker (class II)
- Prolongs plateau phase (class III)
What are the main side effects of sotalol?
- Proarrhythmic (especially QT prolongation * with risk of TdP)
- CCF
- AV blockade
- Asthma
*needed to pass + 1 other
What drug interactions with sotalol prolong the QT?
2 to pass:
1. Drugs which prolong QT:
- E.g. phenothiazines, macrolides, quinolones, antidepressants
2. Drugs which cause hypokalaemia and hypomagnesaemia
3. Myocardial depressant drugs
4. Drugs that increase refractory time and contraction
- E.g. CCBs, class 1a antiarrhythmics
List some drugs used in hypertensive emergencies
3 to pass:
- GTN
- Nifedipine
- Diazoxide
- Hydralazine
- Nitroprusside
- Esmolol
- Labetalol
Describe the pharmacokinetics of sodium nitroprusside
Absorption:
- IV administration
- Onset within minutes *
- Peak effect within minutes
Metabolism:
- Elimination half-life 2mins *
- Duration of action 1-10mins
- To cyanide in RBCs *
- To thiocyanate in liver *
Excretion:
- Renally excreted
*2/4 to pass
What are the potential toxicities of sodium nitroprusside?
- Cyanide toxicity:
- Hypotension
- Metabolic acidosis
- Pink skin
- Tachypnoea
- Hyporeflexia
- Mydriasis
- Coma - Thiocyanate:
- Ataxia
- Blurred vision
- Headache
- Nausea and vomiting
- Tinnitus
- SOB
- Delirium
- Unconsciousness
What are the effects of Ca2+ channel blockers on smooth muscle?
Relax smooth muscle, especially vascular:
- Arterioles more sensitive than veins
- Does affect bronchiolar, GIT and uterine
Why is verapamil more efficacious than dihydropyridines in the treatment of arrhythmias?
- Blockade of L-type channels is more marked in tissues that fire frequently
- Therefore more pronounced effects on tissues less polarised at rest and that depend on Ca2+ channels for activation (i.e. SA and AV nodes)
By what mechanisms do Ca2+ channel blockers control angina?
- Decrease myocardial contractility *
- Decrease O2 demand
- Decrease afterload by relaxing vascular smooth muscle *
- Verapamil/diltiazem have a non-specific anti-adrenergic effect and decrease HR
- Relieve and prevent coronary artery spasm
*needed to pass
What are the actions of acetazolamide?
Carbonic anhydrase inhibitor, acting in:
- Ciliary body
- Choroid plexus
- Proximal renal tubules
What are the toxic effects of acetazolamide?
- Hyperchloraemic metabolic acidosis
- Renal stones (PO43-, Ca2+)
- Renal K+ wasting
- Drowsiness, paraesthesia
- Increased risk of neurological toxicity with renal failure due to reduced elimination
- Hepatic encephalopathy in patients with cirrhosis due to reduced renal excretion of ammonia
How are osmotic diuretics handled by the kidney?
- Freely filtered by glomeruli
- Not reabsorbed
- Causes water retention in the freely permeable sections of the nephron (proximal tubule and descending loop of Henle)
What are the clinical indications for antiplatelet agents?
3/4 to pass:
- IHD
- TIA/CVA
- Pregnancy for prophylaxis of pre-eclampsia
- Post acute coronary intervention
Why is there a delay in the onset of action of warfarin?
- 8-12hr delay due to partially inhibit synthesised and unaltered degradation of vitamin K dependent clotting factors (II, VI, IX, X)
- Depends on degradation half-life in circulation (VII 6hrs, IX 24hrs, X 40hrs, II 60hrs)
