Notes from MCQ

 

 

Q223

Amiloride
* Blocks luminal Na+ channel in the collecting tubules
* Potassium sparing
* Not metabolised by liver
* Long elimination half-time 18-24 hours

Spironolactone blocks the aldosterone receptor and is also a potassium sparing diuretic

 

Q224

Use of sodium nitrate in CN toxicity
--> Methaemoglobinaemia

 

Do a graph for N2O

 

Pharmacodynamics

Mechanism of action

 

Effects

 

Pharmacokinetics

 

 

Pharmaceutics

 

Clinical

 

 

 

Preparation of oxygen for medical use

[James] [???]

Fractional distillation of liquid air

air compressed to 5 bar and cooled to -180C, then distilled

O2 has higher boiling point so nitrogen boils off first

 

Oxygen concentrator

Pressurised air enters molecular sieve and crystalline matris of zeolite preferentially absorbs nitrogen, CO2, and vapour

 

Cylinder O2

Full 137Bar at 15C

Pressure in cylinder dependent on O2 content and ambient temperature

 

Critial temperature = -119C

Boiling point = -183C

 

 

====== Antiplatlet agents ======

 

[James] [???]

== Aspirin ==

 

== ADP receptor antagonist ==

e.g. clopidogrel

75mg/day

 

PK:

rapidly absorbed (50%) with bioavailability unaffected by food or antacids

90% protein-binding

Rapid metabolism in liver to SR26334 --> Elimination half-time = 8 hours

Inhibits P450 2C9 enzyme

 

Mechanism of action

Prodrug converted to active metabolites in liver

Blocks ADP receptors on platelet surface --> Inhibits activation, aggregation, and degranulation

Irreversibly modify ADP receptors, resulting in inhibition for the life of platelet (7-10 days) --> Onset not for 24 - 48 hours

 

SE

Inhibits CYP2C9
--> May affect metabolism of warfarin, phenytoin, and NSAIDS

More rash than aspirin, but less GI bleeds

Bone marrow suppression

Neutropenia

TTP (transient thrombocytopenia)

Hepatic dysfunction

Intracranial haemorrhage

 

 

== Glycoprotein IIb/IIIa antagonists ==

 e.g. tirofiban, abciximab (used in acute coronary syndrome, esp with interventional coronary procedures)

 

Abciximab

Monoclonal antibodies (Fab fragments)

IV administration

Elimination half-time = 12-24 hours

Metabolised by plasma proteases

Duration > 2 hours

 

Tirofibran

nonpepetide

IV administration

Elimination half-time = 2-4 hours

30-60% renal excretion

40-70% biliary excretion

 

Mechanism of action

Act at corresponding fibrinogen receptors on platelet
--> Platelet glycoprotein IIb/IIIa receptors
--> Block fibrinogen binding (the final common pathway of platelet aggregation)
(Also block vWF binding)

Binding of prothrombin to these receptors also enhances its conversion to thrombin

 

SE

Thrombocytopenia

Allergy with monoclonal antibodies of abciximab

Increased bleeding with abciximab

 

== Dipyridoamole ==

100mg QID for thromboembolism prophylaxis after prosthetic heart valves and for protection against ischaemic neurologic events

Elimination half-time = 10 hours

Clearance = 2 mL/kg/min

Oral bioavailability = 50%

Extensive protein-binding (alpha1 acid glycoprotein)

Metabolism in liver

Excreted as glucuronide in bile

 

MOA

Phosphodiesterase inhibitor
--> Increase cAMP

Potentiate prostacyclin and effects of NO in opposing platelet aggregation

Increases concentration of adenosine --> Stimulates adenylate cyclase --> Increase cAMP

 

Increased cAMP inhibits Ca++ release and decrease 5-HT and ADP secretion

 

SE

Potentiate adenosin --> Vasodilation and hypotension

Headache, bronchospasm, N&V, diarrhoea

Cardiac ischaemia, arrhythmia, angina (due to coronary steal)

 

== Dextran 70 ==

Water soluble glucose polymer (polysaccharide)

Wt ~ 70,000 Da

Degraded enzymatically to glucose

Eliminated through kidneys --> Some metabolised

Persists for 72 hours

 

Mechanism

Decreases polymerisation of fibrin and platelet function

 

SE

Allergic reactions --> IgG antibodies

Histamine --> Urticaria, angioedemia, hypotension, bronchospasm

Rouleaux formation

Pulmonary oedema, when used as irrigation during histeroscopy

 

== Prostacyclin ==

Halflife = 3 min (IV)

Also used as inhaled

 

Mechanism

Inhibition of platelet aggregation (binds receptors on platelet that activate adenylate cyclase and increase cAMP)
--> Benefit in pulmonary hypertension secondary to thromboembolic disease

 

SE

Vasodilator

Anxiety, flushing, dizziness, N&V, chest and abdo pain, tachy and bradycardia

Abrupt discontinuation --> Pulmonary HTN and cardiogenic shock

 

== Nitric oxide and nitrates ==

NO inhibits platelet activation, adhesion, and aggregation

Activates guanylyl cyclase
--> Inhibits phosphoinositide 3-kinase
--> Impairs Ca++ influx
--> Inhibits COX-1

NO also decreased GP IIb/IIIa receptor activation in response to thromboin + ADP stimulation

NO also increase platelet cAMP production

 

 

====== Anticoagulant (coumarin derivatives) ======

 

Classification of inotropes

 

 

 

Diuretics

 

C - carbonic anhydrase inhibitor (SE: acidosis)

O - osmotic (manitol SE: Intracranial bleed, fluid shift --> overload, met alkalosis, hypocalcium, allergy, N&V, dehydration)

T - thiazide (DCT)

L - loop (LOH) (SE: ototoxicity, dehydration, hypoglycaemia, interstitial nephritis, met alkalosis, sulphonamide allergy)

A - aldosterone (spironolactone, SE: mineralcorticoid-like effect, hyperkalaemia)

P - potassium sparing

 

 

Antifungal

Azoles - ketoconale

 

 

 

Antihypertensives

A ACE inhibitors (SE: cough, raised potassium, renal failure, anaphylaxis (angioedema))

B betablockers

C calcium channel blockers

D diuretics

E hydralazine, GTN, nitroprusside, IV induction agents

 

 

 

TAAAA

Thrombolytics

Antiplatlet

Anticoagulants

Antifibrinlytics (transamenic acid ?spelling, aprotin ?spelling)

Antidote (vit K, factor 7, FFP, activated protein C)

 

Oral hypoglycaemic agents

Sulfonyurea (1st gen and 2nd gen)
* can cause insulin secretion

Biguanides

Glitazones

Meglitanide (?spelling)