Pharmacology

Question 1

Causes of a reverse hysteresis loop

Answer 1

Secondary messengers
Prodrug–>Active metabolite
Redistribution phase

Question 2

amantadine

Answer 2

NMDA receptor antagonist
used in dyskinesias in PD
fatigue in MS

Question 3

rivaroxaban

Answer 3

Xa inhibitor
Cmax 4 hours; good oral bioavailability
irreversible
inhibits both extrinsic and intrinsic pathways

Question 4

what is the interaction between verapamil and digoxin

Answer 4

raised digoxin levels due to non competitive inhibition of p glycoprotein in renal tubules leading to decreased renal secretion. biliary clearance is also reduced.
also display synergism in their effects on heart rate

Question 5

which antibiotics inhibit cell wall synthesis

Answer 5

beta lactams, glycopeptides, cyclosporin

Question 6

which antibiotics inhibit protein synthesis

Answer 6

aminoglycosides, tetracyclines
chloramphenicol, clindamycin, macrolides, fusidic acid, linezolid aicd
mupirocin

Question 7

which antibiotics inhibit nucleic acid synthesis or activity

Answer 7

folic acid: trimethoprim, sulphonamides
DNA gyrase; fluoroquinolones
RNA polymerase: rifampicin
DNA: nitrofurantoin, metronidazole

Question 8

GWAS

Answer 8

looks at entire genome of a population to find SNPs a/w traits
huge likelihood of random associations - need to do bonferoni correction to control for this
hardy weinberg equilibrium aims to eliminate selection bias (alleles should be equal between all individuals)

Question 9

bioavailability

Answer 9

F = AUC oral / AUC IV

AUC o / dose o) / (AUC iv / dose iv

Question 10

hepatic extraction ratio

Answer 10

HER = 1 - bioavailability

Question 11

Volume of distribution

Answer 11

Vod = dose / concentration

Question 12

loading dose for desired concentration

Answer 12

loading dose = Vod x concentration steady state

Question 13

clearance

Answer 13

Cl = amount of body fluid cleared of substance per unit time
Cl = L / h
does not depend on concentration

Question 14

zero order kinetics

Answer 14

a set amount of drug is eliminated per unit time

slow plug away at sobering up from a big night regardless of how drunk you were

Question 15

first order kinetics

Answer 15

a set proportion of drug is eliminated per unit time
increased elimination with increased concentration

(c/w clearance which does not depend on concentration)

Question 16

albumin

Answer 16

binds acid drugs; other acids will compete for binding

eg: salicylic acid, warfarin, penicillins, sulphonamides

Question 17

alpha1 acid glycoprotein

Answer 17

binds basic drugs

eg: propranolol, quinidine, impramine, lignocaine

Question 18

dialysis

Answer 18

does not affect highly protein bound drugs

or drugs with high VoD (as they are not in the blood)

Question 19

adjusting dose for renal impairment

Answer 19

(1-fu) + (fu x % renal fx remaining)

% renal fx = CrCl/1.5

Question 20

maintenance dose

Answer 20

maintenance dose or infusion rate = clearance x steady state drug concentration

Question 21

half life

Answer 21

t1/2 = 0.7 X Vd/Cl

Question 22

VoD

Answer 22

VoD = dose / peak plasma concentration

assume peak plasma concentration occurs 1 hour post IV infusion

Question 23

how do you increase excretion of an acid drug

Answer 23

alkalinise the urine

eg: salicylate overdose

Question 24

EC50

Answer 24

concentration of drug to give half maximal response

Emax is maximal effect (obtained when all receptors are occupied by the drug)

Question 25

therapeutic index

Answer 25

TI = adverse effect EC50/ therapeutic effect EC50

Question 26

tachyphylaxis

Answer 26

need greater concentration for same effect ie: down regulation of receptors eg: cocaine

Question 27

antagonists

Answer 27

competitive: need increased concentration to achieve effect as competing for the same receptors (curve moves right) non competitive: irreversible binding to receptor so will decrease maximum effect (curve moves down)

Question 28

lithium

Answer 28

SEs: hypothyroid, hyperparathyroid, reduced renal tubular fx toxicity: acute - GI - N, V, D chronic - neurological - ataxia, tremor, confusion increased QTc toxicity worsened by hypovolaemic states as Li is treated like Na+ in the kidney Rx with IVT, very dialysable short half life

Question 29

raloxifene

Answer 29

SERM; used for osteoporosis CI if hx of DVT / PE increases stroke risk if RFxs increases hot flashes

Question 30

digoxin

Answer 30

toxicity: visual change - esp colour confusion nausea, vomiting, abdominal pain

Question 31

carbamazepine

Answer 31

Stevens Johnson Syndrome esp if HLA B1502

Question 32

cetuximab

Answer 32

EGFR inhibitor k ras wild type (does not work with k ras mutant) CRC, adeno lung, SCC head and neck

Question 33

dabigatran

Answer 33

direct thrombin inhibitor prodrug indications: DVT prophylaxis post ortho surgery DVT treatment, non valvular AF CI: pregnancy, CrCl < 30 interactions: rifampicin, verapamil, amiodarone, ketoconazole, quinidine, tacrolimus, cyclosporin, clarithromycin monitor TCT; evidece for increased MI 150mg BD increased GI bleed less ICH than warfarin prothrombinex if life threatening bleeding

Question 34

CYP2D6

Answer 34

``` poor metabolisers 10% cauc ineffective codeine (prodrug) systemic timolol toxic perhexiline cannot metabolise propranolol, quinidine avoid inhibitors (SSRIs) when on tamoxifen as tamoxifen is metabolised to active form by 2D6 substrates: tramadol ```

Question 35

CYP2C9

Answer 35

poor metabolisers 1-3% | 1mg warfarin

Question 36

CYP2C19

Answer 36

poor metabolisers 20% asians | reduced clearance omeprazole

Question 37

acetylation

Answer 37

slow: procainamide, hydralazine --> SLE | isoniazid --> peripheral neuropathy is slow; hepatitis if fast

Question 38

p glycoprotein substrates

Answer 38

``` terfenadine, fexofenadine digoxin daunorubicin, doxorubicin, etoposide, paclitaxel, vinblastine, vincristine colchicine ritonavir ciclosporin ivermectin, loperamide aldosterone, hydrocortisone, dexamethasone, progesterone ,estrogen ```

Question 39

potency

Answer 39

``` potency ED50 (point of x axis where half way) efficacy is Emax (height) ```

Question 40

erlotinib

Answer 40

TKI for lung, pancreatic CA - CYP1A1 metabolism - induced by smoking; need higher doses

Question 41

CYP3A4

Answer 41

substrates tramadol, docetaxel, etoposide, irinotecan, imatinib, vincristine, aprepitant, pred inhibitors: aprepitant, ketoconazole, ciprofloxacin, clarithromycin, ritonavir, verapamil, quinidine inducers: phenobarbitone, phenytoin, rifampicin

Question 42

avoid in pregnancy

Answer 42

``` mycophenolate - both mum and dad leflunomide - washout prior to conception methotrexate sirolimus / everolimus efavirenz ```

Question 43

renal maintenance

Answer 43

induction: cyclophosphamide maintenance: aza for ANCAs; MMF for SLE

Question 44

tamsulosin

Answer 44

1a alpha blocker