Pharmacology Flashcards
(157 cards)
1
Q
What is Pharmacodynamics?
A
How the drug affects the body
2
Q
What is pharmacokinetics?
A
How body affects the drug
3
Q
Describe the 4 aspects of Pharmacokinetics
A
ADME
Administration - route
Distribution - systemic spread
Metabolism - 1st pass metabolism, IV skips this!
Excretion - hepatically or renally
4
Q
Drug Receptor types
A
Ligand-gated ion channels - nicotinic ACh receptors
G Protein Coupled receptors (GPCR’s) - beta-adrenoceptors
Kinase-linked receptors - for growth factors
Cytosolic/nuclear receptors - steroid
5
Q
What questions should you ask when prescribing a drug, with pharmacokinetics in mind?
A
How quickly will drug reach its site of action? How quickly will I see a response?
Drug interactions likely?
Is a dose adjustment needed in certain disease states?
What monitoring is required?
6
Q
What mechanisms do drugs use to permeate membranes?
A
- Passive diffusion through hydrophobic membranes - lipid soluble molecules
- Passive diffusion through aqueous pores - only v small soluble drugs, e.g. lithium
- Carrier mediated drugs - quite unusual, basically when proteins that usually transport sugars, amino acids etc transport drugs
7
Q
How does drug ionisation affect drug absorption?
A
Ionised drugs have poor lipid solubility
∴ only unionised drugs can pass
8
Q
Why are the majority of medications PO?
A
Convenient
Cost-effective
9
Q
Where are medications that are weak bases best absorbed? Why?
A
In the small intestine
bc small intestine has a pH of ~ 6.5 ∴ more likely to be similar pH to pKa of medication (the pH at which ionised & unionised drug is 50/50)
10
Q
Where are medications that are weak acids best absorbed? Why?
A
In stomach
bc stomach has a pH of ~ 3 ∴ more likely to be similar pH to pKa of medication (the pH at which ionised & unionised drug is 50/50)
11
Q
What factors affect the oral drug absorption in the stomach?
A
Gastric enzymes - digest the drug, esp large protein drugs e.g. insulin (∴ never given orally)
Low pH - can degrade
Full stomach = slower absorption
Gastric motility - can be altered by drugs/disease
Prev. surgery
12
Q
What factors affect the oral drug absorption in the small intestine?
A
Drug structure - large/hydrophillic molecules are poorly absorbed
Medicine formulation - i.e. capsule has a coating to control release
Modified release slows rate of absorption (bc less freq dosing)
P-glycoprotein - will remove substrates from endothelial cells back into lumen lol
13
Q
What is first pass metabolism?
A
Metabolism of drugs which prevents them from reaching systemic circulation
(The fraction of drug lost at absorption)
14
Q
What happens during first-pass metabolism?
A
Degradation by enzymes in intestinal wall
&
Absorption from intestine into hepatic portal vein and metabolism via liver enzymes
15
Q
What is bioavailability?
A
Proportion of administered dose which reaches the systemic circulation
16
Q
What is bioavailability (F) dependent on?
A
Extent of absorption and first pass metabolism
NOT on rate of absorption
Varies w/ route of administration and between Px
e.g. tablet has lower bioavailability (F) than IV
17
Q
What is bioavailability expressed as?
A
% or fraction
18
Q
Pros of PR route
A
Local administration
Avoids first pass metabolism
Helps if patients has severe N/V ∴ can’t take meds orally
19
Q
Cons of PR route
A
Absorption is variable
Patient preference
20
Q
Example of PR medication
A
Diazepam suppositories for epileptic seizures
21
Q
Pros of INH route
A
Well perfused large SA
Local administration
22
Q
Cons of INH route
A
Inhaler technique might be ineffective
23
Q
Example of INH route meds
A
Gaseous anaesthetic
Salbutamol inhaler
24
Q
Pros of SC route
A
Faster onset than PO
Formulation can be changed to control absorption rate
25
Cons of SC route
Not as rapid as IV
26
Examples of SC route meds
Long acting insulin for T1DM and T2DM
27
Pros of TD route
Provides continuous drug release
Avoids first pass metabolism
28
Cons of TD route
Only suitable for lipid soluble drugs
Slow onset of action
29
Examples of TD route medication
Fentanyl patches for severe chronic pain
30
What factors influence distribution?
1. Molecule size (small, ↑ distribution)
2. Lipid solubility (if lipophillic, ↑ distribution)
3. Protein binding (if NOT protein bound, ↑ distribution)
31
What is the volume of distribution (Vd)?
Also sometimes known as apparent volume of distribution
Theoretical vol a drug will be distributed in the body
Vol of plasma required to contain the total administered dose
If well distributed, high Vd
If poorly distributed, low Vd
32
What is the blood brain barrier?
Membrane that separates foreign substances in blood from CNS
33
Describe the physical aspect of the BBB
Continuous layer of endothelial cells with tight junctions
Has high number of efflux pumps that remove water soluble molecules
34
How can drugs reach the CNS?
High lipid solubility - can permeate and diffuse across BBB
Intrathecal route
Inflammation - causes BBB to be leaky ∴ drugs can cross
35
In actuality, what must you think about when prescribing drugs, in relation to distribution?
Careful w dosing drugs with a small Vd - using actual body weight in obese patients
e.g. Aciclovir NOT distributed to fat ∴ should be dosed based on ideal body weight, not actual
Distribution changes in diff disease states (i.e. sepsis = leaky blood vessels = BBB penetration)
Age changes body composition, which changes Vd of water soluble drugs
Drugs that can cross BBB have CNS s/e
36
What is drug elimination?
The process by which the drug becomes no longer available to exert its effect on the body
37
Name 2 methods of drug elimination
Metabolism - modification of drug to new chemical entity
Excretion of unchanged drug
38
What are the 2 phases of metabolism?
1. Oxidation / Reduction / Hydrolysis to introduce reactive group to chemical structure. Slightly increase hydrophilicity
By microsomal enzymes e.g. CYP450
2. CONJUGATION. Adds functional group to produce **hydrophilic**, inert molecule.
e.g. glucuronidation
then excreted
39
What cytochrome is mainly responsible for Phase 1 metabolism? Where are these located?
Cytochrome P450 (CYP450)
Mostly in liver (also small intestine, lung)
40
When will CYP enzyme function vary?
Genetic variation
↓ Function in severe liver disease
Interactions w/ drugs/foods which can ↑ or ↓ activity
41
How many CYP450 enzymes are there?
57
42
What CYP enzyme has the substrates caffeine, paracetamol, theophylline and warfarin?
CYP 1A2
43
What CYP enzyme has the substrates ibuprofen and warfarin?
CYP 2C9
44
What CYP enzyme has the substrates codeine and warfarin?
CYP 2D6
45
What CYP enzyme has the substrates simvastatin, warfarin, DOACs, carbamazapine and diltiazem?
CYP 3A4
46
What substrates are associated with CYP**1A2**?
Caffeine, paracetamol, theophylline, warfarin
47
What substrates are associated with CYP**2C9**?
Ibuprofen, warfarin
48
What substrates are associated with CYP**2C19**?
Omeprazole, phenytoin
49
What substrates are associated with CYP**2D6**?
Codeine, warfarin
50
What substrates are associated with CYP**3A4**?
simvastatin, warfarin, DOACs, carbamazapine and diltiazem
51
Which are the most signif CYP for drug metabolism?
3A4, 2C9, 2C19, 1A2, 2D6
52
In actuality, what must you think about when prescribing drugs, in relation to metabolism?
If severe liver impairment, is metabolism reduced?
∴ reduced dose? additional monitoring? avoid??
Drug interactions
Saturation of metabolic pathways can lead to accumulation or toxicity (paracetamol overdose)
53
If normal dose of paracetamol, how is it metabolised?
Via glucuronidation and sulphation to form a non-toxic metabolite
54
If paracetamol overdose, how is it metabolised? What is the result? How do we treat this?
Normal pathway is saturated
∴ Oxidation by CYP2E1
Forms NAPQI (v toxic)
Causes hepatocyte necrosis ∴ liver failure
We would give **IV n-acetyl cysteine** (NAC)
Replenishes body's stores of glutathione
∴ glutathione conjugation
∴ produces a non-toxic metabolite :)
55
When would we give a reduced paracetamol dose?
In low body weight patients
Or if severe hepatic impairment
56
In what forms can drugs/metabolites be excreted?
Liquids - small polar molecules e.g. **urine**, bile, sweat, tears, breast milk
Solids - large molecules e.g. faeces (thru biliary excretion)
Gases - volatiles e.g. expired air
57
What is the first process that accounts for renal excretion?
1. **Glomerular filtration**
Free/unbound drug molecules will pass through
V large molecules will be excluded and will go thru efferent arteriole
58
What is the 2nd process of renal excretion?
2. **Active tubular secretion**
Drug molecules transported from blood into renal tubule thru carriers
(organic anion transporter (OAT) & organic cation transporter (OCT))
Can clear protein bound drugs
Most effective renal clearance mechanism
59
What is the 3rd process of renal excretion?
3. **Passive reabsorption**
Diffusion down conc gradient from tubule into peritubular capillaries
Hydrophobic drugs diffuse easily
Highly polar drugs will be excreted
60
Types of Adverse drug reactions
ABCDEFG
**A**ugmented
**B**izarre
**C**hronic/continuing
**D**elayed
**E**nd of use/withdrawal
**F**ailure of treatment
**G**enetic
61
What should you do if a patient has a Adverse Drug reaction?
Report to MHRA using the YELLOW CARD SCHEME
62
What is Augmented ADR caused by?
Exaggerated effect of drugs pharmacology at therapeutic dose
Usually not fatal
63
What is the most common ADR?
Augmented (80%)
64
When is Augumented ADR dependent on?
Dose dependent
Reversible when drug is withdrawn
65
Give some examples of Augmented ADR
AKI w/ ACE-i
Bradycardia w/ beta blockers
Hypoglycaemia w/ gliclazide, insulin
Resp depression w/ opiates
Bleedings w/ anticoag
66
Describe Bizarre ADRs
Not related to pharm
Not dose related
Can cause serious illness/death
Symptoms don't always resolve when stopping drug
67
Give examples of a Bizarre ADR
Anaphylaxis w/ penicillin
Tendon rupture w/ quinolone abx
Steven Johnson Syndrome w/ IV vancomycin
68
What is a Chronic/Continuous ADR?
An ADR that continues after drug has been stopped
69
Give examples of Chronic/Continuing ADR
Osteonecrosis of the jaw w/ bisphosphonates
HF w/ pioglitazone
70
What is a delayed ADR?
ADRs that become apparent some time after stopping drug
71
Give an example of a delayed ADR
Leucopenia w/ chemo
72
What is an End of Use/Withdrawal ADR?
ADR that develops after drug has been stopped
73
Give examples of End of Use/Withdrawal ADR
Insomnia after stopping benzodiazepine
Rebound tachycardia after stopping BB
74
What could cause a Failure of treatment ADR?
Drug-drug or drug-food interaction
Poor compliance with administration instructions
75
Give examples of a Type F ADR
Failure of bisphosphonates due to taking w/ food
Failure of DOAC due to enzyme inducer (e.g. carbamazepine)
76
What is a Genetic ADR?
When drug causes irreversible damage to genome
77
Give an example of a Genetic ADR
Phocomelia in children of women taking thalidomide
78
Other than the ABCDEFG classification, what is another way of classifying ADRs?
DoTS
**Do**se-relatedness
**T**iming
**S**usceptibility
79
Describe the Do in DoTS
**Do**se relatedness
Looks at the dose you might get a ADR
//
_Hypersusceptibility reaction_
When you get an ADR at a subtherapeutic dose
e.g. anaphylaxis w/ penicillin
_Collateral effect_
ADR at a therapeutic dose
e.g. hypokalaemia w/ loop diuretic
_Toxic effects_
ADR at subpratherapeutic dose
e.g. liver damage w/ paracetamol
80
Describe the T in DoTS
**T**iming
When does ADR develop in relation to the drug taken
TYPES :
Rapid
First dose
Early
Intermediate
Late
Delayed
81
Describe the S in DoTS
**S**usceptibility
Certain patients/groups have specific susceptibility to ADRs
Could be due to :
Age
Gender
Disease states
Physiological states
82
Define Agonist
Have full affinity and FULL efficacy
∴ ↑ Activation of the receptor
83
Define Antagonist
Full affinity and ZERO efficacy
∴ ↓ Activation of the receptor
84
Define affinity
How well a ligand binds to its receptors
85
Define efficacy
How well a ligand successfully activates its receptors
86
Define Potency
Relative strength of the drug
i.e. lower dose needed for response
87
Define a Competitive inhibitor
Binds AT active site
↓ Efficacy reversibly
Affinity is unchanged
88
Define a Non-Competitive inhibitor
Binds AWAY from active site, changes its shape
↓ Efficacy irreversibly
↓ Affinity
89
In terms of the Dose/Response curve, describe competitive inhibitors
Curve shifts to the RIGHT
Drug has less affinity but same efficacy
Same EC50
DRUG IS LESS POTENT
90
What is Ec50?
The conc required for a 50% effect
91
In terms of the Dose/Response curve, describe non-competitive inhibitors
Curve shifts RIGHT & DOWN
Drug has less affinity and less efficacy
EC50 decreases
DRUG IS LESS POTENT
92
Define Bioavailability
How much drug is uptaken systemically for effect
e.g. IV = always 100%
93
What is the therapeutic range?
Upper and lower bounds of safe dose of a drug
(if narrower range, needs more care in dispensing)
94
Drug Targets for drugs
Examples of each
Receptor action (MC!!) - Beta blockers
Enzymes - ACEi
Ion channels - CCB
Transporters - PPI
95
Where does metabolism of drugs occur?
**GIT** - mechanical & chemical digestion, for majority of food
**Renal** - simple, already soluble molecules.
**Hepatic** - more complex, hydrophobic molecules. Undergoes Phase 1 +/- Phase 2 reactions
96
Autonomic vs Somatic?
What transmission falls under what?
Autonomic - automatically, no conscious effort
Parasympathetic and Sympathetic
Somatic - voluntary
Skeletal muscle motor
97
Parasympathetic pre and post synpatic?
ACH - pre
ACH - post
98
Sympathetic pre and post synaptic?
AcH - pre
Noradrenaline - post
99
Skeletal muscle motor what neurotransmitter?
Ach at the NMJ
100
2 Main receptors in Cholinergic Pharm?
Where are they - in reference to synapse?
Nicotinic - Presynaptic
Muscarinic - Postsynaptic
101
Name the main muscarinic receptors
Where do you find them?
M1 - Brain
M2 - Heart
M3 - Lungs!
102
Which condition is related to disrupted Ach Transmission at the NMJ?
Myasthenia Gravis
103
Tx Myasthenia Gravis
Neostigmine
Pyridostigmine
104
S/E of XS Acetylcholine stimulation
**SLUDGE**
**S**alivation
**L**acrimation
**U**rination
**D**efecation
**G**astric distress
**E**mesis
105
Where do we find Alpha 1 & Alpha 2 receptors?
Vessels and sphincters e.g. bladder neck
(Distal circulation)
106
Where do we find Beta 1 receptors?
Heart
107
Where do we find Beta 2 receptors?
Lungs
108
What is tamsulosin?
Alpha 1 blocker
109
Name a Beta 1 agonist
When is it used?
Dobutamine
Cardiogenic shock!!
110
What does a Beta 1 AGONIST do?
INCREASES force (inotropy) and rate (chronotropy) of cardiac contractions
111
What does a Beta 1 ANTAGONIST do?
DECREASES force (inotropy) and rate (chronotropy) of cardiac contractions
112
Name a Beta 1 antagonist
Beta blocker!
113
When are BB CI?
_Absolute_ asthma
114
What does a Beta 2 AGONIST do?
Bronchodilate airways
115
Example of Beta 2 agonist
SABA - salbutamol
116
What is a cardioselective drug?
Give an example
Only act on cardiac tissue
Beta blockers (beta 1 only)
117
Examples of opioids
Morphine
Diamorphine (heroin)
Codeine
Pethidine
118
What is the bioavailability if you take opioids PO?
50%
119
When do you tend to use opioids?
For chronic severe pain relief
Mostly cancer pain
120
5mg diamorphine =
10mg morphine = 100mg pethidine
121
Main S/E of opiate use?
Constipation
122
Opiate over can cause ?
Treatment for this and Route of administration?
Respiratory depression
IV Naloxone
123
Give examples of when you would use blood thinners?
DVT/PE
AF
Prosthetic valves
Bleeding disorders
Ischaemic stroke
MI
124
Give examples of blood thinners
DOACs - Apixaban, Rivaroxaban
Warfarin
LMWH
Alteplase IV
Antiplatelets - Clopidogrel, ticagrelor
125
Warfarin inhibits?
Vit K
Clotting factors 10, 9, 7, 2
126
LMWH inhibits?
Clotting factors 3, 10
127
What does COX-1 do?
Involved in Prostaglandin synthesis
which protects gastric mucosa
128
S/E COX-1 inhibition
Peptic ulcer
129
NSAID MOA?
Inhibits arachidonic acid pathyway COX-1 and COX-2
130
What does COX-2 do?
Involved in inflammation
131
Example of a selective COX-2 inhibitor?
Celecoxib
132
Why don't we use COX-2 selective drugs?
Not as effective
Also expensive
133
Where do Loop diuretics act upon?
Ascending limb
134
MOA Loop diuretics
Na-K-Cl contransporter channels
135
Example Loop diuretic
Furosemide
136
Where do Thiazide Diuretics act on?
DCT
137
Thiazide diuretic MOA
Na-Cl co-transporter
138
Example of Thiazide diuretic
Bendroflumethiazide
139
Where do Aldosterone antagonists act upon?
Collecting duct
140
MOA Aldosterone antagonist
Increases Na+ excretion and retains K+ but acting on aldosterone receptors
141
What is an aldosterone antagonist also known as?
K+ sparing diuretic
142
PPI e.g.
Lansoprazole
143
What does PPI do?
↓ Acidity of GI lumen
144
Nicotinic is assoc w?
CNS
145
Muscurinic is assoc w?
PNS
146
Main S/E of ACEi
Why?
Dry cough
Bc build up of bradykinin in airways
147
Difference between tolerance and dependence?
Tolerance is physiological while dependence is psychological
148
Main S/E of CCB
What condition might this be mistaken for?
Oedema - Ankle swelling
HF
149
What is the first line treatment for Anaphylaxis?
IM 500 micrograms Adrenaline
150
Metformin S/E
GI distress
Stomach pain
151
S/E Sulphonylurea
Hypoglycaemic episodes
Weight gain
152
What is Metformin?
Biguanide
153
S/E Spironolactone
Hyperkalaemia
Stomach cramps
154
S/E Amiodarone
Clubbing
Non-productive cough
Fine crackles on ausc
Reduced chest expansion
Thyroid disease
Corneal deposits
155
S/E Statin
Myalgia
Liver impairment
156
S/E BB
Bradycardia
Bronchospasm
Cold peripheries
157
