Pharmacology Flashcards
1
Q
What do organic molecules consist of?
A
Skeleton of carbon atoms
2
Q
How many and what type of bonds can carbon atoms create?
A
Four bonds. Single, double or triple.
3
Q
What is an aliphatic compound?
A
One of two types of organic molecule. Aliphatic compounds consist of a carbon chain (root) attached to a variety of functional groups.
4
Q
What is an alkANE?
A
Alkanes are groups of organic molecules of different length carbon roots but no functional groups attached. They end in the suffix “ane”. E.g. methane, ethane, butane.
5
Q
Name and describe this functional group
A
Alkene - carbon atom attached to another carbon atom via a double bond. “Kene for carbon”
6
Q
Name and describe this functional group
A
Amine - NH2 functional group
7
Q
Name and describe this functional group
A
Alcohol - contain a hydroxyl (OH) functional group. OH dear.
8
Q
Name and describe this functional group
A
Halides/halogenated compounds - functional group of chloride, bromide, fluoride or iodine atom
9
Q
Name and describe this functional group
A
Carboxylic acids - contain the carboxyl functional group.
10
Q
Name and describe this functional group
A
Ketones - Contain a carbonyl group C=O
11
Q
Name and describe this functional group
A
Amides - contain a C=ONH2 group
12
Q
Name and describe this functional group
A
Ether C-O-C functional group
13
Q
Name and describe this functional group
A
Ester - contain a O-CO group. Make by combining an alcohol and an acid.
14
Q
What is an aromatic compound?
A
Compound that contains a benzene ring.
15
Q
Describe a benzene ring
A
Ring made up of 6 carbon atoms with alternating single and double bonds
16
Q
What is this?
A
Phenol - benzene ring with a hydroxyl (OH) group attached.
17
Q
Define valency?
A
The number of bonds an atom has in its uncharged state
18
Q
What are the two types of volatile anaesthetics?
A
- Halogenated hydrocarbons.
- Halogenated ethers
19
Q
Give 4 examples of halogenated ethers?
A
Sevoflurane, isoflurane, desflurane, enflurane
20
Q
Give 3 examples of halogenated hydrocarbons?
A
Halothane, trichloroethylene and chloroform
21
Q
What are the three components of a local anaesthetic molecule?
A
- Aromatic compound
- Intermediate chain
- Amine group
22
Q
What intermediate chain is used for lidocaine and bupivicaine?
A
An amide group
23
Q
What intermediate chain is used for procaine and tetracaine?
A
An ester group
24
Q
How are esters and amides metabolised and are they generally metabolised quickly or slowly?
A
Esters are metabolised quickly by esterases in the plasma. Amides are metabolised slowing by the liver
25
How can you increase the potency and the duration of action of a local anaesthetic module?
Add a functional group to the aromatic ring or increase the bulk on the amine side chain. Works by increasing lipid solubility and/or protein binding of drug
26
What is the definition of
a) an acid?
b) a base?
Acid - a molecule which donates protons
Base - a molecule which accepts protons
27
What essential functional group does Midazolam contain? Does this make it an acid or a base?
Amine group (NH2). weak base.
28
What happens when midazolam is buffered in an acidic solution?
It becomes ionised and is water soluble.
29
What happens when midazolam enters the bloodstream?
At a physiological pH of 7.4, the amine group on midazolam becomes encorporated into the benzodiazepine ring (pH dependent ring closure) making the drug non-ionised, lipid soluble and able to cross the BBB
30
Define tautomerism and give an example of a drug that tautomerises?
The dynamic interchange between two different forms of a molecular structure depending on the environmental conditions.
Thiopental is an example as it exists in different forms depending on the pH of the solution.
It's preserved in an alkaline solution (pH 10.5) where its ionised then when in the body (pH 7.4), it tautomerises into a non-ionised and lipid soluble state where it can cross the BBB.
31
Define atom
smallest unit of an element with a nucleus containing protons and (usually) neutrons with surrounding orbiting electrons
32
Define proton
A stable, subatomic, positively charged particle found in the nucleus of an atom. Equivalent to the atomic number of the element.
33
Define electron
Stable, subatomic, negatively charged particle. Negligible mass and found in shells surrounding the nucleus of the atom
34
With reference to electrons, what determines the reactivity of an element?
The number of electrons in the valence (outermost) shell of an element determines its reactivity.
35
How many electrons would complete the first and second shell of an element?
2 and 8
36
What is ionic bonding?
Electrostatic attraction between oppositely charged ions. Formed by the transfer of electrons from one atom to another.
37
What type of ion is formed when an atom gains an electron? Is it positively or negatively charged?What is this process called?
When an atom gains an electron it is reduced. (OIL RIG). The ion formed is called an anion which is negatively charged (ANegativelychargedion). Anions are most common in non-metals.
38
What type of ion is formed when an atom loses an electron? What is this reaction called and is it positively or negatively charged?
Cations are formed when atoms lose electrons. They are positively charged and this is known as oxidation.
39
Describe the properties of ionic compounds (e.g. NaCl) with reference to:
- Melting/boiling points
- Solubility
- Ability to conduct electricity
- High melting and boiling points as strong bonds are made so lots of energy needed to break them.
- Soluble in water
- Conduct electricity when melted or dissolved.
40
What is a covalent bond?
A bond formed when atoms share their electrons in their outermost shell to make them complete. Atoms are held together by forces of attraction between positively charged nuclei and negatively charged shared electrons
41
What type of elements tend to form covalent bonds?
Non-metals e.g. oxygen
42
Describe the melting/boiling points of molecules containing covalent bonds and what state they are usually in?
Low melting/boiling points and usually gases or liquids
43
What is co-ordinate bonding?
Where one atom supplies both shared electrons to the bond
44
What is a lone pair?
Pairs of electrons in an atom's outermost (valence) shell that are not involved in covalent bonds e.g. the nitrogen atom in NH3 has one lone pair and the oxygen in H20 has 2 lone pairs
45
What is a polar bond?
A polar bond is when a compound has a bond that is intermediate between ionic and covalent. In a true covalent bond e.g. when a compound is made from two atoms of the same element, the electrons are equally attracted to both atom. However, if a compound has a polar bond, the electrons are more attracted to one atom in a compound which will result in each atom having a positive or negative charge.
46
What is electronegativity?
Electronegativity describes an atom's ability to attract electrons in a polar bond. The "degree of polarity" in a polar bond will depend on the difference in electronegativity of the atoms involved. Electronegativity is highest in elements on the far right and top of the periodic table. It is lowest in elements on the far left and bottom of the table.
47
Using the principles of electronegativity and relating to the structure of the volatile agents, why is desflurane metabolised slower than isoflurane?
Desflurane and isoflurane are identical in structure apart from the alpha carbon atom in desflurane is bonded to a fluorine whereas isoflurane is bonded to a chlorine. Flouorine is more electronegative than chlorine so the bond is more polarised and ionic in character than the C-Cl bond. The C-Fl is stronger so metabolism of desflurane is slower than isoflurane.
48
How can a covalent bond have ionic properties?
A covalently bonded molecule can be polar due to differences in electronegatively of atoms resulting in positive and negatively charged ions.
49
What is a dipole?
A separation of positive and negative charge
50
What is the dipole moment?
Direction and strength of the charge separation in a covalent bond. Weak compared to ionic bonds but shows how a covalent bond has ionic properties.
51
What is the strongest type of intermolecular force?
Hydrogen bond
52
How are hydrogen bonds formed?
a bond between two molecules resulting from an electrostatic attraction between a proton in one molecule and an electronegative atom in the other.
53
What type of intermolecular attraction is this?
Van der Waals' force - weakest type of intermolecular bond where orbiting electrons will cause instantaneous dipole moments by orbiting on one side of the molecule/atom and inducing a dipole in a neighbouring atom/molecule which is then attracted to it.
54
What is this?
Acetylcholine bonding to a receptor site. The ionic bonds formed between positive ammonium and the negative receptor site are not sufficient to stabilise the drug-receptor complex. Van de Waals forces form between the CH3 functional groups, the acetylcholine and receptor and there's a hydrogen bond between the C=O and a hydrogen atom on the receptor
55
What are two ways you can break a covalent bone?
1) Homolytic fission - each element takes one electron to form a free radical.
2) Heterolytic fission - one element takes both electrons so the atoms become oppositely charged ions
56
What type of bond breaking is seen here?
Heterolytic fission - where the more electronegative atom takes the electrons becoming an "nucleophile" and negatively charged. The atom that loses the electrons is called a "electrophile".
57
Are ionic bonds or covalent bonds water soluble?
Ionic bonds. Covalent bonds are lipid soluble.
58
What is an isomer?
Isomers are molecules with the same atomic formulae (same number of oxygen, nitrogen, hydrogen atoms etc.) that have different structural arrangements. They may behave similarly or entirely differently.
59
Define structural isomer
Same molecular formula (same no. of carbon/oxygen/hydrogen etc.) but different chemical formula (different arrangement of atoms).
Can have similar or different properties.
60
Example of structural isomers?
Isoflurane and enflurane
61
What is another work for dynamic, structural isomerisation?
Tautomerism
62
Define tautomerism
dynamic interchange between two different forms of a molecular structure depending on the environmental conditions
63
Give an example of tautomerism that's relevant to anaesthetics.
Sodium thiopental. When stored, it is buffered in an alkaline solution (pH 10.5) to form a sodium salt which is ionised and water soluble. At physiological pH, the molecule undergoes isomerisation forming a lipid soluble compound that's able to cross the BBB.
64
What type of isomer is this and why?
Example of stereoisomer
- same molecular formula.
- same chemical structure
- different spatial configuration.
65
What type of bonds can exist in geometric isomers?
Carbon-carbon double bond (C=C), known as an "alkene" or a ring. The double bond restricts mobility of atoms.
66
What is a cis isomer? What is a trans isomer?
Cis - top image. functional groups (R) exist on the same side of the double bond.
Trans - bottom image. Functional groups on opposite sides of double bond.
67
What is shown here?
An example of optical isomers.
68
Define optical isomer
a molecule where an atom is bound to four different groups. The groups can be arranged in 2 different configurations which are MIRROR IMAGES of each other but are NON SUPERIMPOSABLE. Human hands are a commonly used example of chirality.
69
What is the name for the central atom in optical isomers? What does an atom need to be able to do to become this central atom?
This atom is called the chiral centre. Usually a carbon atom but can be any atom that forms four different bonds e.g. quaternary nitrogen.
70
What is the name for compounds that have a single chiral centre and form non-superimposable mirror images of each other.
Enantiomers - same chemical and physical properties but rotate PLANE POLARISED LIGHT in OPPOSITE directions. Two enantiomers will rotate the plane of polarised light by equal angles but in opposite directions.
71
What is the name of a compound which contains more than one chiral centre?
Diastereoisomer
72
What is "plane polarised light"?
Light in which the vibrations are all in one plane
73
How are enantiomers classified (3 ways) ?
They are classified as either:
1) dextrorotatory (d) enantiomers or levorotatory (l) enantiomers. d enantiomers rotate plane polarised light to the RIGHT. L enantiomers rotate plane polarised light to the Left.
2) + (same as d) or - (same as l)
3) R or S (completely different naming system)
74
What is a racemic (dl) mixture?
A mixture of d and l enantiomers which have no effect on the plane of polarised light.
75
What type naming system is this?
R and S - rectus and sinister. Rectus is clockwise, Sinister is anticlockwise
76
Are diastereoisomers mirror images of each other?
No! They are compounds which have more than one chiral centre which do not form mirror images of each other.
77
Is the compound shown a diastereoisomer or an enantiomer?
Both! Compounds can possess diastereoisomers and enantiomers
78
What is the relevance of isomerisation in medicine?
One isomer can produce the desired effect vs the other having no effect or unwanted side effects. Two enantiomers will have different conformational relationships with a chiral receptor leading to different potencies, intrinsic activities (agonist vs antagonist) and pharmacological responses. Drugs are therefore produced as a single isomer
79
Provide an example of how isomers are useful in medicine
R (-) isomer of bupivicaine - long lasting local anaesthetic
S (+) isomer of bupivicaine
cardiotoxic dysfunction and seizures
80
Provide a second example of how isomers are useful in medicine?
Atracurium is produced as a mixture of 10 isomers each with different pharmacokinetics and potencies.
One isomer, cisatracurium, has various clinical advantages, including:
Three times increase in potency
Minimal autonomic effects
Minimal histamine release
Reduced laudanosine levels
It is produced as a single enantiomer and available commercially
81
Do stereoisomers have the same or different physical, chemical and pharmacological properties
Same properties
82
What is an enantiopure?
A preparation with only a single enantiomer present
83
What makes a molecule water soluble?
A soluble molecule will have a functional group (usually containing nitrogen or oxygen) which is able to polarise and form hydrogen bonds with water molecules. The hydrogen bonds must be stronger than the water molecules existing hydrogen bonds in order for the water's electron clouds to be disrupted. A very large hydrocarbon with just a single functional group is not soluble vs a smaller compound with the same functional group being soluble.
84
What is the difference between strong electrolytes and weak electrolytes?
Strong electrolytes e.g. NaCl will dissociate completely in water forming individual Na and Cl ions (with no remaining NaCl) which dissolve in water by forming hydrogen bonds. Weak electrolytes (CH3 COOH (acetic acid)), only partially dissociate into ions with a large proportion of the molecule remaining unionised.
85
Respectively, are strong and weak electrolytes water or lipid soluble? What factor influences this?
Strong electrolytes are water soluble as they completely dissociate in water forming ions.
Weak electrolytes are water and lipid soluble. Depending on the pH of the solution, only a proportion of the molecule will dissociate into ions, leaving a proportion of the molecule intact. The ability to ionise increases the water solubility of the drug.
86
Give two examples of functional groups that allow small organic molecules to act as weak electrolytes?
-COOH (carboxyl) group
- NH2 (amine) group
i.e. these compounds will partially dissociate in aqueous solutions at pHs relevant to human physiology.
87
Give two examples of functional groups that dissociate at pHs outside 6.5-8.5?
Phenol hydroxyl group (aromatic ring -OH)
Aldehyde "keto" group (R-CH=O)
88
What is this molecule? Is it a weak acid or a weak base? Which functional group determines this?
Aspirin, weak acid, -COOH group (carboxyl).
89
What happens when aspirin is dissolved in water?
Its carboxyl group dissociates forming a COO- and H+.
90
What is pKa?
The pH at which the concentration of the proton donor form is equal to the proton acceptor form.
E.g. in aspirin; the pH at which the concentration of the -COOH (proton donor) group is equal to the COO- group (proton acceptor). The pKa is an indicator as to how readily a functional group gives up or accepts a proton and becomes ionised in an aqueous environment. Not related to acid or base as both of these can have a high or a low pKa.
91
How does morphine act as a weak base when dissolved?
At the appropriate pH, its amine group, NH3 (proton acceptor), becomes ionised by accepting a proton and becoming a quaternary nitrogen (proton donor).
92
What is the equation for acid base reactions?
Proton donor -> -< proton acceptor + H+
93
In acid base reactions, what is the abbreviation of the forward reaction and reverse reaction?
k1 and k2
94
Using k1 and k2 what is the general equation for acid base reactions?
k1 [proton donor] ->-< k2 [proton acceptor] [H+]
95
Are weak acids ionised above or below their pKa?
Above
96
Are weak bases ionised above or below their pKa?
Below
97
A useful table to remember. Are propofol and ketamine weak acids or weak bases?
Propofol - weak acid
Ketamine - weak base
98
Another useful table. Is paracetamol and fentanyl a weak acid or base?
Paracetamol - weak acid.
Fentanyl - weak base
99
The pH of a 2.5% solution of sodium thiopental is 11, why?
The pKa of thiopental is 7.6 so in water, 50% of it is unionised and insoluble in water. This 50% forms a precipitate. However at a pH of 11, the k1 is > k2 and the thiopental will exist in its ionised state at a ratio of 5000:1 so acid precipitation doesn't occur
100
What is pKa?
The negative logarithm of the acid dissociation constant (Ka).
101
What is pH?
The negative logarithm to the base 10 of the H+ concentration
102
What is the point of the Henderson-Hasselbalch equation?
To predict the ratio of ionised to unionised form of a weak acid or base
103
What is the HH equation?
pH = pKa + log ([proton acceptor])/[proton donor]).
104
How can you write the HH equation for a weak acid and base?
weal acid: pH = pKa + log ([A-)/[AH])
weak base: pH = pKa + log ([B/BH+]).
Noted for an acid the ionised form is on top of the equation but its on the bottom for a weak base.
105
What is a buffer?
A substance (or mixture of substances) that minimises the change in pH that would otherwise occurs when a stronger acid or base is added.
106
What does a buffer usually contain?
A weak acid and its conjugate base
107
What is the most common example of a buffer?
Carbonic acid H2CO3 and bicarbonate buffer system (HCO3-)
108
Describe how the carbonic acid - bicarbonate system is an open buffer system?
Carbon dioxide can be excreted by breathing. It is carried to the lungs by diffusing into red blood cells , binding with haemoglobin and reacting with carbonic anhydrase forming carbonic acid.
The hydrogen ions produced in the carbonic-acid-bicarbonate system are also excreted by the kidneys.
109
What is the pKa required for the carbonic acid-bicarbonate buffer system?
6.4
110
Which two buffering systems are important in the renal excretion of hydrogen ions ?
Ammonia: ammonia-ammonium ion is a buffer pair with ammonia production occurring optimally at a low pH.
The phosphate buffer system (dihydrogen phosphate)
Both ammonia and phosphate are produced in the renal tubular cells
111
Which two chemical properties of a drug determine how quickly it reaches the brain?
It's lipid solubility and its pKa - the lipid solubility is important in crossing the blood brain barrier however the pKa is important in determining what proportion of the drug is in its unionised form. The ionised form of the drug crosses the blood brain barrier more readily.
112
What method is used to allow propofol to be used intravenously?
It's prepared as an emulsion in intralipid with the emulsifying agent being egg phosphatide.
113
What is the pH of the stomach and small intestine?
Stomach is 2-3
Small intestine - 8-9
114
When at the BBB, which three factors determine a drug's onset time?
1) Lipid solubility - the more lipid soluble a drug, the faster it can diffuse across the BBB.
2) Protein binding - the higher the available of free drug i.e. not protein bound, the greater the concentration gradient across the BBB and the faster the diffusion rate.
3) pKa - the unionised form favours crossing the BBB.
115
Why does alfentanil (pKa 6.4) have a faster onset time than morphine (pKa 7.9)?
Although alfentanil is more heavily protein bound than morphine, it's lower pKa means that a much higher proportion of the drug exists in its unionised form 100 X less ionised than morphine).
116
If the pKa of fentanyl is 8.4 and pKa of propofol 11, which drug has a quicker offset time when a continuous infusion is turned off?
Propofol.
At physiological pH (7.4), propofol is basically unionised as it's a weak acid so requires a ionises more readily in higher pH solutions. Fentanyl's pKa is much closer to physiological pH's so more of the drug will exist in its ionised form. When an infusion of fentanyl is stopped, the ionised, water soluble version has moved from lipophilic stores to maintain a plasma concentration. When propofol is stopped it does not re-enter the plasma and so its effects wear off more rapidly.
117
Are opioids all weak acids or bases?
All weak bases
