ACEM Pharm part 2 - Sheet1 (1) Flashcards

Question

Lethal dose of paraqat

Answer 1

50-500mg/kg

Answer 2

Initial gastrointestinal symptoms Delayed onset respiratory distress Death may occur after several weeks Oxygen aggravates pulmonary effects

Answer 3

Inhibition of enzymes of oxidative phosphorylation Shock Arrhythmias Encephalopathy Peripheral neuropathy Pancytopenia

Answer 4

absorbed: All mucosal surfaces Widely distributed | Excreted by kidney

Answer 5

inorganic oxides: Inhibition of enzymes, interferes with essential cations, alters membrane structure Inorganic oxides and salts: Anaemia, peripheral neuropathy, nephropathy, hypertension Organic: Encephalopathy

Answer 6

Inorganic oxides and salts: Gastrointestinal and respiratory tracts Organic: All mucosal surfaces Excretion: Organic -Metabolised by liver to lead, excreted in urine and faeces

Answer 7

Inhibition of enzymes and membrane alterations Elemental: Behavioural disturbance (erethism) Gingivostomatitis Peripheral neuropathy pneumonitis Inorganic: (Hg+ less toxic than Hg2+) ATN Organic: CNS effects, birth defects

Answer 8

Elemental: Respiratory tract Inorganic: Gastrointestinal tract Skin Organic: All mucosal surfaces Tend to concentrate in soft tissues, especially kidney

Answer 9

Elemental: Converted to Hg2+ Excreted in urine and faeces Inorganic: Excreted in urine

Answer 10

Nausea Epigastric pain Abdominal cramps Constipation Diarrhoea Black stools

Answer 11

Seen commonly in young children (10 tablets can be lethal) Necrotising gastroenteritis with vomiting, abdominal pain and bloody diarrhoea Shock Improvement followed by severe metabolic acidosis, coma and death Treated with desferrioxamine

Answer 12

Used for iron poisoning Avidly binds to iron Competes for iron binding with haemosiderin and ferritin Iron-chelator complex is excreted in urine

Answer 13

Flushing Gastrointestinal symptoms ARDS

Answer 14

1. CNS: Psychosis, sedation, seizures, coma Antimuscarinic Sympathomimetic: Tremor, insomnia ``` 2. CVS: Orthostatic hypotension Conduction defects (long PR, wide QRS>0.1s, long QT and ST), arrhythmias. ``` 3. Respiratory depression and apnoea. 4. Metabolic acidosis

Answer 15

1. Salicylism: tinnitus, reduced hearing, vertigo. 2. Hyperventilation, fever, dehydration 3. Metabolic acidosis due to salicylic acid dissociation, deranged carbohydrate metabolism and reduced renal function. 4. Respiratory alkalosis due to central stimulation of respiratory centre Eventual renal and respiratory failure

Answer 16

12-16meq/L | Na+ + K+) - (HCO3- + Cl-

Answer 17

``` Methanol Ethylene glycol Lactic acid Cyanide Carbon monoxide Salicylates Metformin ```

Answer 18

``` Alcohols: ethanol intoxication methanol ingestion ethylene glycol ingestion acetone ingestion isopropyl alcohol ingestion ``` Sugars: mannitol sorbitol glucose (in those with insulin resistance, such as diabetics) Lipids: Hypertriglyceridemia Proteins: Hypergammaglobinemia (M. Waldenström)

Answer 19

2 x [Na mmol/L] + [glucose mmol/L] + [urea mmol/L]

Answer 20

Causes include: lactic acidosis ketoacidosis chronic renal failure (accumulation of sulfates, phosphates, urea) ``` intoxication: organic acids (salicylates, ethanol, methanol, formaldehyde, ethylene glycol, paraldehyde, INH) sulfates, metformin (Glucophage) massive rhabdomyolysis ```

Answer 21

``` U - ureterosigmoidostomy S - saline administration (in the face of renal dysfunction) E - endocrine (Addisons, spironolactone, triamterene, amiloride, primary hyperparathyroidism) D - diarrhea C - carbonic anhydrase inhibitors A - ammonium chloride R - renal tubular acidosis P - pancreatitis ```

Answer 22

no, not effective for most drugs

Answer 23

``` Molecular weight Water solubility Protein binding Endogenous clearance Volume of distribution (small) ```

Answer 24

``` Amphetamines, cocaine Benzodiazepines Phenothiazines Digoxin Opioids Quinidine Tricyclics ```

Answer 25

``` Ethylene glycol Methanol Salicylate Theophylline Procainamide ```

Answer 26

Withdrawal - agents with short half lives produce rapidly evolving severe withdrawal. Longer half life produces gradual, less severe withdrawal. Withdrawal similar to alcohol - agitation, nausea and vomiting reduced seizure threshold, delirium, psychosis.

Answer 27

Inhibits phosphodiesterase at high concentrations resulting reduced degradation of cAMP in high intracellular cAMP. Possible inhibition of adenosine receptors.

Answer 28

Causes release of catecholamines from central and peripheral nerves. Produces insidious onset central euphoriant effect. Withdrawal characterised by pronounced and long lasting craving.

Answer 29

Inhibition of dopamine and noradrenaline reuptake Produces marked increased mental alertness and euphoria then may progress to delusions and psychosis. Short acting compared with amphetamines but magnified effect.

Answer 30

Cause central increased catecholamine neurotransmitter release Produces marked increased mental alertness and euphoria then may progress to delusions and psychosis Withdrawal - lethargy, increased appetite, depression Methamphetamine - speed Methyeledoxymethamphetamine - ecstasy

Answer 31

The psychedelic effects of LSD are attributed to its strong partial agonist effects at 5-HT2A receptors but exact mechanism unknown. LSD affects a large number of the G protein-coupled receptors, including all dopamine receptor subtypes, and all adrenoreceptor subtypes, as well as many others. Mechanism unknown ␣ interacts with several serotonin receptor subtypes. Produces dizziness, weakness, tremors, nausea and prominent visual illusions and other perceptive abnormalities. Also causes pupillary dilation, tachycardia and increased blood pressure.

Answer 32

Related to ketamine. May act at opioid, dopamine or glutamate receptors. NMDA antagonist, D2 partial agonist, nAchR antagonist. Produces detachment, disorientation, distortion of body image, nystagmus (vertical and horizontal), sweating, tachycardia, hypertension. Overdose can be fatal (in contrast with LSD).

Answer 33

Produce very similar effects to LSD in high doses though delusions tend to be bizarre. Effects are very long acting (several days). Delirium, fluctuating level of awareness, difficulty in thinking and marked loss of memory are particularly characteristic.

Answer 34

Contains several cannaboids including tetrahydrocannabinol (THC). Stimulates a specific receptor located in basal ganglia, substantia nigra, globus pallidus, hippocampus and brain stem. May also have a non-specific membrane effect. Produces euphoria and characteristic uncontrollable laughter, alteration of time sense, sharpened vision followed by extreme relaxation and dream like states. Tachycardia and conjunctival reddening are characteristic. Therapeutic use likely to increase due to antiemetic and analgesic actions

Answer 35

Large surface area available to adsorb many drugs and poisons. 1 gram has a surface area of 1000m2 Manufactured by heating charcoal under pressure. Most effective in a 10:1 ratio of charcoal to poison.

Answer 36

does not bind: Ions - lithium, potassium, cyanide Heavy metals - iron Hydrocarbons Acids/alkalis Alcohols: ethanol, methanol

Answer 37

Balanced polyethylene glycol-electrolyte solution: used for iron, enteric coated medications, foreign bodies.

Answer 38

acetylcysteine

Answer 39

pralidoxime

Answer 40

bicarbonate

Answer 41

desferrioxamine

Answer 42

digibind, digoxin antibodies

Answer 43

flumazenil

Answer 44

physostigmine

Answer 45

Reduced synthesis of eicosanoid mediators: Irreversible inhibition of cyclooxygenase Reduced synthesis of thromboxane A2 Reduced synthesis of prostaglandins Central blockade of CNS response to IL1 in causing fever

Answer 46

Antiplatelet action lasts for the lifespan of the platelet - thromboxane A2 stimulates platelet aggregation and granule release Antiinflammatory Analgesic Antipyretic

Answer 47

1. Therapeutic range 0-10mg/kg Gastritis, ulceration Impaired haemostasis 2. Anti-inflammatory range 50mg/kg Salicylism: tinnitus, reduced hearing, vertigo. 3. Toxic range 50-150mg/kg hyperventilation, fever, dehydration, metabolic acidosis 4. Serious intoxication >150mg/kg Respiratory alkalosis due to central stimulation of respiratory centre Renal compensation for respiratory alkalosis. Metabolic acidosis due to salicylic acid dissociation, deranged carbohydrate metabolism and reduced renal function. Eventual renal and respiratory failure

Answer 48

Displaces from protein binding (phenytoin, methotrexate) Decreased activity of spironolactone Decreased tubular secretion of penicillin

Answer 49

Orally active Rapidly absorbed. Acidity of stomach keeps aspirin in nonionised form that is more readily absorbed Bound to albumin in low doses. As serum concentration rises, increasing fraction is unbound

Answer 50

Hydrolysed to acetic acid and salicylate by blood and tissue esterases. Salicylate conjugated by liver and excreted by kidney. Demonstrates variable order kinetics ␣ metabolism is saturable and small further increases in aspirin dose results in large rise in salicylate levels. Half life 3-5 hours at low dose, 12 hours at anti- inflammatory doses Alkalinisation of the urine increases rate of excretion of free salicylate Haemodialysis indicated in severe toxicity

Answer 51

Reduced synthesis of eicosanoid mediators Reversible inhibition of cyclooxygenase (COX1, COX2 or both) Reduced synthesis of thromboxane A2 Reduced synthesis of prostaglandins Prostaglandins are important mediators of inflammation Inhibition of mediator release from leukoctes Decreased sensitivity of vessels and pain sensors to bradykinin and histamine Central blockade of CNS response to IL1 in causing fever

Answer 52

Gastritis, ulceration and minor gastrointestinal disturbance Impaired haemostasis Nephrotoxicity and reduced renal function in those with renal disease Hepatotoxicity and increased liver enzymes in those with hepatic disease Oedema, especially if pre- existing heart failure Visual disturbances Aseptic meningitis

Answer 53

Warfarin: risk of fatal haemorrhage due to displacement from albumin Lithium/digoxin: increased plasma levels Antihypertensives: reduced effect

Answer 54

NSAID/aspirin sensitive asthma 3rd trimester of pregnancy: may cause closure of the fetal ductus arteriosus, fetal renal impairment, inhibition of platelet aggregation and delay labour and birth

Answer 55

Orally active Rapidly absorbed. Absorption slowed by food Highly protein bound

Answer 56

Metabolised by liver to inactive metabolites. Excreted in urine and bile Half life 2 hours

Answer 57

10mg/kg in 2 divided doses slow release formulation available may impair feritlity

Answer 58

Mostly excreted unchanged Half life 12 hours

Answer 59

Indomethacin, ketoprofen and diclofenac inhibit lipoxygease and therefore reduce formation of leukotrienes ketoprofen Half life 2 hours

Answer 60

May antagonise the actions of prostaglandins PGE2 and PGF2alpha at uterine receptors

Answer 61

Potent prostaglandin inhibitor 28 times more potent than aspirin PR more rapid T 1/2 4 hours

Answer 62

Patent ductus arteriosus Gout Preterm labour (though may cause closure of the ductus, renal toxicity, delayed labour, impaired haemostasis Dose 50-200mg/day in 2- 3 divided doses

Answer 63

Short-term management of post operative pain Equally effective as 10mg morphine/100mg pethidine IM or panadeine forte Dose 10-30mg IM every 6 hours for a maximum of 5 days

Answer 64

Para-aminophenol derivative Weak prostaglandin inhibitor Probably has COX3 antagonist actions in the CNS

Answer 65

Toxic symptoms include vomiting, abdominal pain, hypotension, sweating, central stimulation with exhilaration and convulsions in children, drowsiness, respiratory depression, cyanosis and coma. Hypokalaemia and ECG changes have also been noted In adults, hepatotoxicity may occur after ingestion of a single dose of paracetamol 10 to 15 g 25 g is potentially fatal. Symptoms during the first two days of acute poisoning by paracetamol do not reflect the potential seriousness of the intoxication. Major manifestations of liver failure such as jaundice, hypoglycaemia and metabolic acidosis may take at least three days to develop.

Answer 66

Alcohol and enzyme inducers :increased risk of toxicity

Answer 67

Orally active | Peak blood levels 30- 60 minutes Food intake delays paracetamol absorption. Partially protein bound

Answer 68

Metabolised in liver In adults at therapeutic doses, paracetamol is mainly conjugated with glucuronide or sulfate. Also metabolised to a toxic metabolite (cyp3a4 and cyp2a1) that is detoxified by conjugation with glutathione Excreted in the urine Elimination half- life varies from one to three hours. Overdose Activated charcoal IV fluids If 15g or more ingested, acetylcysteine

Answer 69

Paracetamol is metabolised in the liver, mainly by conjugation with glucuronide and sulfate. It is also metabolised by cytochrome P450 to form a reactive, potentially toxic, metabolite. This metabolite is normally detoxified by conjugation with hepatic glutathione, to form nontoxic derivatives. In paracetamol overdosage, the glucuronide and sulfate conjugation pathways are saturated, so that more of the toxic metabolite is formed. As hepatic glutathione stores are depleted, this toxic metabolite may bind to hepatocyte proteins, leading to liver cell damage and necrosis.

Answer 70

Acetylcysteine is a sulfydryl (SH) group donor, and may protect the liver from damage by restoring depleted hepatic reduced glutathione levels, or by acting as an alternative substrate for conjugation with, and thus detoxification of, the toxic paracetamol metabolite.

Answer 71

8 hours or less since overdose ingestion. Initial dose 150 mg/kg over 15 minutes, followed by continuous infusion of 50 mg/kg in glucose 5% 500 mL over four hours and 100 mg/kg in glucose 5% 1 L over 16 hours. If more than eight hours have elapsed since the overdosage was taken, the antidote may be less effective. Rumack-Matthew nomogram gives indication of likelihood of toxicity as a function of time since ingestion and plasma levels

Answer 72

Nausea and vomiting Allergic reactions Tachycardia, chest pain Contraindications: Asthma, renal and hepatic failure - administer with caution

Answer 73

Binds to intracellular tubulin, therefore inhibiting leucocyte migration and phagocytosis (also anti- mitotic) Inhibits formation of leukotriene B4 Inhibits urate crystal deposition

Answer 74

Acute gouty arthritis Dose 0.5-1mg then 0.5mg every 2 hours until pain is relieved or diarrhoea occurs Do not exceed 8mg

Answer 75

Diarrhoea (80% in 8-12 hours) Nausea and vomiting Bone marrow suppression (especially in overdose) inhibition of B12 absorption

Answer 76

Hepatic or renal disease Cardiac disease Gastrointestinal disease

Answer 77

Toxic dose >0.5mg/kg Latent period- 2-12 hours: Burning throat pain, bloody diarrhoea, dehydration Second phase 24-72 hours: Shock, renal failure, muscular weakness and ascending paralysis, bone marrow suppression, DIC, multiorgan failure

Answer 78

Rapidly absorbed | Bioavailability 25- 50%

Answer 79

Metabolised by liver, excreted in bile and urine. Some enterohepatic circulation Half life 4 hours

Answer 80

Activated charcoal | Supportive measures

Answer 81

Xanthine oxidase inhibitor Urate formed from amino acids and purines Xanthine oxidase is required for formation of urate therefore its inhibition will decrease production

Answer 82

``` May precipitate acute gout unless given with colchicine or probenicid Rash Nausea and vomiting Bone marrow depression Impaired renal function Impaired hepatic function ```

Answer 83

80% absorbed not bound to plasma proteins Metabolised by xanthine oxidase which it also inhibits Half life 1-2 hours

Answer 84

Sympathetic preganglionic fibres terminate in ganglia in paravertebral chains. Post ganglionic fibres then pass to the organs

Answer 85

Parasympathetic fibres: some terminate in parasympathetic ganglia (ciliary, pterygopalatine, submandibular, otic, pelvic), majority terminate in organs.

Answer 86

All pre-ganglionic autonomic All parasympathetic post-ganglionic All somatic motor

Answer 87

Acetylcholine synthesised in cytoplasm from acetyl-CoA (made in mitochondria) and choline (transported from extracellular fluid by sodium dependent carrier) - enzyme=choline acetyltransferase. Hemicholiniums block choline carrier

Answer 88

Acetylcholine transported from cytoplasm to storage vesicle by proton antiporter. Vesamicol blocks antiporter.

Answer 89

Calcium influx causes the vesicle to fuse with the terminal membrane and release acetylcholine into the synaptic cleft. Synaptobrevin, SNAP and syntaxin required. Botulinum toxin blocks release by enzymatic removal of 2 amino acids from synaptobrevin.

Answer 90

Acetylcholine degraded by acetylcholinesterase into acetate and choline.

Answer 91

Most post-ganglionic sympathetic

Answer 92

Tyrosine carried into cell by sodium dependent carrier. Converted to DOPA by tyrosine hydroxylase. DOPA converted to Dopamine by DOPA decarboxylase. Metyrosine inhibits action of tyrosine hydroxylase.

Answer 93

Dopamine transported into vesicle by a carrier. Reserpine blocks carrier.

Answer 94

Calcium influx causes the vesicle to fuse with the terminal membrane and release noradrenaline into the synaptic cleft. ATP and dopamine beta hydroxylase are also released into the cleft. Tyramine and amphetamines are capable of noradrenaline release by a displacement process that is not calcium dependent. Release can be blocked by bretylium and guanethadine

Answer 95

Noradrenaline diffuses away from the cleft or is transported back into the cytoplasm or into the post-junctional cell. Noradrenaline is then metabolised by MAO and COMT. Reuptake is blocked by cocaine and tricyclic antidepressants.

Answer 96

CNS, sympathetic postganglionic, some pre-synaptic

Answer 97

IP3, DAG, increased calcium

Answer 98

heart, smooth muscle, endothelium, some pre- synaptic

Answer 99

Inhibit adenylyl cyclase, open potassium channels, stimulates release of EDRF.

Answer 100

Exocrine glands, vessels, eye, lungs, GIT, bladder IP3, DAG, increased calcium

Answer 101

Postganglionic neurons, some pre-synaptic cholinergic terminals Open sodium and potassium channels, depolarisation

Answer 102

Skeletal muscle endplates | Open sodium and potassium channels, depolarisation

Answer 103

mostly smooth muscle IP3, DAG, increased calcium

Answer 104

pre-synaptic terminals, platelets, lipocytes, smooth muscle inhibition of adenylyl cyclase, reduced cAMP

Answer 105

heart, brain, lipocytes plus presynaptic stimulation of adenylyl cyclase, increased cAMP

Answer 106

heart, lungs, smooth muscle stimulation of adenylyl cyclase, increased cAMP

Answer 107

lipocytes stimulation of adenylyl cyclase, increased cAMP

Answer 108

B1, B2 (acellerate) | M2 (decellerate)

Answer 109

B1, A1, B2 (increase) | M2 (decrease)

Answer 110

relax a2, b2 contracts M3 sphincters contract a1, relax m3

Answer 111

1. B2, A 2. B2, A 3. B3 4. A2

Answer 112

1. B2 2. M3 3. A1 4. M3

Answer 113

relax: b2 contract: A, M3

Answer 114

1) A1 | 2) A, M

Answer 115

Choline esters: Acetylcholine (both), Methacholine (muscarinic), Carbachol (both), Bethanecol (muscarinic) Alkaloids: Pilocarpine (muscarinic), Nicotine (nicotinic), Lobeline (nicotinic), Muscarine (muscarinic).

Answer 116

1. Glaucoma: pilocarpine, methacholine, carbachol. 2. Paralytic ileus: bethanechol 3. Urinary retention: bethanechol 4. Antimuscarinic drug intoxication.

Answer 117

Choline esters: Poorly absorbed orally. Alkaloids: Well absorbed orally and transcutaneously. Distribution: Choline esters Hydrophilic therefore poorly distributed in CNS Alkaloids: Nicotine very lipid soluble therefore widely distributed in CNS

Answer 118

Choline esters: Hydrolysed in GIT (acetylcholine more than others, carbachol and methacholine negligible) Alkaloids: Renally excreted, increased by acidification of the urine.

Answer 119

catecholamine and non-catecholamine Catecholamines: Adrenaline, Noradrenaline, Isoprenaline, Dopamine Dobutamine Non-catecholamines: Ephedrine Phenylephrine, Amphetamine Indirect acting sympathomimetics: Cocaine Tyramine

Answer 120

agonist: Phenylephrine A1>A2>>>>>B antagonist: prazocin

Answer 121

Agonist: Clonidine A2>A1>>>>>B antagonist: Yohimbine

Answer 122

agonist: Dobutamine B1>B2>>>>A antagonist: Betaxolol

Answer 123

agonist: Terbutaline/Salbutamol (B2>>B1>>>>A) antagonist: Butoxamine

Answer 124

agonist: isoprenaline antagonist: propranolol

Answer 125

D1=D2>>B>>A

Answer 126

Number and function of adrenoceptors may be regulated to modify physiological response. Desensitisation may occur after exposure over a period of time and results in lesser response to further stimulation. Mechanisms: 1. Receptor sequestration -rapid and transient event decrease in receptor availability. 2. Down-regulation -reduced receptors due to reduced synthesis. 3. Receptor phosphorylation - resulting in impaired binding

Answer 127

Sympathomimetic drugs are based on a benzene ring structure with an ethylamine side chain. Substitutions made on the terminal amino group, benzene ring or the alpha or beta carbons modify the affinity of binding at specific receptors. Catecholamine formed by substitution with hydroxy groups on the benzene ring this increase potency but decreases bioavailability and decreases duration of action by making the drug subject to inactivation by COMT. Substitution on the amino group increases beta receptor activity. Substitution at the alpha carbon blocks oxidation by MAO. Substitution on the beta carbon is important for storage.

Answer 128

Adrenaline, Noradrenaline, Isoprenaline, Dopamine, Dobutamine.

Answer 129

Ephedrine, Phenylephrine, Amphetamine.

Answer 130

Adrenaline: Non-selective alpha and beta- adrenergic agonist. Noradrenaline: Non-selective alpha agonist, B1 greater than B2. Isoprenaline: Selective beta agonist Potent beta agonist, little alpha agonist effect. Dopamine: D1 and D2 agonist with beta and alpha actions at high doses. Dobutamine: B1 selective agonist. (Dobutamine is a racemic mixture -the positive isomer has B1 agonist and A1 antagonist actions, the negative isomer has A1 agonist actions - the net effect is positive inotrope action with little peripheral effect hence less reflex tachycardia)

Answer 131

Relatively pure alpha agonist with limited beta action

Answer 132

Some direct non-selective action on adrenoceptors, also causes release of stored catacholamines.

Answer 133

Causes release of stored catecholamines

Answer 134

Methyldopa - centrally acting A2 agonist. Clonidine - centrally acting A2 agonist). causes centrally mediated reduction in TPR (clonidine also causes bradycardia)

Answer 135

Adrenaline: Rise in systolic blood pressure due to positive inotropic and chronotropic effects via B1 receptors. Total peripheral resistance and hence diastolic blood pressure may fall due to vasodilation mediated by B2 receptors. Bolus doses tend to have mainly peripheral vasoconstrictor effect whereas infusions have the effect described above Noradrenaline: Rise in systolic blood pressure due to positive inotropic and chronotropic effects via B1 receptors. Total peripheral resistance and diastolic pressure also increase due to alpha effect and lack of B2 mediated vasodilation

Answer 136

Isoprenaline: Marked increase in cardiac output due to positive inotropic and chronotropic effect mediated by B1 receptors. Total peripheral resistance and diastolic blood pressure fall due to vasodilation mediated by beta receptors. Systolic pressure typically falls by a small amount though may rise. Dopamine: Reduction in TPR mediated by D1 receptors on blood vessels and pre-synaptic D2 receptors that result in reduced noradrenaline secretion. Most important effects are renal vasodilation. At higher doses, dopamine acts on beta receptors then alpha receptors to cause vasoconstriction and has an adrenaline-like action. Dose: Renal 0.5-2ug/kg/min Beta 2-10ug/kg/min Alpha >10ug/kg/min

Answer 137

Increased stroke volume and cardiac output mediated by B1 receptors. Less chronotropic effects. Mild vasodilation, sometimes vasoconstriction.

Answer 138

Phenylephrine: Marked increase in peripheral vascular resistance and decrease in venous capacitance mediated by alpha receptors and resulting in hypertension, and reflex vagally-induced mild bradycardia. Ephidrine: Mainly used as a nasal decongestant, mild central stimulant effect. Amphetamine: Marked central stimulant effect on mood and alertness. Appetite suppressant. Some efficacy in ADHD. Most have marked central stimulant effect, especially amphetamine.

Answer 139

Poor bioavailability after oral administration due to catechol structure and subsequent inactivation by COMT found in gut and liver Poor distribution to CNS due to catechol structure. Metabolised by COMT and MAO and excreted in the urine.

Answer 140

Orally active, longer duration of action. Readily enters CNS, especially amphetamine. Significant fraction excreted unchanged. Weak base therefore excretion enhanced by acidification of the urine.

Answer 141

Cocaine Inhibition of noradrenaline reuptake at noradrenergic synapses Widely distributed and readily enters CNS, short duration of action

Answer 142

Phentolamine imidazoline derivative. Phenoxy- benzamine Prazosin (Piperazinyl quiazoline)

Answer 143

1. Phentolamine: Non selective mixed A1 and A2 antagonist. Reduction in peripheral vascular resistance mediated by blockade of alpha receptors. This may result in a reflex tachycardia. Antagonism of pre- synaptic A2 receptors may cause noradrenaline release. (Also inhibits response to 5HT and H1/H2) 2. Phenoxybenzamine: A1 selective antagonist. (also blocks Ach, H1, 5HT). Blockade of catecholamine induced vasoconstriction. 3. Prazosin: Potent A1 antagonist. Decreased total peripheral resistance due to relaxation of arterial and venous smooth muscle mediated by alpha 1 blockade.

Answer 144

Phentolamine: Reflex tachycardia due to greater release of noradrenaline and its action on beta receptors Phenoxybenzamin: Postural hypotension and reflex tachycardia. Inhibition of ejaculation, fatigue, sedation. Prazosin: Less reflex tachycardia 1st dose hypotension Tends to cause salt and water retention Dizziness Palpitations Headache No effect on lipids

Answer 145

Phentolamine: Poorly absorbed orally. Duration of action determined by half life and rate of dissociation from the receptor. Phenoxybenzamine: Well absorbed orally. Prazosin: Well absorbed orally Highly protein bound

Answer 146

Extensively metabolised by liver | 50% bioavailability. Half-life 3 hours.

Answer 147

1. Propanolol: Non-selective beta antagonist No action at alpha or muscarinic receptors 2. Metoprolol: B1 selective 3. Atenolol: B1 selective. 4. Esmolol B1 selective 5. Labetolol: Mixed B1 antagonist and alpha antagonist 6. Carvedilol: Mixed non-selective beta blocker and alpha antagonist

Answer 148

The following beta blockers also act as membrane stabilisers by sodium channel blockade Acebutolol Betaxolol Labetolol Metoprolol Pindolol Propanolol

Answer 149

CVS Negative inotropic and chronotropic effect on the heart. (including slowed AV conduction and increased PR interval) Increased peripheral vascular resistance due to unopposed alpha effects. Antagonism of the release of renin (B1) resulting in reduced TPR RS Increased airway resistance (largely avoided by B1 selective agents but not completely). Eye Decreased aqueous humour production leading to reduced intraocular pressure. Metabolic and endocrine: Inhibition of catecholamine induced lipolysis and glycogenolysis via B2 receptors. Impair the recovery from hypoglycaemia as this is usually mediated by catecholamines. Masking of clinical signs of hypoglycaemia and impaired recovery from hypoglycaemia Increased VLDL, decreased HDL

Answer 150

Sedation, sleep disturbance, depression, psychotic episodes.

Answer 151

Calcium antagonists - leading to severe hypotension, bradycardia, congestive cardiac failure

Answer 152

Absorption Well absorbed orally. Distribution Large volume of distribution. Propanolol: Lipid soluble Readily crosses BBB Metoprolol: Moderate lipid solubility Atenolol: Low lipid solubility Esmolol: Low lipid solubility

Answer 153

Extensive first pass metabolism Excreted in urine Variable between individuals Low bioavailability Half life 3-6 hours Dose reduction required in hepatic failure

Answer 154

1. Metoprolol: Extensive first pass metabolism Low bioavailability, Half life 3-4 hours 2. Atenolol: Less extensive first pass metabolism Low bioavailability. Half life 6-9 hours 3. Esmolol: Rapidly hydrolysed by esterases in red blood cells. Half life 10 minutes.

Answer 155

ganglion blocking agent: Competitive antagonist at nicotinic cholinoceptors on sympathetic and parasympathetic postganglionic neurons. Causes pooling of blood in capacitance vessels. Abandoned due to side effects ␣ sympathoplegia (excessive orthostsaic hypotension, sexual dysfunction) and parasympathoplegia (constipation, urinary retention, glaucoma, blurred vision, dry mouth) IV administration

Answer 156

Inhibitor of noradrenaline release from postganglionic sympathetic neurons: Guanethidine is transported across the nerve membrane by uptake 1. Concentrated in transmitter vesicles where it replaces noradrenaline causing depletion of noradrenaline stores. Causes reduced cardiac output due to bradycardia and relaxation of capacitance vessels. Postural hypotension common. Overdosage may result in severe hypotension or shock. May induce hypertensive crisis in those with phaechromocytoma due to release of noradrenaline. Effects are attenuated when TCAs are coadministered due to their effect on blocking reuptake. Very large volume of distribution and long half life.

Answer 157

Reserpine blocks carrier mediated transport of dopamine into the vesicle. Results in depletion of dopamine, noradrenaline, and serotonin in central and peripheral neurons. Causes antihypertensive effect by reduction in cardiac output and total peripheral resistance. Effects are largely irreversible and last for several days.

Answer 158

1. Centrally acting alpha agonist. Inhibition of dopa decarboxylase and depletion of noradrenaline A2 actions greater than A1 2. Centrally mediated reduction in total peripheral resistance with variable reduction in heart rate and cardiac output. 3. Mild to moderate hypertension. Pregnancy induced hypertension Dose 0.5-3g/day in divided doses 0.25-1g IV over 20 minutes.

Answer 159

CVS May cause postural hypotension and bradycardia. CNS Sedation and loss of concentration Depression Nightmares. Endocrine: Lactation -mediated by inhibiting action on dopaminergic mechanisms in the hypothalamus. Other: Positive Coombs test is 25%. Interactions May result in lithium toxicity if co-administered

Answer 160

1. Absorption Orally active. Occasional IV use occasional. Distribution Active transport into brain 2. Extensive first pass metabolism. Metabolised in liver ␣ likely production of an active metabolite. Most is renally excreted. Antihypertensive effect in 4-6 hours, clinical effect may last 24 hours due to active metabolite.

Answer 161

1. Centrally acting partial agonist at alpha receptors, causing reduced sympathetic tone and increased parasympathetic tone. Preference for A2 2. Reduction in blood pressure and mild bradycardia. 3. Hypertension

Answer 162

Sedation, dry mouth. Depression. Reactive hypertensive crisis if rapidly withdrawn.

Answer 163

Orally active, bioavailability 75%. Distribution Lipid soluble and rapidly enters the brain. Half life 8-12 hours

Answer 164

1. carbonic anhydrase inhibitor: Carbonic anhydrase most prominent in the luminal membrane of the PCT 2. Profound depression of bicarbonate reabsorption in the proximal tubule Reduced production of bicarbonate by the ciliary body 3. Glaucoma Urinary alkalinisation Metabolic alkalosis Acute mountain sickness Epilepsy Dose 250mg-1g/24hours

Answer 165

Toxicity: Hyperchloraemic metabolic acidosis Renal stones Renal potassium wasting Skin reactions Interactions : Salicylates - increased risk of metabolic acidosis Phenytoin - reduced excretion of phenytoin resulting in toxic levels Contraindications: Hepatic failure - acetazolamide will decrease the urinary loss of ammonia.

Answer 166

Well absorbed orally Increased urinary pH within 30 minutes

Answer 167

1. Inhibition of the Na/K/2Cl cotransporter in the thick ascending limb of the loop of Henle resulting in reduced reabsorption of sodium chloride Indirect increase in calcium and magnesium excretion 3. Acute pulmonary oedema Hypertension Hyperkalaemia Hypercalcaemia Dose 20-80mg PO/IV

Answer 168

``` Toxicity Hypokalaemic metabolic acidosis Dose related ototoxicity Hyperuricaemia Hypomagnesaemia Allergic reactions ``` Hyperbilirubinaemia -displaces bilirubin from albumin Contraindications: Known hypersensitivity to sulphonamides (cross- sensitivity may occur) ARF

Answer 169

Absorption: Well absorbed orally Diuretic response in less than 5 minutes with intravenous use Distribution: Bound to albumin Half life 2-3 hours Diuretic response is proportional to their excretion in the urine One third is filtered, two thirds is secreted by the proximal tubule

Answer 170

Inhibition of sodium/chloride cotransporter in the early DCT Hypertension Congestive cardiac failure Urolithiasis due to idiopathic hypercalciuria Nephrogenic diabetes insipidus Dose 25-50mg/day

Answer 171

Toxicity: Hypokalaemic metabolic alkalosis Hyperuricaemia Hyperlipidaemia Hyponatraemia Allergic reaction

Answer 172

Absorption Well absorbed orally Distribution Bound to albumin Eliminated rapidly by the kidney Half life 5-14 hours

Answer 173

1. Spironolactone: Competitive antagonism of aldosterone at mineralocoticoid receptors Triamterene, amiloride: Direct inhibition of sodium reabsorption in the CD 2. Decreased sodium reabsorption Decreased potassium excretion 3. Most useful when there is a mineralocorticoid excess such as Conn syndrome or secondary aldosteronism due to congestive heart failure

Answer 174

Toxicity: Hyperkalaemia Hyperchloraemic metabolic acidosis Gynaecomastia Interactions: Triamterene and indomethacin have caused acute renal failure

Answer 175

Spironolactone: Metabolised by liver Triamterene: Metabolised by the liver and excreted by the kidney Amiloride: Excreted unchanged in urine

Answer 176

Mannitol : Filtered Not metabolised Not secreted Not reabsorbed Maintains osmotic gradient in the lumen of the tubule and therefore preventing absorption of water Increase urine volume in haemolysis or rhabdomyolysis Reduction in intracranial and intraoccular pressure Dose 1-2g/kg

Answer 177

Extracellular volume expansion -may exacerbate pulmonary oedema of CCF Dehydration

Answer 178

1. Direct acting vasodilator Mechanism unknown -may interfere with calcium entry into the cell and cause electromechanical decoupling. 2. Arterial dilator - little effect on veins. Lowers systemic vascular resistance to cause decreased blood pressure. 3. Severe hypertension. Severe pre- eclampsia Dose Oral : 50- 200mg/day in divided doses IV ␣ 20-40mg slowly

Answer 179

CVS Reflex tachycardia - may provoke angina. (can be used in combination with a beta blocker) Increases plasma renin activity CNS Increased cerebral blood flow Others Headache Nausea Flushing

Answer 180

1. Oral or intravenous preparations 2. Extensive first pass metabolism. (variable between individuals due to acetylation status) Low bioavailability. Half life 2-4 hours. Mostly excreted in urine.

Answer 181

1. Direct acting vasodilator. Acts by activation of guanylyl cyclase resulting in increased cGMP which relaxes smooth muscle. No effect on other smooth muscle 2. Arterial and venous dilator (more active on veins) Lowers peripheral vascular resistance and venous return to cause decreased blood pressure 3. Hypertensive crisis Aortic dissection prior to surgery Dose 0.5-10ug/kg/min if blood pressure is not controlled at maximum rate in 10 minutes the infusion should be terminated 500ug/kg of SNP produces toxic amounts of cyanide

Answer 182

CVS Compensatory tachycardia. Compensatory increase in catecholamines and renin. RS May causes reduced PaO2 due to attenuation of hypoxic pulmonary vasoconstriction CNS: Increased cerebral blood flow and increased intracranial pressure Endocrine: Delayed hypothyroidism can occur due to take up by thyroid tissue. Other: Cyanide combines with cytochrome C and leads to impairment of aerobic metabolism. Accumulation can cause metabolic acidosis, arrhythmias and hypotension. Cyanide toxicity related to rate of infusion rather than dose. Exacerbated by B12 deficiency, hypothermia, renal and hepatic impairment. Thiocyanate toxicity may occur after several days and cause weakness, disorientation and psychosis.

Answer 183

Given by IV infusion. Sensitive to light therefore IV line covered in foil. Distribution Extracellular fluid volume Rapidly metabolised by uptake into red cells Effectively combine with methaemaglobin to form cyanomethaemaglobin One molecule of SNP combines with haemoglobin to form cyanmethaemoglobin and 4 molecules of cyanide Cyanide ions combine with methaemoglobin to form cyanomethaemoglobin. Cyanide also reacts with thiosulphate in the plasma to form thiocyanate. Saturation of the above mechanisms leads to the accumulation of cyanide Free cyanide reacts with cytochromes and prevents their participation in oxidative metabolism, resulting in severe metabolic acidosis

Answer 184

1. Direct acting vasodilator Mechanism unclear May act by opening potassium channels in smooth muscle membrane. May have a calcium antagonist action 2. Arteriolar dilator ␣ little effect on veins. Lowers systemic vascular resistance to cause decreased blood pressure. Effect is rapid and profound and is associated with significant reflex tachycardia. 3. Hypertensive emergencies. Intractable hypoglycaemia Dose 5mg/kg

Answer 185

CVS Excessive hypotension. Reflex tachycardia - may provoke angina. Increased plasma renin activity. Endocrine: Inhibits insulin release.

Answer 186

Intravenous Extensive albumin binding. Metabolised in liver and excreted in urine.

Answer 187

1. Arterial dilator - little effect on veins. Lowers systemic vascular resistance to cause decreased blood pressure. Tends to have a greater effect than hydralazine. Direct acting vasodilator - acts by opening potassium channels in smooth muscle membrane. 2. Severe hypertension refractory to other antihypertensives Dose 5-40mg/day

Answer 188

Headache, nausea, anorexia, palpitations. Reflex tachycardia - may provoke angina.

Answer 189

1. Well absorbed orally Does not enter CNS 2. Metabolised by liver and excreted in urine Half life 4 hours.

Answer 190

1. Inhibition of angiotensin converting enzyme that converts angiotensin I to angiotensin II and inactivates bradykinin. Angiotensin II is a potent vasoconstrictor. Bradykinin is a potent vasodilator. 2. CVS Reduced peripheral vascular resistance due to: Inhibition of renin- angiotensin system Stimulation of the kallikrein-kinin system. Cardiac output and heart rate are unaffected. Most effective in individuals with high plasma renin activity. Effective in improving intrarenal haemodynamics due to reduction in intraglomerular capillary pressure. Subsequent reduction in proteinuria. 3. Hypertension. Diabetes. Congestive cardiac failure. Post myocardial infarction to reduce the risk of heart failure Dose Captopril 25mg tds Enalapril 10-20mg od Lisinopril 10-40mg od

Answer 191

Toxicity: First dose hypotension - profound hypotension especially if hypovolaemic. Dry cough and angioedema - due to effects of bradykinin. Acute renal failure -can occur with all ACE inhibitors particularly associated with renal artery stenosis. due to dependence on renin- angiotensin system for renal function Hyperkalaemia (more likely in renal failure or diabetes) -important consideration with potassium sparing drugs. Mild hepatitis, rare hepatic failure Altered taste. Rash. Interactions: NSAIDs should be avoided as they inhibit prostaglandin synthesis that is crucial to the bradykinin mechanism for inducing vasodilation Contraindications: Pregnancy (2nd and 3rd trimester) due to fetal malformations, fetal hypotension and fetal renal abnormalities.

Answer 192

Captopril Rapidly absorbed. Bioavailability 70% Wide distribution except CNS. Lisinopril: Slowly absorbed Captopril 70% bioavailability. Metabolised to disulphide conjugates and excreted in urine Dose reduction required in renal failure Half life 3 hours. Enalapril - prodrug that is converted to enalaprilat. Lisinopril - a lysine derivative of enalaprilat All others are prodrugs converted to active agents by hydrolysis in the liver Long half lives - up to 12 hours

Answer 193

1. Cause release of NO from vascular smooth muscle endothelium. Nitric oxide causes activation of guanylyl cyclase and an increase in cGMP cGMP causes dephosphorylation of myosin light chain to result in relaxation of muscle. 2. Direct effects: Relaxation of smooth muscle. Veins respond at a lower drug concentration than arteries. Arterioles and pre- capillary sphincters have a lesser response due to local reflex responses and decreased ability to secrete NO. Venodilation causes marked increase in venous capacitance, decreased preload and in most cases reduced cardiac output, thereby reducing myocardial oxygen demand. Systolic BP decreases more than diastolic. Arterial dilation also reduces afterload. There is dilation of the coronary arteries that may reduce spasm. Nitrates tend to causes bronchiolar and gut smooth muscle relaxation also. Indirect effects: Compensatory responses include sympathetic tachycardia and increased contractility. Also retention of salt and water via renin angiotensin system. Overall effect is decreased myocardial oxygen requirement. Relaxation of bronchial and gastrointestinal smooth muscle. Decreased platelet aggregation. Nitrate converted in small quantities to nitrite which reacts with haemoglobin to form methaemoglobin. 3. Stable and unstable angina. LVF. Hypertension. Dose SL 300mcg TD 5-10mg/24hrs IV 10-400mcg/min

Answer 194

CVS Extension of clinical effect : hypotension, tachycardia, headache. Tolerance - smooth muscle develops tolerance after continuous exposure. Tolerance may occur at a cellular level but may also result from compensation (indirect) actions of the drug itself. Clinically important tolerance does not occur with IV infusion. Other Formation of nitrosamines by combination of nitrate/nitrite with amines - potentially carcinogenic. Coronary Steal Syndrome: If two branches of a coronary artery have different levels of obstruction, the more obstructed branch will have relative arteriolar dilation at rest due to local metabolites. If an arteriolar vasodilator is introduced, both most effect will be to the less obstructed arteriole. Resistance in this vessel will fall and steal blood from the more obstructed vessel worsening the angina. Therefore, drugs such as nitrates that do not have a profound effect on arterioles are most effective in angina.

Answer 195

Absorption: High capacity hepatic nitrate reductase removes nitrate groups and therefore limits bioavailability after oral administration to 10% Sublingual route bypasses first pass metabolism. If given orally, much larger does required. Transdermal route also effective. Distribution 60% protein bound metabolised in the liver and red cells by reduction to dinitrates, mononitrates and nitrites. Half-life of short- acting sublingual GTN is 4-8 minutes though clinical effect may persist to 20-30 minutes. Active metabolites can persist for up to 3 hours. Excretion is via the kidney.

Answer 196

1. Dihydropyridine and miscellaneous calcium channel blockers bind to slightly different receptors associated with the (L type) calcium channel. Drugs act from the inner side of the membrane. Binding is more effective to channels in depolarised membranes. (although drug binds to activated and inactivated channels) Binding results in the channel failing to open in response to depolarisation. Decrease in calcium current causes smooth muscle relaxation, reduced contractility and slowing of pacemaker cells. Blockade can be partially reversed by sympathomimetic that increase transmembrane flux of calcium Vascular smooth muscle is most sensitive, but other smooth muscle is partially affected Verapamil and diltiazem may also causes sodium channel blockade Verapamil may have some anti-adrenergic effect 2. Smooth muscle Most types of smooth muscle are affected ␣ vascular smooth muscle is particularly sensitive. Arterioles are more sensitive than veins Results in reduced peripheral vascular resistance Also may reduce coronary artery tone Dihydropyridines have a greater vascular selectivity. Nimodipine more effective in cerebral vessels. Cardiac muscle Verapamil and diltiazem demonstrate cardiac selectivity Calcium channel blockade is more marked in those tissues that fire frequently and depend solely on calcium current such as SA and AV nodes. Atrioventricular nodal conduction and refractory period are prolonged. Verapamil is effective in suppressing early and late delayed after potentials Negative inotrope. Skeletal muscle unaffected by calcium channel blockers as it utilises intracellular pools of calcium. Verapamil may have a specific anti-adrenergic effect.

Answer 197

CVS: Extensions of therapeutic effects ␣ hypotension, bradycardia, AV block, cardiac depression. Hypotension and VF can occur if given for VT. All cause worsening of heart failure Verapamil has greatest cardiac depressant effects followed by diltiazem Dihydropiridines have less cardiac depressant effects and tend to cause a reflex tachycardia Endocrine: Verapamil inhibits insulin release (not significant) and may be useful in cancer chemotherapy General: Flushing Dizziness Nausea Constipation Interactions: Dangerous cardiodepressant effects can occur if co- administered with beta blockers. Verapamil may cause increased blood levels of digoxin. Contraindications: Nifedipine has been associated with increased risk of myocardial infarction when used for hypertension in patients with unstable angina

Answer 198

Absorption Orally active Distribution >90% protein bound All extensively metabolised Variable bioavailability -generally greater than 50% except verapamil (20%) Diltiazem excreted in faeces. Verapamil metabolised by liver and mostly excreted by kidney, remainder by GIT. Half lives Amlodipine 30-50 Nifedipine 4 Felodipine 11-16 Nimodipine 1-2 Diltiazem 3-4 Verapamil 6

Answer 199

Steroid nucleus (lipophilic) attached to a lactone ring (hydrophilic). No ionisable group therefore solubility is not pH dependant. Found in foxglove, oleander, lily of the valley, toads 1. Inhibition of Na+/K+ ATPase Several binding sites are present and digoxin binds to the alpha subunit. Very low concentrations of drug may stimulate the enzyme. Toxic doses ␣ sympathetic effects. 2. Direct membrane actions: Increase in intracellular sodium concentration. Increased intracellular sodium results in increased function of the sodium/calcium exchanger, causing a rise in intracellular calcium. Increased free calcium results in increased intensity of actin/myosin interaction, resulting in increased force of contraction. Increased free calcium also reduces potassium conductance and causes shortening of the action potential. (though initial lengthening of the action potential is characteristic) Inhibition of Na+/K+ ATPase, as well as causing increased intracellular sodium, results in decreased intracellular potassium (toxic effect) and reduced resting membrane potential. More toxic concentrations of digoxin lead to overloading of calcium stores and fluctuation in concentration, resulting in oscillatory depolarising after potentials that may result in ectopic beats ␣ sometimes resulting in bigeminy/VT/VF. Autonomic actions: Low dose -parasympathomimetic effects via central vagal stimulation, sensitisation of baroreceptors and facilitation of muscarinic transmission.

Answer 200

CVS: Arrhythmias - due to direct membrane effect and autonomic effect: AV junctional, ventricular ectopics, bigeminy, VT, VF. GIT: Anorexia, nausea, vomiting, diarrhoea. CNS: Disorientation, hallucinations, visual disturbance of colour perception, convulsions. Endocrine: Gynaecomastia. Interactions: Potassium and digoxin inhibit each others binding to Na/K ATPase Hyperkalaemia therefore reduces digoxin binding and reduces toxicity Hypokalaemia (and hypomagnesaemia) may result in digoxin toxicity (therefore care with diuretics) Hypercalcaemia and hypomagnesaemia increases toxic effects of digoxins as they accelerate cellular calcium overload Quinidine displaces digoxin from binding site but more importantly markedly reduces digoxin clearance Contraindications WPW syndrome: digoxin increases the probability of conduction through alternative pathways. Increased sensitivity of the myocardium in elderly patients

Answer 201

Well absorbed orally. 10% have gut bacteria that inactivate digoxin therefore require higher dose Care when these people are then given antibiotics as they may become digitoxic Distribution Widely distributed in all tissues including CNS Tends to accumulate in heart, kidney and liver due to propensity to bind tissue proteins in these organs 2/3 excreted unchanged by kidneys. Renal clearance proportional to creatinine clearance Dose adjustment required in renal insufficiency Half life 40 hours Loading dose is given Narrow therapeutic window.

Answer 202

Non-emergency administration Oral 125-250ug/day Rapid oral digitalisation Adult 750-1500ug Elderly 500-750ug as a single dose or 3-4 divided doses, then maintenance Emergency parenteral digitalisation Adult 500-1000ug Elderly 250-500ug as a single dose or 3-4 divided doses, then maintenance

Answer 203

More negative potential in phase 4 (ie resting potential) Reduction in the slope of phase 4 More positive threshold potential Prolongation of the action potential duration.

Answer 204

Occur in phase 3 Arise from plateau Exacerbated by slow heart rates Contribute to development of QT related arrhythmias.

Answer 205

``` 1 are sodium channel blockers 1a: Quinidine Procainamide Disopyramide TCAs- shorten action potential duration 1b- shorten action potential duration Lignocaine Tocainide, Mexilitine, Phenytoin 1c- No effect or may minimally lengthen action potential duration Flecainide class 2 - beta blockers Class 3 potassium channel blockers Class 4 calcium channel blockers ```

Answer 206

1. Class 1a antiarrhythmic: Binds to and blocks activated sodium channels. Block results in: Reduced rate of rise of phase 0 of the cardiac action potential, causing lengthening of the action potential Lengthening of the refractory period Alpha adrenoceptor properties (may be prominent with IV injection) 2. Increased QRS and QT intervals 3. Atrial flutter/fibrillation. Ventricular tachycardia

Answer 207

Pro arrhythmogenic Antimuscarinic actions: May inhibit vagal effects - this may result in increased sinus rate and increased atrioventricular conduction syncope Prolonged QT may lead to VF or torsades de pointes in 2-8% Cardiac depression: May cause asystole, more likely at high concentrations and hyperkalaemia. Preceded by 30% increase in QRS duration. Extracardiac: Nausea, vomiting and diarrhoea. Rash, fever, hepatitis Quinidine only Cinchonism - headache, dizziness, tinnitus. Angioneurotic oedema. Interactions: Reduces digoxin clearance therefore increases levels Increased effect with hyperkalemia Inhibition of metabolism of TCAs, beta blockers

Answer 208

1. Well absorbed orally. 80% bound to plasma proteins. 2. Metabolised in liver. 20% excreted unchanged in urine - enhanced by acidic urine. Half life 6 hours.

Answer 209

1. Binds to and blocks activated sodium channels. Block results in: Reduced rate of rise of phase 0 of the cardiac action potential, causing lengthening of the action potential Lengthening of the refractory period Blocks potassium channels and reduces outward repolarising current. Lengthens action potential duration (reflected by a lengthening of QT interval) - reduces the time spent in diastole and therefore makes more activated sodium channels available for blockage. 2. Action potential and refractory period are lengthened Increased QRS and QT intervals 3. Atrial flutter/fibrillation. Ventricular tachycardia

Answer 210

Pro arrhythmogenic Antimuscarinic actions: Mild compared with quinidine syncope Prolonged QT may lead to VF or torsades de pointes in 2-8% Cardiac depression May cause asystole, more likely at high concentrations and hyperkalemia. Preceded by 30% increase in QRS duration. Ganglion blocking actions Can cause hypotension with IV use though usually not a problem with oral use. Extracardiac: Nausea, vomiting and diarrhoea. Rash, fever, hepatitis 0.5% risk of serious blood dyscrasia Drug-induced lupus Interactions Increased effect with hyperkalemia Amiodarone causes increased effect

Answer 211

Oral or intravenous Widely distributed Metabolised in liver. Major metabolite N acetyl procainamide (NAPA) has class 3 actions. Metabolism reduced in slow acetylators Renal excretion important for NAPA - therefore dose adjustment is required in renal failure. Half life of procainamide 3-4 hours. Half life of NAPA is considerably longer and therefore may accumulate.

Answer 212

1. Blocks both activated and inactivated sodium channels. Shortens the action potential thereby increasing diastole. Lignocaine suppresses activity of depolarised arrhythmogenic tissue but has minimal effect on normal tissue. Most cells become drug free in diastole. 2. Action potential and refractory period are shortened 3. Ventricular tachycardia and fibrillation after defibrillation. Local anaesthetic.

Answer 213

CVS Pro arrhythmogenic Depression of cardiac pacemaker activity, excitability and conduction. Negative inotropic effect and decreased peripheral resistance. Exacerbates ventricular arrhythmias in <10%. May causes hypotension. CNS Drowsiness, visual and auditory disturbance, restlessness, nystagmus, shivering, convulsions, CNS depression. Interactions: Drugs that decrease liver blood flow (propanolol, cimetidine) reduce lignocaine clearance.

Answer 214

1. Widely distributed after intravenous administration to highly perfused organs. Extensive first pass metabolism - 3% bioavailability. (note - Tocainide and mexiletine are cogeners of lignocaine that are resistant to first-pass metabolism and have similar effects) 2. Metabolised in liver and plasma. Clearance dependent on hepatic blood flow Excreted in urine. Half life 1.5 hours

Answer 215

Sodium channel blocker Decreases rate of rise pf phase 0 of the cardiac action potential Little effect on action potential duration Lengthens refractory period Greatest action in the His-Purkinje system SVT Pre-excitation syndromes Ventricular arrythymias

Answer 216

Safe drug with few side effects. | Pro arrhythmogenic

Answer 217

Well absorbed orally. | Half life 20 hours, usually given twice daily. Metabolised by liver and excreted by the kidney.

Answer 218

``` 1. Potassium channel blockade - class 3 action Results in lengthening of the action potential even at high heart rates. Increased refractory period ``` ``` Sodium channel blockade - class 1 action Acts on inactivated channels only Most pronounced in tissues that have long action potentials, frequent action potentials or less negative diastolic potentials. ``` Calcium channel blockade - class 4 action ``` Non competitive beta blockade - class 2 action Also causes partial inhibition of beta receptors. ``` 2. CVS Slows sinus rate. Slows AV nodal conduction. Markedly prolongs QT interval. Prolongs QRS duration. Increases refractory period duration. Increases coronary blood flow and reduces myocardial oxygen demand Extra-cardiac effects: Peripheral vascular dilation due to beta and calcium blocking effects. 3. Supraventricular and ventricular tachyarrhythmias including in cardiac arrest protocols. Dose Intravenous 5mg/kg usually administered as an infusion over 20 minutes but can be given as a bolus. Oral 200mg tds reducing to 100- 200mg od after a week.

Answer 219

CVS: Bradycardia or heart block in those with existing nodal disease. May precipitate heart failure. Respiratory effects: Pulmonary fibrosis. Eye effects: Corneal deposits Skin effects: Skin deposits and photodermatitis. Grey skin discolouration with chronic use in 5%. Neurological effects: Peripheral neuropathy, paresthesia, tremor, ataxia, headaches. Thyroid effects: Hypo or hyperthyroidism can occur in 5%. Gastrointestinal effects: Constipation, hepatocellular necrosis. Contraindications: Porphyria

Answer 220

``` Bioavailability 20- 80% 95% protein bound. Small volume of distribution. Active metabolite may accumulate. Excreted in bile, faeces and urine. Half-life highly variable 14-110 days. 15-30 days required for loading. Toxic effects may continue after drug is ceased. ```

Answer 221

``` class II and III Non-selective beta blocker Lengthens the action potential and causes increased refractory period ``` 2. CVS: Negative inotropic and chronotropic effect on the heart. (including slowed AV conduction and increased PR interval) Increased peripheral vascular resistance due to unopposed alpha effects. Antagonism of the release of renin. Increase in length of action potential and refractory period RS: Increased airway resistance (largely avoided by B1 selective agents but not completely). Eye: Decreased aqueous humour production leading to reduced intraocular pressure Metabolic and endocrine Inhibition of lipolysis and glycogenolysis via B2 receptors. used: Supraventricular and ventricular arrhythmias.

Answer 222

CVS: Prolongation of repolarisation may lead to torsades de points - risk greatest at high concentrations. Myocardial decompensation in pre-existing abnormal myocardial function. Decreased perfusion in severe peripheral vascular disease. RS: Airway obstruction in pre- existing asthma/reactive airways. Endocrine: Masking of clinical signs of hypoglycaemia Interactions: Calcium antagonists - leading to severe hypotension, bradycardia, congestive failure

Answer 223

Well absorbed orally | Largely excreted unchanged by kidney therefore dosage adjustment is required in renal impairment

Answer 224

Adenosine Naturally occurring nucleoside Miscellaneous Acts via adenosine receptors Enhanced potassium conductance and inhibition of cAMP-induced calcium influx. Results in marked hyperpolarisation and suppression of calcium- dependent action potentials. 2. Inhibits AV nodal conduction and increases AV nodal refractory period. Mild effects on SA node. 3. SVT Diagnosis of narrow or broad complex tachyarrhythmias Dose 3,6,9,12mg with rapid flush

Answer 225

Transient arrhythmias in >50% including bradycardia and ventricular standstill Generally short lived due to short half life Flushing in 20% Hypotension <1% Shortness of breath and chest burning in 10%. May cause bronchospasm therefore caution in asthmatics. Interactions: Less effective in the presence of adenosine receptor blockers such as caffeine and theophylline. Contraindications 2nd or 3rd degree AV block, sick sinus syndrome Specific risk of torsades in long QT interval

Answer 226

inactive when administered orally. Absorbed into red blood cells and vascular endothelium where it is phosphorylated or deaminated. Half life less than 10 seconds.

Answer 227

Binds to endothelial cell surfaces Biological activity dependent on the presence of antithrombin III that inhibits clotting factor proteases by forming complexes with them. Heparin binds to antithrombin III and causes a conformational change resulting in more rapid interaction with clotting factors IX, X, XI and XII Binding to clotting factors is accelerated 1000 fold. In particular, inactivation of factor X results in reduced conversion of prothrombin to thrombin Higher doses of heparin also inhibit thrombin and therefore reduce conversion of fibrinogen to fibrin One third of molecules in heparin have biological effect. Heparin is not consumed in the binding process. HMW fractions (5000- 30000) have a marked affinity for thrombin. LMW fractions (<9000) inhibit activated factor X but have a lesser effect on thrombin. 2. Prevention and treatment of thromboembolic disease. Treatment of DIC and fat embolism. Priming of vascular catheters -haemodialysis, cardiac bypass machines etc. Treatment of unstable angina and non-Q wave MI Dose: Heparin 5000u bd 1000u/hr Enoxaparin

Answer 228

Bleeding.: Higher risk in elderly and renal failure. Long term use associated with osteoporosis and fractures. Transient thrombocytopenia in 25% of patients. Severe thrombocytopenia in 5%. Can cause paradoxical thromboembolism due to heparin induced platelet aggregation. Contraindications: Active bleeding. Clotting disorders - haemophilia, thrombocytopenia, purpura. Severe hypertension. Recent neurosurgery, eye surgery or LP. A ny condition where the likelihood of uncontrolled bleeding exists. Reversal: Protamine - highly basic peptide that combines with heparin to form a complex that has no anticoagulant activity. Excess protamine also has an anticoagulant effect.

Answer 229

1. Absorption Heparin Peak plasma levels 2- 4 hours after subcutaneous injection Highly bound to plasma proteins LMW heparin Increased bioavailability from subcutaneous site. Distribution Vascular compartment 2. Largely unknown Probable metabolism by the liver

Answer 230

Vitamin K dependent oral anticoagulant Racemic mixture of 2 stereoisomers S isomer is 4 times more potent than R isomer Blocks gamma carboxylation of several glutamate residues in factors II, VII, IX, X and protein C resulting in biologically inactive molecules. Carboxylation is physiologically coupled to Vitamin K metabolism and Vitamin K is oxidised to an inactive form. In order for carboxylation to occur, Vitamin K must be reduced back to an active form. Warfarin inhibits Vitamin K epoxide reductase and therefore prevents formation of active vitamin K.

Answer 231

Bleeding. Toxic to fetus - causes haemorrhagic defects and bone malformations. Cutaneous necrosis due to depression of protein C synthesis. Interactions Increased INR: Metronidazole Fluconazole Trimethoprim - sulfamethoxazole (inhibition of metabolism of S isomer) Cimetidine Amiodarone (Inhibition of metabolism of both isomers) ``` Pharmcodynamic Aspirin (additive effect) 3rd generation cephalosporins (elimination of bacteria in the GIT that produce Vitamin K) Heparin Hepatic disease Hyperthyroidism (increased turnover of clotting factors) ``` Decreased INR: Pharmacokinetic Barbiturates Rifampicin (enzyme induction) Pharmcodynamic Diuretics (increased clotting factor concentration) Vitamin K Hereditary resistance Hypothyroidism (decreased turnover of clotting factors)

Answer 232

1. Absorption Orally active with 100% bioavailability. 8-12 hour delay in effect as pre- synthesised factors must degrade - this takes up to 60 hours in the case of factor II. Maximal clinical effect takes 1-3 days. Distribution Small volume of distribution as tightly bound to albumin. 2. Half life in plasma is 36 hours. Metabolised in the liver and conjugated to glucuronide. Metabolites excreted in urine and faeces.

Answer 233

Fibrinolytic Protein synthesised by group c beta haemolytic streptococci. Combines with plasminogen. Streptokinase/plasminogen complex catalyses conversion of further plasminogen to active plasmin. (plasmin is protected from plasma antiplasmins while it is within the clot) Fibrinolysis Fibrinolytic effect lasts a few hours. APTT elevated for approximately 24 hours Acute myocardial infarction PE Proximal DVT Arterial thromboembolism Dose 1.5 million units over 30-60 minutes

Answer 234

``` Transient hypotension Arrhythmias -1-10% Haemorrhage (clotting factors return to normal after 24 hours Pyrexia Hypersensitivity. ``` Contraindications: Clotting disorder Recent (10/7) major gastrointestinal haemorrhage Recent (2/12) CVA or neurosurgery Recent (10/7) major surgery, trauma or CPR. Uncontrolled hypertension. Pregnancy. Previous use >5/7 <12/12 Recent streptococcal infection (complex is inactivated by streptococcal antibodies)

Answer 235

Intravenous administration, remains intravascular | Half life 23 minutes

Answer 236

t-P A Tenecteplase recombinant tissue plasminogen activator Preferentially activates plasminogen that is bound to fibrin therefore theoretically more specific to formed thrombus. Dose Weight dependent 30-50mg

Answer 237

``` Transient hypotension Arrhythmias - 1-10% Haemorrhage (clotting factors return to normal after 24 hours Pyrexia Hypersensitivity. ``` Contraindications: Recent major haemorrhage Clotting disorder Recent (2/12) CVA or neurosurgery Recent (10/7) major surgery. Uncontrolled hypertension. Pregnancy.

Answer 238

Intravenous administration, remains intravascular Binds to heptic receptors and is catabolised to small peptides Kidney not involved with clearance

Answer 239

Reduced synthesis of eicosanoid mediators Irreversible inhibition of cyclooxygenase Reduced synthesis of thromboxane A2 Reduced synthesis of prostaglandins Central blockade of CNS response to IL1 in causing fever Antiplatelet action lasts for the lifespan of the platelet - thromboxane A2 stimulates platelet aggregation and granule release Antiinflammatory Analgesic Antipyretic

Answer 240

Therapeutic range 0-10mg/kg Gastritis, ulceration Impaired haemostasis Anti-inflammatory range 50mg/kg Salicylism ␣ tinnitus, reduced hearing, vertigo. Toxic range 50-150mg/kg hyperventilation, fever, dehydration, metabolic acidosis Serious intoxication >150mg/kg Metabolic acidosis due to salicylic acid dissociation, deranged carbohydrate metabolism and reduced renal function. Respiratory alkalosis due to central stimulation of respiratory centre Renal compensation for respiratory alkalosis. Eventual renal and respiratory failure Interactions Displaces from protein binding (phenytoin, methotrexate) Decreased activity of spironolactone Decreased tubular secretion of penicillin

Answer 241

Orally active Rapidly absorbed. Acidity of stomach keeps aspirin in nonionised form that is more readily absorbed Bound to albumin in low doses. As serum concentration rises, increasing fraction is unbound Hydrolysed to acetic acid and salicylate by blood and tissue esterases. Salicylate conjugated by liver and excreted by kidney. Demonstrates variable order kinetics ␣ metabolism is saturable and small further increases in aspirin dose results in large rise in salicylate levels. Half life 3-5 hours at low dose, 12 hours at anti- inflammatory doses Alkalinisation of the urine increases rate of excretion of free salicylate

Answer 242

Gp IIb/IIIa antagonist Potent inhibition of platelet function Antithrombotic in unstable angina and myocardial infarction 2. Nausea, dyspepsia, diarrhoea. Haemorrhage. Leukopenia. 3. Guven as IV infusion. Metabolised by liver and excreted in urine

Answer 243

1. Inhibition of ADP pathway of platelets 2. Bleeding Leukopenia. Nausea, dyspepsia, diarrhoea. 3. orally active

Answer 244

Monoclonal antibody that binds to GpIIb/IIIa receptors and prevents binding of fibrinogen and vWF Antithrombotic Used in patients undergoing angioplasty or stent placement

Answer 245

Bleeding Thrombocytopenia Multiple minor toxicities

Answer 246

Intravenous bolus dose or infusion

Answer 247

Inhibition of uptake of adenosine into red blood cells and potentiation of NO Antiplatelet action Also has vasodilator actions Antithrombotic Often combined with aspirin as a slow-release preparation

Answer 248

Potent vasodilator therefore caution in severe coronary artery disease Headache Nausea, vomiting

Answer 249

Orally active Widely distributed Metabolised in the liver Excreted in bile

Answer 250

Inhibits binding of ADP to GpIIb/IIIa and therefore inhibits platelet aggregation Antithrombotic Dose 75mg daily

Answer 251

Toxicity Bleeding | Interactions Aspirin, heparin -additive effect

Answer 252

Orally active Widely distributed Metabolised in the liver Active metabolite is responsible for clinical effect Excreted in bile

Answer 253

Fat soluble - K1 found in food, K2 found synthesised in intestine by bacteria. Necessary for formation of factors II, VII, IX and X Orally active - requires bile slats for absorption. IV should be given slowly. Clinical effect delayed for 6 hours

Answer 254

Polypeptide containing 2 chains (A and B) of amino acids linked by disulfide bridges. Synthesised as part of preproinsulin. Removal of a peptide leader sequence forms proinsulin. Connecting peptide is removed in the granules prior to release Insulin binds with an insulin transmembrane receptor that binds and stimulates a protein tyrosine kinase. Exposure to increased insulin down regulates receptor concentration and affinity.

Answer 255

Glucose enters cells by facilitates diffusion through glucose transporters GLUT1: brain, red cells, placenta, many other organs GLUT2 : B cells, liver, intestine, kidney -transport glucose out of the cell GLUT4 - adipose tissue and muscle A pool of GLUT4 transporters is maintained in the cytoplasm of insulin sensitive cells and when these cells are exposed to insulin the transporters move to the cell membrane. Secondary active transport (intestine and kidney) Utilise sodium dependent glucose transporters - SGLT1 and SGLT2.

Answer 256

Rapid (seconds) Increased transport of glucose, amino acids and potassium into insulin sensitive cells. Intermediate (minutes) Stimulation of protein synthesis Inhibition of protein degradation Activation of glycolytic enzymes and glycogen synthase Inhibition of phophorylase and gluconeogenic enzymes Delayed (hours) Increase in mRNAs for lipogenic and other enzymes. Liver: Decreased glucose output due to decreased gluconeogenesis and increased glycogen synthesis. Increased protein synthesis Increased lipid synthesis Decreased ketogenesis ``` Fat: Increased glucose entry Increased fatty acid synthesis Increased triglyceride deposition Activation of lipoprotein lipase Increased potassium uptake ``` Muscle: Increased glucose entry Increased glycogen synthesis Increased amino acid uptake Increased protein synthesis Decreased protein catabolism Decreased release of gluconeogenic amino acids Increased ketone uptake Increased potassium uptake Increased cell growth

Answer 257

Ultra short acting: Clear solution at neutral pH. Contains small amounts of zinc to improve stability and shelf life Short acting: Clear solution at neutral pH. Contains small amounts of zinc to improve stability and shelf life. Used for DKA. Intermediate: Neutral pH with protamine or phosphate buffer or zinc in acetate buffer. This delays absorption and prolongs duration of action. Long acting: Neutral pH with protamine or phosphate buffer or zinc in acetate buffer. This delays absorption and prolongs duration of action. Insulin can be derived from beef, pork or from humans.

Answer 258

1. Hypoglycaemia Insulin allergy and resistance Lipodystrophy 2. Ultra short acting Short acting Effect within 30 minutes, lasts 5-7 hours. Intermediate Neutral pH with protamine or phosphate buffer or zinc in acetate buffer. Long acting Neutral pH with protamine or phosphate buffer or zinc in acetate buffer. 3. Half life 5 minutes. Binds to insulin receptors and is internalised. Destroyed by insulin protease. 80% is degraded in liver and kidney. (this ratio is reversed in diabetics on insulin)

Answer 259

1. Increased release of insulin from B cells Inhibition of glucagon release Potentiation of insulin action on target tissues Dose Gliclazide 80-160mg/day in divided doses Glimepiride 1-8mg/day in single dose

Answer 260

``` Hypoglycaemia (alcohol predisposes) Tachyphylaxis - B cells may become refractory to response Blurred vision Rash Blood dyscrasias Hepatic toxicity Renal insufficiency ``` Contraindications: Severe renal or hepatic impairment

Answer 261

Well absorbed orally | Half life 5 hours Metabolised by liver and excreted in urine

Answer 262

1. Unclear mechanism Direct stimulation of glycolysis Reduced gluconeogenesis Decreased glucose absorption Reduced plasma glucagon 2. Dose 500mg-3g/day

Answer 263

Nausea, vomiting, diarrhoea Reduced B12 absorption Lactic acidosis - increased risk with renal insufficiency, age and alcohol (does not cause hypoglycaemia) Contraindications Alcoholism Renal or hepatic disease

Answer 264

Well absorbed orally Not bound to plasma proteins Excreted unchanged in urine Half life 1-3 hours

Answer 265

Binds with transmembrane receptor protein that stimulates a GTP-binding signal transducer protein (G protein) that in turn generates an intracellular second messenger. Second messengers include cAMP, calcium and phosphoinositides. Glycogenolysis (liver but not muscle) Gluconeogenesis Lipolysis Ketogenesis Secretion of growth hormone, insulin and pancreatic somatostatin. Potent inotropic and chronotropic effect on the heart independent of metabolic effects and without requiring functioning adrenoceptors Profound relaxation of smooth muscle at high doses Severe hypoglycaemia Beta blocker overdose Oesophageal foreign body Dose

Answer 266

Inhibition of thyroid peroxidase resulting in reduced formation of thyroid hormones Inhibition of peripheral deiodination of T4 Reduced thyroid hormone synthesis Onset of effect may take several weeks due to stored hormone

Answer 267

Nausea, vomiting Rash (10%) Fever Marrow depression (0.5%) Jaundice

Answer 268

Well absorbed orally Accumulates in thyroid gland Half life 6 hours Excreted in urine

Answer 269

Inhibition of organification and release of thyroid hormones Decreases size and vascularity of the gland Pre-operative decrease in gland size and vascularity Thyroid storm

Answer 270

Concentrated by thyroid, emission of beta rays results in parenchymal destruction

Answer 271

Saline diuresis Bisphosphonates (inhibition of bone resorption) Etidronate Calcitonin Gallium (inhibition of bone resorption) Phosphate

Answer 272

Natural agents Hydrocortisone (cortisol) Synthetic agents: Prednisolone, methylprednisolone Betamethasone, Dexamethasone Prednisone is a prodrug of prednisolone

Answer 273

Steroid enters the cell as a free molecule Binds to intracellular receptor that is bound to stabilising heat shock protein Heat shock protein is released and the steroid- receptor complex enters the nucleus and bind to glucocorticoid response element on the DNA This causes regulation of transcription and production of appropriate protein

Answer 274

Cushings syndrome Excessive acid and pepsin secretion by the stomach Myopathy Psychosis Adrenal suppression Contraindications Uncontrolled infection

Answer 275

Oral Topical Intramuscular Intravenous Well absorbed orally Bound to corticosteroid binding globulin and albumin Hydrocortisone, prednisolone and methylprednisolone are short acting agents Betamethasone and dexamethasone are long acting Half life of hydrocortisone is 60-90 minutes Metabolised by liver to active and inactive metabolites and excreted in the urine Dose should be increased for patients on long term therapy during times of stress

Answer 276

Intermediary metabolism: Protein catabolism Gluconeogenesis and decreased peripheral glucose utilisation Ketogenesis Permissive action effects: Required for glucagon and catecholamines to exert their effects Inhibition of ACTH secretion Facilitation of effective water excretion (unknown mechanism) Therapeutic effects: Anti-inflammatory and immunosuppressant effects Due to effects on concentration, distribution and function of peripheral white cells. Increased circulating neutrophils, platelets and red blood cells Reduced lymphocytes, eosinophils, monocytes and basophils Reduced secretion of cytokines Increased neutrophils results in decreased neutrophils at site of inflammation Inhibition of leucocyte function, especially macrophages due to decreased mediator production Reduced synthesis of prostaglandins and leukotrienes via action on phospholipase A2 and COX2 Vasoconstriction Reduced capillary permeability

Answer 277

Hydrocortisone - 1 Prednisolone - 5 Betamethasone - 25 Dexamethasone - 30 Hydrocortisone has mixed glucocorticoid and mineralocorticoid actions, prednisolone has minor mineralocorticoid actions, nil for betamethasone and dexamethasone

Answer 278

Competitive antagonism at H2 receptors. H2 receptors found in gastric enterochromaffin-like cells, cardiac muscle, mast cells and brain Reduced gastric acid secretion 90% reduction in basal, food-stimulated and nocturnal secretion of gastric acid after a single dose Reduced volume of gastric secretion and concentration of pepsin Little effect on heart or blood pressure. Peptic ulceration Oesophagitis and gastritis. Zollinger Ellison syndrome. Prevention of stress ulceration in critically ill. Dose Ranitidine Oral 150mg twice daily Cimetidine 400mg twice daily Famotidine 20mg twice daily

Answer 279

Minor toxicities: Diarrhoea, dizziness, headache, rash. GIT May mask gastric malignancy Reversible cholestasis and hepatitis CNS acute confusion (cimetidine >> ranitidine) Antiandrogen effects Gynecomastia, galactorrhoea. (cimetidine only) Marrow Blood dyscrasias (cimetidine >> ranitidine) (Famotidine free of above effects) Interactions Inhibition of cytochrome P450 and reduction of liver blood flow. Care with warfarin, phenytoin, beta blockers, benzodiazepines, tricyclics, calcium channel blockers, antiarrhythmics, alcohol. (cimetidine >> ranitidine) Histamine antagonists reduce the absorption of ketoconazole Inhibition of renal clearance of drugs (cimetidine >> ranitidine) Contraindications: Porphyria

Answer 280

20% plasma bound. 70% bioavailability. Half life 1-3 hours Mostly renal metabolism.

Answer 281

?Reversible inhibition of parietal cell proton pump

Answer 282

May mask gastric malignancy May increase the risk of gastrointestinal infection Nausea, vomiting, abdominal pain Headache Interactions: Diazepam - decreased clearance Contraindications Severe hepatic dysfunction

Answer 283

Well absorbed orally Highly protein bound | Metabolised by liver and excreted in urine

Answer 284

Somatostain analogue | Reduced portal pressure in chronic liver disease resulting in decreased risk of variceal haemorrhage

Answer 285

Phenothiazine Strong antiemetic and antipsychotic actions Antidopamine action - therapeutic effect and unwanted effects including extrapyramidal disorders and endocrine disturbances. Alpha-adrenoreceptor antagonism, which contributes to cardiovascular side effects, e.g. Orthostatic hypotension and reflex tachycardia. Potentiation of noradrenaline by blocking its reuptake into nerve terminals. Weak anticholinergic action, weak antihistamine action. Weak serotonin antagonism. Prochlorperazine also has an effect on temperature control and blocks conditioned avoidance responses.

Answer 286

Sedation, Hypotension Anticholinergic effects, especially in elderly, especially constipation, dry mouth, blurred vision Severe acute dystonic reactions in children Tardive dyskinesia Neuroleptic malignant syndrome Hypo/hyperthermia Interactions: Enhances the effect of other CNS depressants Contraindications: Hypotension (alpha- adrenoreceptor antagonism) Drowsiness, coma, neuromuscular excitability, convulsions. Miosis and loss of deep tendon reflexes. Hypotension and hypotermia. Activated charcoal effective. Supportive therapy. Avoid adrenaline and lignocaine.

Answer 287

Orally active. | Metabolised by liver and excreted in faeces and urine.

Answer 288

Dopamine antagonist Increased upper gastrointestinal motility Dose Oral-10mg tds Intravenous -10mg tds, slowly Rapid injection leads to feelings of anxiety Daily dose should not exceed 0.5mg/kg

Answer 289

Restlessness, fatigue, drowsiness in 10% Dystonic reaction ␣ more common in children and young adults Tardive dyskinaesia in chronic use Neuroleptic malignant syndrome Interactions May affect absorption of other drugs due to effects on motility Contraindications Phaechromocytoma ␣ causes increased release of catecholamines Epilepsy - may increase the frequency of seizures Porphyria, Parkinson's

Answer 290

Orally active | Metabolised in liver and excreted in urine

Answer 291

5HT3 antagoni

Answer 292

Dizziness Muscle pain Chest pain Seizures Contraindications: IHD Severe hepatic impairment

Answer 293

Orally active Protein bound | Metabolised by liver

Answer 294

First generation H1 antagonist Phenothiazine derivative Other agents: Diphenhydramine Chlorpheniramine Competitive antagonism at H1 receptors. (note that some cardiovascular effects of histamine are mediated by H2 receptors) also have antimuscarinic, anti-adrenergic, antiserotonin actions Anaphylaxis Allergic reactions Motion sickness and vestibular dysfunction. Nausea (can also be used as a local anaesthetic as has some sodium blocking actions) Dose 10-25mg orally, intravenous or intramuscular

Answer 295

Marked sedation. Antimuscarinic actions. Orthostatic hypotension Excitation and convulsions in children. Postural hypotension.

Answer 296

Orally active. Widely distributed. Readily enter the CNS | Extensively metabolised by liver and excreted in urine.

Answer 297

Second generation H1 antagonist Other agents Terfenadine (terfenadine is a prodrug of fexofenadine that lacks cardiotoxic effects) Competitive antagonism at H1 receptors. (note that some cardiovascular effects of histamine are mediated by H2 receptors) also have anticholinergic, anti-adrenergic, antiserotonin actions

Answer 298

Mild toxicities compared with first generation agents Interactions Terfenadine and astemizole metabolised by CYP3A4 which is inhibited by grapefruit, ketoconazole and macrolides ␣ associated with QT prolongation and potentially toxic arrhythmias Fexofenadine is the metabolite of terfenadine and lacks cardiotoxic effects

Answer 299

Widely distributed except CNS | Extensively metabolised by liver and excreted in urine.

Answer 300

Inhibition of cell wall synthesis Penicillins bind to penicillin binding proteins and inhibit transpeptidation in peptidoglycan synthesis and therefore formation of cross- links in the cell wall that confer rigidity. Active against gram positive cocci, gram negative cocci, some anaerobes Destroyed by beta lactamases Inactive against enterococci, some anaerobes, gram negative rods Streptococci Meningococci Enterococci Pneumococci Staphylococci Treponema pallidum Bacillus anthracis Clostridium Dose 10-50mg/kg/day in 3-4 doses orally or IV

Answer 301

Minor toxicities such as nausea, vomiting, diarrhoea Important cause of type I hypersensitivity. Type III hypersensitivity can also occur. 5-8% claim penicillin allergy but only 5-10% of these will have a reaction. High doses in renal failure can causes seizures

Answer 302

Original penicillins such as penicillin G acid labile. Penicillin V is acid stable and well absorbed orally but has poor bioavailability Avoid administration with meals 60% protein bound. Penetrates tissues very well except eye, prostate and CNS - though penetration is better if inflammation is present. Renal excretion 10% by filtration, 90% by tubular secretion. Half-life 30 minutes, increases to 10 hours in renal failure. Dose adjustment required in renal failure Frequent dosing required

Answer 303

Beta lactam antibiotic with resistance to staphylococcal betalactamases. Penicillins bind to penicillin binding proteins and inhibit transpeptidation in peptidoglycan synthesis and therefore formation of cross- links in the cell wall that confer rigidity. Active against gram positive cocci including beta lactamase producing staphylococci Inactive against enterococci, anaerobes, gram negative.

Answer 304

Minor toxicities such as nausea, vomiting, diarrhoea Important cause of type I hypersensitivity. Type III hypersensitivity can also occur. 5-8% claim penicillin allergy but only 5-10% of these will have a reaction. High doses in renal failure can causes seizures Small risk of hepatitis hence introduction of dicloxacillin

Answer 305

Acid stable and well absorbed orally. Absorption impaired by food. Highly protein bound. Penetrates tissues very well except eye, prostate and CNS -though penetration is better if inflammation is present. Hepatic metabolism and rapid renal excretion ␣ 10% by filtration, 90% by tubular secretion. No adjustment in renal failure.

Answer 306

Inhibition of cell wall synthesis Penicillins bind to penicillin binding proteins and inhibit transpeptidation in peptidoglycan synthesis and therefore formation of cross- links in the cell wall that confer rigidity Similar spectrum to penicillin but better penetration of gram negative bacteria, though still sensitive to beta lactamases ``` Streptococci Meningococci Pneumococci (particularly active therefore 1st choice for respiratory infection) Staphylococci Treponema pallidum Bacillus anthracis Clostridium (not enterobacter) Ampicillin effective for Shigella ``` Ampicillin not active against E coli Proteus Haemophilus Klebsiella Pseudomonas Enterobacter Citrobacter Serratia Ticarcillin is also active against Pseudomonas Enterobacter Piperacillin is also active against Klebsiella

Answer 307

1. Beta lactamases: Destroyed by beta lactamases produced by staphylococci, haemophilus, E coli, pseudomonas, enterobacter 2. Alteration on target penicillin binding proteins. Resistant organisms have binding sites with low affinity for binding - particularly seen with MRSA and pneumococcus 3. Poor ability to penetrate outer membrane Gram-negative organisms

Answer 308

Acid stable and well absorbed orally. Highly protein bound. Penetrates tissues very well except eye, prostate and CNS - though penetration is better if inflammation is present.

Answer 309

Resemble beta lactam molecules and protect against many beta lactamasesActive against beta lactamases produced by Haemophilus Neisseria gonorrhoea Salmonella Shigella E coli Klebsiella Legionella Bacteroides Not active against beta lactamases produced by Enterobacter Citrobacter Serratia Pseudomonas

Answer 310

Cefadroxil Cefazolin Cephalexin Cephalothin Cephadrine Cephalosporins bind to penicillin binding proteins and inhibit transpeptidation in peptidoglycan synthesis and therefore formation of cross-links in the cell wall that confer rigidity. Gram positive cocci plus E coli Klebsiella Proteus Anaerobic cocci Peptococcus Peptostreptococcus Not active against: Listeria MRSA Haemophilus Pseudomonas Some proteus Enterobacter Serratia Citrobacter Surgical prophylaxis Uncomplicated UTI, skin and soft tissue infection

Answer 311

Cross allergy between penicillins and cephalosporins is 5-10% - withhold in anaphylaxis only. Toxicity Local irritation. Superinfection.

Answer 312

Well absorbed orally Renal excretion 10% by filtration, 90% by tubular secretion. Half-life 30 minutes, increases to 10 hours in renal failure.Gram positive cocci plus E coli Klebsiella Proteus Anaerobic cocci Peptococcus Peptostreptococcus Plus extended gram negative cover against Haemophilus Some serratia Not active against Listeria MRSA Pseudomonas Some proteus Enterobacter Some serratia Citrobacter Dose adjustment required in renal failure

Answer 313

Cefaclor Cefuroxime Cefoxitin Cephalosporins bind to penicillin binding proteins and inhibit transpeptidation in peptidoglycan synthesis and therefore formation of cross-links in the cell wall that confer rigidity.

Answer 314

Cross allergy between penicillins and cephalosporins is 5-10% - withhold in anaphylaxis only Local irritation. Cefaclor associated with serum-sickness like reaction Superinfection.

Answer 315

Renal excretion 10% by filtration, 90% by tubular secretion. Half-life variable Dose adjustment required in renal failure

Answer 316

Ceftriaxone Cefotaxime Cephtazidime Extended coverage of gram-negative organisms compared with first and second generation. Citrobacter Serratia Haemophilus Neisseria Particularly pseudomonas. Less active against gram-positive organisms. Not active against enterococci or listeria. Treatment of serious infections by susceptible organisms. Treatment of serious infection if organism unknown. Especially useful for CNS infection. Treatment of penicillin resistant infections including MRSA and gonorrhoea Dose 10-50mg/kg/day. Ceftriaxone suitable for once daily dosing.

Answer 317

Allergy Cross allergy between penicillins and cephalosporins is 5-10% - withhold in anaphylaxis only. Toxicity Local irritation

Answer 318

Intravenous dosing. Good tissue penetration, especially into CNS. Half-life 7-8 hours. Metabolised by liver and excreted in bile. No dosing adjustment required in renal failure

Answer 319

Structurally related to beta lactams Inhibition of cell wall synthesis Binds to penicillin binding proteins and inhibit transpeptidation in peptidoglycan synthesis and therefore formation of cross- links in the cell wall that confer rigidity. nfections due to resistant organisms Highly active against resistant pneumococci and enterobacter

Answer 320

Minor toxicities including nausea, vomiting, diarrhoea and skin rashes High doses in renal failure can causes seizures

Answer 321

Inactivated by dehydropeptidases in renal tubules therefore administered with cilastatin

Answer 322

Binds to peptidoglycan and inhibits transglycosylase therefore preventing peptidoglycan elongation and cross-linking that confers rigidity. Active against gram positive bacteria (plus flavobacterium) Bactericidal Synergistic with gentamicin Resistance mechanisms: Alteration of binding site.

Answer 323

Minor reactions in 10% Phlebitis Histamine release (red man/red neck syndrome) Ototoxicity and nephrotoxicity, especially if administered with aminoglycoside

Answer 324

Poorly absorbed orally -used orally for the treatment of resistant clostridium difficile 90% filtered by kidney Dose adjustment required in renal failure Not removed by haemodialysis

Answer 325

Binds to peptidoglycan and inhibits transglycosylase therefore preventing peptidoglycan elongation and cross-linking that confer rigidity. Active against gram positive bacteria (plus flavobacterium) Synergistic with gentamicin

Answer 326

Poorly absorbed orally ␣ used orally for the treatment of resistant clostridium difficile

Answer 327

Poorly absorbed orally -used orally for the treatment of resistant clostridium difficile 90% filtered by kidney Dose adjustment required in renal failure

Answer 328

Potent inhibition of microbial protein synthesis Reversibly binds to 50S subunit of bacterial ribosome Bacteristatic Broad spectrum Not effective for chlamydia Effectively obsolete as a systemic drug due to other less toxic agents Eye infections ␣ due to broad spectrum and good tissue penetration Not effective for chlamydia

Answer 329

1.Toxicity GIT Nausea, vomiting, diarrhoea Bone marrow Commonly causes dose related reversible bone marrow suppression Rare idiosyncratic aplastic anaemia (1 in 30000) Neonates: Grey baby syndrome Interactions: Inhibition of hepatic microsomal enzymes -prologed half life and increased concentrations of phenytoin and warfarin 2. Decreased permeability Production of chloramphenicol acetyltransferase that inactivates the drug

Answer 330

Well absorbed orally Widely distributed Good tissue penetration Metabolised by liver and excreted by kidney Dose adjustment required in hepatic failure

Answer 331

Potent inhibition of microbial protein synthesis Reversibly binds to 30S subunit of bacterial ribosome Enter microorganisms by diffusion and active transport Broad spectrum Active against Rickettsiae, Chlamydiae, Mycoplasma, Vibrio Also active against some protozoa

Answer 332

GIT Nausea, vomiting, diarrhoea Bacterial overgrowth Liver toxicity ATN Bones and teeth: Tooth discolouration due to chelation with calcium Other Photosensitivity Interactions: Enzyme inducers such as phenytoin and carbamazepine reduce half life by 50%

Answer 333

``` Well absorbed orally Absorption not impaired by food Impaired by divalent cations and dairy products 40-80% protein bound Widely distributed except CNS ``` Metabolised by liver, excreted in urine and bile. Bile concentration 10 times serum concentration Dose reduction required in renal failure Doxycycline is excreted by non- renal mechanism and therefore is drug of choice in renal failure Half life 12-16 hours

Answer 334

Potent inhibition of microbial protein synthesis Reversibly binds to 50S subunit of bacterial ribosome Concentrated in polymorphs and macrophages Bacteristatic at low concentrations, bactericidal at high concentrations Erythromycin Semi-synthetic Roxithromycin Clarithromycin Azithromycin Broad spectrum Gram positive (strep>>staph) Gram negative Neisseria Bordetella Rickettsia Treponema Campylobacter Chlamydia Mycoplasma Legionella Less active against haemophilus and staphylococcus Clarithromycin more active against mycobacterium avium intracellulare

Answer 335

Nausea, vomiting, diarrhoea Acute cholestatic hepatitis (semi-synthetic macrolides better tolerated) Interactions: Erythromycin and clarithromycin Inhibition of cytochrome P450 resulting in increased concentrations of theophylline, warfarin, antihistamines Causes increased bioavailability of digoxin Semi-synthetic macrolides relatively free of above effects due to less avid binding to P450

Answer 336

Erythromycin base combined with stearate or ester confers acid stability Widely distributed except CNS Erythromycin Metabolised by liver, excreted in bile No adjustment necessary for renal impairment. Half life 1.5 hours Synthetic macrolides metabolised by liver and excreted in bile and urine therefore dose adjustment in renal failure is recommended

Answer 337

Aminoglycoside enters the bacteria by passive diffusion via porin channels across the outer membrane (this process is aided by penicillins) Aminoglycoside is then actively transported into the cytoplasm Binds to 30S subunit of bacterial ribosome Bactericidal Gram negative Pseudomonas Proteus Enterobacter Klebsiella Serratia E coli Some gram positive activity Streptococci and enterococci are relatively resistant No action against anaerobes Tobramycin is more active against pseudomonas concentration dependent killing is more important than time-dependent killing therefore once daily dosing

Answer 338

Ototoxic, vestibulotoxic and nephrotoxic ␣ more likely in prolonged use, elderly, renal insufficiency and concurrent use of other nephrotoxic substances Ototoxicity manifests mainly as vestibular dysfunction Gentamycin is mostly nephrotoxic and vestibulotoxic (less ototoxicity) Nephrotoxicity occurs in 5- 25% of patients receiving drug for more than 3-5 days Neuromuscular blockade can occur in very high doses

Answer 339

Not orally active -virtually the entire oral dose is excreted in faeces Highly polar compounds poorly distributed to CNS and eye though inflammation increases penetration. Poor activity in low pH or low oxygen tension. Half life 2-3 hours Renally excreted Dose adjustments required in renal insufficiency Trough concentration should be less than 2ug/ml Aminoglycoside clearance is directly proportional to creatinine clearance Cockcroft-gault formula

Answer 340

Resistance mechanisms: Decreased intracellular accumulation due to impaired active transport Decreased binding to ribosome due to production of inhibitory proteins Enzymatic inactivation (note resistance is common) Contraindications Children under 8 years

Answer 341

Decreased intracellular accumulation due to decreased permeability Decreased binding to ribosome due to modification of the binding site by methylase (accounts for 90% of resistance) Enzymatic inactivation by enterobacter

Answer 342

Decreased intracellular accumulation due to abnormal porins or anaerobic conditions Gram positive organisms are resistant by this mechanism Decreased binding to ribosome due to modification of the binding site Enzymatic inactivation by transferases (most important for gram negative resistance ␣ netilmycin is relatively resistant to this)

Answer 343

A nti-folate Sulphonamides are structural analogues of para- aminobenzoic acid that bind to dihydropteroate synthase and competitively inhibit folic acid synthesis Bacteriostatic Bacteriocidal when given with trimethoprim Broad spectrum Gram positive and gram negative actions Includes Chlamydia Stimulates growth of Rickettsia Used in combination with trimethoprim in the treatment of urinary tract infection, respiratory tract infections and in episodes of resistance Resistance common Use is limited by toxicity Very cheap therefore extensive use in 3rd world

Answer 344

``` 5% of patients have side effects Nausea, vomiting, diarrhoea Fever Exfoliative dermatitis Photosensitivity Stevens Johnson syndrome GIT Sulfonamides may precipitate in urine and may cause obstruction Marrow Aplastic anaemia Contraindications Porphyria ```

Answer 345

Orally active (slow) Sulfamethoxazole chosen due to its similar half life to trimethoprim Wide distribution Metabolised in liver and excreted in urine. Metabolised impaired in slow acetylators Dose adjustment required in renal insufficiency Half life 10-12 hours

Answer 346

A nti-folate Inhibition of dihydrofolate reductase Synergistic effect when given with sulphonamide due to sequential action in folate synthesis Used in combination with trimethoprim in the treatment of urinary tract infection, respiratory tract infections, skin infections ``` Broad spectrum Especially E coli Enterobacter Proteus Neisseria Salmonella Klebsiella Haemophilus Not active against Pseudomonas Mycoplasma Mycobacterium Treponema ```

Answer 347

Toxicity Nausea, vomiting, diarrhoea GIT Sulfonamides may precipitate in urine and may cause obstruction Marrow Megaloblastic anaemia Contraindications: Porphyria

Answer 348

Concentrated in prostate, vagina., kidney and lungs Metabolised in liver and excreted in urine. Dose adjustment required in renal insufficiency Half life 10-12 hours

Answer 349

Heterogeneous mixture of sulphated muco-polysacc- harides. | Enoxaparin Low molecular weight heparin

Answer 350

the important quinolones are synthetic fluorinated analogues of nalidixic acid. Nalidixic acid Norfloxacin Ciprofloxacin Ofloxacin Sparfloxacin DNA gyrase inhibitors Block relaxation of positively supercoiled DNA required for normal transcription and replication of bacteria. Active against a variety of gram negative and gram-positive bacteria. Nalidixic acid ␣␣␣␣␣␣␣␣␣␣␣␣␣␣␣␣ systemic levels therefore only used for urinary tract infections. Norfloxacin Least active Ciprofloxacin Particularly active against gram-negative cocci and bacilli including enterobacter, pseudomonas, neisseria, haemophilus and campylobacter. Less effective against gram-positive organisms especially streptococci. Ofloxacin Sparfloxacin Improved gram-positive action. Longer half-life. Anaerobes are generally resistant though intracellular organisms are susceptible.

Answer 351

Well tolerated. General Nausea Diarrhoea Headache Rash May damage growing cartilage therefore not recommended in children unless no other drug available or suitable Little data on pregnancy. Excreted in breast milk. Interactions: Enzyme inducer - increases the metabolism of phenytoin

Answer 352

Well absorbed orally with greater than 80% bioavailability. Concentrates in prostate and kidney. Half-life 3-4 hours. Excreted renally therefore accumulates in renal failure.

Answer 353

Antiprotozoal agent with potent anti-anaerobic actions Reduction of the nitro group produces toxic metabolites Only active against obligate anerobes ``` Bacteroides Fusobacterium Clostridium Anaerobic streptococci Trichomoniasis Giardiasis Amoebiasis ```

Answer 354

General: Nausea, vomiting, diarrhoea Metallic taste Dry mouth Headache Disulfiram-like effect with alcohol Pancreatitis CNS: Ataxia, seizures Interactions Potentiates the effect of warfarin Reduced half life if taken with enzyme inducers phenytoin, phenobarbitone Increased half life if taken with enzyme inhibitors cimetidine

Answer 355

Well absorbed orally Also given rectally and intravenously Metabolised by liver Half life 7 hours May accumulate in hepatic dysfunction

Answer 356

Antiherpes agent Selectively activated by phosphorylation in infected cells only. Acyclovir triphosphate inhibits vial DNA synthesis Active against HSV1 and HSV2 Varicella zoster

Answer 357

Nausea, vomiting Headache | Rapid intravenous administration may be associated with renal insufficiency and neurological toxicity

Answer 358

Oral, topical and intravenous formulations Well absorbed orally, low bioavailability, hence frequent dosing Distributed to most tissues Cleared by glomerular filtration and tubular secretion. Half life 3-4 hours Dosage adjustment required for renal impairment

Answer 359

Uncommon point mutation in the quinolone-binding region.

Answer 360

1. a chemical or physical process that kills micro-organisms 2. a disinfectant with sufficiently low toxicity to use on skin, mucous membranes and wounds 3. a process to remove all micro-organisms, spores and viruses 4. sterilisation using pressurised steam at 120 degrees for 20 minutes

Answer 361

Some bacteria utilise exogenous folate therefore are not susceptible Decreased intracellular accumulation reduced permeability Decreased binding to dihydropteroate synthase Resistance is common

Answer 362

Resistance mechanisms Some bacteria utilise exogenous folate therefore are not susceptible Decreased intracellular accumulation due to reduced permeability Decreased binding to dihydrofolate reductase

ACEM Pharm part 2 - Sheet1 (1) Flashcards

(400 cards)