Pharmacology Flashcards

Question

Fentanyl (Physical, chemical, Pk, Pd)

Answer 1

Fentanyl is a synthetic phenylpiperidine derivative It is used extensively in anaesthesia and critical care for analgesia and sedation It is a potent MOP agonist It can be administered IV/PO/patches/intrathecally Chemical: it is a weak base with pKa 8.4 so is largely ionised in the stomach. Pk Absorbed from the small bowel and has an oral bioavaliability of 33% It is 80-95% protein bound and has a Vd 1-4 L/kg It is very lipid soluble - 600x more than morphine so is rapidly distributed and therefore has a short duration of action It is metabolised into norfentanyl which is inactive and excreted in the urine ``` Pd Similar to morphine but is more potent Causes less histamine release Associate with Bradycardia Chest wall rigidity at high doses ```

Answer 2

Brain especially periaqueductal grey and substantia gelatinosa of spinal cord Mue 1 - analgesia and physical dependence Mue 2 - respiratory depression, reduced peristalsis, euphoria, meiosis

Answer 3

Brian Analgesia, antidepressant, physical dependence

Answer 4

Brain and spinal cord Spinal analgesia Sedation Meiosis

Answer 5

Brain and spinal cord Anxiety, depression, affects memory, involved in tolerance, natural ligand may set body’s natural pain threshold

Answer 6

Tolerance describes the scenario that despite maintaining constant plasma concentrations of a drug more is required to exert the same effect

Answer 7

Diamorphine is a diacetylated morphine derivative and is a prodrug It is used for analgesia, sedation, palliative care, CCF and as a drug of abuse Its metabolites act at MOP & KOP receptors Pk Administered IV/SC/PO/intrathecally Well absorbed but undergoes extensive 1st pass metabolism so has a low oral bioavaliability Protein bound 40% Half life 3 mins Metabolised by plasma enzymes and RBCs (probably esterases) to 6-O-acetylmorphine 6-O-acetylmorphine glucurronidated to morphine 50-60% excreted in urine as morphine derivative Pd As for morphine Less nausea/vomiting/constipation

Answer 8

Alfentanil is a synthetic phenylpiperidine derivative It is short acting opioid used for analgesia, obtunding hypertensive response to airway manipulation and sedation It is highly MOP receptor specific It is only administered IV at dose of 5-25 microgram/kg Pk It’s notable feature is a pKa of 6.5 so 87% of it is UNIONISED at pH 7.4 This more of it is around to exert its effect and despite being less lipid soluble than fentanyl it has a more rapid onset time 85-92% protein bound Vd 0.6 L/kg - this is low for opioids and means that despite of its low clearance its half life is shorter It is metabolised in the liver to noralfetanil and excreted in the urine Pd As for morphine but more potent Causes a vagary mediated bradycardia

Answer 9

Remifentanil is a pure MOP agonist. It is used for intra-operative analgesia and sedation Pk It is only administered IV and has a half life of 2 hours But its effects last only 10 minutes after end of infusion - its metabolism whereby it undergoes rapid ester hydrolysis by non-specific esterases to carboxylic acid derivatives - means that it has a context-INSENSITIVE half-life It is excreted in the urine Pd As more morphine but more potent Bradycardia Rigid chest at high dose

Answer 10

There are 2 types of local anaesthetic 1. AMIDES - eg lidocaine 2. ESTERS - eg (CAPE) - cocaine, amethocaine, procaine = esters

Answer 11

The are intracellular sodium channel blockers and therefore prevent propagation of action potentials along a neurone Unionised drug is lipid soluble so it can cross the neuronal cell membrane. The axoplasm has a pH of 7.1 so more of the drug becomes ionised and its this portion that “block” sodium channels from the inside. It binds to receptors that are either open or inactivated so its more likely to affect nerves that have a rapid firing rate. This is called “state dependent blockade” The membrane expansion theory postulates that in-ionised local anaesthetic dissolves in the neuronal membrane causing swelling and subsequent physical inactivation of the neuronal sodium channels

Answer 12

Lipid solubility

Answer 13

Protein binding

Answer 14

This is primarily effected by pH and pKa and subsequent degree of ionisation Local anaesthetics with a pKa closer to body pH (7.4) will have a higher proportion of unionised drug which can cross the neuronal cell membrane and exert an effect. This explains why local anaesthetics work poorly in infected tissue which has a lower pH and therefore the unionised portion is decreased further Bicarbonate is occasionally added to artificially increased the pH and increased the unionised portion

Answer 15

Intercostal space>Caudal>epidural>brachial plexus>femoral>subcutaneous

Answer 16

Amide local anaesthetic PKa 7.9 so has fast onset 70% protein bound so medium duration of action 3mg/kg alone or 7mg/kg with adrenaline

Answer 17

``` Amide local anaesthetic Racemic mixture of R and S enantiomers 95% protein bound so has a long duration of action Max dose 2mg/kg Cardiotoxic at high doses ```

Answer 18

``` An amide local anaesthetic PKa 8.1 Just the s-enantiomer of bupivicaine Again 95% protein bound Less cardiotoxic that bupivicaine 2mg/kg max dose ```

Answer 19

Amide local anaesthetic 94% protein bound so long duration of action PKa 8.1 More selective sensory neuronal blockage and less motor Less cardiotoxic than bupivicaine Max dose 3.5mg/kg

Answer 20

Amide local anaesthetic pKa 7.9 so fast onset 56% protein bound so medium duration Contained in EMLA cream (lignocaine and prilocaine) Methaemaglobinaemia can occur at high doses due to breakdown product O-toluidine Less toxic that lignocaine Used for IV local anaesthetic - Biers block Max dose 6mg/kg

Answer 21

Ester local anaesthetic Short duration of action Causes profound vasoconstriction Blocks neuronal uptake and stimulates the CNS Side effects include - IHD, HTN, seizures, hallucinations Max dose 3mg/kg

Answer 22

NSAIDS are cyclo-oxygenase inhibitors. They act on the arachnadonic acid pathway. They inhibit the production of prostanoids including thromboxane (vasoconstrictor and platelet aggregator), prostacyclin (vasodilator and prevents platelet plug forming) and prostaglandins . Prostaglandins would otherwise cause inflammation and decrease stimulus required to cause pain

Answer 23

Relative: - renal failure, heart failure, history of GI bleeding, HTN, coagulopathy - Enhances effects of warfarin Absolute - hypersensitivity - Asthmatic in whom it precipitates exacerbations (10-20%) - Avoid in children (except, I think, Kawasaki syndrome)

Answer 24

``` Asthma exacerbation (blocking COX leads to increased leukotriennes) AKI Platelet dysfunction - reduced thromboxane production GI bleeding - prostaglandins required to gastric mucosal integrity (COX 1> COX2) ```

Answer 25

Paracetamol is commonly used for simple analgesia and as an antipyretic It has central action via COX 3 inhibition leading to decreased brain PGE2 and also modulates cannabinoid system Pk It is administered PO/PR/IV It’s absorbed in the small bowel and has an oral bioavaliability of 80% with protein binding 10% It’s metabolism is important - particularly in overdose cases: The majority of it is metabolised to glucuronide and sulphate metabolites (30%) but approximately 10% is metabolised to N-acetyl-p-amino-benzoquinoneimine (NAPQI). This is a toxic metabolite. In normal doses and with normal genetic polymorphism it is rapidly conjugated by glutathione but when this system is saturated NAPQI accumulates causing liver failure. Pd CVS - IV can cause bradycardia and hypotension CNS - analgesia and antipyretic Other - rash, ITP, nephropathy

Answer 26

Aspirin is a salicylic acid derivative It is used for analgesia, as an antipyretic and an anti platelet It is a prodrug that causes irreversible COX 1 inhibition and modified COX 2 activity. It also selectively inhibits thromboxane A2 in platelets and therefore inhibits their aggregation Pk It is a weak acid with a pKa of 3.0 therefore it is poorly ionised in the stomach and is not readily absorbed until it reaches the small bowel 85% protein bound Metabolised in the liver and intestine by ester hydrolysis to salicylic acid Exhibits 1st order kinetics at low dose but zero order at high dose Renal excretion Pd CVS - decreased platelet aggregation and vasodilation is cardio protective RESP - bronchospasm in 10-20% asthmatics GI - risk of GIB, can cause hepatic transaminitis RENAL - local hypoxia and decreased RBF Drug interactions: - warfarin - as NSAIDs are highly protein bound this can displace warfarin and increase its action - Lithium - may increase levels

Answer 27

Diclofenac is a phenylacetic acid derivative It’s used for analgesia and as an antipyretic It inhibits COX1&2 equally Administered PO/PR/IV ``` Pk Well absorbed Bioavaliability of 60% PB 99.5% so can displace oral anticoagulants Low Vd 0.12-17 L/kg Hepatic metabolism and renal excretion ``` Pd Caution in asthmatics GIB Decreased renal perfusion due to decreased prostaglandins Reversible inhibition of platelet function Reduces renin and aldosterone concentration by 70% Increased risk of thrombosis

Answer 28

The VW classification classifies antiarrhythmics according to electrolyte they act on. Group 1 act on fast acting sodium channels 1a - Quinidine, procainamide, disopyramide - increased refractory period 1b - lignocaine, phenytoin, mexiletine - shortens refractory period 1c - Flecainide, propfenone - no effect on refractory period Group 2 - beta blockers Group 3 - K channel blockers (amiodarone, sortalol) Group 4r - Ca channel blockers (verapamil, diltiazem)

Answer 29

They act on fast sodium channels in the cardiac myocyte This increases the time it takes to reach threshold potential, decreases the slope of phase 0 and the cardiac conduction velocity. These sodium channels are not present in the SAN so can be used for abolishing re-entrant arrhythmias Further classified according to their effect on the refractory period - this is usually mediated by the drugs effect on K channels responsible for repolarisation in phase 3

Answer 30

Beta-blockers work by inhibiting beta adrenergic receptors and therefore reducing sympathetic tone on the heart. This reduces the slope on phase 4 of the SAN action potential B-receptors are coupled via G-proteins to calcium channels that open when the receptor is activated. By blocking them less Ca enters the cell and the rate of depolarisation of phase 4 is slower and therefore chronotropy and (due to reduced intracellular calcium presumably) inotropy Also inhibit action of light chain kinase and so decrease the hearts relaxation rate

Answer 31

K channel blockers prevent K efflux out of the cell at the SAN during depolarisation. This decreases the slope of phase 3 of the SAN action potential. This increases the refractory period and reduces arrhythmogenicity

Answer 32

Calcium channel blockers block L-type calcium channel blockers (they do not effect T/N/P calcium channels) Blocking them reduces the phase 0 slope of the SAN action potential, decreasing heart rate. They are also found in cardiac myocytes and blood vessels. By decreasing Ca flux reduces cardiac conduction velocity and contractility

Answer 33

Class 1a antiarrythmic that blocks fast Na channels, increases refractory period and vagal tone Used for termination of SVTs and ventricular arrhythmias Pk - bioavaliability 75%, 90% protein bound and T1/2 5-9 hours, hepatic metabolism and renal excretion Pd CVS - can cause other arrhythmias & hypotension ECG - prolonged PR, wide QRS, long QT CNS - tinnitus, blurred vision, hearing loss, headache, confusion CAUTION!!: - displaces digoxin from binding sites so can cause toxicity

Answer 34

Lignocaine is a amide local anaesthetic and a class Ib anti arrhythmic It is a sodium channel blocker which decreases phase 0 of cardiac action potential and decreases refractory period Pk 33% ionised, pKa 7.9, Vd 0.7-1.5 l/kg, hepatic metabolism and renal excretion

Answer 35

>4micrograms/ml = perioral tingling, dizziness, tinnitus, parasthesia >5 micrograms/ml = altered consciousness, coma, seizures >10micrograms/ml = AV block, refractory hypotension, cardiac arrest

Answer 36

Flecainide is a class Ic anti arrhythmic used for the management of SVT/AF/WPW It blocks fast Na channels prolonging phase 0 of action potential Pk Well absorbed with oral bioavaliability of 90% and protein binding 50%, hepatic metabolism with active metabolites and unchanged drug excreted in the urine Pd CVS - can precipitate conduction disorders, use with caution in patients with AV node disease, negative inotrope so can precipitate heart failure OTHER - headache, dizziness, parasthesia

Answer 37

Amiodarine is a class III anti arrhythmic but also has properties of class I, II and IV. It is used for a wide number of arrhythmias including SVT/VT/WPW Can be given IV or PO Pk - poorly absorbed. Protein binding of 95%, Vd 2-70 L/kg, T1/2 20-100 days!!, hepatic metabolism, expressed in bile, tears and via skin Pd CVS - prolonged QT, hypotension, bradycardia RESP - pneumonitis and fibrosis CNS - peripheral neuropathy and myopathy. Corneal microdeposits GI - metallic taste, hepatitis, cirrhosis SKIN - grey skin, hypersensitive skin ENDO - hypo and hyperthyroidism DRUG INTERACTIONS: - Highly protein bound so can displace other drugs from protein binding - Avoid with other QT prolonging medications - Can cause heart block with other AV node blockers

Answer 38

Digoxin is a glycoside extracted from foxgloves It inhibits the Na/K- ATPase pump meaning there’s less intracellular potassium and more intracellular sodium. There is therefore less Calcium extrusion by the Na/Ca exchange pump because this relies on the concentration gradient. The higher intracellular calcium leads to increased inotropy and the decreased intracellular potassium decreases conduction in the SA and AV nodes slowing heart rate Pk Administered IV or oral (Bioavaliability >70%) Protein binding 25% Vd 5-10 l/kg Half life 35 hours (increased in renal failure) Minimal hepatic metabolism Excreted largely unchanged in the urine Pd CXS - arrhythmias ECG - toxic = long PR, inverted tick; normal = flattened T wave, short QT OTHER: - Anorexia, nausea, diarrhoea, headache, lethargy, visual disturbance, rashes, eosinophilia, gynaecomastia TOXICITY - Treat bradycardia with atropine and pacing - Treat ventricular arrhythmia with phenytoin - “Digibind” - IgG antibody fragments against digoxin. Expensive - used if >20micrograms/l - note Digibind can cause anaphylaxis

Answer 39

A calcium channel antagonist used for the management of SVT/AF/prophylaxis of angina and hypertension It is a class 4 antiarrhythmic that blocks L-type calcium channels so reduces the slop of nodal action potential. It also decreases contractility and causes coronary dilation Pk Well absorbed 90% but undergoes extensive 1st pass metabolism so 25% bioavaliability 90% protein bound Vd 3-5 l/kg Half life 3-7 hours Hepatic metabolism but subject to zero order kinetics Active and unchanged metabolites excreted in urine Pd CVS - can precipitate VF/VT in WPW, CCF in patients with poor LV Caution with b-blockers/digoxin/halothane - can cause severe bradycardia Hypotension Cerebral vasodilation

Answer 40

Beta-blockers block beta adrenergic receptors. Some also have some sympathomimetic activity. There activity is largely governed by their affinity for different Beta receptors (B1 cardioselective) Wide range of uses: HTN, angina, tachycardia, obtund hypertensive reflex, phaeochromocytoma, HOCUM, anxiety, glaucoma, migraine PK Different agents have varying lipid solubility. Atenolol is poorly lipid soluble so poorly absorbed from the gut. But those with high lipid solubility (eg metoprolol) are well absorbed but cross the BBB so cause more CNS side effects. CVS - negative inotrope - increase time in diastole, decreases cardiac O2 demand - Hypotension RESP - bronchospasm CNS - those that cross the BBB causes hallucinations, nightmares, depression, fatigue and decrease IOP GI - dry mouth and GI upset Metabolic - rise in resting BMs, mask signs of hypoglycaemia

Answer 41

Adenosine is a naturally occurring purine nucleoside It is used to differentiate between SVT and VT. If the rhythm is re-entrant it may terminate it. MoA - binds to adenosine (A1) receptors coupled to K channels that open causing hyperpolarised membrane. They are only found in SAN and AVN so adenosine selectively decreased conduction velocity in the nodes. Also decreases cAMP mediated catecholamine stimulation of ventricles Rapid offset Pd RESP - increased PVR, SoB, flushing, bronchospasm, impending doom

Answer 42

Antihypertensive drugs can be classified according to their location of action: Central vs peripheral Centrally acting - clonidine, methyldopa and reserpine (?) Peripherally acting can be subclassified to heart, vascular and renal

Answer 43

Benzodiazepines are a class of psychotropic drug that have hypnotic, sedative, amnesic and muscle relaxant properties. They act to propagate the effects of GABA A receptors increasing chloride uptake and hyperpolarising the cell membrane. Benzodiazepine receptors are coupled to GABA receptors. These receptors are found widely in the CNS. They can be classified according to their duration of action - short <12 hours (midazolam), medium 12-24 lorazepam and long >24 diazepam

Answer 44

Inotropes describes a range of different drugs that all increase the contractility of the heart. They can be classified in 3 subgroups: 1. Drugs that increase intracellular calcium I. Calcium ions II. Drugs that increase intracellular calcium - adrenergic receptor agonists, PDE inhibitors and glucagon III. Drugs effecting the sodium/potassium ATPase 2. Calcium sensitising drugs - Levo 3. Act via metabolic pathways - T3

Answer 45

They can be naturally occurring or synthetic Naturally occurring include - adrenaline, noradrenaline and dopamine Synthetic inotropes include - dobutamine, dopexamine, isoprenaline and salbutamol

Answer 46

Digoxin inhibits the Na/K-ATPase pump on the sarcolemnal membrane and causes an increase in intracellular sodium. Sodium would normally be pumped into the cell by a sodium-calcium exchange pump but this relies on a the concentration gradient of sodium. By increasing intracellular sodium digoxin reduces this gradient meaning less sodium enters the cell and more calcium remains inside. Intracellular calcium causes the positive inotropic effect. This is slightly offset by digoxins other effect to activate the parasympathetic nervous system

Answer 47

Adrenaline is a naturally occurring catecholamine. It is produced in the adrenal medulla and acts on alpha 1, Beta 1 and Beta 2 adrenoreceptors. Adrenoreceptors are G-protein coupled receptors that act to increase influx of calcium. - Alpha receptors are linked to a Gq protein that stimulates phospholipase C to produce IP3 and DAG - Beta receptors are liked to Gs protein that stimulates adenyl cyclase to produce cAMP. this activate protein kinase A (?) Low dose activates beta receptors -> smooth muscle relaxation, glycogenolysis Mid range -> Beta 1 receptors -> inotropy/chronotropy/increased renin release High dose -> alpha receptors -> generalised vaso and veno constriction increasing SVR. Increased after load and preload.

Answer 48

Dopamine is a naturally occurring catecholamine and neurotransmitter. At low dose it acts on D1 and D2 receptor and at higher doses it stimulates beta and then alpha receptors. Previously it had been hoped that low dose dopamine would achieve both an increased inotropy and increased renal blood flow due to the distribution of dopamine receptors. This has not been demonstrated in clinical trials and its use now is fairly limited occasionally used in the paediatric population. Dopamine is a precursor of noradrenaline. It has a half life of minutes and is metabolised by COMT Pd CVS - <5 micrograms/min - low dose D1 receptors - decreased renal vessel resistance - 5 - 10 micrograms/min - Beta 1 - increased HR/contractility/CO/CA blood flow - >10 - alpha - increased SVR RESP - decreased response to hypoxia CNS - modulates extrapyramidal movements, nausea and vomiting RENAL - diuretic effect

Answer 49

Milrinone is a selective phosphodiesterase III inhibitor It is used in cases of low cardiac output By inhibiting PDE III it reduces the degradation of cAMP in cardiac and smooth muscle - Increased intracellular calcium leads to increased biventricular contractility - It alters Ca flux into smooth muscles causing relaxation of vessels (including pulmonary) Pk IV administration, 70% protein bound, T 1/2 2.5 hours, hepatic metabolism and renal excreation (85% unchanged) Pd CVS - increased SV/contractility/No increased cardiac oxygen consumption/Decreased SVR RESP - pulmonary vasodilation

Answer 50

Adrenaline is synthesised from tyrosine via a sequence of steps. Tyrosine: from diet or hydroxylation of phenylalanine in liver Tyrosine -> L-DOPA -> Dopamine -> noradrenaline -> adrenaline Enzymes: 1. Tyrosine hydroxylase 2. DOPA decarboxylase 3. Dopamine Beta-hydroxylase 4. PNMT (only in adrenal medulla)

Answer 51

Levosimendan acts as a calcium sensitiser - it binds to troponin C and stabilises the cross bridges between it and actin-myosin cross bridges. It increases contractility and vasodilation without increase in calcium concentration or oxygen demand ``` Administered as bolus and infusion 98% protein bound T1/2 1 hour hepatic metabolism Renal excretion (85% unchanged) ``` Caution - contra-indicated in severe hepatic/renal failure, ventricular outflow obstruction, severe hypotension/tachycardia, history of torsades de pointes

Answer 52

Synthetic produced analogue of oxytocin Used for induction of labour, following c-section or abortion MoA: It stimulates uterine contraction by binding to sites on muscle cells. Agonist at oxytocin G-protein coupled receptors ``` Effects GU - uterine contraction, can cause hyper stimulation, mild anti-diuretic effect when prolonged CVS - increased SVR, BP, tachycardia GI - nausea/vomiting Rash, anaphylaxis ```

Answer 53

Ergometrine is an ergot alkaloid derivative. It stimulates uterine and vascular smooth muscle by binding to 5-HT3 receptors but also agonises dopamine 2 receptors causing emesis Used as second line uterotonic following C-section or uterine tone Effects: GU - uterine contraction (1 min IV and 5 min IM) CVS - increased SVR and BP (CI in pre-eclampsia), bradycardia and arrhythmias CNS - tinnitus, headache, dizziness GI - severe vomiting and nausea

Answer 54

Carboprost is a prostaglandin analogue that stimulates uterine contraction and is used in post-Parton haemorrhage Given IM Effects: - GU - uterine contraction - RESP - bronchospasm (CI in asthmatics) - CVS - cardiovascular collapse, pulmonary oedema - CNS - headache, dizziness - GI - nausea and vomiting

Answer 55

Antihypertensive drugs can be classified by their location of action 1. Cardiac I - Beta blockers (cardioselective/non-cardioselective/labetalol) 2. Blood vessels I - Direct acting - produce NO which act is of G protein coupled receptors to upregulate guanylate Cyclades and increasing intracellular cGMP -> vasodilation examples - sodium niroprusside and hydralazine (arterial and venous dilation) & GTN/ISMN (predominantly venous dilation) II - Indirect - reduce SVR and preload by various mechanisms CCBs - antagonist at L-type calcium channels in vascular smooth muscles Alpha blockers - prazosin Potassium channel activators - (nicorandil) activators of ATP-sensitive K channels within arterioles causing hyperpolarisation and reduced intracellular calcium -> arteriolar vasodilation. Magnesium 3. Renal - Diuretics - RAAS 4. CNS - centrally acting drugs (eg clonidine and methyldopa) - Ganglion blockers - competitive antagonists at nACh receptors located in parasympathetic and sympathetic ganglia

Answer 56

There are three different forms of heparin: 1. Naturally occurring heparin 2. Unfractionated heparin - binds to and potentiates antithrombin 3. Low molecular weight heparin - directly inhibit factor Xa

Answer 57

1. Haemorrhage 2. Non-immune thrombocytopaenia 3. HIT - IgG antibodies made against heparin after it binds to platelet factor 4 (PF4) - Antibodies consequently bind to and activate platelets causing thrombi and the platelets count to fall 4. Hypotension 5. Osteoporosis

Answer 58

Warfarin is vulnerable to potentiation owing to its high protein binding and metabolism Drugs that potentiate warfarin include: NSAIDs and simvastatin - drugs with high protein binding compete with warfarin and can displace it and increase its anticoagulant effects Similarly states with low plasma protein such as sepsis and pregnancy can do the same Drugs that decrease warfarins metabolism (metronidazole, macrolides and alcohol) will increase the effect Some antibiotics affect the vitamin K producing bacteria in the gut flora and so increase the effect of warfarin Diet - foods such as St. John’s wort, ginger and ginseng can increase the effect Thyroid status also has an impact - hypothyroidism reduces its effect

Answer 59

1. Antiplatelet 2. Heparins 3. Oral anticoagulants 4. Fibrinolytics

Answer 60

Aspirin - COX inhibitor - prevents platelet thromboxane release Dipyridamole - platelet phosphodiesterase inhibitor - inhibits platelet adhesion to damaged vessel walls (inhibits adenosine uptake), potentiates the effect of prostaglandins and, at high doses, inhibits phosphodiesterase causing lower intra-platelet calcium Clopidogrel - ADP binding inhibitor - Irreversibly binds to P2Y12 receptor (ADP receptor) and prevents the glycoprotein IIb/IIIa receptor from transforming into its active form (prasugrel and ticagrelor also ADP binding inhibitors) Tirofiban/Abciximab/Eptifinatide - glycoprotein IIb/IIIa receptor antagonists so block the final common pathway of platelet aggregation

Answer 61

Anionic, mucopolysaccaride, organic acid containing many sulphate residues 5000-25000 daltons Binds to antithrombin III forming thrombin-antithrombin complex. At low dose Factor Xa inhibited. (As dose increases factors 9,11,12 also inhibited) Given IV/IM/SC Given negative charge it is highly protein bound and has low lipid solubility Metabolised by hepatic heparinases and excreted in the urine

Answer 62

Haemorrhage Thrombocytopaenia (Type 1 and 2) Hypotension Osteoporosis

Answer 63

Formed from the depolymerisation of heparin 2000-8000 Da Inhibit factor Xa but have little effect at forming thrombin-antithrombin complex ``` Advantages: Once daily dosing Less impact on platelets Reduced need for monitoring Reduced affinity for VWF ```

Answer 64

Positively charged molecule that neutralises the anticoagulant effect of heparin Given intravenously at a dose of 1mg for every 100 units of heparin

Answer 65

Warfarin is a coumarin derivative that inhibits the reduction of vitamin K which is required to generate active clotting factors 2,7,9,10 Takes ~ 72 hours to take effect Side effects - haemorrhage - teratogenicity - Drug interactions - Drugs that impair coagulation, displace off protein binding and impair metabolism Absorption from gut Highly protein bound hepatic metabolism

Answer 66

Fibrinolytics are used to break down clots usually in cases of acute occlusion where there is appropriate risk-benefit They work on the plasminogen - plasmin reaction to upregulate the clot break down effect of plasmin The commonly used include streptokinase, alteplase and urokinase Streptokinase - from group C beta-haemolytic strep - forms a complex with plasminogen which facilitates its conversion to active plasmin Complications - haemorrhage, CVS ( arrhythmias post reperfusion) & allergic Alteplase - a glycoprotein that becomes activated only when it binds to fibrin inducing the conversion from plasminogen to plasmin - means that systemic fibrinolysis occurs to a lesser extent.

Answer 67

Dabigatran - direct thrombin inhibitor - a prodrug that is converted to active metabolites and then NOT metabolised further - renal excretion therefore caution must be taken in renal failure. Caution with use with phenytoin, ketoconazole, carbamazepine and rifampicin Rivaroxaban - direct factor Xa inhibitor- oral bioavailability of 80-100%, 70% hepatic metabolism so renal function less important. Caution with CYP3A4 inducers (but less so than dabigatran) Apixaban - same MoA as rivaroxaban - 50% bioavailability, onset over few hours

Answer 68

Warfarin - vitamin K, prothrombin complex concentrate Dabigatran - idarucizumab or dialysis Rivaroxaban/apixaban - andexanet alfa

Answer 69

Warfarin - INR <1.4 Dabigatran - 48-96 hours Rivaroxaban - 48 hours Apixaban - 24-48 hours Heparin Unfractionated - 4 hours or normal APTT Prophylactic LMWH - 12 hours Treatment dose LMWH - 24 hours

Answer 70

Fondaparinux is a synthetic pentasaccharide factor Xa inhibitor. Fondaparinux binds antithrombin and accelerates its inhibition of factor Xa.

Answer 71

Danaparoid and lepirudin which available for use in the UK, whereas argatroban is used in North America

Answer 72

``` MW 197 BP 50.2 SVP 32.3 MAC 0.75 B:G 2.4 O:G 224 ```

Answer 73

``` MW 184 BP 48.5 SVP 33.2 MAC 1.17 B:G 1.4 O:G 98 ```

Answer 74

``` MW 184 BP 56.5 SVP 23.3 MAC 1.68 B:G 1.8 O:G 98 ```

Answer 75

``` MW 168 BP 23.5 SVP 89 MAC 6.6 B:G 0.42 O:G 29 ```

Answer 76

``` MW 200 BP 58.5 SVP 22.7 MAC 1.8 B:G 0.7 O:G 80 ```

Answer 77

``` MW 44 BP -88 SVP 5200 MAC 105 B:G 0.47 O:G 1.4 ```

Answer 78

``` MW 131 BP -108 SVP x MAC 71 B:G 0.14 O:G 1.9 ```

Answer 79

Infancy Hyperthermia hyperthyroidism Catecholamines and sympathomimetics Chronic opioid Chronic alcohol use Acute amphetamines Hypernatraemia

Answer 80

Old age and neonates ``` Pregnancy Hypotension Hypothermia Hypothyroidms Alpha 2 agonists Sedatives Acute alcohol and opioid Chronic amphetamines Lithium ```

Answer 81

CVS - decreased contractility, SVR and BP RESP - increased RR, decreased TV and increased PaCO2 CNS - Increased CBF, decreased CMRO, EEG burst suppression

Answer 82

CVS - Increased HR, Decreases SVR and BP (no effect on contractility) RESP - Increased RR and decreased TV - PaCO2 increased CNS Increased CBF, decreased CMRO2,

Answer 83

CVS - decreased contractility and SVR, increased HR, decrease BP RESP Increased RR and decreased TV increased PaCo2 CNS Increased CBF, decreased CMRO, epileptiform activity

Answer 84

CVS decreased contractility and SVR, increased HR, decreased BP. POSSIBLE CORONARY STEAL RESP decreased TV, increased RR, decreased PaCO2 CNS Increased CBF, decreased CMRO

Answer 85

CVS decreased contractility, HR, SVR and BP. Increased sensitisation to catecholamines RESP increased RR and decreased TV. Unchanged PaCO2 CNS Increased CBF, decreased CMRO

Answer 86

Many different mechanisms 1. physiochemical interaction (antacids/sugamadex) 2. Enzymatic interaction (ACEI) 3. Voltage gated ion channels (LA) 4. Receptros (extra vs intracellular)

Answer 87

Receptor linked ion channel Producers of intermediate messengers Regulators of gene transcription

Answer 88

A protein containing a region to which a ligand binds specifically to elicit an effect Usually protein or glycoprote - found at cell membrane, within intracellular organelles or within the nucleus

Answer 89

Pentameric: GABA-A and nACh Inotropic glutamate: NMDA (2subunits NR1 and NR) - stimulation increases calcium permeability and causes CNS excitation - N2O, Xenon, ketamine inhibit

Answer 90

G-PROTEIN COUPLED RECEPTORS - Transmembrane proteins - Binding of ligand on extracellular side leads to a conformation changes that activates the G-protein - Galpha-GDP -> Galpha-GTP which dissociates and activates or inactivates effector protein. The alpha-subunit then breaks down the GTP to regenerate the alpha-GDP subunit and rejoins the beta-gamma complex - Gi (opioid) - inactivates adenylyl cyclase - Gs (adrenoreceptors) - activates adenylyl cyclase - Gq - Activate PHOSPHOLIPASE C to form inositol triphosphate and diacylglyercol - causing calcium release from the endoplasmic reticulum and activation of protein kinase C ``` Tyrosine kinase (insulin and growth factors) - ligands bind to alpha subunits and cause phosphorylation of intracellular tyrosine kinase on beta subunits with subsequent intracellular effects ``` Guanylyl Cyclase - Receptors with intrinsic guanylyl cyclase activity - Stimulation causes increase in intracellular cGMP which phosphorylates intracellular enzymes

Answer 91

Gq - Activate PHOSPHOLIPASE C to form inositol triphosphate and diacylglyercol - causing calcium release from the endoplasmic reticulum and activation of protein kinase C

Answer 92

Steroids | Thyroxine

Answer 93

TFAA Trifluroacetic acid hapten complex

Answer 94

``` Receptors Ion channels Enzymes Neurotransmitters Hormones transport systems Physiochemical ```

Answer 95

Physiochemical - chelation and neutralisation Pharmacokinetic - Absorption, distribution, metabolism, excretion Pharmacodynamic - Summation - Synergyism - Potentiation - Antagonism

Answer 96

``` Aspirin Morphine Codeine Diltiazem Propanolol Verapamil Hydralazine ```

Pharmacology Flashcards

(120 cards)