pharmacology Flashcards

Question

what is the difference between agonist and antagonists?

Answer 1

both bind to receptors, but only agonists bind and activate receptors

Answer 2

affinity efficacy

Answer 3

strength of binding of drug to receptor, the strength of each drug-receptor complex therefore affinity is strongly linked to receptor occupancy

Answer 4

each individual drug receptor interaction is transient, with many interactions only lasting milliseconds - at any given moment a particular drug molecule might be bound to a receptor, or it may have unbound and may currently be free with the potential to bind another receptor therefore if two drugs were added to the tissue (i.e. same number of receptors available), the drug with the higher affinity will form stronger drug receptor complexes thus at any given moment, it is more likely that more of this drug will be bound to receptors

Answer 5

ability of an individual drug molecule to produce an effect once bound to a receptor

Answer 6

antagonists partial agonists full agonists

Answer 7

drug has affinity for the receptor but no efficacy effectively 'blocking' a receptor when bound to it prevents an agonist from binding to the receptor and inducing activation

Answer 8

drug has affinity for the receptor and sub-maximal efficacy when bound to the receptor, it can produce a partial response, but cannot induce the maximal response from that receptor

Answer 9

drug has affinity for the receptor and maximal efficacy produces the maximal response expected from receptor when bound to it

Answer 10

concentration or dose of a drug required to produce a defined effect

Answer 11

determine the concentration or dose of a drug required to produce a 50% tissue response called EC50 (half maximal effective concentration) or ED50 (half maximal effective dose)

Answer 12

concentration that produced a 50% response is EC50 in some cases it is difficult to assess what a 50% response is (e.g. what does a 50% improvement in breathlessness look like?) therefore dose of drug that produced the desired effect in 50% or the individuals tested is used (ED50)

Answer 13

the lower the dosage required to produce a particular effect, the more potent the drug is (often compared using ED50)

Answer 14

potency is related to dose, efficacy is not highly potent drugs produce a large response at relatively low concentrations highly efficacious drugs can produce a maximal response - effect not particularly related to drug concentration

Answer 15

efficacy more important - drug should induce a maximal response potency only gives dose needed to produce a response if 2 drugs have equal efficacy, potency does not matter (maximal response with the less potent drug can be achieved by administering a slightly higher concentration)

Answer 16

absorption distribution metabolism excretion

Answer 17

passage of a drug from site of administration into plasma

Answer 18

fraction of the initial dose that gains access to the systemic circulation

Answer 19

absorption deals with the process for drug transfer into the systemic circulation bioavailability deals with the outcome of drug transfer into the systemic circulation (i.e. how much) determined by site of administration- e. g. IV administration of drug - absorption (process for drug passage): injecting dose into circulation - bioavailability: 100% (hypothetical)

Answer 20

IV oral inhalational dermal (percutaneous) intra-nasal

Answer 21

bulk flow transfer (i.e. in the bloodstream) diffusional transfer (i.e. molecule by molecule across short distances)

Answer 22

if IV is used, bulk flow transfer will deliver drug to intended site of action other routes - in order for the drug to reach the bloodstream it is first going to need to diffuse across at least one lipid membrane

Answer 23

pinocytosis diffusion across aqueous pores diffuse across lipid membranes carrier mediated transport

Answer 24

small part of cell membrane envelopes chemical molecule and forms a vesicle chemical released on other side of membrane e.g. insulin access to brain but rarely used to transport drugs

Answer 25

most pores are less than 0.5nm in diameter very few drugs are this small therefore there is little movement of drugs across this aqueous route

Answer 26

diffusion across lipid membrane down concentration gradient carrier mediated transport (transmembrane protein binds drug molecules on one side of membrane, transfers them across to the other side - can be against concentration gradient using ATP)

Answer 27

large proportion of drug molecules are given orally need to be water soluble to dissolve in the aqueous environment of GI tract and be available for absorption

Answer 28

ionisation drugs are either weak acids (e.g. aspirin) or bases (e.g. morphine) - donate/accept protons respectively when ionised unionised form of drug retains more lipid solubility - more likely to diffuse across plasma membranes

Answer 29

dissociation constant (pKa) for that drug pH in that particular part of the body

Answer 30

if drug pKa and tissue pH are equal, drug will be equally dissociated between the two forms (i.e. 50% ionised and 50% unionised) as pH decreases below pKa (more acidic tissue): unionised form starts to dominate (equilibrium shifts to the left) as pH increases above pKa (more basic tissue): ionised form starts to dominate (equilibrium shifts to the right)

Answer 31

if drug pKa and tissue pH are equal, drug will be equally dissociated between the two forms (i.e. 50% ionised and 50% unionised) as pH decreases below pKa (more acidic tissue): ionised form starts to dominate (equilibrium shifts to the right) as pH increases above pKa (more basic tissue): unionised form starts to dominate (equilibrium shifts to the left)

Answer 32

weak bases poorly absorbed from stomach due to low pH causing high drug ionisation - ions are "trapped" in the stomach weak acids can be absorbed from the stomach (low pH allows them to stay unionised) but when they become ionised due to higher physiological pH ions may become "trapped" in the blood

Answer 33

transport proteins weak bases become "trapped" in the stomach - however, when the small intestine is reached, many transport proteins will allow absorption from GI tract weak acids become "trapped" in blood - however, most tissues have transport proteins that could move the ionised drug out of the bloodstream into the tissue

Answer 34

renal tubule biliary tract blood brain barrier gastrointestinal tract

Answer 35

(overcoming ion trapping) drug access to the bloodstream (absorption from GI tract) drug access to certain tissues (absorption across blood brain barrier) excretion of drugs from the body (excretion from the kidney of the GI tract)

Answer 36

when a drug is absorbed it is then distributed to various tissues where they eventually take effect

Answer 37

regional blood flow plasma protein binding capillary permeability tissue localisation

Answer 38

different tissues receive different amounts of cardiac output therefore more drug will be distributed to those tissues that receive most blood flow distribution can change depending on circumstances: - during exercise there is more blood flow to muscles - after a large meal the stomach and intestines will receive more blood flow

Answer 39

drugs often bind to plasma proteins (e.g. albumin) when they reach systemic circulation only free drug is available to diffuse out of the blood and access tissues - bound drugs cannot leave the blood until they dissociate from the protein free drug + protein binding site ↔ drug-protein binding site

Answer 40

free drug concentration affinity for the protein binding sites plasma protein concentration

Answer 41

e. g. albumin - albumin blood concentration: 0.6mmol/l - each molecule has 2 binding sites - therefore binding capacity: 1.2mmol/l drug plasma concentration required for clinical effect is generally less than 1.2mmol/l therefore plasma proteins are never saturated with drugs

Answer 42

mostly due to particular affinity for protein binding sites for a particular drug e.g. acidic drugs bind particularly well to albumin, therefore tend to be more heavily plasma protein bound

Answer 43

continuous blood brain barrier fenestrated discontinuous

Answer 44

most capillaries in the body have the continuous structure if drugs are very lipid soluble then they can diffuse across the endothelial cell and access the tissue

Answer 45

endothelial cells aligned in single file with small gap junctions between the cells

Answer 46

continuous structure, but with tight junctions between endothelial cells

Answer 47

continuous blood brain barrier fenestrated discontinuous

Answer 48

most capillaries in the body have the continuous structure if drugs are very lipid soluble then they can diffuse across the endothelial cell and access the tissue

Answer 49

endothelial cells aligned in single file with small gap junctions between the cells

Answer 50

continuous structure, but with tight junctions between endothelial cells

Answer 51

blood brain barrier's capillary structure

Answer 52

if very small, can pass through gap junctions otherwise, via carrier proteins

Answer 53

kidney is a key tissue involved in excretion of chemicals (including many drugs) fenestrations allow for some small drugs to pass from blood to kidney tubules which will enhance excretion of these drugs

Answer 54

big gaps between capillary endothelial cells

Answer 55

fenestrations - circular windows within endothelial cells that allow for passage of small molecular weight substances (including some drugs)

Answer 56

kidney glomerulus

Answer 57

kidney is a key tissue involved in excretion of chemicals (including many drugs) fenestrations allow for some small drugs to pass from blood to kidney tubules which will enhance excretion of these drugs

Answer 58

both lipid and water soluble drugs diffuse out of the blood into the brain down a concentration gradient, establishing an equilibrium between the blood and brain however, equilibrium position is different in lipid and water soluble drugs - lipid soluble: equilibrium more heavily weighted towards retention in the brain as brain has higher fat content water soluble: equilibrium more heavily weighted towards retention in the plasma as blood has the higher water content therefore a larger proportion of the lipid soluble drug will be 'localised' in the brain as compared with the water soluble drug

Answer 59

oxidation (produces electrophiles) reduction (produces nucleophiles) hydrolysis (produces nucleophiles)

Answer 60

(most common mechanism) all oxidation reactions start with a hydroxylation step using the cytochrome P450 system to incorporate oxygen into non-activated hydrocarbons

Answer 61

mostly cytochrome P450

Answer 62

phase 1 – introduce a reactive group to the drug phase 2 – add a conjugate to the reactive group

Answer 63

oxidation reduction hydrolysis

Answer 64

(most common mechanism) all oxidation reactions start with a hydroxylation step using the cytochrome P450 system to incorporate oxygen into non-activated hydrocarbons

Answer 65

incorporation of certain functional groups (-OH, -COOH, -SH, NH2) or unmasking existing groups in the parent drug produces metabolites with functional groups that serve as a point of attack for conjugating systems of phase 2

Answer 66

phase 1 of drug metabolism often produces pharmacologically active metabolites sometimes the parent drug has no activity of its own - will only produce an effect once it has been metabolized to the respective metabolite (i.e. pro-drugs)

Answer 67

transferases transfer the substituent group onto the phase 1 metabolite

Answer 68

attachment of a substituent group to functional groups produces metabolites that are more water soluble and are usually inactive to facilitate excretion in the urine or bile

Answer 69

for electrophiles: - glutathione conjugation for nucleophiles: - glucoronidation - acetylation - sulfation

Answer 70

orally administered drugs are mostly absorbed from the small intestine and enter the hepatic portal blood supply - therefore pass through the liver before reaching systemic circulation drug is heavily metabolised so not much active drug will reach systemic circulation

Answer 71

glomerular filtration active tubular secretion (or reabsorption) passive diffusion across tubular epithelium

Answer 72

extent of first pass metabolism varies amongst individuals, therefore the amount of drug reaching the systemic circulation also varies therefore drug effects and side effects are difficult to predict

Answer 73

via kidney (in urine) via liver (in bile)

Answer 74

via lungs in breast milk

Answer 75

glomerular filtration active tubular secretion (or reabsorption) passive diffusion across tubular epithelium

Answer 76

extent to which drug use each of the 3 major routes for drug excretion in the kidney varies between drugs also impacted by the rate of metabolism

Answer 77

urine pH varies from 4.5 to 8 acidic drugs are better reabsorbed at lower pH basic drugs are better reabsorbed at higher pH

Answer 78

only 20% of renal plasma is filtered at the glomerulus, the rest passes onto the blood supply to proximal tubule - more drug delivered to proximal tubule than glomerulus

Answer 79

depends on transporters 2 active transport carrier systems within the proximal tubule capillary endothelial cells (one for acidic drugs, one for basic drugs) both systems can transport drugs against a concentration gradient

Answer 80

phase 2 metabolites tend to be more water soluble than the parent drug therefore less well reabsorbed

Answer 81

urine pH varies from 4.5 to 8 acidic drugs are better reabsorbed at lower pH basic drugs are better reabsorbed at higher pH

Answer 82

leads to reabsorption from kidney tubule as glomerular filtrate moves through the kidney most of the water filtered is reabsorbed if drugs are more lipid soluble they will also be reabsorbed, diffusing across the tubule back into the blood

Answer 83

hepatocytes transport some drugs from plasma to bile - mostly via transporters (similar to those in the kidney) very effective at removing phase 2 glucuronide metabolites drugs transported to bile are excreted into intestines, eliminated in faeces

Answer 84

glucuronide metabolite is transported into bile metabolite is excreted into the small intestine and is hydrolysed by gut bacteria - releases glucuronide conjugate loss of glucuronide conjugate increases molecule's lipid solubility increased lipid solubility allows greater reabsorption from small intestine back into the hepatic portal blood system for return to liver molecule returns to the liver - a proportion will be re-metabolised, but a proportion may escape into the systemic circulation to continue to have effects on the body

Answer 85

primary effect: metformin activates AMPK in hepatocyte mitochondria inhibits ATP production blocks gluconeogenesis and subsequent glucose output secondary effect: blocks adenylate cyclase which promotes fat oxidation both help to restore insulin sensitivity

Answer 86

5′-AMP-activated protein kinase (AMPK) (enzyme)

Answer 87

hepatocyte mitochondria

Answer 88

GI side effects (20-30% of patients) - abdominal pain - decreased appetite - diarrhoea - vomiting particularly evident when very high doses are given - slow increase in dose may improve tolerability high doses may produce high lactic acid levels (low risk) low blood glucose

Answer 89

highly polar structure, requires organic cation transporter-1 (OCT-1) to access tissues

Answer 90

in the presence of endogenous insulin i.e. with some residual functioning pancreatic islet cells

Answer 91

sitagliptin

Answer 92

primary effect: inhibiting DPP-4 action (enzyme is present in vascular endothelium and can metabolise incretins in plasma)

Answer 93

secreted by enteroendocrine cells help stimulate the production of insulin when it is needed (e.g. after eating) reduce the production of glucagon by the liver when it is not needed (e.g. during digestion) slow down digestion and decrease appetite

Answer 94

DPP-4 (enzyme)

Answer 95

vascular endothelium

Answer 96

upper respiratory tract infections (5% of patients) flu-like symptoms (e.g. headache, runny nose, sore throat) serious allergic reactions (skin rash, increased upper respiratory tract infections)/ avoid in patients with pancreatitis (less common)

Answer 97

do not cause weight gain

Answer 98

some residual pancreatic beta-cell activity | since they act mainly by augmenting insulin secretion

Answer 99

gliclazide

Answer 100

inhibit ATP-sensitive potassium (KATP) channel on the pancreatic beta cell (controls beta cell membrane potential) inhibition causes depolarisation depolarisation stimulates Ca2+ influx and subsequent insulin vesicle exocytosis

Answer 101

ATP-sensitive potassium channel (ion channel)

Answer 102

pancreatic beta cell

Answer 103

weight gain (likely) hypoglycaemia (2nd most common)

Answer 104

some residual pancreatic beta-cell activity | since they act mainly by augmenting insulin secretion

Answer 105

concurrent administration with metformin

Answer 106

when concomitant glucose-lowering drugs are prescribed

Answer 107

dapaglifozin

Answer 108

reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule reduces glucose reabsorption, increases urinary glucose excretion

Answer 109

SGLT2 (transport protein)

Answer 110

proximal convoluted tubule

Answer 111

uro-genital infections due to increased glucose load (5% of patients) slight decrease in bone formation can worsen diabetic ketoacidosis (stop immediately)

Answer 112

weight loss reduction in BP

Answer 113

depends on normal renal function less effective in patients with renal impairment

Answer 114

metformin DPP-4 inhibitors SGLT2 inhibitors sulphonylureas

Answer 115

lamotrigine sodium valproate diazepam levetirecetam

Answer 116

blocks voltage gated Na+ channels, preventing Na+ influx prevents depolarisation of glutamatergic neurones and reduces glutamate excitotoxicity

Answer 117

voltage gated Na+ channels

Answer 118

rash drowsiness

Answer 119

Steven-Johnson's syndrome suicidal thoughts

Answer 120

lamotrigine introduced gradually - important in reducing frequency and severity of allergic skin reactions

Answer 121

inhibits GABA transaminase (prevents GABA breakdown) directly increases GABA concentrations pre-synaptically in the synapse indirectly prolongs GABA in the synapse (extraneuronal metabolism of GABA is slowed, slows GABA removal from synapse) increased GABA availability

Answer 122

GABA transaminase (inhibitory presynaptic terminal)

Answer 123

stomach pain diarrhoea drowsiness weight gain hair loss

Answer 124

hepatotoxicity teratogenicity pancreatitis

Answer 125

broad CYP (cytochrome P450) enzyme inhibitor increases serum concentration of many co-administered drugs

Answer 126

increases Cl- influx in response to GABA binding at GABA A receptor increased Cl- influx associated with hyperpolarisation of excitatory neurones

Answer 127

benzodiazepine site on the GABA A receptor

Answer 128

drowsiness respiratory depression (if IV or at high dose)

Answer 129

haemolytic anaemia jaundice

Answer 130

development of tolerance

Answer 131

addiction prone individuals more likely to become dependent on diazepam

Answer 132

inhibition of synaptic vesicle protein SV2A in excitatory presynaptic terminal, prevents vesicle exocytosis reduction in glutamate secretion reduces glutamate excitotoxicity

Answer 133

metabolism of levetiracetam has no effect on cytochrome P450 enzyme system

Answer 134

sertraline citalopram fluoxetine venlafaxine mirtazapine

Answer 135

serotonin reuptake inhibition causes accumulation | serotonin in CNS aids regulation of mood, personality, and wakefulness

Answer 136

serotonin transporter

Answer 137

GI effects (nausea, diarrhoea) sexual dysfunction anxiety insomnia

Answer 138

partial inhibition

Answer 139

mild inhibition

Answer 140

gradually decreased

Answer 141

serotonin reuptake inhibition causes accumulation | serotonin in CNS aids regulation of mood, personality, and wakefulness

Answer 142

serotonin transporter

Answer 143

GI effects (nausea, diarrhoea) sexual dysfunction anxiety insomnia

Answer 144

mild antagonism

Answer 145

gradually decreased

Answer 146

serotonin reuptake inhibition causes accumulation | serotonin in CNS aids regulation of mood, personality, and wakefulness

Answer 147

serotonin transporter

Answer 148

GI effects (nausea, diarrhoea) sexual dysfunction anxiety insomnia

Answer 149

mild antagonism of 5HT2A and 5HT2C receptors

Answer 150

complete inhibition of CYP2D6 significant inhibition of CYP2C19

Answer 151

caution with warfarin

Answer 152

potent inhibitor of serotonin reuptake than norepinephrine reuptake (noradrenaline in CNS implicated in emotional regulation and cognition)

Answer 153

serotonin transporter noradrenaline transporter

Answer 154

GI effects (nausea, diarrhoea) sexual dysfunction anxiety insomnia (at higher doses) hypertension

Answer 155

gradually decreased

Answer 156

antagonises central presynaptic alpha-2-adrenergic receptors - causes increased serotonin and norepinephrine release antagonises central 5HT2 receptors - leaves 5HT1 receptors unopposed, causing anti-depressant effects

Answer 157

alpha-2 receptor 5-HT2 receptor (high affinity for H1 receptor causes sedation, low affinity for 5-HT3 receptor has anti-emetic effect)

Answer 158

weight gain sedation (low probability of sexual dysfunction)

Answer 159

causes exacerbation, suppresses REM sleep beneficial impact on sleep continuity and duration (sedation due to histamine H1 receptor blocking)

Answer 160

angiotensin converting enzyme (ACE) inhibitors calcium channel blockers thiazide or thiazide-like diuretics angiotensin receptor blockers

Answer 161

ramipril (pro-drug) lisinopril perindopril

Answer 162

inhibit angiotensin converting enzyme prevent conversion of angiotensin I to angiotensin II

Answer 163

angiotensin converting enzyme (ACE)

Answer 164

cough hypotension hyperkalaemia (care with K+ supplements or K+-sparing diuretics) foetal injury (avoid in pregnant women) renal failure (in patients with renal artery stenosis) urticaria/angioedema

Answer 165

eGFR serum potassium

Answer 166

pro-drugs | require hepatic activation to generate active metabolites required for therapeutic effects

Answer 167

amlodipine felodipine

Answer 168

block L-type calcium channels (predominantly on vascular smooth muscle) causes decreased in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation (i.e. muscular contraction) resultant vasodilation reduces peripheral resistance reduced cardiac contraction and cardiac output

Answer 169

L-type calcium channel

Answer 170

ankle oedema constipation palpitations flushing/headaches

Answer 171

dihydropyridine type

Answer 172

bendro-flumethiazide (thiazide) indapamide (thiazide-like diuretic)

Answer 173

block Na+, Cl- co-transporter in early apical DCT Na+ and Cl- reabsorption is inhibited osmolarity of tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct (decreased blood volume, decreased venous return, decreased cardiac output)

Answer 174

sodium/chloride cotransporter

Answer 175

hypokalaemia hyponatremia metabolic alkalosis (increased hydrogen ion excretion) hypercalcemia hyperglycaemia (hyperpolarised pancreatic beta cells) hyperuricemia

Answer 176

lose diuretic effects within 1-2 weeks of treatment

Answer 177

vasodilating properties (more pronounced for thiazide-like diuretics)

Answer 178

losartan irbesartan candesartan

Answer 179

these agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)

Answer 180

angiotensin receptor

Answer 181

hypotension hyperkalaemia (care with K+ supplements or K+-sparing diuretics) foetal injury (avoid in pregnant women) renal failure (in patients with renal artery stenosis)

Answer 182

angiotensin receptor blockers are not as effective anti-hypertensive agents as ACE inhibitors ACE inhibitors are cheaper

Answer 183

pro-drugs | require hepatic activation to generate active metabolites required for therapeutic effects

Answer 184

salbutamol fluticasone mometasone budesonide montelukast

Answer 185

β2 receptor agonist on airway smooth muscle cells activation reduces Ca2+ entry - prevents smooth muscle contraction, prevents constriction (adrenaline binds to β2 adrenergic receptor to cause bronchodilation)

Answer 186

beta 2 (β2) adrenergic receptor

Answer 187

palpitations/agitation tachycardia/arrhythmias hypokalaemia (at higher doses)

Answer 188

short acting beta agonist (SABA)

Answer 189

2.5 - 5 hrs

Answer 190

beta 2 selectivity is not absolute beta 1 is also activated (causing cardiac side effects)

Answer 191

via effects on sodium/potassium ATPase

Answer 192

co-administration with corticosteroids

Answer 193

(multiple actions on many different cell types) directly decreases number of inflammatory cells (eosinophils, monocytes, mast cells, macrophages, dendritic cells etc.) and number of cytokines they produce affects IL-5 to prevent growth, differentiation, and activation of eosinophils

Answer 194

glucocorticoid receptor

Answer 195

sore throat hoarse voice opportunistic oral infections

Answer 196

growth retardation in children hyperglycaemia decreased bone mineral density immunosuppression effects on mood (etc.)

Answer 197

greater affinity

Answer 198

oral bioavailability <1%

Answer 199

(multiple actions on many different cell types) directly decreases number of inflammatory cells (eosinophils, monocytes, mast cells, macrophages, dendritic cells etc.) and number of cytokines they produce

Answer 200

sore throat hoarse voice opportunistic oral infections

Answer 201

growth retardation in children hyperglycaemia decreased bone mineral density immunosuppression effects on mood (etc.)

Answer 202

greater affinity

Answer 203

oral bioavailability <1%

Answer 204

(multiple actions on many different cell types) directly decreases number of inflammatory cells (eosinophils, monocytes, mast cells, macrophages, dendritic cells etc.) and number of cytokines they produce

Answer 205

glucocorticoid receptor

Answer 206

glucocorticoid receptor

Answer 207

sore throat hoarse voice opportunistic oral infections

Answer 208

growth retardation in children hyperglycaemia decreased bone mineral density immunosuppression effects on mood (etc.)

Answer 209

less potent

Answer 210

oral bioavailability >10%

Answer 211

antagonises CysLT1 leukotriene receptor on eosinophils, mast cells and airway smooth muscle cells decreases eosinophil migration, bronchoconstriction, inflammation induced oedema

Answer 212

CysLT1 leukotriene receptor

Answer 213

diarrhoea fever headaches nausea or vomiting

Answer 214

mood changes anaphylaxis

Answer 215

at least 2 hours before initiating exercise

Answer 216

NSAIDS PPIs histamine (H2) receptor antagonists paracetamol (aka acetaminophen)

Answer 217

ibuprofen naproxen diclofenac

Answer 218

inhibit cyclo-oxygenase enzyme (COX) - rate limiting step for production of all prostanoids (prostaglandins, thromboxanes) from parent arachidonic acid prostanoids act through many prostanoid receptors, produces highly complex array of actions

Answer 219

anti-inflammatory (and most analgesic and antipyretic actions) related to COX-2 inhibition unwanted effects mostly a result of COX-1 inhibition

Answer 220

cyclo-oxygenase (COX) enzyme

Answer 221

gastric irritation ulceration bleeding

Answer 222

perforation reduced creatinine clearance, possible nephritis bronchoconstriction in susceptible individuals (contraindicated in asthma) skin rashes & other allergies, dizziness, tinnitus.

Answer 223

adverse cardiovascular effects (hypertension, stroke, MI)

Answer 224

chronic renal failure

Answer 225

post-viral encephalitis (Reye’s syndrome)

Answer 226

analgesics - mild to moderate pain relief (e.g. musculoskeletal pain, headache, dysmenorrhoea) antipyretics - reduce fever anti-inflammatory drugs - chronic control of inflammatory diseases (e.g. rheumatoid arthritis, osteoarthritis) anti-aggregatory agent (aspirin only) - inhibit platelet aggregation in patients at risk of stroke or MI

Answer 227

omeprazole lansoprazole

Answer 228

irreversible inhibitors of H+/K+ ATPase in gastric parietal cells weak bases, so accumulate in acid environment of parietal cell canaliculi (concentrates and prolongs duration of action) (omeprazole plasma half-life approx. 1 h but single daily dose affects acid secretion for 2-3 days) PPIs inhibit basal and stimulated gastric acid secretion by >90%

Answer 229

H+/K+ ATPase (‘proton pump’)

Answer 230

headache diarrhoea bloating abdominal pain rashes

Answer 231

gastric cancer

Answer 232

reduced function in antiplatelet medication e.g. clopidogrel, when platelet function is monitored

Answer 233

generally given orally degrade rapidly at low pH so administered as capsules containing enteric-coated granules

Answer 234

PPIs are pro-drugs - converted into 2 reactive species at low pH react with sulphydryl groups in H+/K+ ATPase responsible for transporting H+ ions out of the parietal cells

Answer 235

ranitidine cimetidine

Answer 236

structural analogues of histamine are competitive antagonists of H2 histamine receptors inhibit stimulatory action of histamine released from enterochromaffin-like (ECL) cells on gastric parietal cells surface inhibit gastric acid secretion (histamine receptors increase acid production via cAMP dependent activation of H+/K+ ATPase - less acid production means less corrosive environment, less irritation of stomach wall due to damaged mucosal barrier)

Answer 237

histamine H2 receptors

Answer 238

diarrhoea dizziness muscle pains transient rashes

Answer 239

inhibits cytochrome P450 may retard the metabolism and potentiate the effects of a range of drugs

Answer 240

various - includes oral anticoagulants and TCAs

Answer 241

undergoes first pass metabolism

Answer 242

ranitidine plasma half-life 2-3 h - well tolerated

Answer 243

low dose over-the-counter formulations available from pharmacies for short term use without prescription

Answer 244

mechanism of action unclear (current hypothesis) both central and peripheral actions possibly involving interactions with a COX-3 isoform (inhibition of prostaglandin synthesis), cannabinoid receptors or the endogenous opioids interactions at 5HT or adenosine receptors also proposed

Answer 245

nervous tissue

Answer 246

not yet well defined - COX-3 isoform?

Answer 247

few side effects at therapeutic doses no gastric irritation but in overdose serious hepatotoxicity may occur occasional allergic skin reactions

Answer 248

little anti-inflammatory activity

Answer 249

good analgesic for mild-to-moderate pain some antipyretic activity

Answer 250

identify the patient’s problem

Answer 251

specify the therapeutic objective

Answer 252

select a drug on the basis of comparative efficacy, safety, cost and suitability

Answer 253

discuss choice of medication with patient (and carer) and make a shared decision about treatment

Answer 254

write a correct prescription

Answer 255

counsel the patient on appropriate use of the medicine

Answer 256

make appropriate arrangements for follow up

Answer 257

fasting glucose > 7 HbA1c > 48mmol/L (6.5%) - diabetes blood pressure high - hypertensive HDL < 50mg/dl LDL > 100mg/dl, triglycerides > 150mg/dl - dyslipidaemia BMI 30-34.9 - obesity overall, metabolic syndrome?

Answer 258

lose weight – reduced adiposity should help reduce insulin resistance linked to diabetes reduce blood pressure – reduce CVD risk improve lipid profile – reduce CVD risk reduce blood glucose – reduce complications (microvascular and (atherosclerotic) macrovascular) associated with prolonged elevated blood glucose

Answer 259

offer standard release metformin (500 mg per day, oral) support person to aim for 48 mmol/mol

Answer 260

consider dual therapy with: - DPP-4 inhibitors e.g. sitagliptin (100 mg per day, oral) - SGLT2 inhibitors e.g. dapaglifozin (5 mg per day, oral) - sulphonylureas e.g. gliclazide (40-80 mg per day) - pioglitazone (15-45 mg per day) support person to aim for 53 mmol/mol (7.0%)

Answer 261

consider triple therapy with: - metformin, a DPP-4i and an SU - metformin, pioglitazone and an SU - metformin, pioglitazone or an SU, and an SGLT-2i or insulin-based treatment support person to aim for 53 mmol/mol (7.0%)

Answer 262

decreases glucose production by liver increases insulin sensitivity of body tissues anorexiant effect (appetite suppression, thereby reducing caloric intake)

Answer 263

relation to absorption - shows that metformin has a mechanism to leave small intestines and access the hepatic portal vein relation to distribution - shows that metformin has a mechanism to access the liver - shows that metformin can access the kidney tubules

Answer 264

increased incidence of heart failure

Answer 265

90% of standard dose (‘unchanged’, active) of oral metformin excreted via kidney

Answer 266

no adjustment needed

Answer 267

monitor eGFR in 3-6 months

Answer 268

do not initiate metformin if already taking metformin, consider 50% dose decrease

Answer 269

contraindicated

Answer 270

patient health questionnaire 9 (PHQ 9)

Answer 271

0-4 - none/minimal 5-9 - mild 10-14 - moderate 15-19 - moderately severe 20-27 - severe

Answer 272

indicative of moderate depression | major depressive disorder includes minor, moderate and severe depression

Answer 273

alleviate depressive symptoms: - improve mood - help with sleep difficulties - improve self-esteem - improve ability to think clearly reduce the likely functional impairment the depressive symptoms have on daily life: - improve personal relationships - improve job performance

Answer 274

citalopram

Answer 275

both erythromycin and citalopram prolong QT interval - most manufacturers advise avoiding 2+ drugs that do this severe interaction

Answer 276

torsades de pointes

Answer 277

increasing age female sex disease metabolic disturbance (notably hypokalaemia)

Answer 278

as SSRI dose increases, dropouts due to adverse effects increases reduction in depression rating begins at 1.0 at 0 mg, peaks at 30 mg, returns to 1.0 by 80 mg 20-30 mg is optimal dose to manage adverse effects

Answer 279

limited receptor numbers

Answer 280

risk of drug interactions risk of serotonin syndrome withdrawal symptoms relapse

Answer 281

washout high starting doses

Answer 282

noradrenaline mediates the sympathetic nervous system effects on the heart > 150 mg per day - adrenergic effects > 300 mg per day - increased BP, increased HR

Answer 283

Q-risk = 14.9% stage 1 hypertension

Answer 284

set reasonable blood pressure reduction goals (previous case reduce below 140/90 mmHg) reduce cardiovascular risk associated with increased morbidity and mortality (modifiable risk factors = obesity and smoking) no new medication that interferes with upcoming procedures/other treatment

Answer 285

shows risk of heart attack or stroke within 10 years e.g. score of 12% - in a population of 100 all of whom have the same risk factors, 12 are likely to die of heart attack/stroke within 10 years

Answer 286

monitor at least every 5 years

Answer 287

start drug treatment if there is: target organ damage CVD renal disease diabetes 10 year CVD risk >10%

Answer 288

start drug treatment

Answer 289

clinic BP 140/90 mmHg or over

Answer 290

measure of body's ability to eliminate a drug clearance by means of various organs of elimination is additive elimination of drug may occur as a result of processes that occur in the liver, kidney, and other organs

Answer 291

length of time required for drug concentration to decrease to half of its starting dose in the body

Answer 292

time required for a drug to reach peak concentration in plasma the faster the absorption rate, the lower the time to peak plasma concentration

Answer 293

felodipine has higher plasma clearance, shorter elimination half life and shorter time to peak plasma levels therefore causes dose dependent decrease in systolic and diastolic BP along with reflex tachycardia amlodipine has slow onset and longer half life - slow onset mitigates reflex tachycardia

Answer 294

inhibits angiotensin converting enzyme (ACE) on pulmonary and renal endothelium prevents conversion of angiotensin I to angiotensin II causes vasodilation, less salt and water retention, less aldosterone secretion

Answer 295

angiotensin II causes efferent vasoconstriction (increased pressure for filtration) - helps maintain GFR when renal perfusion is low (renal artery stenosis, volume depletion, older people with congestive heart failure)

Answer 296

hyperkalaemia usually aldosterone increases Na+ reabsorption and water in distal convoluted tubule at the expense of K+ (increasing plasma volume and blood pressure) A increasing the gene expression and availability of: - Na+ ion permease enzyme - more Na+ crosses from the lumen to the inside of the renal tubular cell - Na+/K+ATPase on the peritubular side of the renal tubular cell - transfer increased cytosolic Na+ into peritubular fluid (so lower intracellular electronegativity) - citrate synthase - more activity within the mitochondria for more ATP (for Na+/K+ATPase) less aldosterone from the adrenal cortex means overall reduction Na+ and water reabsorption, allows K+ retention

Answer 297

diuretic needs to move from the blood it is transported on basolateral side, uses a transporter on apical side only then can it access the sodium chloride transporter on the apical side of distal tubule

Answer 298

increase delivery from early distal tubule

Answer 299

kidney becomes tolerant to the diuretics due to rebound activation of renin angiotensin system consequent increasing sodium reabsorption counteracts diuretic effect

Answer 300

further vasodilating action (not as well understood)

Answer 301

6-12 months

Answer 302

first presentation of asthma no allergic trigger, and most likely precipitated by the viral infection hard to objectively diagnose asthma in children < 5 years old no evidence that this is atopic at the moment, based on history

Answer 303

short term = relief - relieve symptoms of breathlessness and expiratory wheeze during the acute asthma attack long term = prevention - dampen/prevent late phase of the asthma attack - reduce the risk of further asthma attacks. - attempt to improve lung function

Answer 304

early phase - bronchospasm - immediate decrease in forced expiratory volume some recovery in between late phase - inflammation (up to 6 hours after early phase) - further decrease in forced expiratory volume

Answer 305

SABA (salbutamol)

Answer 306

inhaled has local effects oral has systemic effects (undergoes first pass metabolism etc.)

Answer 307

post ganglionic PSNS nerve releases acetylcholine binds to M2 and M3 muscarinic receptor on bronchial smooth muscle causes bronchoconstriction

Answer 308

many drug solutions can deliver combinations minimal patient co operation required can deliver to all ages concentration and dose can be modified normal breathing pattern

Answer 309

1 - exhalation 2 - lack of absorption from lungs 3 - mucociliary clearance (trapped by cilia or mucous) 4 - swallowed (down oesophagus rather than trachea) 5 - some absorbed across mucous membrane in oral cavity and pharynx

Answer 310

inhalation indicator makes it easier to coordinate breathing in and pressing your puffer increased space allows better delivery to lungs

Answer 311

asthma can be exacerbated by viral infection common viral infections (e.g. rhinovirus) release mediators that specifically activate eosinophils eosinophils can induce epithelial damage (e.g. due to release of major basic protein) increased susceptibility to viral infections (and therefore increased likelihood of asthma exacerbation)

Answer 312

first pass inactivation

Answer 313

targets CysLT1 receptor (Cysteinyl leukotriene receptor 1) located on eosinophils/mast cells/airway smooth muscle decreases smooth muscle constriction, eosinophil migration and oedema

Answer 314

NSAIDs generally work by blocking the production of prostaglandins (both leukotrienes and prostaglandins derive from arachidonic acid) if the leukotriene pathway is blocked, more prostaglandin will be formed to combat NSAID effect

Answer 315

pain from osteoarthritis that limits daily activities upper abdominal pain since starting naproxen

Answer 316

treat pain from osteoarthritis to ensure it is not interfering with daily living (or at least minimising the effect on activities) treat new stomach pain, ideally without impacting on treatment of osteoarthritis pain (these objectives are trade-offs)

Answer 317

target – COX enzymes (naproxen is non-selective i.e. inhibits COX1 & COX2) location – peripheral nociceptive nerve endings (analgesia) effect – COX produces prostaglandins that do not directly cause pain themselves, but sensitise peripheral nociceptors mediators (bradykinin and histamine) which causes pain (NSAIDs inhibit COX) indirect effect on pain – PGs mediate inflammation therefore NSAIDs will reduce inflammation

Answer 318

increased activity in descending inhibitory pathways decreased excitation of transmission neuron desensitise peripheral nociceptors

Answer 319

target – COX I enzyme location – gastric mucosal cells effect – inhibited prostaglandin production means inhibition of prostaglandin mediated protection of gastric mucosa

Answer 320

increase bicarbonate release increase mucous production increase blood flow

Answer 321

GP mistake communication failure

Answer 322

3 options: stop the gel switch to ibuprofen stop NSAIDs completely

Answer 323

stop NSAIDs where possible | offer full dose PPI therapy for 4-8 weeks e.g. omeprazole 20 mg once daily

Answer 324

NSAIDs leave stomach wall exposed to the effect of acid, which is causing pain PPIs reduce the acid production

Answer 325

treatment algorithm states that patients should be given 20mg omeprazole once a day for 4-8 weeks data suggests that most patients prescribed PPIs are treated for at least 3 months (above the recommended treatment duration of 4-8 weeks) at twice the standard treatment dose i.e. 40mg versus 20mg. nearly 50% are still on 40mg after 12 months (data does include PPI use for indigestion or dyspepsia)

Answer 326

PPIs increase fracture risk (worsens chances if patient has osteoporosis) (mechanism of action is unclear- main theory) absorption of calcium salts is pH dependent change in pH induced by PPIs causes reduction in absorption and decrease in calcium available for bone

Answer 327

generalised tonic-clonic seizures EEG shows interictal epileptiform discharge (IED) - increased risk of seizure recurrence

Answer 328

eliminate seizures or reduce their frequency to the maximum degree possible avoid the adverse effects associated with long-term treatment aid patients in maintaining or restoring their usual psychosocial and vocational activities, and in maintaining a normal lifestyle

Answer 329

must document advice to contact DVLA that they cannot drive

Answer 330

absence focal generalised tonic-clonic myoclonic

Answer 331

lose awareness of your surroundings for a short time - stare blankly into space - look like they're "daydreaming" - flutter their eyes - make slight jerking movements of their body or limbs

Answer 332

strange feeling that's hard to describe "rising" feeling in your tummy – like the sensation in your stomach when on a fairground ride a feeling that events have happened before (déjà vu) unusual smells or tastes tingling in your arms and legs an intense feeling of fear or joy stiffness or twitching in part of your body, such as an arm or hand remain awake and aware

Answer 333

up to 15 secs, will not remember

Answer 334

sometimes referred to as warnings or auras - can be a sign that another type of seizure is about to happen

Answer 335

lose sense of awareness, make random body movements, such as: - smacking your lips - rubbing your hands - making random noises - moving your arms around - picking at clothes or fiddling with objects - chewing or swallowing unresponsive to anyone, no memory of it

Answer 336

2 stages tonic stage – lose consciousness, body goes stiff, may fall to the floor clonic stage – limbs jerk about, may lose control of bladder or bowel, may bite tongue or the inside of cheek, might have difficulty breathing

Answer 337

normally stops after a few minutes, some last longer may have a headache, difficulty remembering what happened may feel tired or confused afterwards

Answer 338

some or all of your body suddenly twitches or jerks, like you've had an electric shock (often happen soon after waking up)

Answer 339

usually only a fraction of a second but many can occur in a short space of time

Answer 340

tonic - all your muscles suddenly become stiff (like the first stage of a tonic-clonic seizure), may lose balance and fall over atonic - all muscles to suddenly relax, so you may fall to the ground - tend to be very brief, usually able to get up straight away

Answer 341

sodium valproate

Answer 342

lamotrigine or carbamazepine

Answer 343

ethosuximide or sodium valproate

Answer 344

ethosuximide

Answer 345

lamotrigine or carbamazepine

Answer 346

carbamazepine or levetiracetam

Answer 347

sodium valproate

Answer 348

levetiracetam or topiramate

Answer 349

sodium valproate

Answer 350

sodium valproate (pregnancy prevention programme)

Answer 351

sodium valproate: first line in absence, tonic-clonic, tonic/atonic, myoclonic ``` can cause: - neural tube defects - decreased IQ - autism after in utero exposure ```

Answer 352

drug-drug interaction COC appears to have an impact on lamotrigine blood levels – coadministration leads to a reduced level of lamotrigine in the blood

Answer 353

reduced seizure control but no contraceptive failure

Answer 354

reduce lamotrigine absorption - less gets into the blood in the first place enhance lamotrigine metabolism - more cleared from the blood enhance lamotrigine excretion - enhance clearance from the blood

Answer 355

appears to have no effect

Answer 356

increase lamotrigine dose

Answer 357

oestrogen = "seizure promoting" increased seizure frequency during oestrogen peak COC taken over four weeks: - first three weeks: active drug - fourth week: nothing or ‘dummy’ fourth week - no COC affecting liver enzymes (usually induces UDPGA): - liver enzymes normalise - lamotrigine levels increase

Answer 358

decrease lamotrigine in fourth week

Answer 359

dizziness drowsiness diarrhoea loss of balance abnormal eye movement trouble speaking

Answer 360

midazolam others require IV access

Answer 361

may increase

Answer 362

lamotrigine dose may be reduced due to fears of harming the unborn child pregnancy may lead to changes in liver metabolism - lamotrigine levels may decrease (so increased seizure risk)

Answer 363

check serum lamotrigine at the beginning of pregnancy and during the second and third trimester dose could then be adjusted as described

Answer 364

change oral contraceptive to long-term progesterone implant (e.g. Implanon/Nexplanon) progesterone = "seizure inhibiting"

Answer 365

differences in concentrations of drug reaching the tissues (i.e. factors affecting absorption, distribution, metabolism and excretion of the drug) differences in response of the target tissues to the same degree of stimulation (i.e. factors such as variation in receptor sensitivity, number and distribution)

Answer 366

absolute differences in dose administered relative overdose or underdose

Answer 367

(deliberate or accidental) error in prescription or dispensing patient non-compliance drug formulation

Answer 368

environmental exposure to chemicals, including other drugs food intake fluid intake age disease

Answer 369

enzyme induction enzyme inhibition

Answer 370

drugs may interact chemically with components of food; this may alter their absorption (e.g. bisphosphonates chelated by Ca, Mg, Fe so not absorbed with food) foods delay gastric emptying and alter gastric pH

Answer 371

most drugs are better absorbed if taken with water e.g. may dissolve better fluids may stimulate gastric emptying

Answer 372

more body water than adults poorer renal function, with immature tubular secretion an immature blood brain barrier lower capacity for drug metabolism

Answer 373

decreased absorptive surface of small intestine altered gastric and gut motility increased rate of gastric emptying

Answer 374

reduced lean body mass and body water, relative increase in fat lipid soluble drugs have increased volume of distribution and decreased blood levels water soluble drugs have decreased volume of distribution and increased blood levels reduced plasma albumin, so fewer plasma protein binding sites

Answer 375

splanchnic and hepatic blood flow decrease by 0.3 – 1.5%/year liver size and hepatocyte number decrease hepatic enzyme activity and induction capacity decrease

Answer 376

reduced renal mass reduced renal perfusion reduced glomerular filtration rate reduced tubular excretion (steady decline is normal - situation worsened in renal disease)

Answer 377

elderly tend to be more sensitive to CNS active drugs

Answer 378

drug absorption drug distribution drug metabolism drug excretion organ sensitivity

Answer 379

general nutritional status GI disorders congestive heart failure kidney failure liver failure other acute or chronic disease states

Answer 380

unbalanced diets may lead to deficiency states and enzyme abnormalities starvation – decreased plasma protein binding and metabolism obesity – increased lipid fraction

Answer 381

e.g. achlorhydria, coeliac disease, Crohn’s disease altered drug absorption

Answer 382

reduced splanchnic blood flow intestinal mucosal oedema reduced hepatic clearance

Answer 383

decreased drug excretion leading to toxicity water overload leading to changes in drug concentrations in different body fluid compartments

Answer 384

reduced metabolism reduced first pass metabolism (hence increased bioavailability) decreased biliary secretion and hence decreased removal decreased albumin synthesis and hence reduced plasma protein binding

Answer 385

increased external bleeding (nose bleed) increased internal bleeding (bruising) warfarin metabolised by cytochrome P450 pathway Cyt P450 inhibited by clarithromycin, so increased plasma levels of warfarin

Answer 386

other antibiotics of same class (i.e. macrolides): e.g. erythromycin some antibiotics of other classes: e.g. quinolones like ciprofloxacin some systemic antifungal drugs: e.g. fluconazole proton pump inhibitors (PPIs) - for peptic ulcers: e.g. omeprazole some anti-HIV drugs, especially protease inhibitors

Answer 387

International Normalized Ratio (INR) - standardized measure of blood clotting time

Answer 388

ratio of a patient's prothrombin time (‘test’) to a control (‘normal’) sample, raised to the power of the ISI (International Sensitivity Index) value for the tissue factor used (usually 0.94 - 1.4) (test PT / normal PT) ᶦˢᶦ

Answer 389

increased bleeding (decreased clotting) bleeding risk increased

Answer 390

less bleeding (increased clotting) thrombosis risk increased

Answer 391

normal: 0.9-1.2 normal in atrial fibrillation: 2.0-3.0 (thrombosis risk increases <2.0) >4.0 serious bleeding risk increases

Answer 392

contains hypericin (inducer of cytochrome P450) (hyperforin also has this effect) increases metabolism of warfarin, decreasing its concentration and making it less effective (less anticoagulant effect)

Answer 393

fewer enzyme inducers than inhibitors but drugs that induce Cyt P450 include: rifampicin: antibiotic used in TB therapy (onset/duration of induction can depend on half-life) carbamazepine and phenytoin, as well as older and largely obsolete antiepileptic drugs phenobarbitone and primidone griseofulvin (antifungal drug)

Answer 394

serum potassium

Answer 395

digoxin binds to the Na+/K+ exchange ATPase on cardiac myocytes and nodal tissue competes with K+ for its binding site hypokalaemia means more digoxin binding (less competition by K+) - therefore, enhanced therapeutic and adverse effects of digoxin (heart ‘block’)

Answer 396

means more digoxin binding (less competition by K+) therefore, enhanced therapeutic and adverse effects of digoxin (heart ‘block’)

Answer 397

indication of possible kidney disease - possible reduced kidney function and therefore reduced digoxin clearance more digoxin in system, enhanced therapeutic and adverse effects of digoxin

Answer 398

measure plasma levels of digoxin directly – recognised target range for these

Answer 399

(pharmacokinetic) metabolism by liver of some drugs is reduced in older patients – so more temazepam (pharmacodynamic) older patients may have increased sensitivity to drugs, even if metabolism is normal (may relate to changes in receptor number or function or other)

Answer 400

metabolism of many drugs affected by malnutrition warfarin: similar to a drug which inhibits cyt pathway (e.g. clarithromycin) – therefore, more warfarin malnutrition also decreases plasma protein levels (warfarin is heavily plasma protein bound) - decreases oxidative metabolism (warfarin is metabolised by oxidation) - decreases GFR (increased likelihood of adverse drug reaction)