23. Pharmacology: Part 1 (-Anticonvulsants) Flashcards
Branch of medicine concerned with the USES, EFFECTS, and MODES OF ACTION of drugs
Pharmacology
Branch of pharmacology concerned with the EFFECTS OF DRUGS and the MECHANISM of their action (“action of drug on the body”)
Pharmacodynamics
Branch of pharmacology concerned with the MOVEMENT OF DRUGS within the body (“action of body to the drug”)
Pharmacokinetics
Pharmacokinetics steps: “ADME”
Absorption
Distribution
Metabolism
Excretion
Main site of absorption in the body
Jejunum of small intestine
BQ: Primary solubility of drug to be absorbed?
Form of drug that is EASY TO ABSORB
Lipid soluble form
Major site of metabolism
Liver
converts drugs into water soluble form to easily excreted by the kidney
Liver
Form of drug that is EASY to EXCRETE
Water soluble
Major site of excretion
Kidney
Study of drug’s harmful effects
Toxicology
General rule: Kailan nagiging toxic yung drug?
Pag na-“overdose”
Has “Adsorption” property (nagsstick sakanya yung toxins; diretso sa excretory system) to prevents ORALLY taken drugs TOXICITY
Activated charcoal
INDUCES VOMITING (emetic) ; can be used pag nasa GIT pa yung drugs na tinake para di na pumunta sa circulatory system
Syrup of Ipecac
BQ: It is the “accumulation of drug” because it cannot be excreted by the body?
Cumulation
“Cumulation” or accumulation of drug in the body is associated with what organ damage?
- Liver damage - clearance rate: ⬇️ (marereduce yung nacconvert na Lipid soluble ➡️ WATER soluble)
- Kidney damage - Normal yung liver:nacoconvert yung drug into water soluble BUT hard to excrete!
BQ: Drugs contraindicated for GLAUCOMA?
Diazepam
Anticholinergic drugs
BQ: What is the most common allergenic drug?
Penicillin
BQ: Drugs SAFE FOR PREGNANCY
Local anesthetics : lidocaine
Analgesics : biogesic
Sedative-Hypnotics
*AMOXICILLIN (safe!)
BQ: study of DAMAGE TO FETUS during development
Teratology
Most critical period of development of fetus?
1st trimester: organogenesis
Examples of Teratogenic drugs
- Tetracycline :tooth discoloration (til 8y/o)
- Thalidomide
- An anti cancer drug {no effect sa pregnant rats=no effect ; clinical trial=dysplastic tissues: bata kulang body parts}
BQ: study of drug DOSAGE
Posology
Process of DRUG UPTAKE from the site of administration towards the bloodstream
Absorption
“Enteral”
Oral
Rectal
“Parenteral” - uses needle
IV IM Intradermal Subcutaneous Intrathecal
Most common route; easy to administer
Oral route
Suppositories
Rectal
Route with 100% bioavailability; bypasses the first pass effect; “TOTAL ABSORPTION”
- (100ml inject = 100ml circulatory system)
Intravenous
Term: Dose ng drug na nakakarating sa circulatory system
Bioavailability
Most common site of IV administration
Antecubital region
BQ: Most common muscle used in IM administration
Vastus lateralis
Other muscles that can be used in IM administration
- Gluteus maximus - BQ: (“superolateral”/upper outer corner)
- Deltoid
Used during skin testing to determine if patient has drug allergy
Intradermal
Why intradermal during skin test?
Least and slow absorption
administration of drug in the SPINAL
Intrathecal
Fastest route if the target site is the BRAIN; (sedation)
Inhalational
Degree of needle insertion in IV
35 degrees
Degree of needle insertion in IM
90 degrees
Degree of needle insertion in Intradermal
0 - 15
{sa boards: piliin yung LOWEST value}
Degree of needle insertion in Subcutaneous
45 degrees
Most common drug administered subcutaneously
Insulin
BQ: Which route bypasses membranes?
Intravenous
- diretso na sa circulatory system
BQ: Which route bypasses ABSORPTION process?
IV
- distribution na agad
Drug properties that influence absorption
Must be “weak acids / weak bases”
- they become MORE LIPID SOLUBLE (mas madali iabsorb sa circulatory system)
ph of blood = 7.4
✨ WEAK ACIDS (pH of 6)
- weak acids are attracted to HIGHER pH levels
- 6 ❤️ 7.4
✨ WEAK BASES (ph of 8)
- weak bases are attracted to LOWER pH levels
- 8 💜 7.4
Amount of drug that reaches the circulatory system after administration
Bioavailability
Synonymous terms to “water soluble” drugs
Hydrophilic
Lipid INSOLUBLE
Ionized
Synonymous terms to “lipid soluble”
Fat soluble
Hydrophobic
Water INSOLUBLE
UNionized
Drug solubility that is UNABLE to cross the PHOSPHOLIPID bilayer
Very hydrophilic (very water soluble) - hindi makakatagos sa membrane
Solubility of drug that is UNABLE to be absorb due to INSOLUBILITY IN AQUEOUS FLUID
Very very hydrophobic/lipid soluble
- insoluble sa aqueous fluid ng intestinal area: hindi nalulusaw sa tubig
In reality: What must be the “drug’s solubility” to be absorbed?
Drugs must be SLIGHTLY HYDROPHILIC and LARGELY HYDROPHOBIC
Mej water soluble pero MAS lipid soluble
BQ: Primary solubility of drug to be absorbed (sa boards)
Lipid soluble
Phenomenon of drug metabolism whereby the CONCENTRATION OF ORALLY TAKEN DRUGS IS REDUCED before reaching the systemic circulation
First pass effect
Responsible for First Pass Effect
Liver
- dadaan muna yung drug sa portal vein to liver(metabolizes drug) bago makarating sa target site
Bioavailability is influenced by (3):
Drug solubility
Route
First pass effect
Ability of drug to move from circulatory system into their target sites
(- Once na pumasok na sa blood stream)
Distribution
Once the pumasok drug sa circulatory system: Meron 2 forms: (active and inactive)
- Free ionized drug - may effect agad; free floating drug
2. Bound drug - reserve; bounded to albumin
Most common binding site of drugs?
Albumin
Tendency of a substance to separate or dissociate from its binding
Dissociation constant (Kd)
Lower Kd ⬇️:
Separation -
Duration of effect -
Onset of action -
Lower Kd ⬇️:
Separation - lesser ⬇️
Duration of effect - longer
Onset of action - slower distribution
Higher Kd ⬆️:
Separation -
Duration of effect -
Onset of action -
Higher Kd ⬆️:
Separation - higher ⬆️
Duration of effect - shorter
Onset of action - faster distribution
BQ: Most important microsomal enzyme of Liver?
Cytochrome P450
FUNCTIONS OF LIVER
- Lipid soluble to lipid insoluble
- “Water soluble” easily excreted by the kidney - Active drug to INACTIVE drug
- detoxification (kasi yung hindi pwdeng magstay na active yung drug: kahit sya yung may effect, toxic pa din) - PRODRUGS ➡️ ACTIVE FORM
- prodrug = “inactive drug”
- para maconvert to active need muna mag pass sa LIVER
-
Examples of PRODRUGS (inactive drugs=no effect) that must go to the LIVER to be activated:
- Aspirin (Acetylsalicylic acid) ➡️ Salicylates
- Codeine ➡️ Morphine
- Alcohol ➡️ Ethanol
2 types of Local anesthesia:
Amide - “ii”
Ester - “i”
Metabolism of Local anesthetics: “EPAL”
Ester - Plasma
Amide - Liver
Most common topical anesthesia?
Benzocaine
Exception: dalawang “ii” PERO ester
piPEROcaine
Exception: Amide but metabolized in BOTH liver and plasma
Articaine - (“maarti” : metabolized sa liver and plasma)
BQ: local anesthesia used if allergic in both ester and amide
Diphenhydramine Hcl (Benadryl) - injected!!
BQ: Plasma enzyme (metabolism)
Plasma pseudocholinesterase
Drugs metabolized in PLASMA
Ester LA
Succinylcholine
BQ: primary use of succinylcholine
For laryngospasm
Major organ for excretion
Kidney
Drug excreted by the lungs
Nitrous oxide (laughing gas)
Drugs or substances excreted by BREAST MILK
Alcohol
Caffeine
Cocaine
Nicotine
Time required for a drug to REDUCE HALF of its initial value
Half life (t1/2)
Rate at which the active drug is removed from the body
Clearance
Amount of drug eliminated is CONSTANT and is NOT DEPENDENT on the CONCENTRATION of drug in plasma fluid
Zero order kinetics
- constant: clearance rate
- not constant: half life
Examples of drugs that follow ZERO ORDER KINETICS
Alcohol - (clearance rate=15ml/hr)
Phenytoin
Aspirin
Amount of drug eliminated is DEPENDENT on the CONCENTRATION of drug in plasma fluid (most drugs follow this)
First order kinetics
- may “constant half life”
BQ: Which drug has more chances of CUMULATION
a. Zero order kinetics
b. First order kinetics
c. Same
Zero order kinetics: ⬆️ cumulation
( if ⬆️ dose = LONGER to eliminate)
- Sa first order: kahit increase yung dose=may certain time na maeeliminate ung drug (CONSTANT HALF LIFE)
Dosage of drug needed to produce an effect
Potency
More potent ⬆️
Dose needed =
⬆️ More potent = ⬇️ dose needed
⬇️ Less potent
Dose needed =
⬇️ potent = ⬆️ dose needed
“Potency” of Fentanyl vs Morphine (narcotics: for pain)
Fentanyl (effect: 2-3mcg) MORE POTENT than Morphine (effect: 200-800mcg)
Refers to the EFFECT of a DRUG
Efficacy
⬆️ Efficacy:
Efficacious =
⬆️ Efficacy
⬆️ MORE efficacious
⬇️ Efficacy:
Efficacious =
⬇️ Efficacy:
⬇️ LESS efficacious
“Efficacy” of Fentanyl vs Morphine
Fentanyl LESS EFFICACIOUS than Morphine
Morphine MORE EFFICACIOUS than Fentanyl
Maximum effect of a drug where NO EFFECT is added even though DRUG DOSE is INCREASED (Limit)
“Maximal effect” or “Ceiling effect”
{ ⬆️ dose = ⬆️ effect until MAXIMAL EFFECT is reached }
BQ: Does doubling the dose, doubles the effect? Yes/No
No - because it will reach “maximal effect”: no effect even you add more dose
It refers to how well the drug can be used in REAL WORLD
“Effectiveness”
Drug can have HIGH EFFICACY but ⬇️Effectiveness: “effective pero nakakamatay agad or mas toxic”
Dose-Effect (“Dose-Response”) Rel:
- The effects of a drug are dose dependent
- (either Therapeutic or Toxic)
- It can be shown into 2 types of DOSE RESPONSE CURVES:
Graded dose-effect curve
Quantral Dose-effect curve
Curve that describes the Degree of response of a SINGLE BIOLOGICAL UNIT (cell or human) to a given drug dose
Graded Dose-Effect Curve
Graded dose effect curve
Y-axis:
X-axis:
Graded dose effect curve
Y-axis: effect
X-axis: dose
Curve that describes relationship between the increasing drug dosage and the percentage of POPULATION that shows the drug’s pharmacological and lethal effects
Quantal Dose Effect Curve
Curve that detects the “MARGIN OF SAFETY” of a drug by comparing the therapeutic dose and toxic dose
Quantal Dose effect curve
Quantal Dose effect curve
Y-axis:
X-axis:
Quantal Dose effect curve
Y-axis: Population
X-axis: Dose
BQ: Formula of Therapeutic Index
TI = LD50/ED50 (“TLE”)
BQ: dose of drug that has THERAPEUTIC EFFECT in 50% of population
ED50 (“median EFFECTIVE DOSE”)
BQ: dose of drug that has LETHAL EFFECTS in 50% of population
LD50 (“median lethal dose”)
Example of drug that has narrow therapeutic index (drug very lethal)
- Chemotherapeutic agents
2. Digoxine - antihypertensive drug that has VERY NARROW TI
Targets of drug action:
- Receptors
- Enzymes
- Drugs acting as Physical or Chemical agents
Examples of Drugs with RECEPTORS as target sites:
- Narcotics
- receptor: mu kappa delta - Cholinergic drugs
- receptor: muscarinic
Examples of Drugs with ENZYMES as target sites:
- MAO-Inhbitors
- (Mao breakdown excitatory nt “DoNES”)
- MAO-I : “antidepressant” = iniinhbit yung MAO : ⬆️DoNES - Anti acetylcholinesterase or Anticholinesterase
- reduce action of “Acetylcholinesterase”
- used to improve muscular contraction
BQ: Anti-acetylcholinesterase or Anticholinesterase is used in what disease?
Myasthenia gravis: “muscle weakness”
- to improve muscular contractions
Ability of drug to BIND to its target site
Affinity
- (“ALL DRUGS have AFFINITY”)
Ability of drug to produce an EFFECT after binding to its target site
- (kaya niya “iactivate yung receptor”)
Intrinsic activity
- (“NOT ALL can activate receptor/have intinsic activity”)
Examples of drugs that acts as physical or chemical agents (ginagaya ung sa body)
Epinephrine
Insulin
Part of body where drugs interact to produce their effects
Receptors
Drugs that have AFFINITY + INTRINSIC ACTIVITY
Agonists
- (example: Ach)
Drugs that has ✅affinity but no ❌ intrinsic activity (hindi kayang iactivate yung receptor)
Antagonist
Elicits a MAXIMAL RESPONSE by activating all or a portion of the receptors
Full agonists
Acetylcholine : Agonist/Antagonist?
Ach = Agonist!
- Ach: Parasympathetic
- ✅ Affinity: Nagbbind to sa “muscarinic receptor” ng lahat ng effector organs ng parasympathetic (ex. Lacrimal glands)
- ✅ Intrinsic act: Inaactivate ng Ach yung muscarinic receptor ng lacrimal glands to depolarize para magproduce ng tears
Anticholinergic drugs: Agonist/Antagonist?
Antagonists : Anticholinergics
- Belladonna alkaloids (atropine and scopolamine)
- nagaact sa sympathetic NS
- ✅Affinity - nagbbind sa muscarinic receptors
- ❌Int act - doesnt activate receptor
- 📌 Pinaprevent nya lang yung pag bind ng “Ach” sa muscarinic receptor para hindi maactivate!
- 📍 wala tlgang effect sa receptor: Prevents effects of parasympathetics ➡️ ✅sympa effects
Anticholinergic drugs: Belladonna alkaloids (2)
Atropine
Scopolamine
What type of antagonist are the anticholinergic drugs (atropine and scopolamine)?
Competitive antagonists
- nakikipagcompete sa cholinergic drugs
Type of antagonist that competes with the receptor of agonists
- which results to decrease POTENCY ⬇️ (dose needed to produce effect)
Competitive antagonists
Type of antagonist that has its OWN Receptors; doesnt compete
- results in decrease EFFICACY ⬇️
Non competitive
BQ: Naloxone is an ANTAGONIST of what drug?
Narcotics
- (morphine, codeine, heroin)
BQ: Flumazenil is an ANTAGONIST of what drug?
Benzodiazepines
BQ: DOC to reverse narcotic effects
Naloxone
If wala sa choices: go for Naltrexone
Intrinsic activity of >0 and <1
- act as antagonist and agonist
- naactivate lng ung receptor partially
- produces LESS maximal response even all receptors are occupied
Partial agonist
Theory: Drug effect is proportional to the RATE at which the drug and receptor combine
- (both agonist and antagonist have affinity and intrinsic activity; “immediate binding of drug t receptor dun magkakaeffect then dahan dahan mawawala ung effect”)
Paton’s Rate Theory
Paton’s rate theory: Drug associates quickly and disassociates immediately to the receptor, to be able to reassociate again.
Agonists (pag mabilis association and dissociation ng drug)
Paton’s rate theory: drug associates, but dissociates much SLOWER, therefore REASSOCIATION to the receptor is also SLOWER
Antagonists (pag mabagal dissociation)
More accepted drug receptor interaction theories: Clark’s or Paton’s?
Clark’s occupational theory
Sedative hypnotics are drugs that are used for:
Sedation - feeling asleep
Hypnosis - sleep
Muscle relaxation
Feeling asleep; “loss of anxiety”
Sedation
Type of sedation: awake and relax
Minimal or conscious
Type of sedation: feeling asleep but can follow commands
Moderate
Type of sedation: sleep but can be awaken
Deep sedation
“Medically induced coma”
General anesthesia
2 classifications of sedative hypnotics
Barbiturates - with Barbaric acid
Non barbiturates - without
Active ingredient of Barbiturates that produces sedative effect
Barbaric acid
Barbiturate used to induce general anesthesia
Ultra short acting
- fast induction because “very lipid soluble”
- but rapid recovery
Ultra short acting barbiturates
ultra mura - “TM”
Thiopental
Methohexital
Stage 1 Gen Anes
🔺Anterograde Amnesia (hindi nagfform ng new memories)
🔺analgesia (absence of pain)
Stage 1 - 4 of General anesthesia by?
Guedel’s stages of general anesthesia
Type of amnesia na hindi nagfform ng new memories
Anterograde amnesia (50 first dates) - example pag "drunk" = nakakalimot ka
Type of amnesia na nabubura yung old memories
Retrograde memories (meteor garden)
End of stage 1 and Start of stage 2 GA:
Unconscious patient
Stage with “delirium”
- very unstable patient: high bp, seizure, etc
- ayaw na ayaw ng anesthesiologist dto kasi madaming complication dito
Stage 2 GA
Most stable stage of General anesthesia?
Stage 3 : surgical anesthesia
Stage 4 GA:
Stage 4: respiratory depression ➡️ death
Kailan umaabot sa stage 4 of GA?
Overdose
Used to maintain stage 3 general anesthesia
Long acting barbiturates
Where very lipid soluble drugs are stored
Adipocytes
BQ: Short acting barbiturates (“SPENT”)
Secobarbital
Pentobarbital
BQ: Intermediate acting drugs
“Kalahati” = “AmBuy”
Amobarbital
Butabarbital
BQ: Long acting barbiturate or sedative hypnotics (pag hndi mo alam, eto na sagot)
Phenobarbital
Mephobarbital
Primidone
Type of barbiturate used in insomia
Short acting
Intermediate acting
Type of barbiturate or sedative hypnotic used during epileptic seizures
Long acting
BQ: Most commonly used “non barbiturate” in patients
Chloral hydrate (orally)
Non barb for insomia
Flumazepam (benzodiazepines)
Non barb found in alcohol beverages
Ethanol
Classifications of DIPHENHYDRAMINE Hcl
- H1 blocker : anti histamine📌(primary use)
- sedative
- local anes if allergic to amide/ester
- slight anticholinergic effect
Regulates “sleep wake cycle” in sedative hypnotics can affect what system
RAS
Reticular activating system
Most common inhibitory nt?
GABA
Sedatives vs GABA
Sedatives ENHANCES Gaba
Drug Components of lethal injection
Thiopental
Pancuronium bromide
Potassium chloride
Primary use of sedative hypnotics?
Sedation
Induces general anesthesia (ultrashort)
BQ: “Any drug that acts on CNS can cause drug dependence” True or False?
True
Adverse effect of sedative hypnotics = reddish skin
Stimulates PORPHYRIN PRODUCTION
DO NOT COMBINE Sedatives hypnotics with what drugs?
CNS depressants: "SNAB" Sedative hypnotics Narcotics Alcohol Benzodiazepines
Depressants (“SNAB”)
Sedative hypnotics
Narcotics
Alcohol
Benzodiazepines
Respiratory depression - death is seen during what stage of general anesthesia
Stage 4
Property of CNS depressants (shouldnt be combined because it has excessive effects ⬆️⬆️)
Synergistic (1+1= >2)
1+1=0
Antagonistic (cancels effect)
1+1=2
Additive
BQ: Sedative-Hypnotics produces ANALGESIA. True/False?
Falseeeeeee
BQ: Sedative-Hypnotics produces DRUG DEPENDENCE. True/False?
Trueeeee
“Anticonvulsants” are aka:
Anti seizure
Anxiolytics
Anti anxiety
Minor tranquilizers
Primary use of anticonvulsant drugs
Anti-epileptic or anti seizure
Antianxiety
Type of seizure: abnormal activity in just ONE PART of the brain
Partial seizure
Type of seizure: abnormal activity in ALL parts of the brain
Generalized seizure
“PETIT MAL”
- Absence of consciousness; absence of movements for few seconds
Absence seizure
Type of Generalized seizure: Awake; muscles are jerking for few seconds to few mins
Myoclonic
“Drop seizure”
- Absence of muscle tone
- Awake; muscle relaxation for few seconds to few min
Atonic
- most common type of generalized seizure
- Unconscious
- muscle stiffness + jerking movts few mins
Tonic clonic
“Grand mal”
Tonic clonic
Petit mal
Absence seizure
Drop seizure
Atonic seizure
“Repeated grand mal” 30mins seizure
Status epilepticus
BQ: DOC for tonic clonic seizures and status epilepticus
Diazepam (benzodiazepines)
Pag wala to sa choices: go for phenytoin
BQ: Examples of Calcium Channel Blockers
Nifepidine
Verapamil
Brand name of phenytoin
Dilantin sodium
Dental side effect of phenytoin
Gingival hyperplasia
Drugs assoc with gingival hyperplasia
Phenytoin
Cyclosporins
Calcium channel blockers (nifedipine / verapamil)
Brand name of Carbamazepine
Tegretol
BQ: DOC for Tic Douloureux (painful spasms)
Carbamazepine
BQ: Common antiseizure drugs (except:)
- Benzodiazepines (Diazepam)
- Phenytoin (Dilantin Na)
- Carbamazepine (Tegretol: Tic douloureux)
BQ: 4. VALPROIC ACID
BQ: 5. Barbiturates (least) - mainly a “sedative hypnotic”
Mechanism of action of antiseizure drugs
Potentiates GABA (-) receptors and inhibitory nt
Drug uses of anticonvulsants or antiseizure drugs
- Anti convulsanr or anti seizure or anti epileptics
- Preoperative sedation (anti anxiety)
- Induction of Gen Anes
BQ: Anticonvulsants used to induce general anesthesia? Which is the most common?
Benzodiazepines
✅ Midazolam : most common; most lipid soluble
📌 Diazepam
❌ Lorazepam : least common; least lipid soluble
Primary adverse effect of anticonvulsants
Severe sedation
*And paradoximal excitement (nakabold hahaha) : “stimulatory effect”
Other adverse effects of anticonvulsants
✅Severe sedation ✅ Paradoximal excitement - Drug dependence - Respiratory depression : stage 4 - overdose - Drug induced gingival hyperplasia
BQ: anti-seizure + anti-arrythmic drug
Phenytoin
Drug interaction of anticonvulsants
Potentiates other CNS depressants
wag icocombine bec synergistic 1+1=>2
Benzodiazepines are metabolized SLOWLY by the
Liver
BQ: active metabolite of benzodiazepines
Dimethyldiazepam
BQ: Diazepam is slowly and poorly absorbed in what route of administration?
IM!!
Diazepam: oral and Iv
BQ: Drugs with slight anticholinergic effects (“DiTriBeAM”)
Diphenhydramine Hcl Tricyclic antidepressants Benzodiazepines Antipsychotic Meperidine - "Demerol" (narcotic agent)