the rest of the stuff

Question 1

Explain PK-PD correlation

Answer 1

coupling between drug plasma concentration and drug effect, allows for the inference of drug action based only on plasma concentration

Question 2

bioavailability (F) formula and definition

Answer 2

(AUC(oral)/AUC(IV))*(dose(IV)/dose(oral), definition: A measure of the drug available to the systemic circulation over time after administration

Question 3

sites of first-pass metabolism

Answer 3

enterocytes and liver

Question 4

apparent volume of distribution (Vd) definition and formula

Answer 4

Vd = amount administered/Cnaught, definition: a primary pharmacokinetic parameter, the apparent volume of space into which a drug can distribute after dosing

Question 5

what happens in phase I drug metabolism?

Answer 5

drug –> derivative via addition of reactive functional group e.g. -OH

Question 6

what happens during phase II drug metabolism?

Answer 6

derivative –> conjugate, via the conjugation of some compound, e.g. glucuronic acid, to the derivative via the reactive functional group

Question 7

Example of prodrug activation

Answer 7

L-DOPA –> dopamine via DOPA decarboxylase

Question 8

Paracetamol overdose explanation

Answer 8

NAPQI is a toxic derivative of paracetamol produced by CytP450. Once GSH is depleted, NAPQI accumulates leading to toxic hepatic necrosis

Question 9

Clearance definition and formula

Answer 9

Definition: volume of blood cleared of a drug per unit time, the other primary PK parameter apart from Vd. formula = urinary [drug] * urinary volume/time /plasma[drug] OR total drug amount in plasma/area under curve

Question 10

1/2life formula. About 4-5 half lives –> total elimination of the drug

Answer 10

T1/2 = 0.693 * Vd/CL, Ke = CL/Vd

Question 11

antacids - chemical antagonists, don’t bind to a receptor to elicit an effect

Answer 11

aluminium/magnesium hydroxide

Question 12

an inhibitor of excitatory neurotransmission

Answer 12

lithium

Question 13

anti-coagulant

Answer 13

warfarin

Question 14

Osmotic diuretic used to treat increased intracranial pressure

Answer 14

mannitol

Question 15

What is affinity defined as?

Answer 15

A measure of the probability that the drug-receptor complex will form, via Kd dissociation constant = ([D][R]/[DR]). Affinity determines the drug concentration required for the formation of a therapeutically significant number of DR complexes

Question 16

How to calculate bound drug?

Answer 16

bound = Bmax * [D] / [D] + Kd

Question 17

Efficacy (alpha) and some examples

Answer 17

Efficacy is the ability of a drug to initiate downstream signalling. Agonists have efficacy of 1, antagonists have efficacy of 0, partial agonists have efficacy between 1 and 0. Inverse agonists (e.g. antihistamines) have negative efficacy because they reduce the activity of a constitutively active receptor

Question 18

Potency

Answer 18

Dose required to produce a given degree of response (EC50)

Question 19

How to calculate the effect of a drug

Answer 19

Effect = Emax * [D] / [D] + EC50

Question 20

Chemical antagonism

Answer 20

2 drugs combining in solution and the effect of the active drug is lost prior to receptor involvement

Question 21

Physiological antagonism

Answer 21

2 drugs causing opposing effects via distinct mechanisms

Question 22

Pharmacological antagonism

Answer 22

2 drugs that have the same receptor, may be competitive or non-competitive (irreversible i.e. covalent)

Question 23

A nasal decongestant, alpha1 receptor agonist –> Gaq signalling

Answer 23

phenylephrine

Question 24

Photon-activated GPCR

Answer 24

rhodopsin, functions via transducin Gat, activates cGMP-specific phosphodiesterases leading to a decrease in cGMP levels and closure of Na+/Ca2+ channels –> neuronal hyperpolarisation

Question 25

Homologous GPCR desensitisation

Answer 25

Phosphorylation of the G protein carboxy terminal by GRK –> internalisation in endosomes. When ligand levels are low, G protein may be phosphorylated and re-activated

Question 26

Heterologous GPCR desensitisation

Answer 26

Affects multiple GPCR systems, e.g. if some second messenger/enzymes that is shared becomes uncoupled. PKA/PKC-mediated

Question 27

local anaesthetic, MOA is sodium channel blocking

Answer 27

lidocaine

Question 28

these Ca2+ ion channels participate in skeletal muscle contraction

Answer 28

dihydropyridine receptor (voltage-gated) and ryanodine receptor (ligand-gated)

Question 29

L-type Ca2+ channel blocker, for use in the treatment of angina/tachyarrythmias

Answer 29

verapamil

Question 30

bind to alosteric sites on GABA receptors, potentiate the inhibitory effect of GABA, anti-anxiety/epileptic, sedative, hypnotic, anaesthetic

Answer 30

benzodiazepines. uses: anti-epileptic, anti-anxiety, sedatives

Question 31

Selective antagonist to nicotinic acetylcholine receptors

Answer 31

alpha-bungarotoxin –> paralysis

Question 32

ACE inhibitors

Answer 32

catopril, enalopril

Question 33

angiotensin receptor antagonists

Answer 33

losartan, valsartan

Question 34

renin inhibitors

Answer 34

aliskeren

Question 35

treatment for bedwetting/diabetes insipidus via vasopressin V2 receptor agonism –> anti-diuretic

Answer 35

desmopressin

Question 36

selective V2 vasopressin receptor antagonist, leads to increase in urine volume, used to treat hyponatremia

Answer 36

conivaptan

Question 37

cGMP analogue PDE5 inhibitor (original)

Answer 37

sildenafil citrate, promotes erection by maintaining high cGMP levels. Side effect = blue-tinted vision due to ocular PDE6 antagonism. Also leads to bleeding due to high cGMP inhibiting clotting in platelets

Question 38

cGMP analogue PDE5 inhibitor (long-lasting)

Answer 38

tadalafil, promotes erection by maintaining high cGMP levels

Question 39

treatment for hypertensive crisis

Answer 39

nitroprusside, raises NO levels –> vasodilation

Question 40

treatment for angina pectoris

Answer 40

nitroglycerine, raises NO levels –> vasodilation. Contraindicated by sildenafil citrate use due to potentially lethal drop in blood pressure

Question 41

PDE4 inhibitor, used in the treatment of COPD

Answer 41

roflumilast

Question 42

sustained erection in the absence of stimulation

Answer 42

priapism, indicative of clotting

Question 43

Higher pA2 value –> more potent competitive antagonist

Answer 43

formula: look at the schild plot. Antagonist concentration needed to give a dose ratio of 2. Dose ratio = EC50 in the presence of antagonist/EC50 in the absence of antagonist.