Pharmacology Flashcards
1
Q
What is pharmacokinetics?
A
What the body does to a drug
2
Q
What are the four actions of drugs in the body?
A
- Absorption
- Distribution
- Metabolism
- Excretion
3
Q
What are mechanisms of absorption? (4)
A
- Active transport
- Diffusion
- Facilitated diffusion
- Endocytosis
4
Q
What are the variables of absorption? (4)
A
- pH
- Vascularity (e.g. shock reduces SC absorption)
- Surface area
- Contact time (e.g. with food = slower gastric emptying)
5
Q
What is the definition of bioavailability?
A
Rate and extent to which an administered drug reaches the systemic circulation (e.g. IV = 100%)
6
Q
What is first pass effect?
A
A phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. First have to pass
- Intestinal lumen
- Intestinal wall
- Liver
- Lungs
7
Q
Where are microsomal enzymes located? Give an example.
A
SER e.g. cytochrome p450
8
Q
What is the role of microsomal enzymes in a) phase 1 rxns and b) phase 2 rxns?
A
Phase I reactions – biotransform substances
Phase II – glucuronidation
9
Q
Where are non- microsomal enzymes located? Give an example.
A
Cytoplasm and mitochondria e.g. conjugases/esterases/alcohol dehydrogenase
10
Q
What is the purpose of phase 1 metabolism?
A
polarise lipophilic drugs, reduction / oxidation / hydrolysis
catalysed by cytochrome P450 system
11
Q
What is the purpose of phase 2 metabolism?
A
conjugation, e.g. glucuronic acid, polarisation of drugs to be excreted by renal or biliary systems
12
Q
What is first order metabolism?
A
catalysed by enzymes, rate of metabolism directly proportional to drug concentration
13
Q
What is zero order metabolism?
A
enzymes saturated by high drug doses, rate of metabolism is constant, e.g. ethanol, phenytoin
14
Q
What is pharmacodynamics?
A
- What the drug does to the body
- Its effect on cellular receptors via signal transduction
15
Q
Are microsomal enzymes seen more in phase 1 or phase 2 reactions?
A
Phase 1.
Non- microsomal = phase 2
16
Q
Which cranial nerves are parasympathetic?
A
CN 3, 7 , 9 , 10
17
Q
What neurotransmitter do
a) parasympathetic
b) sympathetic
post- SYNAPTIC nerves release?
A
BOTH release acetylcholine
18
Q
What kind of receptor does acetylcholine act on?
A
NICOTINIC receptor
19
Q
What neurotransmitter do
a) parasympathetic
b) sympathetic
post-GANGLIONIC nerves release and what do they act on?
A
a) acetylcholine -> muscarinic receptor
b) noradrenaline -> alpha/beta adrenoreceptors
20
Q
What is the principal neurotransmitter in the body?
A
Acetylcholine
21
Q
What receptor does Ach interact with in the somatic nervous system?
A
Post-synaptic nicotinic receptors at the neuromuscular junction.
22
Q
Give examples of adverse muscarinic agonist effects.
A
- Diarrhoea.
- Urination.
- Miosis.
- Brachycardia.
- Emesis (vomiting).
- Lacrimation.
- Salivation.
23
Q
Give 2 examples of Ach action in the CNS.
A
- Motion sickness; Ach stimulates the vomiting centre in the brain.
- Ach leads to increase dopamine re-uptake and so can worsen the symptoms of Parkinson’s.
24
Q
Briefly describe catecholamine synthesis.
A
Tyrosine -> L-DOPA -> Dopamine -> Noradrenaline -> Adrenaline.
25
What is the function of α1 activation?
1. Vasoconstriction (raise blood pressure)
| 2. Increased closure of internal sphincter of the bladder
26
What is the primary function of α2?
α2 is responsible for pre-synaptic inhibition; it inhibits NAd release.
27
Give an example of an alpha 1 agonist/antagonist
```
agonist = phenylephrine (nasal decongestant)
antagonist = Tamsulosin ( treat BPH)
```
28
What would an α1 adrenergic antagonist do?
1. Vasodilation.
| 2. Relaxation of bladder neck = reduced resistance to bladder outflow.
29
What are the primary functions of β1?
1. Increased cardiac effects e.g. force, rate and conduction.
2. Increased renin secretion.
30
What would a β1 adrenergic antagonist do?
1. Reduce CO.
| 2. Reduce renin secretion.
31
Give an example of a beta 1 agonist and their use
epinephrine/dopamine (inotropes) e.g. in septic shock
32
Give an example of a beta 2 agonist and their use
SABA/LABA e.g. in asthma
33
What diseases could an β1 adrenergic antagonist be used in the treatment of? Give an example of a drug
Hypertension, angina and arrhythmia
| e.g. selective/non-selective beta blockers ( atenolol=just B1, propanolol B1/2 so may cause wheeze)
34
How do beta blockers lower blood pressure?
By reduction in cardiac output and gradual
| reduction in central sympathetic outflow activity
35
What is the action of an INOTROPIC drug?
Affects the force of cardiac contraction
36
What is the action of a CHRONOTROPIC drug?
Affects the heart rate
37
Is propanolol positively or negatively inotropic?
negatively inotropic
38
Give some of the diseases beta blockers are used to treat
```
- Angina
• MI prevention
• High blood pressure
• Anxiety
• Arrhythmias
• Heart failure
```
39
What are some of the side effects of beta blockers
* Tiredness
* Cold extremities
* Bronchoconstriction
* Bradycardia
* Hypoglycaemia
* Cardiac depression
40
Give an example of a parasympathetic muscarinic antagonist. What would it's action be
Atropine
| Used in life-threatening bradycardias and in cardiac arrest (blocks M2 whcih is responsible for slowing heart rate)
41
Give examples of antibiotics which act on bacteria cell wall
1. Beta lactams (penicillin/cephalosporin)
2. Vancomycin
3. Polymyxins
42
Give examples of antibiotics which act on nucleic acid synthesis
1. Trimethoprim
| 2. Quinolones
43
Define pain.
An unpleasant sensory and emotional experience associated with actual or potential tissue damage.
44
Define acute pain.
Pain caused by nociceptor activation. It is of short duration,
45
Define chronic pain.
Pain that is on-going or persistent, it lasts for >3-6 months.
46
Define neuropathic pain.
Pain caused by a primary lesion or dysfunction of the nervous system.
47
Define nociceptive pain.
Pain caused by actual or potential damage to non neural tissue, it is due to nociceptor activation.
48
Are A delta fibres myelinated or unmyelinated?
Myelinated
49
Are C fibres myelinated or unmyelinated?
Unmyelinated
50
Describe the type of pain that A delta fibres conveys.
Quick, sharp, localised. (A=acute)
51
Describe the type of pain that C fibres conveys.
Slow, dull, spread out.
52
What does potency mean?
Measure of how well a drug works
53
What is an agonist?
A compound that binds to a receptor and activates it
54
What does affinity mean?
Describes how well a ligand binds to the receptor
55
What does efficacy mean?
Describes how well a ligand ACTIVATES the receptor. (only agonists show efficacy)
56
What are the main actions of NSAIDs and give examples of drugs.
- Analgesic
• Anti-pyretic (reduces fever)
• Anti-inflammatory
e.g. ibuprofen/ASPIRIN
57
How is the mechanism of NSAIDs?
They inhibit the enzyme
cyclooxygenase (COX1/2) which are
responsible for prostoglandin synthesis. Prostaglandins are responsible for inflammation and pain. Therefore NSAIDs reduce symptoms of inflammation and pain.
58
What is a disadvantage of long term NSAID use?
NSAIDs can cause gastric bleeding. They inhibit COX 1 which is needed for prostaglandin synthesis and prostaglandins are needed for gastric mucus production.
59
Give an example of ACEi and its function
Ramipril (anti - hypertensive)
60
What is the mechanism of ACEi?
- Work by inhibiting ACE thereby preventing the conversion of angiotensin I to angiotensin II
```
- This means there is less angiotensin II so less bind to
angiotensin receptors (AT1) resulting in reduced vasoconstriction and thus hypertension
```
- There is also less aldosterone release further reducing hypertension
61
Give a side effect of ACEi
DRY COUGH
- angioedema
- AKI/hyperkalaemia
- hypotension
62
Give an example of a COX inhibitor
aspirin/paracetamol/NSAID
63
How does aspirin work?
IRREVERSIBLY blocks the active site of the COX enzyme resulting in IRREVERSIBLE INACTIVATION -> Decreased TXA = Decreased Platelet Aggregation = Increased Bleeding Time
64
What kind of drug is clopidogrel/ticagrelor?
ADP receptor inhibitor/p2y12 inhibitor
65
How do P2Y12 inhibitors work?
Block ADP Receptors = Inhibit Platelet Aggregation
66
What is pain treatment focused on?
1. Reducing excitatory neurotransmitters and nerve excitation.
2. Enhancing inhibitory neurones.
67
What is an adverse drug reaction?
A noxious and unintended response to a drug.
68
Rawlins-Thompson system: Describe a type A adverse drug reaction.
- Augmented.
- Very common.
- Predictable from physiological effects of the drug.
- Often dose related.
69
Rawlins-Thompson system: Describe a type B adverse drug reaction.
- Bizarre.
- Unpredictable.
- Immunological mechanisms and hypersensitivity.
- Often there is a history of allergy.
70
Rawlins-Thompson system: Describe a type C adverse drug reaction.
- Chronic.
| - Occurs after long term therapy.
71
Rawlins-Thompson system: Describe a type D adverse drug reaction.
- Delayed.
| - Occurs many years after treatment.
72
Rawlins-Thompson system: Describe a type E adverse drug reaction.
- End of use.
| - Withdrawal reaction after long term use; complications of stopping medication.
73
What is the treatment for a type A adverse drug reaction?
Reduce the dose.
74
What is the treatment for a type B adverse drug reaction?
Withdraw drug immediately!
75
Why are drug interactions such a big problem today?
1. Ageing population.
2. Polypharmacy.
3. Increased use of over the counter drugs.
76
Give 5 patient risk factors for drug interactions.
1. Old age.
2. Polypharmacy.
3. Renal disease.
4. Hepatic disease.
5. Genetics.
77
Give 3 drug related risk factors for drug interactions.
1. Narrow therapeutic index.
2. Steep dose/response curve.
3. Saturable metabolism.
78
Name 3 types of drug interaction.
1. Synergy; interaction of 2 compounds leads to a greater combined effect.
2. Antagonism; one drug blocks another.
3. Other.
79
How might drug interactions affect drug metabolism?
If a drug inhibits or induces CYP450 it might affect the metabolism of another drug.
80
How does grapefruit juice affect CYP450? And what drugs might this impact on?
Grapefruit juice is a CYP450 inhibitor, it affects CYP3A4 specifically and increases the bioavailability of some drugs e.g. Ca2+ channel blockers and immunosuppressants.
81
What is morphine metabolised to?
Morphine 6 glucuronide.
82
Give 5 side effects of opioid use.
1. Respiratory depression.
2. Sedation.
3. Nausea.
4. Vomiting.
5. Constipation.
83
Describe the dose-response curve for morphine.
As dose increases response increases. This association is initially rapidly and then the graph plateaus. It is not sigmoidal!
84
Name a protein that can inhibit apoptosis.
BCL-2; it inhibits pro-apoptotic proteins e.g. caspase and therefore inhibits apoptosis.
85
What disease might develop in someone with a non-functional BCL-2 protein?
Cancer.
86
Where are mast cells found?
They are only found in tissues, not in the blood!
87
Name a local anaesthetic.
Lidocaine.
88
How do local anaesthetics work?
They inhibit pain by stopping impulse conduction in sensory nerves.
89
What drug inhibits ACh release at the NMJ?
Botulinum toxin.
| It is used to treat urinary incontinence and also cosmetically as a muscle relaxant.
90
Describe the action of botulinum toxin at the NMJ,
Botulinum toxin inhibits Ach release at the NMJ. Protease degrade vesicle proteins.
91
How do diuretics work?
They inhibit 'symporters' in the loop of henle.
| - This leads to increased H2O excretion and decreased salt reabsorption and so BP decreases.
92
Give an example of loop of henle diuretics.
- Furosemide, act on the ascending loop.
| - Thiazides, act on the distal tubule.
93
How can drugs be developed?
1. Serendipity, by chance. e.g. penicillin.
| 2. Rational drug design. e.g. propranolol.
94
Describe how rational drug design works.
Rational drug design is focused on developing an antagonist from an agonist. It looks at solubility, electrostatic charge and bulk.
95
How does heparin work?
Activates Antithrombin (decreased thrombin and factor Xa)
96
What are the SE of heparin?
Bleeding, thrombocytopenia (heparin-induced thrombocytopenia), osteoporosis
97
How does warfarin work?
Anti-Vitamin K = Decreased FII (prothrombin)/VII/IX/X and Protein C/S
98
What are SE of warfarin?
Bleeding, Skin/Tissue Necrosis, Teratogenic
99
How does RAAS respond to LOW BP?
1. Baroreceptors in afferent vascular walls detect low pressure
2. Decreased Na+ transport to macula densa cells
3. Increased sympathetic stimulation (beta 1)
4. JG cells release RENIN
100
What are the effects of angiostensin II? (6)
1. Systemic arteriole vasoconstriction
2. Kidney efferent>afferent constriction = Increase
3. Glomerular Pressure = Maintain GFR despite lowered overall kidney blood flow
4. Kidney proximal tubule/thick ascending limb Na+/H+ exchanger stimulation = Increased Na+/HCO3/H20 reabsorption
5. Adrenal cortex = Aldosterone release
6. Posterior Pituitary = ADH release
101
What are the functions of ACE?
Catalyses conversion of angiotensin I to angiotensin II
| Degraded by bradykinin
102
How do loop diuretics e.g. FUROSEMIDE work?
Inhibit Na/K/Cl cotransporter of thick ascending limb
103
When are loop diuretics used?
Oedematous States (HF, Cirrhosis, Nephrotic Syndrome, Pulmonary Oedema), HTN, Hypercalcaemia
104
What are SE of loop diuretics?
ototoxicity, hypokalaemia, dehydration, AKI, gout
105
How do thiazide diuretics work?
Inhibit Na/Cl cotransporter of distal tubule
106
What is a spironolactone?
Competitive aldosterone receptor antagonists in collecting tubules (K+ SPARING)
107
Give some of SE for corticosteroids
- weight gain
- buffalo hump/ moon face
- depression/anxiety
- thin skin
- hypertension
108
How does methotrexate work?
prevents folate synthesis = prevents DNA synthesis
109
Describe monitoring for pts on methotrexate
baseline, every 2-3 months
| CXR, FBC, LFT, U&E (not cxr every 2 months)
110
What are the consequences of prescribing a drug with a narrow therapeutic ratio? (example?)
Increased risk of toxicity, decreased chance of effective dose e.g. digoxin, vancomycin)
111
What is the procedure for poisoning <1hr of ingestion?
PO activated charcoal
112
What is the pathology of paracetamol overdose?
1. Phase 2 conjugation pathway saturated
2. Alternative pathway used = NAPQI = glutathione depletion
3. Glutathione depletion = liver/renal necrosis
113
How do you treat paracetamol overdose?
IV N-acetylcysteine
