Pharmacology Flashcards
what are the inter related processes of pharmacokinetics (4)
- absorption
- distribution
- metabolism
- excretion
what are the interrelated processes of pharmacodynamics (4)
- receptors
- ion channels
- enzymes
- immune system
what is pharmacokinetics
the relationship between drug dose, concentration in bodily fluids and tissues, and time
Simply: what the body will do with a given drug
what is absorption
The processes by which a drug moves from the site of administration to the bloodstream.
what are possible routes of administration (7)
- Oral
- inhalational
- transdermal
- transmucosal- ( sublingual/ buccal, rectal/ suppositories, nasal spray)
- subcutaneous
- intramuscular
- intravenous.
what factors affect absorption (3)
- Physical properties of drug
- Solubility
- Diluent
- Binders
- Formulations - Dose
- Site/Route.
what is volume of distribution
Apparent volume into which a drug is distributed throughout the body’s compartments (tissues. fat, muscle) relative to its concentration in the plasma
what factors affect volume of distribution (4)
- Lipid solubility
- Protein binding
- Ion binding- electrical charge
- Molecular weight- smaller easy to cross membrane
what is the formula for Vd
total quantity of drug/ plasma concentration in steady state
what is bioavailability
its the fractional dose of a drug that is actually able to reach the systemic circulation
what is phase 1 metabolism
is metabolism that results in the loss of pharmacologic activity through cleavage or formation of a new or modified functional group ( oxidation, reduction, hydrolysis)
what is phase 2 metabolism
is metabolism that involves conjugation of the parent drug or phase 1 metabolite with endogenous compounds ( glucuronidation, sulfation. acetylation)
what is hepatic clearance
it is the volume of blood/plasma that is completely cleared of drug by the liver per unit of time
what is terminal half life
Time required for the plasma concentration to decrease by 50% during the terminal phase of decline
what is clearance
Represents the volume of blood or plasma from which the drug is completely eliminated in unit time (ml/min)
which organs are primarily responsible for drug clearance (2)
- liver
- kidneys
what is pharmacodynamics
Relationship between a drug’s mechanism of action and the biochemical and physiologic response produced in the body.
Simply put: What does the drug do to the body.
how do drugs exert their effect
by interactions with receptors, or cellular macromolecules, located throughout the body.
what is the therapeutic index
Ratio of LD50 to ED50.
what is the minimal alveolar concentration (MAC Value)
its the concentration of an anesthetic gas that when inhaled prevents 50% of subjects from responding to noxious stimulus
( it helps quantify the potency of inhaled anesthetic agents)
what are pharmacodynamic interactions (6)
- Agonism- stimulation of receptor.
- Antagonism- inhibition of receptor.
- Synergism- enhanced effect.
- Additivity- combined effect.
- Partial agonism- partial stimulation
- Inverse agonism- reversal of receptor activity.
what is the general anesthesia triad
- hypnosis (unconsciousness)
- analgesia
- paralysis
hypnosis can be achieved via by what routes (2)
- intravenous
- volatiles
paralysis can be achieved by what methods (2)
- depolarizing
- non depolarizing
what are intravenous anesthetics used for(2)
- during induction and maintenance of hypnosis
- amnesia- to reduce anxiety, stress and improve patient comfort
what are the types of amnesia (2)
- Anterograde-inability to form new memories
- Retrograde-loss of existing memory
what is an ideal intravenous anesthetic (6)
- Rapid onset + rapid recovery
- Storability: Long shelf-life at room temperature
- Pleasant effect during the induction phase
- Safety following extravasation or inadvertent intra-arterial injection
- Analgesic at sub-anesthetic concentrations
- Minimal cardiovascular and respiratory depression
what effects dont you want from an intravenous anesthetic (7)
1.toxic effects
2. emetic effects
3. pain on injection
4. histamine release or hypersensitivity reaction
5. interference with other drugs
6. stimulation of porphyria
7. unpleasant experiences in the peri-operative phase
what makes IV anesthetics have rapid onset (2)
- iv administration leads to fast delivery into well vascularized tissue
- rapid diffusion across the blood brain barrier due to
- lipid solubility
- protein binding (low?)
what causes IV anesthetics to have rapid recovery (3)
- rapid redistribution
- rapid elimination
- metabolism
what are examples of IV anesthetics (2)
- Barbiturates
- thiopental
- methohexitone - Non-barbiturates
- propofol
- ketamine
- etomidate
what IV anesthetics are commonly used in malawi (3)
- Thiopentone
- Ketamine
- Propofol
what is the MOA of thiopentone (3)
- Prolonged GABA dependent Cl- channel opening
- Rapid onset (one arm-brain-circulation time)
- Short duration of action
what are effects of thiopentone (4)
- Antiepileptic activity
- Minor degree of muscle relaxation
- Hypotension
- Histamine release
thiopentone is unsafe in what
porphyria
what happens with repeated administration/ infusion of thiopentone
has long half time
what is the MOA of ketamine
NMDA receptor antagonist
how is ketamine metabolized
Ketamine is demethylated to the active metabolite norketamine by hepatic P450 enzymes
what are the effects of ketamine (8)
- Produces sympathetic nervous system stimulation, increasing circulating levels of adrenaline and noradrenaline- increased blood pressure
- causes a dissociative anesthesia
- Analgesia (acute, chronic, Complex reginal pain syndrome)
- Anesthesia
- Hallucinations
- Bronchodilatation
- Anti-depressive
- Airway reflexes are maintained
how can ketamine be given (5)
- IV
- IM
- rectally
- orally
- inhalational
what are ways of taking ketamine recreationally (2)
- orally
- inhalational
what happens during the dissociative state of ketamine (5)
- Detachment from one’s body & external world (depersonalization & derealization)
- Mimics schizophrenia
- Unaware of own identity
- Sensation of floating, euphoria
- Loss of time perception
in adults you give ketamine with what
benzodiazepine
what is the MOA of propofol
Affects GABA Chloride channels
what are the properties of propofol (2)
- Highly lipid soluble
- Oil-in-water emulsion
what additives are found in propofol (3)
- soybean oil
- glycerol
- egg lecithin
where can propofol be used (3)
- Induction & maintenance of general anaesthesia
- Sedation in ICU
- Sedation for other procedures
who should give propofol
persons trained in its use because it has a narrow therapeutic range
what needs to be readily available when giving propofol
advanced airway management
what are the effects of propofol (4)
- Rapid onset of anaesthesia (one arm-brain circulation time).
- Rapid recovery.
- Little accumulation
- Reduces laryngeal reflexes (ideal for use with LMA)
propofol is safe to use in what (2)
- porphyria
- malignant hyperthermia
what are side effects of propofol (6)
- Reduces laryngeal reflexes
- Dose dependent_ fall in SVR, no reflex tachycardia, slight fall in CO
- Considerable fall in BP
- Pain on injection
- Spontaneous excitatory movements (misinterpretation can happen)
- Crosses placenta (not used in obstetrics)
what are the inhalational anesthetics ( volatiles) (6)
- Halothane
- Isoflurane
- Enflurane
- Sevoflurane (standard in rich countries)
- Desflurane
- Xenon
how does a lipid soluble anesthetic affect the MAC
the MAC will be lower and the greater the potency
when mixing gases MAC values are what
additive
what is oil:gas partition coefficient
Measure of the lipid solubility
therefore has a close relationship to MAC and therefore potency
what is the meyer overton hypothesis
is the theory of anesthetic action which proposes that the potency of an anesthetic agent is related to its lipid solubility- the hypothesis hypothesis proposed that once a sufficient number of anesthetic molecules were dissolved in the lipid membranes of cells within the central nervous system, anesthesia would result by a mechanism of membrane disruption.
what is the blood: gas coefficient
Expresses the solubility of a gas in blood
e.g. Low coefficient = low solubility = rapid onset
what are effects of halothane (8)
- 20-25% metabolized in the liver (hepatotoxic)
- Cardiac dysrhythmias
- Increased cerebral blood flow and ICP
- Reduced myocardial contractility, HR, CO, BP
- Reduced TV
- increased RR & PaCO2
- reduced laryngeal reflexes & airway resistance
- Uterine relaxation (cave obstetrics)
what is halothane like (2)
- colourless liquid
- pleasant smell
what is isoflurane like (2)
- Colourless volatile liquid
- has an irritant smell
comparing isoflurane to halothane what is the difference (2)
- Isoflurane has a Lower blood gas solubility than Halothane and therefore provides rapid onset of and recovery from anesthesia
- isoflurane increases cerebral blood flow and ICP less than halothane
what are the effects of isoflurane (8)
- Lower blood gas solubility that Halothane and therefore provides rapid onset of and recovery from anesthesia
- Low toxicity to liver and kidneys
- Increases cerebral blood flow and ICP( less than Hal)
- Does not cause arrhythmias(does not increase myocardial sensitivity to adrenaline)
- Little effect on myocardial contractility.
- Dose dependent fall in blood pressure due to decrease in SVR
- Reduced TV
- increased RR
what are the types of muscle relaxants (2)
- depolarizing
- suxamethonium - non-depolarizing
i) Steroids
- vecuronium
- rocuronium
- pancuronium
ii) Esters
- atracurium
how does suxamethonium work (3)
- mimics action of acetylcholine, binding to nicotinic receptors on the muscle causing depolarization
- rapid onset of action- 1min
- it is short acting 4-6 mins after observable muscle fasciculation
what are the undesirable effects of suxamethonium (7)
- Mild to severe muscle fasciculation which can lead to increased CO, BP, ICP
- Myalgia
- Hyperkalemia (burns, neurological conditions, peripheral nerve injuries, renal failure, acidosis) which can lead to cardiac arrest
- Dual block
- Increased intraocular pressure
- Malignant hyperpyrexia
- Parasympathetic effects
what is the most widely used non depolarizing agent
vecuronium (its cheap)
how does vecuronium work (4)
- Little CVS effects
- Moderately short onset of action – 2min
- Moderate duration of action – 20min
- Rare Histamine release
how does rocuronium work (3)
- Fast onset of action (60 sec) – similar to Suxamethonium
- Longer duration of action than Vecuronium
- Less potent but otherwise similar to Vecuronium
what metabolizes atracurium
Hofmann degradation into Laudanosine and ester hydrolysis
atracurium is the drug of choice in what condition (2)
- renal failure
- hepatic failure
what are side effects of atracurium (2)
- severe Histamine release
- profound hypotension
where do you store atracurium
fridge because its unstable
