Pharmacology

Question 1

What is the difference between pharmacodynamics and pharmacokinetics?

Answer 1

-dynamics: effect of drug on the body (biological effects), -kinetics: effect of the body on the drug (ADME - absorption, desorption, metabolism, excretion)

Question 2

What is the difference between drugs and medicine?

Answer 2

Drugs are chemicals of known structure. Medicines intend to have a therapeutic effect.

Question 3

What is the difference between selectivity and specificity?

Answer 3

Selectivity means able to distinguish. Specificity is absolute selectivity.

Question 4

What is an agonist?

Answer 4

A chemical that binds to a receptor to produce a response

Question 5

What is an antagonist?

Answer 5

A chemical that binds to a receptor and blocks binding of another chemical.

Question 6

What is the equation for agonism? Give the rate constant names.

Answer 6

A + R AR AR*
Where forward reactions are K1 and B
And reverse reactions are K-1 and a

Question 7

In the agonism equilibrium, there are two steps. What are the names of these? Which rate constants increase them?

Answer 7

Affinity and efficacy. K1 and Beta respectively

Question 8

What is the equation for antagonism? How does it differ from agonism?

Answer 8

B + R BR. No efficacy, as no activation required

Question 9

What is ED50/EC50?

Answer 9

The concentration of a drug at which it is half optimal

Question 10

What is the name for two drugs which have equal EC50 values?

Answer 10

Equipotent

Question 11

Draw the concentration against effect graph for agonism and antagonism. Describe the differences in affinity and potency.

Answer 11

View notes. Potency is equal in an agonist and a non-competitive inhibitor, but affinity decreases with the antagonist. Potency is reduced in a competitive agonist, but affinity is constant. Note: LOG units.

Question 12

Describe the three main types of cell signalling.

Answer 12

Autocrine - within own cell. Paracrine - locally (ECF). Endocrine - long distance (vascular)

Question 13

What are the five main types of receptor?

Answer 13

Ligand and voltage gated, GPCRs, kinase-linked, nuclear

Question 14

Describe how internal nuclear receptors may be activated.

Answer 14

Steroids diffuse into cell, bind to response element, form dimer, enter nucleus

Question 15

Describe the chemical makeup of G protein receptors, and the G proteins themselves.

Answer 15

Receptors - 7 alpha helices, with an NH2 and COOH group. G protein - alpha, beta, gamma subunit

Question 16

How is a G-protein activated?

Answer 16

Guanine nucleotide exchange - GDP is replaced by GTP. Units dissociate, until GTP is again hydrolysed to GDP

Question 17

Describe briefly the adenylyl cyclase GPCR pathway.

Answer 17

GPCR activates adenylyl cyclase, which converts ATP to cAMP. cAMP, by PKA, causes intracellular effect

Question 18

Describe briefly the phospholipase C GPCR pathway.

Answer 18

GPCR activates PLC, converts PIP2 into IP3 and DPG. DPG phosphorylates ser/thr amino acids, causing Ca2+ release.

Question 19

Which two types of drug movement require no energy?

Answer 19

Passive/facilitate diffusion - hydrophobic vs channels

Question 20

Which two types of drug movement require energy?

Answer 20

Active transport, endocytosis

Question 21

State the Henderson-Hasselbalch equation.

Answer 21

pH = -log(10) [HA]/[A-] + pKa

Question 22

Derive the Henderson-Hasselbalch equation.

Answer 22

Key equations: pH = -log[H], pKa = -logKa, Ka = acid dissociation constant
HA H + A. Equilibrium so
Ka = [H][A] / [HA]. Rearrange for [H]
[H] = [HA]Ka / [A]. Sub for pH, separate out Ka
-log[H] = -log[HA]Ka / [A]
pH = -log[HA]/[A] - logKa. Sub in pKa
pH = -log[HA]/[A] + pKa (note change of sign)

Question 23

At which conditions does pH = pKa? Why?

Answer 23

When the acid is exactly half dissociated, as [HA][A] = 1, so -log[HA][A] = 0. Refer to Henderson Hasselbalch

Question 24

What is ion trapping?

Answer 24

Where a drug gets stuck on one side of a membrane that seperates two different compartments, each with different pH.

Question 25

Why do only weak acids and bases get ion trapped?

Answer 25

Weak acids and bases dissociate (partially) into both ionised and unionised forms

Question 26

Use Henderson-Hasselbalch to explain ion trapping.

Answer 26

Weak acids ionise at alkaline pHs and vice versa. If the pH of an environment is acidic, weak acids will remain neutral and weak bases ionised. If the pH of an environment is basic, weak acids will be ionised and weak bases neutral. In their ionic form, drugs cannot cross membranes without a channel/active transport, so are trapped.

Question 27

What are the four main body compartments?

Answer 27

Oral, plasma, adipose, bone/teeth

Question 28

What is metabolism in the liver?

Answer 28

Processing of the drug for removal and to reduce bioavailability in the blood.

Question 29

Describe phase 1 metabolism.

Answer 29

Drug is oxidised/reduced/hydrolysed to an active/toxic metabolite, which is then conjugated to be excreted.

Question 30

What is volume of distribution (Vd)?

Answer 30

The theoretical volume of drug that would be required to be taken to maintain the distribution through the body.

Question 31

Considering the volume of the body is about 41 litres, which types of drug may be more/less than this for their Vd value and why?

Answer 31

> 41 = hydrophobic, < 41 = hydrophillic. Able to diffuse more easily/not as easily

Question 32

What is the formula for Vd? How may its value be clinically determined?

Answer 32

Vd = dose/[drug]plasma. [Drug]plasma is calculated by taking a blood sample and centrifugation.

Question 33

Why does an increased Vd decrease [drug]?

Answer 33

The drug binds increasingly to plasma protein reducing availability

Question 34

Where does drug secretion principally occur?

Answer 34

The kidneys

Question 35

Describe the [drug]plasma spectrum.

Answer 35

Too low - sub-therapeutic. Middle - absorption/elimation occur simultaneously. Too high - toxic effects

Question 36

What is the formula for elimination half life?

Answer 36

t1/2 = 0.693 x Cl

Question 37

When is drug steady state reached?

Answer 37

After about 5 drug half lives

Question 38

Which factors can increase Vd (and hence increase t(1/2)?

Answer 38

Decreased muscle mass, increased fluid, obesity

Question 39

Which substance is responsible to clearance in the kidney and how can this have an effect of elimination half life?

Answer 39

CP450. Induction reduces, inhibition prolongs

Question 40

What is clearance (Cl)? How is it calculated?

Answer 40

Cl = rate of elimination / [drug]plasma. It is a flow parameter.

Question 41

What is the definition of steady state metabolism?

Answer 41

When rate of administration = rate of elimination

Question 42

Describe the voltage course of a normal nerve cell depolarisation.

Answer 42

Upstroke, overshoot, downstroke, undershoot (back to resting potential)

Question 43

In a nerve cell depolarisation, describe what causes upstroke and what causes downstroke.

Answer 43

Upstroke - Na+ channels dominating K+ channels. Downstroke - K+ channels dominating Na+ (which have been inactivated)

Question 44

Describe the neurotransmitters of pre- and post- synaptic ganglia.

Answer 44

ALL PRE- are cholinergic (ACh) and then sympathetic post- are NA.

Question 45

What is the name of the type of receptor present between pre- and post-synaptic ganglia?

Answer 45

Nicotinic

Question 46

Describe the structure of nicotinic receptors. Which drug can block them?

Answer 46

5 subunits. Hexomethonium

Question 47

Describe how neurotransmitters reach their target.

Answer 47

Neurotransmitter synthesis -> storage -> wave of depolarisation -> Ca2+ channels open -> exocytosis

Question 48

Which structures degrade noradrenaline?

Answer 48

Monoamine oxidase, catechol-o-methyltransferase

Question 49

How is acetylcholine degraded?

Answer 49

By acetylcholinesterase, which splits it into acetate and choline for re-uptake into the cell