Pharmacology Flashcards
(214 cards)
1
Q
Paracetamol PK
A
A: PO/ IV/ PR
D: Peak blood levels are reached 30-60min following oral administration.
Minimal PB
T1/2 2h - prolonged liver failure and tox
M: hepatic 95% glucoronidation and sulfation
5% is metabolised via P450 dependant glutathione conjugation pathway
E:<5% is excreted unchanged.
2
Q
Paracetamol toxicity in OD mechanism
A
glucuronidation and sulfation saturated.
P450 pathway becomes important.
Metabolised to the toxic reactive metabolite NAPQI .
NAPQI is detoxified by glutathione (GSH) but is depleted in toxicity.
NPAQI reacts with nucleophilic cellular proteins.
Causes direct cellular injury, ROS further enhances toxicity
3
Q
Signs + symptoms paracetamol toxicity
A
Liver injury can lead to liver failure (centrilobular necrosis).
GI: Nausea, Vomiting, diarrhoea, abdominal pain.
CNS: dizziness, disorientation, coma (high doses).
Metabolic: HAGMA.
Renal failure (Tubular necrosis).
4
Q
Sodium valproate PK
A
A: PO/ IV high bioavailability
D: Peak plasma 2 hours, highly protein bound, low VD, T1/2 9-18h
M: Hepatically to glucuronide conjugate
E: in urine
5
Q
Describe capacity limited protein binding kinetics
A
Sodium Valproate highly bound to plasma proteins (90%) at lower concentrations
This mechanism is saturated at higher concentrations leading to an increase in free drug
–> apparent increased clearance of drug at higher doses and reduction T1/2:
variable clearance
Thus dosage is preferred as a sustained release preparation
6
Q
Mechanism of beta blockers
A
- Bind to beta receptors in the heart, lung and endocrine tissue.
- Beta receptor activation by circulating catecholamines is antagonized by beta blockers
- Selective bind Beta 1 receptors only, non-selective bind Beta 1 and 2 receptors.
- Most are pure antagonists
7
Q
Metoprolol PK
A
- Absorption: rapid and complete, given orally (onset 1-2 hours) and intravenously (onset 20mins when
infused over 10mins) - Bioavailability: 50% due to first pass effect
- Distribution: 3.2 to 5.6L/kg LARGE; crosses the blood brain barrier
- Protein binding: 10-12% to albumin
- Metabolism: Extensively hepatic via CYP2D6, significant first pass effect
- Half-life elimination: 3-4 hours in adults
- Excretion: Urine 95%
8
Q
SE Beta blockers
A
- Cardiac: hypotension, bradycardia, heart block, depressed myocardial contractility, heart failure, dizziness
- Neurological - fatigue, depression, sexual dysfunction, nightmares
- Vascular - peripheral vasoconstriction, Raynaud’s, claudication
- Respiratory - bronchospasm
9
Q
Types of exogenous insulin
A
Ultra short - llispro, aspart, glulisine
Short - neutral (actrapid)
Mixed - aspart with protamine, neutral with isophane
Long - glargine, detemir, isophane
10
Q
Insulin administration regimens
A
- Basal bolus - short with meals, long OD/BD
- Continuous SC infusion of short with boluses as needed
- Split mixed OD/ BD
- IV infusion in DKA
11
Q
Adrenaline PK
A
A: IV/PO/SC/neb
D: onset seconds, duration 2m, 50% PB, does not cross BBB
M: Terminated synaptic terminals, met by COMT and MAO
E: urine
12
Q
Effects of adr by organ
A
Cardio - chrono and iono
Vasc - vasoconstrict
GI - relaxation smooth muscle
Resp - bronchodilation
Salivation - reduced
Eye - pupillary dilation, dec IO pressure
Liver - inc glycogenolysis
Metabolic acidodis
Lipolysis
13
Q
Mechanism phenytoin
A
Na channel blockade leading to inc GABA and decreased glutamate
14
Q
Drugs that interact with ACEi
A
NSAIDs - make les effective
Potassium supplements
Diuretics - hypotension
Anaesthetics - hypotension
Lithium - hyperkalaemia
K sparing diuretics - hyperkalaemia
Other nephrotoxics - AKI
15
Q
Gentamicin mechanism
A
Aminoglycoside
Bacteriocidal
Inhibitis protein synhesis acting on 30s ribosome
Conc dependant killing
O2 dependant diffusion
16
Q
Gentamicin PK
A
A: IV/ IM, 5mg/kg
D: minimally PB, T1/2 2-3h, post antibiotic effect
M: not
E: renal
17
Q
Benefits of ARBs over ACEi
A
no effect on bradykinin therefore no cough or angiooedema
more complete inhibition of action angiotensin II
18
Q
Mechanism of salbutamol
A
Binds B2 adrenergic receptor
Stimulates adenyl cyclase –> inc cAMP
Bronchodilation
Inhibition release bronchoconstrictor mediators from mast cells
19
Q
Mechanism digoxin
A
Inhibitor NaKATPase
- inc intracel Na and dec K
- in intracellular Ca -> inc inotropy (contractility)
Electrical effects
- shortens AP and atrial and vent refractory period
- increased automaticity
Parasympathetic effects at low dose (symp at high)
20
Q
Factors predisposing to digoxin toxicity
A
Electrolyte imbalance
Drugs e.g. amiodarone (inc conc), potassium depleting drugs
Organ disease - renal failure or hypothyroidism
21
Q
Mechanism paracetamol toxicity
A
Goes from 1st to 0 order kinetics
Conjugation with glucuronide and sulphide becomes saturated
Glutathione becomes depleted
22
Q
Mechanism NAC
A
Sulfhydryl donor restoring glutathione levels
Alternate substrte toxic metabolite
NAPQI back to paracetamol
23
Q
Mechanism of TCA
A
inhibition of seratonin and NA reuptake
Aslo blocks: Na, K, M1, H1, alpha 1
24
Q
Clinical manifestations TCA OD
A
- Cardiac - tachy, prolonged QRS and QTc, hypotension (anti alpha 1)
- Neurological - decreased GCS, seizure
- Anticholinergic - mydriasis, warm, urinary retention
25
Clopidogrel PK
A: PO, 75-600mg, pro drug
D: T1/2 30-60m life span of plt effect
M: Activated by cyp450
E: Urine and faeces
26
Classes of thrombolytic agents
TPA e.g. tenecteplase
Streptokinase - protein synthed by streptococci
27
Mechanism of TPA
converts plasminogen to plasmin
Plasmin major fibrinolytic enzyme
28
Side effects of prazosin
Hypotension and dizziness
Reflex tachycardia
Headache
Lassitude
29
Ibuprofen PK and PD
PK - good absorption not changed by food, highly PB, highly metabolised p450
PD - non selective reversible COX inhibitor
Inhibits PG synthesis
Antipyretic, analgesic, anti-inflammatory
30
Mechanism ondansetron
Predominantly peripheral 5HT3 antagonist on intestinal vagal
Some effect centrally CRTZ and vomiting centre
Good for vagal mediated e.g. post op and chemo, less motion sickness
31
SE ondansetron
Headache, dizziness, constipation
Small increase QTc
32
Dose related side effects carbamazepine
cerebellar - nystagmus, ataxia, diplopia
drowsiness
anticholinergic
hypotension
33
Carbamazepine drug interactions
Enzyme inducer - reduced wararin, phenytoin, OCP
34
Side effects metronidazole
neuro - headache and dizziness
Gastro - metallic taste and N+V
Disulfiram like effect
Thrombophlebitis
35
Organisms treated by azithromycin
gram +ve and some -ve
staph, strep
haemophylis, chlamydia
mycoplasma and legionella
campylobacter
36
Systemic effects ketamine
NMDA receptor antagonist
CVS - stable
Neuro - dissociative anaesthesia nystagmus
Respiratory - airway reflexes in tact
37
Mechanism verapamil
Blocks voltage gated calcium channels decreasing calcium influx to cell
Decreases AV nodal conduction and cardiac contractility
38
Definition 0 order kinetics
Independent of drug concentration elimination occurs at constant rate
39
Mechanism vancomycin
Glycopeptide
Bacteriocidal
Inhibits cell wall synthesis
40
Organisms targeted by vancomycin
Gram +ve - staph MRSA
G +ve anaerobes - c dif
41
Factors affecting lignocaine absorption
Dose
Blood flow
Site
vasoconstrictors
Drug tissue binding
42
Mechanism benzos
bind gabaA receptor
Increased frequency chloride channel opening and GABA transmission
43
Mechanism atropine
Competitive reversible muscarinic ACH receptor antagonist
44
Atropine PK
A: IV/ top/ PO
D: wide, T1/2 2h, crosses BBB
M: 40%
E: renal (60% unchanged)
45
PK octreotide
A: IV
D: T1/2 80m
M: Liver
D: kidney 20% unchanged
46
Clinical use octreotide
Oesophageal bleed
Sulphonylurea OD
Carcinoid tumour
47
Bupivocaine PK
A: SC
D: Onset 28m, T1/2 3-5h, duration 4-8h, highly PB, wide VD
M: H E: R
48
Bupivocaine toxic effects
Arrhythmia + hypotension + arrest
Seizure
Sedation
49
Paracetamol MOA
Selective cox2 inhibitor
50
How does azithromycin differ from other macrolides
Single daily dosing
T1/2 2-4d vs 2-4h
Higher tissue penetration
Excreted in the urine unchanged
51
Ciprofloxacin pk
Iv/po/top
Dose 500mg po BD or 400mg TDS IV
Bioavailability 0.8+
T1/2 3-5h
Renal elimination (dose adjust cr cl<50)
52
Spectrum ciprofloxacin
Excellent gram -ve
Moderate gram +ve
Staph
Mycoplasma
Legionella
Pseudomonas
Anthrax
UTI, bacterial diarrhea, STI, bone and joint
53
MOA ciprofloxacin
Blocks DNA synthesis
DNA gyrase inhibitor
54
Suxamethonium MOA
Depolarising NMB
Causes blockade at motor endplate nicotine receptors
phase 1 depolarising
Opens channels and causes depolarisation motor end plate
Membranes remain depolarised and unresponsive to subsequent impulses
Phase 2 desensitising
55
Suxamethonium PK
Onset 30-60s
Duration 2-8m
Hydrolysed by plasma cholinesterase
56
Suxamethonium SEs
Bradycardia
Muscle pain
Hyperkalaenia
Raised IO and intragastric pressure
Malignant hyperthermia
Prolonged paralysis with reduced cholinesterase
57
Oxycodone PK
A: oral good bioavailability
D: wide VD, t1/2 3-4 (longer cr)
M: hepatic, low first pass metabolism compared others
E: renal
58
Mechanism sulphonylureas
Increase release insulin
Inhibit k efflux
Cause Ca influx causing insulin release
M hepatic
E renal
59
Distribution half life propofol + elminination
Distribution - 2-4m
Elimination - 4-23m
60
Limit adverse effects with propofol - methods
Titrate small doses
Care with benzos and opiates
Reduce dose elderly
Caution hemodynamically unstable
61
Adenosine MOA
Naturally occuring nucleoside
Blocks av conduction
Activates inward rectifier k channel - hyperpolarises cell
62
Drugs interacting adenosine
Reduced effect by theophylline
Increased effect by dipyridamole
63
Factors affecting local anaesthetic absorption
Dose
Site
Tissue blood flow
Combined with vasoconstrictors
64
Mechanism ARBs
Competitive selective antagonist AT1 receptor
Vasodilation and inhibition aldosterone secretion
65
Contraindications ARBs
Non diabetic renal failure
Pregnancy
RAS
Allergy
66
Factors affecting clearance
Concentration - dose / bioavailability
Elimination - blood flow to kidney and liver, protein binding
67
Rivaroxaban PK
A: oral
D: small VD, highly PB, max level 3h, T1/2 5-14
M hep E renal
68
Rivaroxaban vs warfarin
No monitoring
More rapid onset/ offset
Less drug interaction
Wider therapeutic index
However not suitable in renal failure
69
Alcohol PK
Rapid GI absorption
VD toral body water
Peak 30m
1st to 0 order kinetics
Metabolized alcohol dehydrogenase
Excreted in lungs and urine
70
MOA octreotide
Somatostatin analogue
Inhibits insulin and gastrin release
Reduced portal vein pressure
71
Fentanyl PK
A: IV due to high 1st pass
Also trans dermal, intranasal, sc
D: duration 1-2h
M: hepatic with no active metabolites
72
Mechanism action metoclopromide
Dopamine D2 antagonist at CTZ
Increased oesophageal motility
Increased LOS pressure
Increased gastric emptying
73
Metoclopramide side effects
CNS: Anxiety, restlessness, insomnia
Dystonic reaction, parkinsonian effects
Prolactinaemia
74
Ondansetron side effects
Headache, dizziness, constipation
Mild increase QTc
75
Mechanism penicillins
Beta lactam abx
Bacteriocidal
Bind PBP
Interfere transpeptidation of bacterial cell wall synthesis
76
Side effects flucloxacillin
Allergy and anaphylaxis
Hepatic cholestasis
GI
Renal interstitial nephritis
77
Ketamine PK
Iv
Highly lipid soluble
Effect terminated by redistribution
Elimination half life 2-3h
Hepatic metabolism
Renal excretion
78
Dexamethasone vs hydrocortison
30* more potent and longer acting
79
Antiinflammatory and immunosuppressive effects of glucocorticoids
Suppress inflam mediators inc cytokines
Inhibit macrophages and APCs
Affect concentration, distribution and function peripheral leukocytes
80
Midazolam PK
A: IV IM PO
D: poor oral bioavailability, water soluble, highly PB
T1/2 1.5-2.5h
M H ER
81
How to calculate dose
Vd x target conc
82
Side effects doxycycline
Teeth and bone discolouration
Photosensitivity
Nausea and vomiting
Helatotoxicity
83
Indications doxycycline
Malaria
Resp
STIs
Skin e.g. acne
Vibrio e.g. cholera
84
Spectrum ceftriaxone
Not degraded by betalactamases
Gram +ve and extended gram -ve
Active against haemophilis and neisseria
Not antipseudomonal
T1/2 8h
85
Effects of amiodarone on the heart
Increases action potential duration due to blockade of K current
Prolings QT due to block K
86
Lithium side effects
Neuro - ataxia, tremor, confusion
Thyroid - reversible hypothyroidism
Renal - polyuria and polydypsia (nephrogenic diabetes insipidus)
Cardio - oedema
87
Lithium PK
A PO good
D TBW, T1/2 20h
M not
E unchanged in urine
88
Mechanism of GTN
Increased NO activated cGMP leading to smooth muscle relaxation
89
Effects and indication GTN
Venodilation - reduced venous return
Arterial dilation - Decreased BP
Decreased myocardial O2 consumption
ADR hypotension, headache, reflex tachycardia
Angina, MI, pulmonary oedema, hypertensive emergency, adjunct aortic dissection
90
Gliclazide PK
A: good bioavailability
D: highly PB, t1/2 12h
M: hepatic to inactive
E: renal
91
SE sulphonylureas
Hypoglycaemia
GI
92
Mechanism metoclopromide dystonic reaction
Dopamine antagonist causing imbalance between anticholinergic and dopaminergic transmission basal ganglia
93
Mechanism benztropine
Antimuscarinic
Blucks muscarinic anticholinergic receptors
94
What is vitamin K
Fat soluble vitamin
Usually synthesized by bacteria in colon
95
Mechanism warfarin reversal
Anticoagulant
Prevents reductive metabolism inactive vitamin K to active form
Therefore produces biologically inactive 2,7,9,10,c,s
Vit K activates 2,7,9,10
Onset 6h
Complete 24h
96
Features digoxin toxicity
Hyperkalaemia
Yellow green vision
GI upset
Arrhythmias or heart block
Lethargy and headache
97
Why is fluclox on empty stomach
Inactivated by gastric acid
Binds to food proteins
98
Mechanism of vecuronium
Non depolarising neuromuscular blocker
Competitive antagonist for ACh at nicotinic receptors at the neuromuscular junction
99
Vecuronium PK
Highly polar
Poor GI absorbtion
Onset 1m
Max 3-5
Duration 30m
Half life 20-40m
Rapidly distributed to extracellular space
Hepatically metabolised
Majority eliminated by liver
100
Which receptors does NA work on
Mainly alpha 1 and some 2
Small on beta 1 and 2
101
How does NA increase BP
Alpha 1 vasoconstriction in TPR and diastolic
Beta 1 myocardial contractility inc SBP
N.b minimal change in HR due to baroreflex
102
Salbutamol PK
A: many, rapid and completely absorbed alveoli, oral first pass 50%
Rapid onset, max 15-30m
Half life 3-6 hours
M h E r
103
Mechanism morphine
Mu delta kappa agonist
Reduces pre synaptic glutamate transmission
Inhibits post synaptic neurons
104
Mechanism opiate induced respiratory depression
Inhibition of brainstem respiratory controls, less sensitive to hypercapnoea
105
Clinical effects and dose of mannitol
Draws water out of cells and reduces intracellular volume
Reduces intraocular pressure
Diuresis
Hypernatraemia and hyperkalaemia
1-2mg/kg over 15m
106
Adverse effects ACE inhibitors
Dry cough and angioedema
Hypotensions
ARF
Hyperkalaemia
107
Duration lidocaine and bupivocaine
Lidocaine 1-2h or 2-4 with adrenaline
Bupivocaine 3-6h
108
Contents plasmalyte
Osmolality 294
Na140
Cl 98
K5
Mg 1.5
Acetate 27
Gluconate 23
109
Benefits hartmanns over saline
Less hyperchloraemic acidosis
Bicarbonate can help buffer acidosis
110
Adverse effects sodium valproate
Hepatotoxicity
N&V
Cerebellar
Fine tremor
Weight gain, hair loss
Thrombocytopenia
Teratogenic
OD - coma and cerebral oedema
111
Sodium valproate interactions
Enzyme inhibitor
Decreases metabolism phenytoin and carbamazepine
112
Classification of corticosteroids
Anti-inflammatory action - dex 30x more potent hydrocortisone
Mineralocorticoid activity - fludrocortisone 250x hydrocortisone
Length - dex and beta long
113
Drug potency definition
Dose or concentration needed to achieve 50% maximal effect
114
Define bioavailability
Fraction of unchanged drug reaching the systemic circulation
115
Metformin PK
A: Well absorbed
D: not PB, T1/2 1.5 - 3h
M: not
E: unchanged urine
116
Factors affecting bioavailability
Extent of absorption - gut wall metabolism, hydrophobic or hydrophilic
First pass metabolism - liver metabolism before reaches systemic circulation
Rate of absorption - site of administration and drug formulation
117
Toxic effects of magnesium
Flushing
Hypotension
Arrhythmia
Loss of reflexes
Respiratory depression
118
Use of magnesium
Eclampsia and pre
Anticonvulsant
Antiarrhythmic
Bronchodilator
Lowers BP
119
Mechanism of heparin
binds endogenous antithrombin and enhances its activity. Antithrombin inhibits factors 2,9,10
120
Side effects heparin
Bleeding, heparin induced thrombocytopenia, osteopoerosis, mineralocorticoid deficiency
121
Advantages LMWH
Have equal efficacy, increased SC bioavailability,
require less frequent dosing, and less monitoring
122
Side effects of quinolones
Prolonged QT
Deranged LFTs
Nausea, vomiting, diarrhoea
Photosensitivity
Rash
Tendonitis and cartilage damage
Allergy
123
Furosemide PK
A PO/ IV
Bioavailability 50 (10-100)
Highly pb
Peak 30m IV, 1h oral
Half life 1.5-2h
Minimal hepatic metabolism
50 conjugated in kidney 50 unchanged
124
Side effects furosemide
Electrolyte - hypo k na MG
Hypotension
Metabolic alkalosis
Allergy
Ototoxicity
125
Mechanism acyclovir
Inhibits viral DNA synthesis
Irreversible binding to viral DNA polymerase
126
Acyclovir PK
Oral or IV
Short half life 2.5h
Wide distribution
Low oral bioavailability
Mostly excreted unchanged in urine
127
Side effects acyclovir
Nausea vomiting diarrhea
Tremor delirium.
Renal dysfunction
128
Route and dose of olanzapine
Oral or parenteral
10-20mg
129
Haloperidol PD
D2 antagonist
High EPSEs
Minimal 5ht and H1 blockade
Minimal hypotension
130
Drug biotransformation
Metabolism to allow drugs to become inactive or by increasing excretion by making them more hydrophilic or metabolism them to a less active agent
131
Phase 1 and 2 reactions
1 - unmasking functional group to become more polar metabolite
2 - conjugation with endogenous substrate to become highly polar conjugate
132
Metabolism suxemethonium
Rapid phase 1 hydrolysis by pseudocholinesterase and butyrcholinesterase
133
Factors determining VD
Drug factors - lipid solubility, pk, protein binding
Patient factors - age, gender, body fat
134
VD TCAs
High
High tissue conc in well perfused organs e.g. heart and brain
135
Therapies to reduce TCA tissue distribution
Alkalinisation increases plasma protein binding of free drug
136
Moxifloxacin PD
Improved activity against gram positive inc s pneumonia
Gram -ve
Modest anaerobic
Atypical - mycoplasma and chlamydia
TB
137
Mechanisms of drug interactions with warfarin
PK enzyme induction and inhibition
Altered PB
PD syngergism, competitive antagonism (vit K)
138
Tenecteplase va streptokinase
Tenecteplase clot specific
Tenecteplase can be given as bolus
Streptokinase higher risk allergy or anaphylaxis
139
Tenecteplase va streptokinase
Tenecteplase clot specific
Tenecteplase can be given as bolus
Streptokinase higher risk allergy or anaphylaxis
140
Metronidazole PK
PO IV
Good oral bioavailability
Low pb
Half life 7.5
Metabolized liver
Excreted kidney
141
Metronidazole MOA and spectrum
Disrupts electron transfer chain DNA
Bacteriocidal
Anaerobic positive and negative e.g. c dif and bacteroides
Antiprotozoal against giardia
142
Metronidazole MOA and spectrum
Disrupts electron transfer chain DNA
Anaerobic positive and negative e.g. c dif
Antiprotozoal against giardia
143
MOA osetalmivir and zanamivir
Neuraminidase inhibitors, disrupt viral replication
Active against flu a and b
144
Side effects vancomycin
Red man syndrome
Ototoxicity and nephrotoxicity
Phlebitis
145
Rifampicin MOA
RNA polymerase inhibitor
Bacteriocidal
146
Rifampicin side effects
rash, nephritis, thrombocytopenia, cholestasis, orange body fluids
Hepatically excreted, well absorbed
147
Cause tachyphylaxis GTN
Decreased NO release due to decreased sulfyhdryl groups
Systemic compensation with salt and water retention
148
Clinical effects midazolam
Anti convulsant
Anxiolytic
Amnesic
Sedative hypnotic
Antiemetic
149
Antipseudomonal antibiotics
CMAC
Cephalosporins (x3)
Meropenem
Aminoglycosides
Ciprofloxacin
150
Spectrum of chloramphenicol
Aerobic and anaerobic
Positive and negative
Ricketsia not chlamydia
151
What is an antiseptic
Chemical disinfectant applied to living tissue
Decreases number of organisms by killing, removing or diluting them
Generally low toxicity
152
Mechanism resistance to fluoroquinolones
Point mutations on quinolone binding region
Change in permeability of organisms
153
Fluoroquinolone side effects
Prolonged QT
GI
Rash
Photosensitivity
LFTs
Cartilage growth inhibition in kids
154
Norfloxacin vs ciprofloxacin
Ciprofloxacin greater activity against gram positive and negative
155
Bacterial resistance to gentamicin
Transferase inactivates drug
Impaired cell entry
Altered ribosomal receptor protein
156
Bacterial resistance to gentamicin
Transferase inactivates drug
Impaired cell entry
Altered ribosomal receptor protein
157
Advantages single daily dosing gentamicin
Decreased time above toxic level
Concentration dependant killing
158
What is an antagonist
Antagonists bind to receptors but do not activate them
They prevent agonist from activating receptors
159
Difference between competitive and non competitive antagonist
Competitive - competes with agonist for same binding site, agonist still able to evoke effect at increasing concentration
Non competitive - binds allosterically causing the receptor to no longer be available for binding, effect cannot be overcome with increasing doses agonist
160
Effect competitive antagonist has on concentration effect curve
Shifts down
Effect on Y axis
161
Definition elimination half life
Time taken to change the drug in body by half during elimination
162
Clinical use half life
Dosing
Time to steady state
163
Aspirin side effects
GIT - NV, peptic ulcer, gi bleed
Resp - bronchospasm, worsening asthma
Allergy and rash
LFT derangement
CNS headache tinnitus dizziness
164
Mechanism action colchicine
Anti-inflammatory effect - binds tubulin and inhibits WBC migration
Inhibits formation leukotriene B4
165
Mechanism action colchicine
Anti-inflammatory effect - binds tubulin and inhibits WBC migration
Inhibits formation leukotriene B4
166
Side effect cox2 inhibitors
Celecoxib, meloxicam
Renal toxicity
GIT
Thrombosis
167
Tramadol moa
blocks seratonin and NA uptake
Weak mu agonist
Tox - seizures, N&V
Has active metabolite
168
Tramadol PK
Good oral bioavailability
High vd
Hepatic metabolism with active metabolite
Half life 6h
Urinary excretion
169
Solubility characteristics NO
Low solubility in blood
High art tension rapidly
Rapid equilibrium in brain
Fast onset and offset action
170
MOA NO
Activates GABA A receptors directly
171
Organ effects NO
CNS analgesic and amnesia
Renal reduced gfr
CVS myocardial depression
Resp reduced response to co2 and hypoxia
172
Rationale benzodiazepines in etoh withdrawal
Down regulation GABA receptors in etoh dependence
Overcome neuroexcitatory symptoms of gaba deficiency
173
Spectrum penicillin G
Gram positive rods and coccu
Anaerobes
Gram -ve cocci
Staph, strep, meningococci
174
Mechanism atypical antipsychotics
Serotonin receptor antagonists
Weaker dopamine antagonists
175
Side effects atypical antipsychotics
EPSEs
Antimuscarinic
Orthostatic hypotension
Weight gain
NMS
Agranulocytosis
176
Full vs partial agonist
Full can evoke maximal response but partial cannot
177
Mechanism of trimethoprim
Inhibits DNA synthesis
Inhibits bacterial digydrofolate reductase
Bacteriostatic unless with sulfonamide
178
Resistance to trimethoprim
Reduced cell permeability
179
Charcoal not effective against
Lithium, potassium
Alcohol, cyanide
Effective against carbamazepine
180
Uses and se penicillamine
Wilson's disease and copper poisoning
NV hypersensitivity
181
Uses and se penicillamine
Wilson's disease and copper poisoning
NV hypersensitivity
182
Side effects promethazine
Sedation
Hypotension (alpha blockade)
Anticholinergic
Antidopaminergic
183
Drug interactions with amiodarone
Inc digoxin levels
P450 inhibitor and inc INR with warfarin and phenytoin
184
Fleicanide pk
PO, good bioavailability
Half life 20h
H
R
185
Lidocaine vs other class 1 antiarrhythmics
Does not prolong AP
186
Class 1 antiarrhythmic action on AP
A prolong
B nil
C minimal
187
Na nitroprusside
IV, rapid onset, short half life
Metabolized to cyanide in RBC then thiocyianate in liver
Cyanide hypotension, flushing, metabolic acidosis
Thiocyanoate ataxia blurred vision
188
Mechanism calcium channel blockers control angina
Decrease inotropy and oxygen demand
Decrease afterload by relaxing vascular smooth muscle
189
Mechanism calcium channel blockers control angina
Decrease inotropy and oxygen demand
Decrease afterload by relaxing vascular smooth muscle
190
Difference in side effects dihydropyridines and non
Flushing headache and tachycardia vs bradycardia
Both hypotension
191
Indications verapamil
Angina, htn, atrial arrhythmia
192
Side effects mannitol
Extra cellular volume expansion
Dehydration
Hypernatraemia
193
Mechanism aspirin
Irreversible inhibition cox 1 and 2
Cox 1 antiplatelet inhibits synthesis thrombose A2
Cox 2 inhibits PG synthesis
194
Indications antiplatelets
IHD
TIA/ CVA
Prophylaxis in pre-eclampsia
195
Mechanism clopidogrel
Anti platelet irreversible ADP receptor blocker
196
Clopidogrel PK
Prodrug
Activated in liver by p450
Elimination half life 1 h but effects last life span of plt
Loading 300-600mg then 75mg OD
197
Types of antiplateket agent
Cox inhibitor aspirin
ADP inhibitor clopidogrel
Gp2b3a inhibitor abciximab
198
Mechanism heparin
Binds to antithrombin and ENHANCES its activity
Inhibits 2, 9, 10
199
Heparin reversal
Protamine
200
Drugs not affected by age
Salicylate
Warfarin
Oxazepam
Lidocaine
Ethanol
201
PK in children
Body size and composition - more water, Altered distribution
Reduced fat in preterm
Decreased hepatic metabolism longer half lives
Decreased albumin
Gfr lower in newborns
202
Efficacy
Maximal effect a drug can produce when all the receptors are occupied
203
Factors affecting potency
Affinity of receptors for drug and coupling efficiency
204
Factors affecting potency
Affinity of receptors for drug and coupling efficiency
205
Activation of second messengers
Method of transmembrane signaling
Drug binds receptor extracellular side Plasma membrane
Activates g protein on cytoplasmic side EFFECTOR element
Activates second messenger which mediates response
206
Examples of second messengers
CAMP via adnyl cycles mobilized fat and carbs
CGMP via NO relaxes smooth muscle
207
Examples of transmembrane signaling
Via second messenger
Lipid soluble through membrane to intracellular
Via transmembrane receptor
Ligand gated transmembrane ion channels
208
Main mechanisms for spare receptor phenomenon
Numerical - limited substrate with excess receptors
Temporal - prolonged effect after transient binding
209
Factors affecting extent and rate of drug absorption
Route
Formulation e.g. enteric coating
Solubility
Surface area e.g. lungs vs stomach
210
Drug ionization and lipid solubility
Highly ionized water soluble
Unionized lipid soluble
211
Drug ionization and lipid solubility
Highly ionized water soluble
Unionized lipid soluble
212
Volume of distribution
amount of dug in body / conc drug in plasma
213
Side effects prochlorperazine
Acute dystonia
Sedation
Anticholinergic
214
When to alter dose ondansetron
Hepatic failure
