Pharmacology 3: the basics Flashcards
what is an alkane
Carbon to carbon chains with hydrogen attached. No functional groups
Alkanes all contain no functional groups and are named as follows:
* Methane (1C)
* Ethane
* Propane
* Butane
* Pentane (5C)
* Hexane
* Heptane
* Octane
* Nonane
* Decane (10C)
Draw the structure of:
1. Alkene
2. Amine
3. The alcohols
4. Halides
5. carboxylic acid
6. ketones
7. amides
8.ethers
9. esters
FYI Amine groups (R-NH2 have a lone pair so can accept a proton–> ammonium group (R-NH3)
Phenols are weak acids in that they can donate a proton
- what is an aromatic compound.
- when is it named a phenol
- aromatic compounds have a 6 carbon benzene ring.
- It is named phenol with an -OH group
what is the chemical structure of volatile anaesthetic agents
either ethers (-c-o-c)
or halogenated hydrocarbons.
The addition of Cl or Br increase potency
e.g Isoflurane Mac 1.2%, C4H2CL2F5O.
-Halothane MAC 0.75% C2HBrClF3
The others have F but not F and Cl and Br
Fluoride and ether group increase stability of the molecule.
1.What is the structure of LA
- List the Esters
- List the amides
3 parts:
-aromatic group (benzene ring)
-intermediate chain (amide group HN-C=O or ester -O=C-O-
- Ester LA are more shorter acting as metabolised by plasma cholinesterase (pseudocholinesterase) which also metabollises sux, where as remi is metabolised by non-specifc plasma esterases.
e.g Cocaine, procaine (Novocain), tetracaine, benzocaine, chloroprocaine
Ester LAs have a higher risk of allergic reactions due to formation of PABA as a metabolite
- Amides
e.g lidocaine, bupivacaine, ropivacaine, mepivacaine, prilocaine, articaine.
Metabolised by P450 enzymes
longer duration
less incidence of allergic reactions
what is an acid
what is a base
an acid is a proton donor
a base is a proton acceptor
Tell me about midazolams structure and changes
Midazolam ring closes at phys pH becoming lipid soluble and non-ionised
Midazolam has an amide group (NH2) meaning it is a weak base and can accept electrons to form an ammonium ion.
In acidic environments, it is buffered and ionised to become water soluble.
Midazolam pKa=6.15.
onset 1-2 min IV, 30 min PO, IM 10-15mins
Duration- 1-2 hours (all routes)
At physiological pH, the amine group is incorporated into a bexo rin and the ring becomes closed making it non-ionised, lipid soluble and can cross the BBB. Ring closure is pH dependent
Tell me about thiopentals structure and changes
Thiopental is a weak acid prepared in an alkaline environment to make it ionised and water soluble as an enol by substituting a proton for sodium.
At physiological pH it undergoes tautomerization (transforms) into a lipid soluble molecule to bind to the proton and become unionised again as a ketone.
Acid or base?
1.thiopental
2. propofol
3. etomidate
4.Ketamine
- what happens when a drug is 2 pH units away from 7.4
1.thiopental- acid
2. propofol- acid
3. etomidate- base
4.Ketamine-base
when a drug is 2 pH units away from 7.4, the drug is either 99% or 1% ionised.
e.g bicarb pKA is 6.1
Log 1=0 ( pH 6.1)
pH6.1 =1
pH 7.1=10
pH 8.1=100
pH 9.1=1000
(ratio of ionised: unionised)
what is the henderson-hasslebach equation
described how the pH of the environment influences the equilibrium between acid base.
pH=pka + log (proton acceptor/proton donor)
Log1=0, therefore pKa is the pH at which the concentrations of the above are equal.
For a weak base: pH =pka +log (B/BH+)
bases ionise below
for weak acid pH= pKa = log (A-/AH)
Acids ionise above.
what is the ph of
stomach?
intestines?
pKa of:
Aspirin (weak acid)
Ibuprofen (weak acid)
Paracetamol (weak acid)
Morphine (weak base)
stomach=1-5-3.5
intestine=8
pKA
-Aspirin (weak acid) 3.5 (absorbed well in stomach however most absorption occurs in small intestine due to larger surface area * longer contatc time than in the stomach!)
-Ibuprofen (weak acid) 5.9 (some in stomach, most in small intestine)
-Paracetamol (weak acid) 9.4
-Morphine (weak base) 7.9
e.g Morphine is a weak base with pKa 7.9 so will mostly be ionised in stomach pH. It will be better absorbed in the intestine because it will have a higher proportion in its unionised form, thus able to be lipid soluble.
1.what determines if a drug can cross the BBB in large amounts (leading to faster onset)
- what is pKA and protein binding of morphine
- what is pka and protein binding of alfentanil
a.pka
b. lipid solubility
c. proportion of unbound drug (>protein binding means less available and thurs unfavourable concentration gradient)
- Morphine (weak base) pKa 7.9, 40% protein bound
- Alfentanil (weak base) pKa 6.4 90% protein bound. but due to alfentanil being 100x less ionised than morphine, it has a much greater onset
how does ionisation affect duration
delete if this gets confusing
the more ionised , the greater effective concentration in plasma away from lipid stores, thus greater duration of action.
e.g propofol is more unionised than fentanil and therefore has a reduced duration of action as it is redistributed into tissues like fat and plasma conc decreases quickly
- what is an isomer?
- example of structural isomer
- What is tautomerization
- an isomer is a molecule with the same molecular formula, but atoms arranged in a different way.
- structural isomers have different chemical structures(arrangement of atoms) & thus different physiological and pharmacological properties e.g isoflurane &
enflurane. - Tautomerization is a form of dynamic structural isomerism where 2 structural isomers exist in equilibrium
e.g thiopental, the -SH(Thiol) group displaces the sodium (-SNA) following exposure to an acidic environment. The thiol then undergoes tautomerization to thione(-c=s) which is lipid soluble.
Midaz may be referred to as undergoing tautomerisation, though is is not true isomerism as H20 is eliminated upon ring closure.
- what are geometric isomers, and give example
- geometric isomers occur in molecules with alkene group as there is no free rotation around -C=C-
-they may be cis or trans.
-e.g Mivacurium
- what are optical isomers, give example
optical isomers occur when 4 different groups are attached to the same atom.
-mirror image, but non-superimposable.
-pair of optical isomers are known as enantiomers which have same chemical and physical properties but rotate plane polarised light in opposite directions.
Dextro-> rotates to right
Levo-> rotates it to the left
An equal mixture is known as a racemic mixture and has no overall effect on the plane of polarised light.
Clockwise (R)
Anticlockwise (S)
e.g Atracurium, Tramadol, Methohexital
Clinical implications of Isomers
2 isomers may produce different responses, have different potencies, intrinsic activity & pharmacological response.
e.g
-Ketamine
S(+) is the useful anaesthetic agent(s for so good)
R (-) causes agitation, post-op pain, emergence reactions
-Bupivicaine:
S(+) prolonged anaesthesia
R(-) convulsant & cardiotoxic side effects
-Atracurium- mix of 10 different isomers.
cisatracurium benefits:
-3 x potency
-minimal autonomic effects
-minimal histamine release
-reduced laudanosine levels
Mepivacaine, prilocaine, bupivicaine, ropiviciane all exist as pairs of optical isomers. S-isomer is favourable as:
-increased vasoconstriction (prolonges duration of action)
-reduced cardiotoxicity
-Reduced motor blockade
Tell me about atracurium as an isomer
-Atracurium- mix of 10 different isomers.
cisatracurium benefits:
-3 x potency
-minimal autonomic effects
-minimal histamine release
-reduced laudanosine levels
how much of hartmanns or Normal sodium chloride remains intravascularly in plasma?
what is nacl made from?
25%
0.9% nacl = 150 mmol Na, 150 mmol Cl osmolality=300
hartmanns: 131 Na, 111 Cl, K 5, Ca 2, HCO3 28 (more isotonic)’, osmolality 278
The normal blood osmolality is typically 275–295 mOsm/kg.
