Pharmacology basics

Question 1

What are aliphatic compounds?

Answer 1

Contain carbon chain with functional groups attached

Question 2

What do all aromatic compounds contain?

Answer 2

Benzene ring

Question 3

How does barbituric acid become active?

Answer 3

Addition of phenyl group = anticonvulsant
Addition of alkyl group = hypnotic

Question 4

What happens if O2 is substituted for Sulfur in Barbituric acid?

Answer 4

Increases solubility allowing drug to cross BBB

Question 5

How are volatiles divided?

Answer 5

• Ethers (Iso/Sevo/Desflurane)
• Halogenated hydrocarbons (Halothane, Chloroform)

Question 6

How is a halogenated hydrocarbons potency & stability increased?

Answer 6

Potency: Chloride/bromide
Stability: Fluoride

Question 7

What are the compounds found in local anaesthetics?

Answer 7

Aromatic group
Amine group
Intermediate chain

Question 8

What are the 2 main functional groups in LA?

Answer 8

Ester
Amide

Question 9

Which anaesthetics are esters?

Answer 9

Procaine
Tetracaine

Question 10

Which LA are amides?

Answer 10

Lidocaine
Bupivacaine

Question 11

What does the type of linkage in an LA determine?

Answer 11

Speed of metabolism
Esters = Fast, by plasma esterase
Amides = Slowly, in liver

Question 12

What increases the potency/duration of a LA?

Answer 12

• Increased lipid solubility
• Protein binding (inc amide side chain or add groups)

Question 13

What makes a molecule an acid or a base?

Answer 13

• Acid = Molecule that donates protons
• Base = Molecule that accepts protons

Question 14

What is the role of the functional group of a drug?

Answer 14

Affects whether drug is an acid or base

Question 15

What happens to Midazolam at physiological pH?

Answer 15

• Contains amine group
• Amine group incorporated into benzodiazepine ring
• Renders drug non-ionised, lipid soluble
• Able to cross BBB

Question 16

What happens to Thiopental in a pH of 10 and pH 7.4?

Answer 16

• 10: Ionised and water soluble
• 7: Non-ionised lipid soluble molecule able to cross BBB

Question 17

What are the properties of ionic compounds?

Answer 17

• Electron transfer
• High melting & boiling points
• Soluble in water
• Conduct electricity

Question 18

What elements tend to form covalent bonds?

Answer 18

Non-metallic e.g oxygen

Question 19

What affects the polarity of a molecule?

Answer 19

The electro-negativity

Question 20

Why is Desflurane metabolised slower than Isoflurane?

Answer 20

• Desflurane has higher electro-negativity
• Results in stronger bonds

Question 21

What are the 3 types of attraction between molecules?

Answer 21

• Van der Waals forces: Weakest
• Dipole-Dipole: Attraction between polar molecules
• Hydrogen bonding: Strongest, H+ bonded to strongly electronegative atom

Question 22

How does intermolecular attraction affect GA?

Answer 22

• GA acts by disrupting molecular associations due to VdW/Hydrogen bonds within lipid membranes
• Includes the H+ bonds in OH & NH groups formed within neurotransmitters receptors
• Also formation of H+ bonds e.g aromatic rings & volatiles

Question 23

What are most types of bonds between drug and receptor?

Answer 23

Ionic

Question 24

How do bonds work on acetylcholine?

Answer 24

• +vely charged ammonium ion forms ionic bond with -ve receptor
• VdW force between CH3 group on ach & receptor reinforces stability
• H+ bond

Question 25

How is a covalent bond broken?

Answer 25

1) Homolytic fission: Each element takes 1 electron to form a free radical (Needs UV or high temp) 2) Heterolytic fission: 1 element takes both electrons so 2 oppositely charged ions formed

Question 26

What makes molecules water soluble?

Answer 26

- Ability of compound to disrupt normal attraction between H2O molecules (due to Hydrogen bonding) - Functional groups in a drug can provide regions that can polarise their electron cloud allowing interaction

Question 27

What is pKa?

Answer 27

- The pH at which the conc of the proton donor form is equal to that of the proton acceptor form - Indication of how readily a functional group gives up/accepts a proton to become ionized

Question 28

What do the nitrogen atoms on neuromuscular blocking agents do?

Answer 28

- Reduces lipid solubility - Increases water solubility

Question 29

What are the cell surface receptors and what is their function

Answer 29

- G protein coupled: Hormones, neuropeptides, neurotransmitters - Ligand gated: synaptic transmission (Cys-Loop receptors, Glutamate recepts, P2X recepts, CNG channels, TRP)

Question 30

What are the intracellular receptors and what is their function

Answer 30

- Steroid receptors: Steroids, Thyroxine, Vit D, Retinoic acid

Question 31

What are the enzyme-linked receptors and what is their function

Answer 31

- Tyrosine Kinase: Peptide GF, GH, Cytokines, Prolactin - Tyrosine Phosphatase: Unknown - Serine Kinase: Transforming GF B - Guanylate Cyclase: ANP

Question 32

How do G-Protein Coupled receptors work?

Answer 32

- 7 transmembrane domains coupled to intracellular heterotrimeric G Protein complex - Activated by ligand binding - Induces conformational change leading to dissociation of G protein - Reduces receptor-ligand affinity results in agonist release - Alters conc of 2nd messenger molecule or produces a change in membrane potential - Modulate funciton of downstream proteins to produce cellular response - Intrinsic GTPase activity allows returning to resting state

Question 33

How do ion channels work?

Answer 33

- From aqueous channel in lipid bilayer allowing charged particles to pass - 2 types: Voltage-gated & ligand-gated

Question 34

How do voltage-gated ion channels work?

Answer 34

- Open/close in response to changes in voltage across membrane - Alpha subunit forms channel pore - Confers both ion selectivity & sensitivity - Other subunits stabilise & modulate function - At normal MP channels are closed - When membrane depolarised channels have conformational change allowing them to open

Question 35

How do ligand-gated ion channels work?

Answer 35

- Open in presence of extracellular ligands - Inotropic: Binding site & transmembrane ion channel integral to 1 protein. Binding alters activity- rapid synaptic transmission - Metabotropic: Transmitter binding site & effector are separate. Coupled via G-protein which alters activity- slower onset

Question 36

What does the Cys-Loop receptor family include?

Answer 36

- Nicotinic Ach receptors (Excitatory) - Inotropic serotonin (5-HT3) (Excitatory) - GABA A (Inhibitory) - Glycine (Inhibitory) Each receptor has 5 homologous subunits - 4 transmembrane segments & extracellular N-terminus for neurotransmitter binding

Question 37

How do Tyrosine Kinase receptors work?

Answer 37

- Molecule binds - Kinase activity stimulated - Tyrosines are phosphorylated - Intracellular proteins bind to phospho-tyrosine docking sites

Question 38

What receptors are linked to cytoplasmic enzymes?

Answer 38

- TNF - Cytokines - Integrins - IL-1 receptors Important in post-op inflammation, immune response, allergies, pain & tissue repair

Question 39

What is constitutive activity?

Answer 39

- GPCRs able to spontaneously become active without agonist/ligand attachment

Question 40

What are drug receptor binding sites described as?

Answer 40

- Orthosteric: Endogenous activators bind - Allosteric: Modulatory sites distinct from the active site

Question 41

What are allosteric functions?

Answer 41

- Drugs binding at multiple distinct binding sites distant from agonist binding sites - Causes changes altering receptor function

Question 42

What is signal amplification?

Answer 42

- Usually receptors coupled to enzymes - Binding initiates cascade of intracellular responses eg activation of second messenger molecules

Question 43

What is signal dampening?

Answer 43

- Limits physiological response to drug - Receptors undergo desensitisation via downregulated expression, receptor internalisation by endocytosis or receptor phosphorylation - Seen as tachyphylaxis or tolerance -