ACEM Pharm part 2 - Sheet1 (1) Flashcards

Question 1

Q

List the common air pollutants

Answer

A

Carbon monoxide	52% 
Sulphur oxides	14% 
Hydrocarbons	14% 
Nitrogen oxides	14% 
Particles	4%

Question 2

Q

Toxicity of carbon monoxide?

Answer

A

Colourless, tasteless, odourless by product of incomplete combustion
Combines reversibly with haemoglobin to form carboxyhaemoglobin 220 times more avid binding than oxygen

An individual breathing air containing 0.1% CO (1000ppm) would have a carboxyhaemoglobin level of 50%

Question 3

Q

Treatment of carbon monoxide poisoning?

Answer

A

Removal of source ABC Oxygen
Room air at 1atm, elimination half life of CO 320 minutes

100% oxygen at 1atm elimination half life 80 minutes
100% oxygen at 2atm elimination half life 20 minutes

Question 4

Q

List 3 classes of insecticides and give examples?

Answer

A

Chlorinated hydrocarbons:
DDT Lindane

Organophosphates and carbamates:
Parathion Malathion

Naturally-derived insecticides:
Pyrethrum

Question 5

Q

Give an example of a herbicide

Question 6

Q

Give examples of commercially available cholinesterase inhibitors? list 3 types with examples

(Indirect-acting cholinoceptor stimulants)

Answer

A

Alcohols - edrophonium.
Carbamates - neostigmine, physostigmine
Organo- phosphates - parathion, malathion.

Interact with acetylcholinesterase and therefore blocks the hydrolysis of acetylcholine.

Question 7

Q

What are the mechanisms of the 3 types of cholinesterase inhibitors?

How long does the effect last for each of the 3 classes?

Answer

A

Alcohols - short lived reversible binding lasting 2- 10 minutes.

Carbamates -2 step hydrolysis to form a covalent bond, lasts 30mins-6hours

Organophosphates - initial hydrolysis results in a phosphorylated active site. This undergoes aging that involves strengthening of the phosphorus-enzyme bond that may last for hundreds of hours.

Question 8

Q

What are the effects of cholinesterase inhibitors at a molecular level?

Answer

A

Effects are similar to direct acting cholinomimetics. At the NMJ, therapeutic effects prolong and intensify the physiological action of acetylcholine resulting in increased strength of contraction.

Higher does may result in fibrillation.

Question 9

Q

What are the clinical indication for the 3 types of cholinesterase inhibitors?

Answer

A

Alcohols (edrophonium):
Diagnosis of myasthenia gravis = tensilon test.

Carbamates (neostigmine, physostigmine):
Reversal of non- depolarising neuromuscular blockade. Myasthenia gravis Glaucoma
Paralytic ileus Urinary retention

Organo-phosphates (parathion, malathion): Glaucoma

Question 10

Q

Side effects of cholinesterase inhibitors (describe muscarinic and nicotinic effects separately)

Answer

A

Muscarinic agonists: nausea, vomiting, diarrhoea, salivation, sweating, vasodilation, bronchoconstriction.

Nicotinic agonists: CNS stimulation, convulsions, coma, flaccid paralysis, hypertension and cardiac arrhythmias.

Organophosphates may also cause delayed neurotoxicity

Question 11

Q

Absorption and distribution of

1) carbamates?
2) organophosphates?

Answer

A

Carbamates - absorption poor due to permanent charge and lipid insolubility. Physostigmine has better absorption due to tertiary amine group.

Organophosphates - well absorbed from skin, lung, gut, conjunctiva and distributed into CNS.

Distribution:

Carbamates - distribution in CNS negligible. Physostigmine is widely distributed.

Organophosphates - widely distributed including the CNS.

Question 12

Q

Metabolism and excretion of

1) carbamates?
2) organophosphates?

Answer

A

Carbamates: majority of the dose is excreted in the urine.

Organo-phosphates: Malathion is rapidly metabolised to inactive products and therefore relatively safe. Parathion is metabolised less effectively and is therefore more toxic.

Question 13

Q

What are 2 naturally occuring antimuscarinic agents?

Answer

A

Atropine: found in Atropa belladonna (deadly nightshade) and datura stramonium

Hyoscine: found in hyoscyamus niger

Question 14

Q

What are the 2 types of synthetic antimuscarinic agents?

Answer

A

Tertiary amines - pirenzepine, tropicamide

Quaternary amines - propantheline, glycopyrrolate, ipratropium, benztropine.

Question 15

Q

How does atropine work?

Answer

A

Competitive antagonist of acetylcholine at muscarinic receptors. Reversible blockade.

No distinction between M1,2 and 3

Salivary, bronchial and sweat glands are the most sensitive.

Question 16

Q

What are the organ effects of atropine?

Answer

A

Mydriasis
Cycloplegia
Decreased lacrimal secretion
Tachycardia (note - may cause initial bradycardia at low dose)
Increased contractility
Arterial constriction (Dilation - high dose direct effect)
Venoconstriction (Dilation - high dose direct effect) Bronchiolar smooth muscle relaxation
Decreased mucus secretion
Gut relaxation
Contraction of sphincters
Decreased salivary, gastric and pancreatic secretion.
Bladder wall relaxation
Bladder sphincter contraction Uterus smooth muscle relaxation
Decreased sweating
Drowsiness, confusion, hallucinations, dysarthria

Question 17

Q

Clinical uses of antimuscarinic agents?

Answer

A

Bradycardia due to increased vagal tone, including cardiac arrest -Atropine

Cholinomimetic (direct or indirect) poisoning -Atropine

Mydriasis -Tropicamide, Atropine

Motion sickness -Hyoscine

Bronchodilation -Ipratropium

Diarrhoea - Atropine

Urinary urgency -Oxybutynin

Question 18

Q

Toxicity of antimuscarinic agents?

Answer

A

In adults, toxic effects are an extension of the clinical effect.
Children are sensitive to hyperthermic effects that are centrally mediated.

Produce very similar effects to LSD in high doses though delusions tend to be bizarre. Effects are very long acting (several days).

Delerium, fluctuating level of awareness, difficulty in thinking and marked loss of memory are particularly characteristic.
Contraindications Glaucoma.

Question 19

Q

Absorption and distribution of antimuscarinic agents?

Answer

A

Absorption
Naturally occurring agents: Well absorbed from gut, skin and conjunctival membranes.

Synthetic agents (quaternary amines) : only 10-30% absorbed orally.

Distribution:
Naturally alkaloid esters of tropic acid - widely distributed.
Synthetic antimuscarinic agents (quaternary amines) - mostly peripheral distribution.

Question 20

Q

Metabolism and excretion of antimuscarinic agents?

Answer

A

Metabolised in liver and excreted in urine

Half life 4 hours

Question 21

Q

What is pralidoxime?

Answer

A

Cholinesterase regenerator:
The Acetylcholinesterase enzyme has two parts to it. An acetylcholine molecule bound at both ends to both sites of the enzyme, is cleaved in two to form acetic acid and choline. In organophosphate poisoning, an organophosphate binds to just one end of the acetylcholinesterase enzyme [ the esteric site ], blocking its activity. Pralidoxime is able to attach to the other half [ the unblocked, anionic site ] of the acetylcholinesterase enzyme.It then binds to the organophosphate, the organophosphate changes conformation, and loses its binding to the acetylcholinesterase enzyme. The conjoined poison / antidote then unbinds from the site, and thus regenerates the enzyme, which is now able to function again.

After some time though, some inhibitors can develop a permanent bond with cholinesterase, known as aging, where oximes such as pralidoxime can not reverse the bond

Question 22

Q

What is pralidoxime?

Answer

A

Hydrolysis of phosphorylated acetylcholinesterase
Slows aging process
Pralodoxime is only effective if aging has not occurred

Question 23

Q

Dosing of pralidoxime?

Answer

A

Pralidoxime is initially administered intravenously in a dose of 1 to 2 g. Signs of recovery appear rapidly. If the symptoms reappear, then an infusion of 2.5% is infused at a rate of 0.5 g/hour.

Question 24

Q

What is paraqat and why is it toxic?

Answer

A

herbicide

Paraquat forms a potent free radical that accumulates in the lung: Oedema, alveolitis, progressive fibrosis

Question 25

Q

Lethal dose of paraqat

Answer

A

50-500mg/kg

Question 26

Q

Toxidrome of paraqat?

Answer

A

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

Question 27

Q

How does arsenic affect tissues and what effects does this cause?

Answer

A

Inhibition of enzymes of oxidative phosphorylation

Shock Arrhythmias Encephalopathy Peripheral neuropathy Pancytopenia

Question 28

Q

How is arsenic absorbed and excreted?

Answer

A

absorbed: All mucosal surfaces Widely distributed

Excreted by kidney

Question 29

Q

How does lead affect tissues and what effects does this cause?

Answer

A

inorganic oxides: Inhibition of enzymes, interferes with essential cations, alters membrane structure

Inorganic oxides and salts: Anaemia, peripheral neuropathy, nephropathy, hypertension
Organic: Encephalopathy

Question 30

Q

How is lead absorbed and excreted?

Answer

A

Inorganic oxides and salts: Gastrointestinal and respiratory tracts
Organic: All mucosal surfaces

Excretion:
Organic -Metabolised by liver to lead, excreted in urine and faeces

Question 31

Q

How does mercury affect tissues and what effects does this cause?

Answer

A

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

Question 32

Q

How is mercury absorbed?

Answer

A

Elemental: Respiratory tract

Inorganic:
Gastrointestinal tract
Skin

Organic:
All mucosal surfaces
Tend to concentrate in soft tissues, especially kidney

Question 33

Q

How is mercury excreted?

Answer

A

Elemental: Converted to Hg2+
Excreted in urine and faeces

Inorganic: Excreted in urine

Question 34

Q

Symptoms of iron toxicity

Answer

A

Nausea Epigastric pain Abdominal cramps Constipation Diarrhoea
Black stools

Question 35

Q

Symptoms of iron overdose?

Answer

A

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

Question 36

Q

What is desferrioxamine?

Answer

A

Used for iron poisoning

Avidly binds to iron
Competes for iron binding with haemosiderin and ferritin

Iron-chelator complex is excreted in urine

Question 37

Q

Side effects of desferroxamine?

Answer

A

Flushing
Gastrointestinal symptoms
ARDS

Question 38

Q

Toxic dose of tricyclic antidepressants?

Question 39

Q

Toxic side effects of tricyclic antidepressants?

Answer

A

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.

Respiratory depression and apnoea.
Metabolic acidosis

Question 40

Q

Toxicity of salycilates?

Answer

A

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

Question 41

Q

Norml anion gap?

Answer

A

12-16meq/L

Na+ + K+) - (HCO3- + Cl-

Question 42

Q

What causes an increased anion gap metabolic acidosis?

Answer

A

Methanol
Ethylene glycol 
Lactic acid 
Cyanide 
Carbon monoxide 
Salicylates 
Metformin

Question 43

Q

What is the osmolar gap and what are some causes of increased osmolar gap?

Answer

A

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)

Question 44

Q

What is the calculated osmolality?

Answer

A

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

Question 45

Q

Causes of increased anion gap metabolic acidosis?

Answer

A

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

Question 46

Q

Causes of normal anion gap metabolic acidosis?

Answer

A

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

Question 47

Q

Is peritoneal dialysis an option for getting rid of drugs?

Answer

A

no, not effective for most drugs

Question 48

Q

What determines whether a substance is dialisable?

Answer

A

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

Question 49

Q

What drugs is dialysis ineffective for?

Answer

A

Amphetamines, cocaine
Benzodiazepines 
Phenothiazines 
Digoxin 
Opioids 
Quinidine 
Tricyclics

Question 50

Q

What drugs is dialysis effective for?

Answer

A

Ethylene glycol
Methanol 
Salicylate 
Theophylline 
Procainamide

Question 51

Q

Features of benzo and barbiturate withdrawal?

Answer

A

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.

Question 52

Q

Mechanism of caffeine as a stimulant?

Answer

A

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

Question 53

Q

Mechanism of nicotine?

Answer

A

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

Question 54

Q

Mechanism of cocaine?

Answer

A

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.

Question 55

Q

Mechanism of amphetamine?

Answer

A

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

Question 56

Q

Mechanism and effects of LSD?

Answer

A

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.

Question 57

Q

PCP mechanism and effects?

Answer

A

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).

Question 58

Q

Effect of antimuscarinics (in drug abuse setting)?

Answer

A

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.

Question 59

Q

Pharmacological profile of marijuana?

Where does it act?

Answer

A

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

Question 60

Q

How does activated charcoal work as a decontaminant?

Answer

A

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.

Question 61

Q

What substances is activated charcoal not effective for?

Answer

A

does not bind:

Ions - lithium, potassium, cyanide
Heavy metals - iron Hydrocarbons
Acids/alkalis
Alcohols: ethanol, methanol

Question 62

Q

What is whole bowel irrigation and what substances is it useful for?

Answer

A

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

Question 63

Q

Antidote to paracetamol?

Answer

A

acetylcysteine

Question 64

Q

Antidote for anticholinesterases? (organophosphates and carbamates)?

Answer

A

pralidoxime

Answer 63

A

bicarbonate

Answer 64

A

desferrioxamine

Answer 65

A

digibind, digoxin antibodies

Answer 66

A

flumazenil

Answer 67

A

physostigmine

Answer 68

A

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 69

A

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

Antiinflammatory Analgesic Antipyretic

Answer 70

A

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
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 71

A

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

Answer 72

A

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 73

A

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 74

A

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 75

A

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 76

A

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

Answer 77

A

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 78

A

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

Answer 79

A

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

Answer 80

A

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

may impair feritlity

Answer 81

A

Mostly excreted unchanged Half life 12 hours

Answer 82

A

Indomethacin, ketoprofen and diclofenac inhibit lipoxygease and therefore reduce formation of leukotrienes

ketoprofen Half life 2 hours

Answer 83

A

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

Answer 84

A

Potent prostaglandin inhibitor 28 times more potent than aspirin

PR more rapid
T 1/2 4 hours

Answer 85

A

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 86

A

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 87

A

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

Answer 88

A

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 89

A

Alcohol and enzyme inducers :increased risk of toxicity

Answer 90

A

Orally active

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

Answer 91

A

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 92

A

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 93

A

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 94

A

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 95

A

Nausea and vomiting
Allergic reactions
Tachycardia, chest pain

Contraindications: Asthma, renal and hepatic failure - administer with caution

Answer 96

A

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

Answer 97

A

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 98

A

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

Answer 99

A

Hepatic or renal disease
Cardiac disease
Gastrointestinal disease

Answer 100

A

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 101

A

Rapidly absorbed

Bioavailability 25- 50%

Answer 102

A

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

Answer 103

A

Activated charcoal

Supportive measures

Answer 104

A

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 105

A

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

Answer 106

A

80% absorbed not bound to plasma proteins

Metabolised by xanthine oxidase which it also inhibits
Half life 1-2 hours

Answer 107

A

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

Answer 108

A

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

Answer 109

A

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

Answer 110

A

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 111

A

Acetylcholine transported from cytoplasm to storage vesicle by proton antiporter.

Vesamicol blocks antiporter.

Answer 112

A

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 113

A

Acetylcholine degraded by acetylcholinesterase into acetate and choline.

Answer 114

A

Most post-ganglionic sympathetic

Answer 115

A

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 116

A

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

Answer 117

A

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 118

A

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 119

A

CNS, sympathetic postganglionic, some pre-synaptic

Answer 120

A

IP3, DAG, increased calcium

Answer 121

A

heart, smooth muscle, endothelium, some pre- synaptic

Answer 122

A

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

Answer 123

A

Exocrine glands, vessels, eye, lungs, GIT, bladder

IP3, DAG, increased calcium

Answer 124

A

Postganglionic neurons, some pre-synaptic cholinergic terminals

Open sodium and potassium channels, depolarisation

Answer 125

A

Skeletal muscle endplates

Open sodium and potassium channels, depolarisation

Answer 126

A

mostly smooth muscle IP3, DAG, increased calcium

Answer 127

A

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

Answer 128

A

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

Answer 129

A

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

Answer 130

A

lipocytes stimulation of adenylyl cyclase, increased cAMP

Answer 131

A

B1, B2 (acellerate)

M2 (decellerate)

Answer 132

A

B1, A1, B2 (increase)

M2 (decrease)

Answer 133

A

relax a2, b2
contracts M3

sphincters contract a1, relax m3

Answer 134

A

B2, A
B2, A
B3
A2

Answer 135

A

relax: b2
contract: A, M3

Answer 136

A

1) A1

2) A, M

Answer 137

A

Choline esters: Acetylcholine (both), Methacholine (muscarinic), Carbachol (both), Bethanecol (muscarinic)

Alkaloids: Pilocarpine (muscarinic), Nicotine (nicotinic), Lobeline (nicotinic), Muscarine (muscarinic).

Answer 138

A

Glaucoma: pilocarpine, methacholine, carbachol.
Paralytic ileus: bethanechol
Urinary retention: bethanechol
Antimuscarinic drug intoxication.

Answer 139

A

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 140

A

Choline esters: Hydrolysed in GIT (acetylcholine more than others, carbachol and methacholine negligible)

Alkaloids: Renally excreted, increased by acidification of the urine.

Answer 141

A

catecholamine and non-catecholamine

Catecholamines:
Adrenaline, Noradrenaline, Isoprenaline, Dopamine Dobutamine

Non-catecholamines:
Ephedrine
Phenylephrine, Amphetamine

Indirect acting sympathomimetics:
Cocaine
Tyramine

Answer 142

A

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

Answer 143

A

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

Answer 144

A

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

Answer 145

A

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

Answer 146

A

agonist: isoprenaline
antagonist: propranolol

Answer 147

A

D1=D2»B»A

Answer 148

A

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:

Receptor sequestration -rapid and transient event decrease in receptor availability.
Down-regulation -reduced receptors due to reduced synthesis.
Receptor phosphorylation - resulting in impaired binding

Answer 149

A

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 150

A

Adrenaline, Noradrenaline, Isoprenaline, Dopamine, Dobutamine.

Answer 151

A

Ephedrine, Phenylephrine, Amphetamine.

Answer 152

A

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 153

A

Relatively pure alpha agonist with limited beta action

Answer 154

A

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

Answer 155

A

Causes release of stored catecholamines

Answer 156

A

Methyldopa - centrally acting A2 agonist.
Clonidine - centrally acting A2 agonist).

causes centrally mediated reduction in TPR (clonidine also causes bradycardia)

Answer 157

A

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 158

A

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 159

A

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

Answer 160

A

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 161

A

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 162

A

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 163

A

Cocaine

Inhibition of noradrenaline reuptake at noradrenergic synapses

Widely distributed and readily enters CNS, short duration of action

Answer 164

A

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

Answer 165

A

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)
Phenoxybenzamine: A1 selective antagonist. (also blocks Ach, H1, 5HT). Blockade of catecholamine induced vasoconstriction.
Prazosin: Potent A1 antagonist. Decreased total peripheral resistance due to relaxation of arterial and venous smooth muscle mediated by alpha 1 blockade.

Answer 166

A

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 167

A

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 168

A

Extensively metabolised by liver

50% bioavailability. Half-life 3 hours.

Answer 169

A

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

Answer 170

A

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

Answer 171

A

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 172

A

Sedation, sleep disturbance, depression, psychotic episodes.

Answer 173

A

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

Answer 174

A

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 175

A

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

Answer 176

A

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

Answer 177

A

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 178

A

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 179

A

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 180

A

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

Answer 181

A

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 182

A

Absorption Orally active. Occasional IV use occasional.
Distribution Active transport into brain
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 183

A

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

Answer 184

A

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

Answer 185

A

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

Answer 186

A

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

Answer 187

A

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 188

A

Well absorbed orally Increased urinary pH within 30 minutes

Answer 189

A

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
Acute pulmonary oedema Hypertension Hyperkalaemia Hypercalcaemia
Dose 20-80mg PO/IV

Answer 190

A

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 191

A

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 192

A

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 193

A

Toxicity: Hypokalaemic metabolic alkalosis Hyperuricaemia
Hyperlipidaemia
Hyponatraemia
Allergic reaction

Answer 194

A

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

Answer 195

A

Spironolactone: Competitive antagonism of aldosterone at mineralocoticoid receptors

Triamterene, amiloride: Direct inhibition of sodium reabsorption in the CD

Decreased sodium reabsorption Decreased potassium excretion
Most useful when there is a mineralocorticoid excess such as Conn syndrome or secondary aldosteronism due to congestive heart failure

Answer 196

A

Toxicity: Hyperkalaemia Hyperchloraemic metabolic acidosis Gynaecomastia

Interactions: Triamterene and indomethacin have caused acute renal failure

Answer 197

A

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

Answer 198

A

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 199

A

Extracellular volume expansion -may exacerbate pulmonary oedema of CCF
Dehydration

Answer 200

A

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

Answer 201

A

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 202

A

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

Answer 203

A

Direct acting vasodilator.
Acts by activation of guanylyl cyclase resulting in increased cGMP which relaxes smooth muscle.
No effect on other smooth muscle
Arterial and venous dilator (more active on veins)
Lowers peripheral vascular resistance and venous return to cause decreased blood pressure
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 204

A

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 205

A

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 206

A

Direct acting vasodilator Mechanism unclear
May act by opening potassium channels in smooth muscle membrane.
May have a calcium antagonist action
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.
Hypertensive emergencies.
Intractable hypoglycaemia
Dose 5mg/kg

Answer 207

A

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

Answer 208

A

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

Answer 209

A

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.
Severe hypertension refractory to other antihypertensives
Dose 5-40mg/day

Answer 210

A

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

Answer 211

A

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

Answer 212

A

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.
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.
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 213

A

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 214

A

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 215

A

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.
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.

Stable and unstable angina. LVF. Hypertension.
Dose SL 300mcg TD 5-10mg/24hrs IV 10-400mcg/min

Answer 216

A

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 217

A

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 218

A

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
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 219

A

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 220

A

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 221

A

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

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.
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 222

A

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 223

A

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 224

A

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 225

A

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 226

A

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

Answer 227

A

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 228

A

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)
Increased QRS and QT intervals
Atrial flutter/fibrillation. Ventricular tachycardia

Answer 229

A

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 230

A

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

Answer 231

A

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.
Action potential and refractory period are lengthened
Increased QRS and QT intervals
Atrial flutter/fibrillation. Ventricular tachycardia

Answer 232

A

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 233

A

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 234

A

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.
Action potential and refractory period are shortened
Ventricular tachycardia and fibrillation after defibrillation.
Local anaesthetic.

Answer 235

A

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 236

A

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)

Metabolised in liver and plasma.
Clearance dependent on hepatic blood flow
Excreted in urine.
Half life 1.5 hours

Answer 237

A

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 238

A

Safe drug with few side effects.

Pro arrhythmogenic

Answer 239

A

Well absorbed orally.

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

Answer 240

A

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.

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.
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 241

A

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 242

A

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 243

A

class II and III
Non-selective beta blocker
Lengthens the action potential and causes increased refractory period

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 244

A

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 245

A

Well absorbed orally

Largely excreted unchanged by kidney therefore dosage adjustment is required in renal impairment

Answer 246

A

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 247

A

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 248

A

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 249

A

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 250

A

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 251

A

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
Largely unknown Probable metabolism by the liver

Answer 252

A

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 253

A

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 254

A

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.
Half life in plasma is 36 hours.
Metabolised in the liver and conjugated to glucuronide. Metabolites excreted in urine and faeces.

Answer 255

A

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 256

A

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 257

A

Intravenous administration, remains intravascular

Half life 23 minutes

Answer 258

A

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 259

A

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 260

A

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

Answer 261

A

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 262

A

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 263

A

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 264

A

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 265

A

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

Answer 266

A

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 267

A

Bleeding Thrombocytopenia Multiple minor toxicities

Answer 268

A

Intravenous bolus dose or infusion

Answer 269

A

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 270

A

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

Answer 271

A

Orally active
Widely distributed

Metabolised in the liver Excreted in bile

Answer 272

A

Inhibits binding of ADP to GpIIb/IIIa and therefore inhibits platelet aggregation

Antithrombotic
Dose 75mg daily

Answer 273

A

Toxicity Bleeding

Interactions Aspirin, heparin -additive effect

Answer 274

A

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

Answer 275

A

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 276

A

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 277

A

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 278

A

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 279

A

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 280

A

Hypoglycaemia Insulin allergy and resistance Lipodystrophy
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.
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 281

A

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 282

A

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 283

A

Well absorbed orally

Half life 5 hours Metabolised by liver and excreted in urine

Answer 284

A

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

Answer 285

A

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 286

A

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

Answer 287

A

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 288

A

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 289

A

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

Answer 290

A

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

Answer 291

A

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 292

A

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

Answer 293

A

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

Answer 294

A

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

Answer 295

A

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 296

A

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

Answer 297

A

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 298

A

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 299

A

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 300

A

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 301

A

Minor toxicities: Diarrhoea, dizziness, headache, rash.

GIT
May mask gastric malignancy Reversible cholestasis and hepatitis

CNS
acute confusion (cimetidine&raquo_space; ranitidine)
Antiandrogen effects Gynecomastia, galactorrhoea. (cimetidine only)

Marrow
Blood dyscrasias (cimetidine&raquo_space; 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&raquo_space; ranitidine)
Histamine antagonists reduce the absorption of ketoconazole
Inhibition of renal clearance of drugs (cimetidine&raquo_space; ranitidine)

Contraindications: Porphyria

Answer 302

A

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

Answer 303

A

?Reversible inhibition of parietal cell proton pump

Answer 304

A

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 305

A

Well absorbed orally Highly protein bound

Metabolised by liver and excreted in urine

Answer 306

A

Somatostain analogue

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

Answer 307

A

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 308

A

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 309

A

Orally active.

Metabolised by liver and excreted in faeces and urine.

Answer 310

A

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 311

A

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 312

A

Orally active

Metabolised in liver and excreted in urine

Answer 313

A

5HT3 antagoni

Answer 314

A

Dizziness Muscle pain Chest pain Seizures

Contraindications: IHD
Severe hepatic impairment

Answer 315

A

Orally active Protein bound

Metabolised by liver

Answer 316

A

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 317

A

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

Answer 318

A

Orally active. Widely distributed. Readily enter the CNS

Extensively metabolised by liver and excreted in urine.

Answer 319

A

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 320

A

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 321

A

Widely distributed except CNS

Extensively metabolised by liver and excreted in urine.

Answer 322

A

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 323

A

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 324

A

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 325

A

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 326

A

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 327

A

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 328

A

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 329

A

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

Answer 330

A

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 331

A

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 332

A

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 333

A

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

Answer 334

A

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 335

A

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 336

A

Cross allergy between penicillins and cephalosporins is 5-10% - withhold in anaphylaxis only

Local irritation. Cefaclor associated with serum-sickness like reaction
Superinfection.

Answer 337

A

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

Answer 338

A

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 339

A

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

Answer 340

A

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 341

A

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 342

A

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

Answer 343

A

Inactivated by dehydropeptidases in renal tubules therefore administered with cilastatin

Answer 344

A

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 345

A

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

Answer 346

A

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 347

A

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 348

A

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

Answer 349

A

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

Answer 350

A

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 351

A

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

Decreased permeability
Production of chloramphenicol acetyltransferase that inactivates the drug

Answer 352

A

Well absorbed orally
Widely distributed
Good tissue penetration

Metabolised by liver and excreted by kidney
Dose adjustment required in hepatic failure

Answer 353

A

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 354

A

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 355

A

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 356

A

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 357

A

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 358

A

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 359

A

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 360

A

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 361

A

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 362

A

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 363

A

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 364

A

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 365

A

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 366

A

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 367

A

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 368

A

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 369

A

Toxicity Nausea, vomiting, diarrhoea

GIT
Sulfonamides may precipitate in urine and may cause obstruction

Marrow
Megaloblastic anaemia

Contraindications: Porphyria

Answer 370

A

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 371

A

Heterogeneous mixture of sulphated muco-polysacc- harides.

Enoxaparin Low molecular weight heparin

Answer 372

A

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 373

A

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 374

A

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 375

A

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 376

A

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 377

A

Well absorbed orally Also given rectally and intravenously

Metabolised by liver
Half life 7 hours
May accumulate in hepatic dysfunction

Answer 378

A

Antiherpes agent
Selectively activated by phosphorylation in infected cells only.
Acyclovir triphosphate inhibits vial DNA synthesis

Active against HSV1 and HSV2 Varicella zoster

Answer 379

A

Nausea, vomiting Headache

Rapid intravenous administration may be associated with renal insufficiency and neurological toxicity

Answer 380

A

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 381

A

Uncommon point mutation in the quinolone-binding region.

Answer 382

A

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

Answer 383

A

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

Answer 384

A

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